Aloys Hüttermann

Aloys Hüttermann
The Hydrogen Bond

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Aloys Hüttermann
The Hydrogen
Bond
A Bond for Life

Author
Dr. Aloys Hüttermann
ah@mhpatent.de
ISBN 978-3-11-062794-7
e-ISBN (PDF) 978-3-11-062801-2
e-ISBN (EPUB) 978-3-11-062804-3
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Preface
Are you one of those people who usually skip the preface of a book? I am definitely
one of them, which is why drafting this preface was actually the hardest part of
writing this book.
In my book, I would like to elaborate on hydrogen bonding. I have chosen this
subject because I wanted to present to you a book about a field of chemistry that
– first of all, is easy enough to understand without needing a university degree
– second, also plays an important role in our everyday lives and
– third, is also highly relevant in modern science, so as not to only present deca-
des-old findings.
Although these three attributes actually conflict with each other, I believe that my
subject, hydrogen bonding, is an exception and indeed meets all these require-
ments. You will see that this type of bond is well worth studying.
This book is roughly divided into three sections. After giving you an explana-
tion of what a hydrogen bond is (first section), I will guide you through everyday
phenomena (second section) all the way to modern science in which hydrogen
bonds play an important role (third section). By “modern”, I mean individual re-
search projects and even some entire areas of research that only came into being a
few years ago.
Of course, I also wrote this book because I enjoy writing. So I hope you will
enjoy reading it!
Düsseldorf, November 2018
Aloys Hüttermann
https://doi.org/10.1515/9783110628012-201
Contents
Preface V
1 Before getting started 1
2 The “bond” in hydrogen bonding 11
3 The “water” in hydrogen bonding 15
4 The order in the ice 21
5 Dissolving like sugar in water 27
6 Soaps and cells 35
7 Recognise your vis-à-vis 45
8 Jerry Donohue and the DNA 51
9 How to make hydrogen bonds visible 61
10 “Now let’s step on the accelerator” 71
11 Substances that build themselves 89
12 Like Avalokiteśvara and Durga 97
13 Conclusion and acknowledgements 115
Bibliography 117
Index 121
1 Before getting started
This book deals with what is called hydrogen bonding.

The word “bond” implies or means that something “comes together”. In a
broader sense, chemistry is basically all about bonding. A hydrogen bond is a bond
between molecules. To understand this in greater detail, we first need to take a look
at how bonds work to begin with.
I am going to start with the very basics – but don’t worry, it’s not that hard to
understand! So, if what I am about to tell you is something you already learnt in
school, feel free to go straight to the next chapter.
Before I get into bonds, I would like to talk about the “building blocks” that are
capable of forming bonds in the first place. The essential building blocks in chemis-
try are elements. You have probably heard of that. These elements basically repre-
sent letters of a chemical alphabet, meaning all existing compounds are made up
exclusively of these elements, just like all words of our (written) language are made
up of letters of the alphabet.
Just like all letters have a name – namely “A”, “B”, “C” and so on – every ele-
ment has a name and a symbol that are used worldwide. Most of them are derived
from Latin or Greek. For example, silver is called “Ag” (short for “argentum” = Latin
for “silver”) and hydrogen “H” (short for “hydrogen” = Greek for “water-former” –
which is a good name, because water actually contains hydrogen). While many
metals have been known and named since ancient times – mostly metals such as
iron, silver and gold – most of the other elements were named by those who discov-
ered them. For a long time, names were chosen based on a property of the element,
such as in the case of hydrogen. Oxygen, for example, has the symbol “O” for “oxy-
genium” = “acid-former”, because it is found in many acids that were known in
those days. It was thought that the fact that acids are acidic was due to the presence
of oxygen. Although this turned out to be incorrect, the name was left unchanged.
Naming conventions changed slightly over the years and, mainly in the nine-
teenth century, many elements were named after cities or countries, usually the
country of the person who discovered the element. This includes “Ga” (short for
“gallium” = France) – right next to “Ge” (short for “germanium” = Germany).
France is represented twice, by the way, because there is also “Fr” = francium. The
element “Po” = polonium gained unfortunate fame due to the poisoning of Russian
Putin critic Alexander Litvinenko in 2006. By contrast, no elements were named
after Great Britain and the United States during that period (which I find surpris-
ing), while the small Swedish village of Ytterby inspired the names of as many as
four elements because of the minerals found in the nearby Ytterby mine: yttrium
“Y”, ytterbium “Yb”, terbium “Tb” and erbium “Er”.
Today, more than 100 chemical elements are known, but only about 90 of them
are stable enough to be used in chemistry on a larger scale. The other elements are
https://doi.org/10.1515/9783110628012-001
2 1 Before getting started
radioactive and decay within a short period of time. But, of course, they are still
given a name and a symbol! Apart from the tradition of naming elements after cities
or countries, the names of famous scientists have established themselves as a par-
ticularly popular choice. That is why, alongside elements such as americium “Am”
(America did get the honour, after all), californium “Cf”, berkelium “Bk” (named
after the Californian university town of Berkeley) and its German counterparts
darmstadtium “Ds” as well as hassium “Hs” (for the German state of Hesse), there
is also einsteinium “Es” (after Albert Einstein), curium “Cm” (after Marie Curie) and
roentgenium “Rg” (after Wilhelm Röntgen), among many others. The most recently
named element is oganesson “Og” (after Juri Ogenasjan, one of the co-discoverers),
discovered at the Joint Institute for Nuclear Research in Dubna, Russia.
All these elements are listed in what is called the “periodic table of elements”,
because many properties of the elements repeat periodically.
More than 90 elements used in chemistry are metals, such as iron or copper.
The chemistry of these elements is (usually) called “inorganic chemistry”.
Only a small number of elements, about ten, are of particular interest for this
book, with the most important ones being carbon, hydrogen, oxygen and nitrogen.
They have the symbols C (for carbon), H (for hydrogen), O (for oxygen) and N (for
nitrogen). The chemistry of these elements, specifically that of carbon, is (usually)
called “organic chemistry”.
Dating back to a time when chemistry was still relatively young and many things
were not yet fully understood, the terms “inorganic” and “organic” are actually out-
dated. But since they turned out to be rather practical, they continue to be used. It was
long believed that “organic” material, namely, molecules that can be obtained from
living organisms such as animals or plants could not be synthesised from “dead” or
“inorganic” materials such as minerals. The formation of organic materials was
thought to always require a kind of vital force called “vis vitalis”, allowing organic ma-
terials to form only from other organic materials. However, in 1828, German chemist
Friedrich Wöhler was able to demonstrate that this was not the case by producing an
organic material, urea, from inorganic starting materials. There is no essential differ-
ence between organic and inorganic materials; a “vis vitalis” is not required. But since
minerals usually do have a different composition than compounds that are found in
animals or plants, these terms continue to be used for classification.
But there is no need to go into this any further. Instead, let us start with this
essential question: Why do elements form bonds, anyway?
That is a good question, because actually there are elements that hardly form
any bonds and are “happy by themselves”. These elements are noble gases and are
called helium, neon, argon, krypton and xenon. These noble gases exist in the form
of atoms, which means “alone”. They hardly form any bonds at all, not even with
themselves (hence the name “noble”). Instead, the individual atoms in every noble
gas occur in the form of balls that are floating around at different speeds depending
on the temperature. But every atom is completely independent and has nothing to
1 Before getting started 3
do with the others. Only when noble gases are cooled to a very low temperature do
they turn liquid due to the slower movement and several other effects, which we
need not discuss any further. But a noble gas has to get very cold for that to hap-
pen. Helium, for example, only turns liquid at –268 °C (−450 °F).1 That is only 5
degrees above absolute zero! The melting point of neon, the next larger noble gas,
is at a “milder” −246 °C (−410 °F) and that of argon is at –186 °C (−303 °F). Due to
these properties, it took a long time for noble gases to be discovered, despite the
fact that argon makes up almost 1% of the atmosphere, making it more than a thou-
sand times more common on the Earth than silver or gold! The discoverers of argon
thought it was a bit “inert” because it does not react (Greek: argos). The other
Greek-derived names of the noble gases also attest to the fact that they stand apart
from the other elements: krypton is derived from kryptos = hidden, neon from
neos = new, xenon from xenos = foreign. Helium is derived from helios = sun, be-
cause helium had already been confirmed to exist on the sun by 1868 and would
not be discovered on the Earth until much later, in 1895.
So, how come noble gases hardly ever form bonds?2 It is because of their inter-
nal structure.
An element can be distinguished from another by the number of negatively
charged electrons and positively charged protons. If nothing else has happened to
the element, the number of electrons and protons is identical. The simplest element
is hydrogen with one electron and one proton, followed by helium with two elec-
trons and two protons, and so on. The protons are located in the atomic nucleus
along with the neutrons, which are not relevant in this case, while the electrons are
in the shell that surrounds the atomic nucleus.
The elements are arranged in what is called the “periodic table of the elements”
in order of increasing atomic number, comparable to the way letters are arranged in
the alphabet.
It has been discovered that certain numbers of electrons are special, namely 2,
10, 18, 36 and 54. Elements with these numbers of electrons have special chemical
stability. Why is that?
Using a model that is relatively simple but perfectly sufficient for this purpose,
you can visualise how electrons are not simply present in the atomic shell, but dis-
tributed across several shells that resemble the layers of an onion. Whenever a shell
is full, there is great stability.
1 Although Daniel Gabriel Fahrenheit (1686–1736) was a German physicist, Germany uses the com-
mon Celsius scale, named after Swedish physicist Anders Celsius (1701–1744). That is why all tem-
peratures in the German original version were indicated in degree Celsius. However, this English
version includes the Fahrenheit scale as well as mph.
2 I intentionally wrote “hardly ever” because there are, in fact, a few known noble gas compounds.
However, it is pretty difficult to get noble gases to react and two of the five noble gases (namely
helium and neon) still have no known chemical compounds.
The shells can hold different numbers of electrons. The first shell closest to the
atomic nucleus can hold two electrons, the next two shells can hold eight electrons
and the two after those 18, with the shells being filled from the inside out. Explain-
ing why exactly it is that way would be going too far. All in all, we can basically
visualise it as follows:
Atomic nucleus 2 electrons

8 electrons
8 electrons
18 electrons
18 electrons
It is not by chance that noble gases have these “magic numbers” where the elec-
trons exactly fill the shells! Helium has two electrons (i.e. the first shell is full),
neon 10 (i.e. the first two shells are filled), argon 18 (the first three), krypton 36 (the
first four) and xenon 54 (the first five).
The other elements that do not have these numbers of electrons are therefore
often “tempted” to also reach a condition where one of these “magic numbers” is
present – they form bonds.
How can this happen? There are basically three different possibilities:
1.1 An atom loses or gains electrons
This type of bond is found in sodium chloride, which is the salt you put in your
food. Chemically, salt consists of two elements, namely sodium and chlorine.
As shown in the periodic table, sodium has 11 electrons, which is one more
than neon. While sodium’s two innermost shells are completely filled, there is only
one single electron in the third shell. But this does not mean that sodium is unsta-
ble. On the contrary, sodium is essentially a stable metal.
However, having ten electrons would make it even more stable, as we have
seen earlier. That is why sodium “strives” to lose one electron to reach neon’s
“magic number” of stability. Well, sodium does not strive, of course, because it has
1.1 An atom loses or gains electrons 5
no will of its own. But for the purpose of this book, I will to stick with this kind of
figurative language.
The exact opposite is the case with chlorine. It has 17 electrons, with the first
two shells being completely filled and the third containing seven electrons. The
next “magic number” would be reached by argon having 18 electrons, which means
gaining one additional electron.
When you combine sodium and chlorine to produce a reaction (which happens
very easily – it is actually relatively dangerous), sodium donates one electron to
chlorine. Both have now reached a “magic number”, with sodium having 10 and
chlorine 18 electrons.
But even in its new state, sodium still has eleven protons, because the atomic
nucleus, which contains the protons, is never involved in a chemical reaction. But
now it only has ten electrons. Since electrons are negatively charged and protons
are positively charged, one negative charge is now lacking – in other words, there
is now one excess positive charge.
This means sodium is now electromagnetically charged, having a single posi-
tive charge. Such particles are called ions – simply meaning that an electric charge
is present. Hence, sodium chloride does not contain (metallic) sodium, but sodium
ions. This distinction is important, because sodium ions differ from metallic sodium
in a great number of properties.
Again, the exact opposite is the case with chlorine. It now has one extra nega-
tive charge. Sodium chloride thus contains “chloride ions”. To indicate that the
chlorine is negatively charged, it is called “chloride”, hence the full name “sodium
chloride”.
At this point, I would now like to give you a brief overview of how chemical
reactions are visually represented. Let us start with chlorine. Prior to gaining an
electron, there were seven electrons in chlorine’s outermost shell – the inner ones
are irrelevant, because they are completely filled – sometimes written as dots sur-
rounding the chlorine. This is done using chlorine’s chemical symbol “Cl”. When
adding one more electron (abbreviation: e–), the shell is full. But chlorine is now
electrically charged, which is indicated by a superscript minus sign. Altogether, it
looks something like this:
The above figure is called a chemical equation. The starting substances of the reac-
tion, in this case the chlorineatom and the electron, are called reactants and are
placed to the left of the arrow. The products, which are the substances formed by
the reaction, are placed to the right of the arrow. In this case, the product is a chlo-
ride ion. Usually, chemical equations only include those substances that are in-
volved in the reaction.
An equivalent equation can be written for sodium. Previously, sodium’s outer-

most shell contained only one electron. As with chlorine, the inner shells are not
relevant. When sodium loses its electron, a positively charged sodium ion is
formed, expressed by the superscript plus sign:
Combining these two chemical equations produces the following equation:
As you can see, there is an electron on both sides of the equation. This can simply
be crossed out, shortening the equation as follows:
This equation now looks better to a chemist. Chemical equations should ideally
contain only elements and no longer include any electrons; otherwise, it is very
likely that something went wrong. Since this is not the case here, this equation has
turned out alright.
It is important that there is no chemical “cohesion” between the sodium ions
and the chloride ions in the salt. Once the electron is exchanged, ions act similar to
noble gases and are “happy by themselves”. They are present in sodium chloride in
the form of balls – much like the noble gases discussed earlier.
However, the ions are charged. Unlike with noble gases, which have no charge,
this causes an attractive force between them. Sodium ions and chloride ions attract
each other like magnets. Negative attracts positive and vice versa, just like the posi-
tive and negative poles of a magnet.
But the difference between the two ions and a magnet is that every magnet has
a positive pole and a negative pole. That is not how it works in sodium chloride.
The sodium by itself is the positive pole and the chlorine (or chloride) by itself is
the negative pole. But the actual attraction is very similar.
This attractive force causes sodium chloride to be a solid instead of a gas. This is
called an ionic bond, although the word “bond” is actually not quite correct. It would
be more appropriate to call it “ionic attraction”, but the term “ionic bond” has still
become established in chemical terminology. I will address this in more detail later.
This bond is very strong, by the way. Pure sodium chloride is extremely stable
and only melts at 808 °C (1,487 °F). By comparison, zinc melts at 419 °C (786 °F)
and silver at 960 °C (1,760 °F).
1.2 Two atoms share electrons 7
1.2 Two atoms share electrons
In addition to the possibility of one atom losing an electron and another gaining it,
it is also possible for two atoms to “share” an electron. This works as follows:
Let us take hydrogen, which has one electron. To reach a “magic number”,
hydrogen could lose this electron. Then it would have none (zero is also a “magic
number”), with only the proton being left. In reality, this does happen very often.
We will get to this later.
The other possibility would be to gain one electron. Hydrogen would then have
two electrons, reaching helium’s “magic number”. But it is relatively difficult for
hydrogen to gain one electron, because hydrogen is very small. After all, that sec-
ond electron needs to go somewhere! While there are some compounds in which
hydrogen is negatively charged (known as hydrides), they are not that easy to pro-
duce. Hydrides were not known by chemists until after World War II.
The third possibility is that two hydrogen atoms form a bond, producing a mol-
ecule. A molecule is understood to be any chemical compound that consists of
more than one atom.
In this bond, the two electrons, one of each hydrogen atom, are basically
“available” to both hydrogen atoms. They are positioned in the (imaginary) middle
of the bond. There are always two electrons in a bond and never just one or three,
for example.
By forming a molecule, each hydrogen atom has “access” to the other’s elec-
tron. This means that both hydrogen atoms now “possess” two electrons, so both
hydrogen atoms have reached a “magic number”!
This can also be visually represented using dots, with “H” being the chemical
symbol for hydrogen:
The two dots positioned between the two atoms forming the bond are usually writ-
ten as a dash to show that they form a bond. A dash then represents two electrons.
I am sure you have seen this before. The above representation would then look as
follows:
The big difference between this bond and sodium chloride is that hydrogen con-
tains a true bond, which means that the two hydrogen atoms are firmly attached to
each other. This is also called an atomic bond, to emphasise that in this case the
atoms are really “stuck” together. This is also emphasised by using the term “hy-
drogen molecule” or H2, for short. Unlike the spherical shape of sodium or chloride
in sodium chloride, a hydrogen molecule looks more like a dumbbell. The energy
that is needed to break a hydrogen molecule up again is exceptionally great, requir-
ing temperatures of several thousand degrees or voltages of 3,000–4,000 V!
The chemically correct term for this type of bond is “covalent bond”. This name
means (when translated) that two atoms “cooperate” by sharing bonding electrons,
which were previously also called “valences”. I will therefore always use the term
covalent in the following chapters.
Atoms can also form more than one covalent bond with each other, like nitrogen,
for example. Nitrogen has seven electrons, which means it is three shy of neon’s
“magic number” of ten. The first shell is completely filled with two electrons while
the second shell contains five electrons. The number it needs to reach is eight.
Two electrons can be added per bond, with one coming from each partner. Ni-
trogen therefore needs three bonds to reach the “magic number”. That is exactly
what happens in nature. A nitrogen atom forms three covalent bonds with another
nitrogen atom, basically gaining three additional electrons by producing a nitrogen
molecule (N2). The magic number has been reached!
The figure also shows the more common representation using dashes on the right.
Again, one dash represents two electrons. It is also important to note about this re-
presentation that the two electrons that fully remain with a nitrogen atom are also
represented as a dash. They are also called “electron pairs“. The representation is a
bit figurative, but not completely wrong. As a matter of fact, these electron pairs are
very important, as we will see later.
1.3 Many atoms form what is called a “metallic bond”
A metallic bond – as its name implies – is found in almost all metals, such as iron,
copper, gold or silver. But their bonding relationships are comparatively compli-
cated and not easy to explain. Luckily, metallic bonds are not required for the pur-
poses of this book. That is why I will skip metallic bonds and move on without
explaining them any further.
How can we predict what bond is present in a chemical substance? And how can
we determine which element forms which bond?
It is not that easy and depends on the situation. I will give you an example: In
sodium chloride, chlorine is negatively charged, as we have discussed. In chlorine
gas, chlorine forms a covalent bond with itself.
It makes sense: Chlorine needs an additional electron to reach a “magic num-
ber”, as we have seen. If one chlorine atom were to simply “take away” an electron
1.3 Many atoms form what is called a “metallic bond” 9
from another, it would reach a “magic number” – but the other chlorine atom
would be even further away from it than before!
So, if chlorine forms a covalent bond instead, both chlorine atoms can reach the
“magic number” of 18 electrons, with eight being in the third shell. The result is a
chlorine molecule (Cl2). Cl2 is a green gas, hence chlorine’s name, which is derived
from chloros = Greek for green.
However, chlorine still has a strong “attractive force” for electrons, which means it
has a tendency to form a chloride ion with a single negative charge. That is why
chlorine gas reacts extremely easily with other substances and is also very toxic.
But once chlorine has received its electron, it is comparatively “friendly”. Chloride
ions are relatively non-toxic. After all, salt can be eaten.
Oxygen is another example. For instance, in a reaction between carbon
and oxygen, when done correctly, a compound called carbon dioxide or CO2 is
formed.
As the name suggests, this compound contains two oxygen atoms and one car-
bon atom. Carbon has six electrons, with four being in its second shell, and there-
fore needs another four electrons to reach a “magic number”. Oxygen has eight
electrons, with two being in the first shell and six in the second, and therefore
needs another two electrons.
In CO2, carbon (chemical symbol: C) forms two covalent bonds with each of
the oxygen atoms (chemical symbol: O). In other words, carbon forms a double
bond with each of the oxygen atoms, enabling all of the atoms to reach a “magic
number”:
The situation is different with calcium oxide. Calcium oxide is “burnt lime”, a com-
pound most readers are probably familiar with. It consists of calcium (chemical
symbol: Ca) and oxygen (chemical symbol: O), abbreviated as CaO.
Calcium has 20 electrons, which is two more than argon. Its first three shells
are filled, with two electrons remaining in the fourth. The same thing that happens
with sodium chloride happens with calcium oxide. Calcium donates its two elec-
trons to oxygen, allowing both to reach a “magic number”.
But covalent bonds and ionic bonds may also occur next to each other. Since this
will be important in a few sections later in my book, I will briefly address it below.
A good example of such a mixed bonding situation is potassium cyanide,
which, at least according to Peter Gabriel, is one of the ingredients in the magic
wands used by cheerleaders. Potassium cyanide consists of three atoms, namely po-
tassium, nitrogen and carbon. Since you are already familiar with nitrogen and car-
bon, let me now introduce you to potassium: Potassium, “K”, can be thought of as
something like sodium’s “big brother”, situated in the periodic table between cal-
cium and argon. This means it has 19 electrons, with its first three shells being filled
and the fourth holding a single electron.
When examining the bonding situation in potassium cyanide, it becomes ap-
parent that carbon and nitrogen are connected by a covalent triple bond, compara-
ble to that of nitrogen in the atmosphere. However, carbon has one fewer electron
than nitrogen, so only nitrogen is happy while carbon still needs one electron.
No problem! Potassium donates its solitary electron, thereby reaching argon’s

electron status of 18 electrons. Now all involved atoms have reached a “magic
number”.3
This produces a total of two ions, one positively charged potassium ion and one
negatively charged ion consisting of nitrogen and carbon. This is also called cya-
nide or cyanide ion. As described earlier, carbon and nitrogen form as many as
three covalent bonds in a cyanide ion. The name is derived from Greek (ky-
anos = blue) and stems from the intense colour of ferric ferrocyanide, which is also
known as Prussian blue. This also inspired the German name for hydrogen cyanide,
“Blausäure” (“blue acid”), even though it is actually perfectly clear and colourless.
3 I would like to briefly point out that potassium cyanide cannot be produced the way the two
equations suggest! They only serve to explain the bonding situation and are therefore rather
“formalistic”.
2 The “bond” in hydrogen bonding
The hydrogen bond was not included among the bonds discussed in the previous
chapter. This was done for a reason, because this bond differs significantly from
other bonds. But before we actually get to hydrogen bonding, we first need to take
another closer look at the first two types of bonds from the previous chapter.
In reality, bonding is still a bit more complicated. In addition to the possibilities
1 (ionic bonding, in which electrons travel from one atom to another) and 2 (cova-
lent bonding, in which the electrons are positioned in the middle between two
atoms), there are some in-between possibilities. This is best visualised by imagining
that the two electrons in a bond are not positioned in the middle between the two
atoms, but closer to one of the atoms.
As long as the electrons are not too far away from the middle, both atoms can
still “access” both electrons. If the electrons travel further to one side, a situation
occurs where the bond is not yet “broken”, but basically only one atom gets to use
the so-called bonding electrons.
If the electrons are pulled to one side even more strongly, you can imagine the
bond being broken, resulting in an ionic bond like the one we know from sodium
chloride. Of course, the bond does not actually “break” in reality – a covalent bond
does not form in the first place.
Hence, what determines the position of the bonding electrons in the bond? It
depends primarily on the two atoms involved.
Logically, you can imagine that in bonds formed between two identical atoms –
such as the hydrogen molecule H2 or the chlorine molecule Cl2 – the bonding elec-
trons are positioned exactly in the middle. In a bond between carbon and hydrogen,
the electrons are also pretty much exactly in the middle.
By contrast, in an oxygen–hydrogen bond, the bonding electrons are distrib-
uted very unequally and positioned very close to the oxygen. Still the bond, how-
ever, exists, thus allowing hydrogen to reach the “magic number”. This is also true
of chlorine-hydrogen and nitrogen-hydrogen bonds.
In an effort to calculate the specific differences, a measurement called electro-
negativity was introduced and calculated for almost every element. So, if two atoms
have identical or similar electronegativity, the electrons tend to be positioned in the
middle. If the difference in electronegativity is slightly bigger – but not too big – a
bond is formed where the electrons are closer to one side, namely that of the more
electronegative element. If the differences in electronegativity are too big, an ionic
bond is formed instead of a covalent bond.
I will not go into the individual numerical values – especially because there are
various calculation methods and some of the values may differ depending on the
method used. For the purposes of this book, it is sufficient to distinguish between
three groups:
https://doi.org/10.1515/9783110628012-002
12 2 The “bond” in hydrogen bonding
Chlorine, oxygen and nitrogen (group 1) have high electronegativity while hy-
drogen and carbon (group 2) are moderately electronegative and the vast majority
of metals such as sodium and calcium (group 3) have low electronegativity.
Whereas bonds between atoms of one group tend to have “equal rights”, bonds
between atoms of groups 1 and 2 are “unequal”, with the electrons being closer to
the element from group 1. Atoms of groups 1 and 3 form no covalent bonds at all
and instead form ionic bonds like in sodium chloride. Bonds between atoms of
groups 2 and 3 are a bit more complicated, but since they are not required for this
book, I will leave those out.
Let us take a look at the bond between oxygen and hydrogen. Oxygen is in
group 1 and hydrogen in group 2, producing a covalent bond in which the electrons
are closer to oxygen. So, what happens as a result of the unequally distributed
electrons?
What happens is something very important and crucial: The bond itself is no
longer equal. This type of bond is also called polar bond. This implies that this
bond basically contains a negative and a positive pole, with the negative pole being
located at the more electronegative atom and the positive pole at the other atom. By
contrast, bonds in which the electrons are positioned closer to the middle are
known as non-polar bonds.
Let us examine this using a substance you know well: water. Water consists of
three atoms, namely one oxygen atom and two hydrogen atoms.
As we have learned, oxygen has six electrons in its second shell. By bonding
with two hydrogen atoms, which can each form one bond, water is produced. It
has the following structure (shown using dots on the left and dashes on the
right):
The figure on the right shows the two electron pairs on the oxygen atom that are
made up of the four electrons which have remained with the oxygen atom.
However, as I have mentioned, in a bond between oxygen and hydrogen, the
electrons are positioned closer to the oxygen rather than being distributed equally.
As a result, oxygen has a slightly negative charge and hydrogen has a slightly posi-
tive charge. However, the electrons are still in a covalent bond, without forming
any ions where the electrons would be with one element only. This is indicated by
adding the Greek symbol “δ” instead of just writing “–” or “+”. Hydrogen is given a
δ– and oxygen a δ+:
2 The “bond” in hydrogen bonding 13
This means that the electrons in this bond are closer to oxygen than to hydro-
gen, producing a kind of semi-positive charge on the hydrogen and a semi-negative
charge on the oxygen.
However, these semi-positive and semi-negative charges cause δ+ and δ– to at-
tract each other – similar to what happens in sodium chloride! In addition to the
normal covalent bonds in water, further bonds form between the water molecules.
They can basically be represented as follows:
The oxygen atom in the water molecule has another four electrons, or two electron
pairs, represented by two dashes, that are not involved in the bonds with the hydro-
gen atoms. They are also known as “free electron pairs”. An attractive force now
forms between hydrogen and each of oxygen’s free electron pairs, which is usually
also called a bond in chemical terminology. More specifically, it is called a hydro-
gen bond – which brings us to the actual subject of our book. As an example, two
of these hydrogen bonds in water are shown as dashed lines in the above figure.
Why is a hydrogen bond called hydrogen bond, anyway? Quite simply because
a hydrogen atom is often involved as δ+ in these bonds and because the hydrogen
bond was first discovered in molecules that contain hydrogen. But a hydrogen
bond is not limited to hydrogen. On the contrary, there are many so-called hydro-
gen bonds that do not contain any hydrogen at all. For the purpose of this book, a
hydrogen bond is defined as follows:
A hydrogen bond is the attractive force between a positive charge, either a true positive
charge, such as the one in Na+, or a δ+ charge, such as the one in water, and a free electron
pair of another atom.
But I would like to emphasise straight away that there are major differences be-
tween a hydrogen bond and a normal covalent bond. The two atoms in a covalent
bond are tightly attached to each other. For example, neither of the two hydrogen
atoms of a hydrogen molecule can simply detach from the bond and move away
from the other. A lot of energy is required to accomplish this – and the hydrogen
molecule is destroyed in the process!
This is different in a hydrogen bond, where the individual bonding partners
can easily move away from each other – and do so all the time. Hydrogen bonds are
also more flexible in terms of length and position than covalent bonds, which are
very rigid formations.
14 2 The “bond” in hydrogen bonding
The best way to imagine the difference between a hydrogen bond and a cova-
lent bond is to think of the Vienna Opera Ball, with the dancers being the
molecules.
When you are dancing at the Vienna Opera Ball, there is basically a true molec-
ular bond between you and your hand. Although it is theoretically possible to sepa-
rate you from your hand, it would be very cruel and difficult and you would then
not really be whole anymore!
But in this large ballroom, there are many couples dancing a waltz. When the
waltz is finished, the couples usually separate and change dance partners. But
while they are dancing, each couple also forms a bond, even though this bond may
sometimes be a bit shorter or longer and does not necessarily always move in the
same direction. So, when the male dancer makes a turn and knows how to dance a
waltz, the female dancer will follow accordingly. Otherwise, he will step on her
feet. . . but in any case, any move he makes produces a response from her. This
bond between the dancers is comparable to a hydrogen bond.
If we installed a camera on the ceiling and filmed the entire ballroom for an
extended period of time, we would see that, on average, most of the dancers are
attached to another person. The dance partners change from time to time – but al-
most all involved in the dance are, on average, not alone.
Something similar happens in water, but now you need to imagine the dance
partners switching constantly instead of splitting up all at once after each piece of
music, like when dancing a waltz. In addition, each water molecule can form a
bond with not just one, but several water molecules! This creates a kind of “three-
dimensional network of dancers”. I have to admit, this is now getting a bit difficult
to imagine. But it will at least give you a rough idea of what happens in water,
where every water molecule is bound to several other water molecules by hydrogen
bonds.
So, despite not being a “true” covalent bond, a hydrogen bond is still very
much existent and important.
3 The “water” in hydrogen bonding
As already mentioned in Chapter 1, the word “hydrogen” in hydrogen bond is derived

from Ancient Greek, hýdor = water. More specifically, hydrogen means “water-former”.
So, what significance does this hydrogen bond have for water? A crucial one!
The hydrogen bonds in water are often largely responsible for the way water looks
and acts in nature.
Water is a truly remarkable compound. Most people are not amazed by the sur-
prising properties of water, but that is only because water is found everywhere on
our planet. If water had not been known before and were to be newly synthesised
by chemists at a university’s chemistry department or a Max Planck Institute,
people would be stunned by the amazing properties of water. The chemists in-
volved would have a good chance of getting a delightful call from Stockholm,
inviting them to accept a Nobel Prize.
For example, one of the remarkable properties of water is the fact that it is liq-
uid under normal conditions, such as 25 °C (77 °F) and normal pressure. The boiling
point, that is, the temperature at which water becomes a gas, is remarkably high,
namely, 100 °C (212 °F). The Celsius scale is even based on water’s boiling and melt-
ing point, as most of you probably know. So, the number 100 was not picked at
random. But why is this property of water so remarkable?
It becomes apparent when examining the behaviour of compounds that are
structurally very similar to water. For example, a compound called methane or CH4
is formed when the oxygen atom in the water molecule is replaced by a carbon
atom and two more hydrogen atoms are added, because carbon needs four bonds
to be happy, as we have seen. It consists of one carbon atom at the centre, with
four hydrogen atoms attached to it. In the next chapter, we will discuss this com-
pound in more detail. It can be visually represented as follows:
You are also familiar with methane, although you may not necessarily know it by
this name. Methane is the primary component of natural gas. As the word natural
gas implies, methane is gaseous under normal conditions. It only becomes liquid at
very low temperatures, namely, at −161 °C (−258 °F). That is really very cold! Liquid
methane is therefore usually not found on the Earth, but it does occur in space,
such as on Saturn’s moon Titan, where there are entire lakes and rivers of liquid
methane.
https://doi.org/10.1515/9783110628012-003
16 3 The “water” in hydrogen bonding
There is also a comparable compound of nitrogen and hydrogen. Nitrogen

forms three bonds, with three hydrogen atoms being attached to one nitrogen atom.
The resulting compound is called ammonia or NH3 and can be visually represented
as follows:
You may have heard the name ammonia before. About 100–120 years ago, ammonia
was used as a refrigerant in refrigerators. Because ammonia is highly toxic, it was
replaced by chlorofluorocarbons in the 1920s, which was thought to be a huge step
forward at the time, until the hole in the ozone layer was discovered. But that is
another story.
In any case, ammonia is also gaseous under normal conditions. The temper-
atures required to turn it into a liquid are not quite that low, namely, only −33 °C
(−28 °F). But there is still a difference of 133 °C (272 °F) to the boiling point of
water. This is almost exactly the same difference as that between ammonia (boil-
ing point: −33 °C/−28 °F) and methane (boiling point: −161 °C/−258 °F). It is start-
ing to become apparent that the 100 °C boiling point of water is indeed pretty
high.
The situation is similar when replacing oxygen by yet other elements, such as
sulphur to produce hydrogen sulphide (a gas that strongly smells of rotten eggs –
hopefully it does, because if you cannot smell it anymore, its concentration is so
high that you would be almost dead because of how toxic it is), phosphor to pro-
duce phosphine (which is also toxic and stinks pretty badly) or chlorine to produce
hydrogen chloride (which is not exactly healthy, either) – all of which are gaseous
compounds that look as follows:
Hydrogen sulphide Phosphine Hydrogen chloride
What happens when we replace hydrogen instead of oxygen? It is not much of an

improvement. When replacing the two hydrogen atoms by a second oxygen atom,
the result is O2, the oxygen found in the atmosphere. Oxygen becomes liquid at
even lower temperatures than methane, with its melting point being −183 °C
(−297 °F)!
When replacing hydrogen by chlorine, a compound called dichlorine monoxide
is formed. Although it is not particularly stable or easy to produce, it is also gaseous!
Dichlorine monoxide
Other elements are not doing any better either. As you can see, water is pretty unique
in its property of being liquid under normal conditions. But this is essential for your
daily life! If water were usually a gas, it would be pretty hard to imagine that you and
I could even exist. So, that is just one reason to treat water with respect.
Why is that? To better understand this property, let me first give you a brief
overview of the terms solid, liquid and gaseous. Known as the three states of mat-
ter, they refer to the form in which matter exists at different temperatures. From a
scientific point of view, the temperature of matter is simply a measurement for the
movement of the atoms or molecules it consists of. The higher the temperature, the
faster the atoms move.
The gaseous state of matter may be the easiest to imagine. A gaseous com-
pound is largely characterised by freedom. The individual molecules are sepa-
rate from each other and are floating through space. Of course, that is an
idealisation, because if the individual molecules in a gas were truly free and
independent from each other, there would never be something like wind. But
on the whole, imagining a gas as an accumulation of individually separate mol-
ecules (or atoms, in the case of noble gases) is not too far from reality. If the
specific gas and the temperature are known, it is even possible to calculate the
average speed of the individual gas particles. For example, nitrogen, the main
component of air, has a speed of more than 1,800 km/h (1,120 mph) at room
temperature.
How come not all compounds are gaseous, anyway? That is because in many
compounds, there are opposing or attractive forces that hold together the individual
particles the compound consists of. I will get to that later. As a general rule, it can
be assumed that the vast majority of compounds would be gaseous at room temper-
ature if only the kinetic energy of their particles played a role.
A compound is therefore naturally gaseous at higher temperatures, because
that is when the individual particles move the most, enabling the resulting en-
ergy to overcome any opposing forces. The specific temperature varies from
compound to compound. For example, temperatures of −195 °C (−319 °F) and
higher are enough for nitrogen, while sodium chloride needs more than 1,465 °C
(2,670 °F)!
A solid compound has a rigid structure. The individual molecules are arranged
next to each other like bricks in a wall. Ideally, there is perfect order. Of course,
that is not always the case, but overall, a solid compound can be thought of that
way. The structure of sodium chloride is a good example. Sodium chloride can be
visualised as follows:
The positive sodium ions (the smaller balls) are each surrounded only by negative
chloride ions (the larger ones) and vice versa. This is due to the fact that positive
and negative charges attract each other – but negative and negative charges repel
each other (positive and positive ones do the same, of course). Because of this struc-
ture, the like-charged ions are kept apart from each other and are surrounded only
by oppositely charged ions. Calcium oxide, which I introduced to you in Chapter 1,
has exactly the same structure, by the way, but is made up of calcium and oxygen
ions instead of sodium and chloride ions.
It makes sense that solids occur mainly at low temperatures, because that is
when the individual particles move the least. Solids that remain solid even at
higher temperatures are characterised by strong attractive forces that prevent the
individual particles from moving too far from their position and thereby breaking
up the structure into which they are arranged in the solid state. In sodium chloride,
this is caused by the electromagnetic attraction between the positive sodium ions
and the negative chloride ions. As explained above, this force is very strong in so-
dium chloride, which only turns liquid at 808 °C (1,487 °F).
In a liquid, the situation is different, and it is also not that easy to imagine a liquid.
Many properties of liquids, including those everybody knows, are still being researched
and even experts are still unsure about how a liquid is structured in all its details. One
way to attempt to understand this is to imagine that even though the molecules in a
liquid are constantly moving, closely adjacent molecules or atoms still form a defined
structure. However, this structure does not extend throughout the entire liquid, as
would be the case in a solid, but instead “breaks off” after a short length. But even in a
liquid, there definitely have to be attractive forces that bond at least closely adjacent
molecules to each other. Otherwise, the compound would be a gas instead of a liquid.
In water, these attractive forces are almost exclusively the result of hydrogen
bonds, as has been measured. Because each water molecule is bonded to several
other water molecules, these bonds are in the aggregate extremely strong, causing
the high boiling point of 100 °C (212 °F). According to estimates, water without any
hydrogen bonds would have a melting point of −100 °C (−148 °F) and a boiling
point of −75 °C (−103 °F), which would be 100 °C (148 °F) and 175 °C (251 °F) less,
respectively, than seen in nature!
Only when the temperature exceeds 100 °C (212 °F) does the resulting move-
ment of the water particles cause the structure of the molecules to be broken up
due to the increased movement. Water then becomes gaseous.
At this point, it is helpful to once again compare methane, ammonia and water
in greater detail. The molecules are shown again below (from left to right).
Methane Ammonia Water
You can see that no hydrogen bonds can exist in methane, because this would re-
quire carbon to have free electron pairs, which are not present. Moreover, the bond
between carbon and hydrogen is almost non-polar, so a δ+ charge on the hydrogen
atom does not exist either. You may remember from the previous chapter that hydro-
gen and carbon are classified into the same group (group 2) of electronegativity. This
means that the electrons in a bond between these two elements would be positioned
roughly in the middle. Since methane also contains no ionic bonds, there are neither
hydrogen bonds nor electromagnetic forces to counteract the movement of the par-
ticles. That is why it is not surprising that methane is gaseous at room temperature.
Why does methane turn liquid at some point, anyway? After all, there is a
difference of more than 80 °C or 150 °F between the boiling point of methane
(−161 °C/−258 °F) and the boiling point of neon (−246 °C/−410 °F). This question is
actually not that easy to answer. Methane, among many other similarly structured
compounds, has been found to contain the so-called van der Waals forces, which
cause methane to become liquid at a sufficiently low temperature – but at a higher
temperature than neon, which has no such forces. But we need not go into this any
further. In any case, methane does not contain any hydrogen bonds that would at-
tract two methane molecules to each other. van der Waals and other forces are
much, much weaker, as can be measured. Even a comparatively low energy such as
the kinetic energy between the particles suffices to separate the methane molecules
from each other, thereby turning methane into a gas.
The situation is different in ammonia. This is partly because it has polar bonds,
with nitrogen being δ− and hydrogen δ+. If you remember the previous chapter, ni-
trogen is in group 1 and hydrogen in group 2, so the electrons are closer to nitrogen.
Nitrogen also has another free electron pair, as we can see, proving that hydrogen
bonds do exist in ammonia.
But when comparing water and ammonia, you will see that the relationship be-
tween the hydrogen atoms and the free electron pairs in ammonia is a bit awkward.
There are too many hydrogen atoms – namely, three – compared to the single elec-
tron pair. When applied to the Opera Ball analogy, this would mean that there are
three times as many gentlemen as there are ladies. So all the ladies are dancing but
more than half of the gentlemen are standing around without a partner.
It is therefore not surprising that the boiling point of ammonia ranks almost ex-
actly in the middle between those of methane and water. Ammonia does have hy-
drogen bonds that cause it to become gaseous at much higher temperatures than
methane – but it does not have as many as water because of the awkward ratio be-
tween the bonding partners. Hence, methane has a boiling point of−161 °C (−258 °F)
while ammonia boils at−33 °C (−28 °F) and water at 100 °C (212 °F).
4 The order in the ice
Water has another absolutely remarkable property that is a true miracle when you
look at it more closely, even though everybody may be aware of it. It is the fact that
water is less dense as a solid than as a liquid. More specifically, water is most dense
at 4 °C/39 °F (even more specifically, at 3.983 °C/37.4 °F). At higher or lower tem-
peratures, the density of water starts to increase again. The difference in density
between solid and liquid water is considerable, with water expanding by about 9%
when freezing. That is why the ice cubes in a nicely chilled cocktail float at the top
instead of the bottom.
What is so miraculous about this?

Just think about it: This property causes water on the Earth to be liquid even at the
bottom of the deepest ocean. If water were most dense in its solid state as ice, the
pressure at the bottom of the ocean would instantly cause it to turn to ice.
Moreover, water freezes from the top down instead of from the bottom up. On a
lake or other body of water, a layer of ice initially forms at the surface and then ex-
pands downwards.
But in 99.9% of all known compounds, it is exactly the other way round. They
are most dense in the solid state, meaning the most molecules are present per litre
or cm3 (or mm3, depending on the volume you are looking at). This is because they
have the greatest order when they are in the solid state. When they are liquid, the
individual molecules need more space, because they are constantly moving. Fewer
molecules fit into a given space than in the solid state, meaning the density is
lower.
If water were a completely normal chemical compound, it would be a disaster
for life on the Earth! Even at the equator, the ocean would be solid ice below a
depth that is no longer reached by enough sunlight (maybe about 50–100 m below
the surface, I don’t know the exact depth) all the way down to the bottom. Consid-
ering that oceans are, on average, several kilometres deep, more than 99% of the
world’s oceans would consist of ice. At the poles, the Earth would even be frozen
solid!
Because water freezes from the top down, it also forms a kind of natural protec-
tive barrier against freezing solid. That is not the case with all other substances,
which freeze from the bottom up. Needless to say, life as we know it would be al-
most impossible to imagine under these conditions.
Why is that?
Again, this can be explained by hydrogen bonding. But to do so, I first need to ex-
plain the spatial arrangement of atoms in water in a bit more detail, again using the
figures of methane, ammonia and water we have already seen in the previous
chapter:
https://doi.org/10.1515/9783110628012-004
22 4 The order in the ice
Methane Ammonia Water
Let us start with methane. In the above figure, a methane molecule looks as if it were
flat “like a pancake”. But this is not the correct spatial structure that methane has in
nature. Its structure can be examined using appropriate methods and we know pretty
exactly what it looks like. You can also picture methane’s structure by imagining that
the four bonds originating from the carbon atom try to move away from one another
as far as possible. This is partly due to the fact that the hydrogen atoms need space –
but mainly because the bonds are formed by electron pairs. Electrons are negatively
charged, so the further the electron pairs are away from each other, the better.
Take a moment and try to imagine it. It’s not that easy!
When expressed in mathematical terms, the object we are imagining would be
called a tetrahedron. A tetrahedron looks like a pyramid, but unlike the pyramids of
Giza, it has a triangle as the base instead of a square. The carbon atom sits at the
centre, and the hydrogen atoms in the corners. (Any old-school fantasy role-playing
gamers among you will of course be familiar with this object: a D4). Altogether, it
looks like this:
It is actually amazing that the real structure of a methane molecule can be derived
from this simple consideration, because it is almost a perfect match. According to
the rules of mathematics, the angle which the two hydrogen atoms and the carbon
atom would need to form a tetrahedron is (H–C–H) 109. 5°. This is actually the case
in reality!
The structure of the ammonia molecule can be visualised by imagining that one
of methane’s hydrogen atoms is replaced by nitrogen’s electron pair. This would
look as follows:
In the above figure, the electron pair is shown looking a bit like a distorted “Ameri-
can football”, which – for reasons that would take too long to explain – is a fairly
decent approximation. An electron pair takes up more space than a covalent bond.
In somewhat simplified terms, this is because a covalent bond ends with a hydro-
gen atom that slightly pulls the electrons in its direction. This does not happen with
an electron pair. Since the electron pairs repel each other, the structure is slightly
“distorted” or “modified” to give unbound electron pairs a bit more space. This re-
sults in an H–N–H angle which is slightly smaller than that of methane, but not
much. It is 106. 8°.
Water has two electron pairs, so its structure looks something like this:
Accordingly, the resulting angle is still slightly smaller than that of methane,
namely 104. 5°. The representation from the previous chapter, in which water was
drawn in a linear manner, therefore does not conform to reality. Water has an
angle. But this does not fundamentally change the network of hydrogen bonds
formed in water.
When water turns into solid ice, something very odd happens: Ice accumulates
in such a way that tetrahedrons are formed, just like in methane – the only differ-
ence being that oxygen instead of carbon is now at the centre. However, oxygen
only forms two covalent bonds with hydrogen, with the two remaining spots being
“occupied” by the electron pairs. But each oxygen atom in ice is still surrounded by
four hydrogen atoms. How does that work? It is relatively simple: The other two
bonds in the tetrahedrons formed in ice are now hydrogen bonds instead of cova-
lent bonds.
This would not be a big deal; after all, these bonds also exist in liquid
water. But what is remarkable is that hydrogen bonds in ice have the same
length and the same direction as covalent bonds. Covalent bonds and hydrogen
bonds thus take on the same structure. When applied to the Opera Ball anal-
ogy, this would be like tying a pair of dancers together so that the dance part-
ners can no longer move away from each other, let alone increase or reduce
the distance between them.
What exactly does ice look like? The exact structure is a bit complicated. For a
better understanding, let us first take a look at an “ice tetrahedron”.
It is important to note that only two of the hydrogen atoms have a covalent
bond with the oxygen atom at the centre. The other two are bonded to another
oxygen atom, which is not shown here. These hydrogen atoms are represented
by the dashed lines. To these hydrogen atoms, the oxygen atom is only bonded
by the hydrogen bonds – but this is not relevant here, as we have seen. The
tetrahedrons now stack up like in the figure below, which shows a fragment of
the structure:
You have to imagine that every tetrahedron contains an oxygen atom at the centre
and a hydrogen atom in each corner.
When the ice melts, the individual water molecules regain some freedom to
move. The water molecules now “remember” that hydrogen bonds and covalent
bonds are not the same thing. This has major consequences: In a covalent bond,
the distance between the bonding partners is fixed and does not change unless
great energy is used. For example, it is similar to how the distance between your
hand and your elbow is fixed. Trying to change it would not be that easy!
But when you are dancing with someone, it is very much possible to move a little
bit closer to each other or further apart during the dance, even if it is only a few centi-
metres. You can still keep dancing without any problem. The situation is similar with
hydrogen bonds that have a higher degree of freedom than covalent bonds.
But in liquid water, the individual water molecules are no longer bound by the
rigid structure of the ice. This allows them to move closer to each other – if only a
little bit – because the hydrogen bonds and the covalent bonds now no longer have
the same structure. In keeping with the analogy, it would be as if the restraints be-
tween the dancers had been loosened and they could now move a bit closer to each
other again.
When looking at the structure of ice as shown above, you will notice that there
is still some space between the tetrahedrons – the structure is not completely
“dense”. However, water cannot make use of this space while being solid, because
it is bound by the structure. This is different when water is liquid. In the liquid
state, the individual molecules are far less squeezed into a rigid structure.
In liquid water, everything “wiggles into place” in such a way that some of this
space can still be used. As a result, more water molecules can now fit into a given
space – not that many, but enough to produce a difference in density that causes
water to be most dense at 4 °C (39 °F).
Conversely, when water freezes, the dance partners are getting tied to each
other again, at a precisely defined distance and in the rigid structure shown above.
This procedure of “being locked in position” takes up a bit more space than when
the water molecules can position themselves as close to each other as they “like”.
This causes water to expand. The resulting force is so great that it can even break
rock!
When heating water to temperatures above 4 °C (39 °F), the individual water
molecules move increasingly faster as the temperature rises and therefore need
more space. This means the density decreases as water expands. But this is
completely normal and happens in all compounds.
The miraculous thing about water is its state at the temperature range between
0 °C (32 °F) and 4 °C (39 °F), a phase during which its density increases rather than
decreases despite the rising temperature. In somewhat simplified terms, this sur-
prising behaviour is due to the fact that covalent bonds and hydrogen bonds in ice
are treated as if they were the same, even though they are not. Only when water
turns liquid does it “remember” that there is a difference.
Therefore, the next time you see an ice cube in your drink, remember what a
miracle it is that it floats at the surface instead of sitting at the bottom. You owe
your life to this fact!
5 Dissolving like sugar in water
You may have heard the expression “We are not made out of sugar”, which I always
loved to hear as a kid when I was being reprimanded for not wanting to go outside
in the rain. But why does sugar dissolve in water?
In other words, why is water a good, and sometimes even great, solvent for
some substances, but not for others?
It is actually very simple: Water best dissolves those substances that are chemi-
cally similar to it and with which it can easily form hydrogen bonds. Substances
with a different chemical structure dissolve less well in water.
How can we find out which substance dissolves well in water which does not?
“Very easy”, you might say, “I’ll just take some water and try it out.” That is true, of
course, and, when in doubt, it would also be the method of choice. So, let me re-
phrase this question: How can we assess which substance dissolves well in water
and which does not, based on its chemical structure alone?
That is not that difficult either. Let us start with a simple substance: alcohol. In
chemical terminology, however, the alcohol that is in your beer or wine is called
ethanol instead of alcohol. That is because the term alcohol is used in chemistry to
refer to a whole class of substances – the alcohol we know is just one of them. The
chemical structure of ethanol looks like this:
You can see here that two carbon atoms are bonded to each other. That is nothing
unusual. In organic chemistry, the branch of chemistry that deals primarily with
carbon compounds, having two carbon atoms in one molecule is not that much.
Carbon is one of very few elements that can form long chains or rings. In organic
chemistry, this is so ubiquitous that carbon is often seen as more of a basic frame-
work of a compound – similar to bricks in a wall.
In ethanol, it can also be observed that five of the six available carbon binding
sites (because carbon always forms four bonds) are taken by bonds with hydrogen.
In organic chemistry, this is also a common occurrence found in the vast majority
of organic compounds.
The fact that carbon forms chains or rings while the remaining bonds are
formed with hydrogen led chemists to radically simplify the above-shown molecu-
lar notation. I will give you a brief explanation of how this is done, because it will
https://doi.org/10.1515/9783110628012-005
28 5 Dissolving like sugar in water
also make things easier for me in the following chapters. When using this notation,
ethanol looks like this:
Now that is really easy to write! As you can see, each bend – and the end – of this
zigzag line represents a carbon atom. Unless indicated otherwise, all bonds are
filled with hydrogen atoms.
Sometimes things are not made quite as simple and at least the end is indi-
cated, which then looks like this:
This notation significantly shortens ethanol at first glance. But this is permissible,
because the chemical properties of organic molecules are usually not attributed to
the carbon chain, but to the other atoms that are attached to the carbon chain.
Hence, it was discovered that many of ethanol’s properties are still present
when the carbon chain is lengthened by one atom. The resulting compound is
called propanol and looks like this:
In the shorthand or bond line notation:
This is why almost all molecules that contain an OH group are collectively called
alcohols. To a chemist, alcohols are therefore an incredible multitude of compounds.
I will take this opportunity to insert some additional information about carbon.
If you get your chemistry right, carbon forms very, very long chains. When
reaching a certain length, these are usually called polyethylene in chemical termi-
nology. You know it as the material used for plastic bags. The name is derived from
the production method and need not be explained in more detail. But in this case,
there are tens of thousands, sometimes even hundreds of thousands, of carbon

atoms linked together!
In addition, carbon has the ability to form more than a single bond with itself.
This means there are also double bonds and even triple bonds. For example, adding
a double or triple bond to propanol also results in the formation of stable molecules
that are called allyl alcohol and propargyl alcohol and look like this:
Allyl alcohol Propargyl alcohol
In the shorthand notation:
Allyl alcohol Propargyl alcohol
In addition, carbon also forms rings, with pentagonal and hexagonal rings being
particularly stable. Hexagonal rings with alternating single and double bonds are
even more stable. These rings – which are actually “flat as a pancake” – are also
called benzene rings, because the simplest of these molecules is called benzene
and looks like this:
You may be familiar with the name of a slightly more complex molecule in which
two such rings are connected: naphthalene, which used to be the primary compo-
nent of mothballs. It is also flat and has the following structure:
For all these reasons, there are far more known chemical compounds in organic
chemistry than in inorganic chemistry, about 30–40 times as many.
But let us get back to ethanol. The very first visual graphical depiction of
ethanol is – again – not correct in terms of the real structure of ethanol. Etha-
nol actually looks more like it is shown in the shorthand notation, which is
slightly “jagged”:
In this representation, the carbon atoms are not marked with a C, but are
instead represented as “crossings”. The structure can be best visualised by
imagining two methane tetrahedrons linked together, with one being upside
down:
Of course, one tetrahedron has an oxygen atom attached to it, which is not
shown here. The zigzag or shorthand notation is therefore pretty close to chemical
reality, which is one reason why it is so commonly used.
Ethanol is divided into two parts, if you will. The left part consists of carbon–
carbon and carbon–hydrogen bonds. These bonds each have the bonding electrons in
the middle – the bonds are non-polar, meaning they have no positive or negative pole.
The right, slightly shorter part consists of oxygen and hydrogen attached to a
carbon chain. While the bonding electrons in the bond between oxygen and carbon
are slightly closer to the oxygen atom (but are not really positioned on one side),
the oxygen–hydrogen bond is clearly polar, with oxygen having a δ– and hydrogen
a δ+. Oxygen also has two additional free electron pairs that are shown in the figure
below:
Non-polar part
Polar part
Water can therefore form hydrogen bonds with the right, polar part in a similar way
as it does with itself. It cannot do the same with the non-polar part of the molecule,
but that is not a problem with ethanol. The hydrogen bonds with ethanol’s polar
part are so strong that they cause ethanol to mix completely with water, as you
know from experience. You can basically imagine it as follows:
The situation is different when the non-polar part becomes bigger, because then
things obviously get increasingly “difficult” for water. The next longer alcohol,
propanol, the structure of which is also shown above, also dissolves completely in
water. The next longer alcohol after that with four carbon atoms is butanol. It no
longer dissolves completely in water, having a solubility of 80 g in 1 L. With the
next higher alcohols, it continues to get even more difficult until reaching those
that do not dissolve at all. For example, one extreme case is the following molecule:
It still contains a somewhat lonely OH group in the bottom left corner, but apart
from that, it is a true carbon–hydrogen monster. This molecule’s solubility in water
is virtually zero. The name will sound familiar to you. It is called cholesterol, indi-
cating that it contains an alcohol group.
The situation is different with sugars. In chemical terminology, the name sugar
means something entirely different than in everyday language, with the term sugar
also standing for a whole group of substances. You may be aware of this because
there are other sugars apart from common household sugar, such as glucose, malt-
ose, fructose or lactose. These names stand for various compounds that are all clas-
sified as sugar from a chemical point of view.
What all sugars have in common is the high number of OH groups in the molecule.
(Does this mean sugars can chemically also be called alcohols? Yes, they can . . . al-
though this may be a little confusing. Strictly speaking, sugars are a subgroup of alco-
hols. But pointing out this fact will not help you when the police pull you over. . .).
The structure of household sugar, chemically also called sucrose , is shown below:
You will notice that this compound is relatively complex, even though it is sold by
the kilo in supermarkets and consumed in even larger quantities if you have young
children. That is true! I will not go into any more detail about its specifics. I only
want to show that household sugar has eight OH groups and therefore dissolves in
water . . . like sugar in water! The solubility of sugar in water has been measured. At
20 °C (68 °F), 1.97 kg of sugar dissolves in 1 L of water. Such a solution contains
almost twice as much sugar as water!
I will stay in the kitchen for a bit longer and move on from sugar to salt. Salt dis-
solves in water in a considerable amount, specifically 359 g in 1 L at 20 °C (68 °F),
although it does not contain any OH groups at all! How is this possible?
Again, it is actually quite simple if you remember the definition of a hydrogen
bond from Chapter 3. Let me repeat:
A hydrogen bond is the attractive force between a positive charge (either a true positive
charge, such as the one in Na+, or a δ+ charge, such as the one in water) and a free electron
pair of another atom.
This is why the present case offers even two opportunities for hydrogen bonds. In
addition to forming between Na+ and the free electron pairs of the oxygen in water,
they also form the other way around between hydrogen’s δ+ charges in water and
the chloride ion’s free electron pairs. Remember, chloride has as many as four of
them and is also negatively charged.
A close examination of the dissolution of sodium chloride in water found that
the sodium ion forms hydrogen bonds with the surrounding water molecules – and
not just one, but several. Altogether, six water molecules become attached to so-
dium. This can be visualised as follows:
The same happens in chloride. Again, each chloride ion in water is bonded to six
water molecules. But the chloride ion is negatively charged and has a total of four
free electron pairs, resulting in hydrogen bonds between the hydrogen atom in the
water molecule and the chloride.
These hydrogen bonds cause salt to dissolve in water.

There is a final topic to mention: Chloride and sodium are separated in the pro-
cess. In water, sodium and chloride are almost completely separate from each
other. That is not the case with sugar. Although sugar dissolves in water, each indi-
vidual sugar molecule remains the whole. By the way, this difference used to puzzle
chemists for a long time in the nineteenth century, and Svante Arrhenius’ discovery
of the fact that sodium chloride “splits up” (or “disassociates” in scientific terminol-
ogy) while sugar does not earned him a Nobel Prize in 1903.4
Arrhenius was actually a very prolific scientist who even predicted the green-
house effect in 1895! He thought it would actually not be such a bad thing because
then it would stay warm all year round . . . did I mention that he was from Sweden?
4 Bear in mind that sodium chloride is otherwise an incredibly stable substance, considering its
high melting and boiling points (808 and 1,465°C, respectively), as we have discussed. But in
water, sodium chloride instantly loses its stability.
6 Soaps and cells
In the previous chapter, I gave you several examples of substances that dissolve
well in water. So which substances dissolve poorly in water?
They are mainly substances that cannot form hydrogen bonds at all or only
with difficulty – namely all substances in which most of the bonds are non-polar. It
is just like in the kitchen with your salad dressing: The sugar (if you use any), the
salt and the vinegar dissolve well in water, but the oil does not. It floats on top.
That is because salad oil is non-polar.
Chemical laboratories perform most experiments in rather non-polar mixtures,
by the way. That is because many compounds of chemical interest do not dissolve
in water. Instead, other substances are used, such as chloroform or petroleum
ether, which is pretty similar to the petrol you put in your car.
Is it possible to tell whether a substance is polar or non-polar by looking at it?
Yes, it is. Basically, it is really simple: The more carbon and hydrogen atoms and
fewer other atoms a substance contains, the more non-polar it is and the more
poorly it dissolves in water.
Fats are a good example. Everybody knows that fats, just like oils, do not dis-
solve in water. Although there are many different fats, the vast majority of them
have a very similar structure, which is as follows:
The circled portion on the left is always the same. Chemically speaking, it is called a
triglyceride, but what that means exactly need not be explained here in any more de-
tail. Only the right portion, namely the length and structure of the chains, differs from
fat to fat. Oils like your salad oil, for example, basically also look like that, by the way.
As you can see, fats do have oxygen atoms, but that is not enough to form a
sufficient number of hydrogen bonds. The carbon chains are simply too long.
But when a substance like soda lye is added to a fat, something very interesting
happens – a process known as saponification. In this reaction, the fat shown above
is split into four parts:
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36 6 Soaps and cells
The part highlighted in dark grey, resembling an “m”, forms a molecule called glycerol.
But this is not important in this case. The other parts, highlighted in slightly lighter
grey, form what are called fatty acids. They are the ones that matter in the following
section. These fatty acids differ significantly from the fat from which they form is an
important aspect. I will explain this in greater detail, using one of these fatty acids, a
fatty acid sodium salt, as an example to be studied more closely. It looks like this:
The big difference to the chemical structure of fat is the left part, which, even more
specifically, looks like this:
The carbon chain is abbreviated here as “R” (for “residue”). That is very common in
chemistry – chemists like to be lazy about that, or focus on what is essential, de-
pending on which way you look at it. This compound is known as a carboxylic acid
or, even more specifically, as a carboxylic acid salt. These compounds will be dis-
cussed in more detail later. But what is already apparent and sufficient for now is
that this carboxylic acid salt has as many as five free electron pairs on the two oxygen
atoms. At the same time, there is also a negative charge on one of the oxygen atoms,
similar to the cyanide ion of potassium cyanide from the very first chapter. This part
of the molecule is therefore very much capable of forming hydrogen bonds. The long
carbon chain on the other side does not “get along” well with water.
Thus, when adding this compound to water, something very interesting hap-
pens. The molecules arrange themselves into a sphere, with the carbon chains
being on the inside and the carboxylic acid groups at the surface:
The carboxylic acid salts are shown in this image as described below:
In chemical terminology, these spheres are called micelles. What is the purpose of
these micelles? Well – the purpose is implied by the name of the original reaction:
saponification. These fatty acid salts and the micelles that form out of them are ex-
actly what we know as soaps! As a matter of fact, soap was made from fat using ex-
actly the same process for centuries. There even used to be a profession called
“soaper” that was devoted entirely to carrying out this reaction and making soap out
of fat. Nowadays, there are hardly any soapers anymore, apart from a few exceptions,
such as Tyler Durden in the movie “Fight Club”. Soaps are produced industrially and
are essentially made from petroleum. But I am just mentioning this in passing.
As you all know, soap can be used to clean laundry or to wash our hands, of
course. Most importantly, soap removes fat from laundry. This would be difficult to
do with water alone, mainly because of the poor solubility of fat in water. But soap
makes it much easier, and here is why: Soaps are present in the form of micelles,
which are non-polar on the inside, because that is where the carbon chains are
located. This allows fats to be present inside the micelles, where they are basically
dissolved. So, adding an aqueous soap solution to laundry – combined with a little
bit of scrubbing – causes the fat to be stored inside the micelles:
But the micelle as a whole is soluble in water, simply because the carboxylic acid
groups are arranged on the outside and are thereby able to form lots of hydrogen
bonds with water. When removing the laundry from the soap solution, the micelle
and the fat it contains remain in the water. This is how soap makes it possible to
get the fat into water and thereby remove it from laundry!
I am going to tell you about another great way to clean laundry later on in
Chapter 10. But let us now move on from household chores to modern research, be-
cause researchers have been asking themselves the exact opposite question: How
do we get sodium chloride out of water – and into “oil” (i.e. a non-polar solvent)?
This is not that simple, because both the sodium and the chloride ions in so-
dium chloride are charged! How is that supposed to work? When you add salt to
your salad oil, no matter how long you shake and try to dissolve it, it is not going to
happen! “Well”, you might say, “it doesn’t matter, because we’ve got water to dis-
solve sodium chloride. We don’t need oil.”
In cooking, it really may not make any difference, but, as is often the case in
scientific research, there is a lot more to it.
But, on that note, I first need to show you something else, because the arrange-
ment as a micelle is not the only one that fatty acids are known to have. There is
another one that is absolutely essential for life on the Earth, including your life and
mine. Under certain circumstances, fatty acids arrange in such a way that the car-
boxylic acid groups are facing not only the outside, but also the inside, forming
what is called a liposome:
As you can see, a liposome resembles a hollow sphere. It has an interior space that
is filled with water and is surrounded by a kind of border. This border consists of
two layers of fatty acids arranged in such a way that the carbon chains are facing in
and the carboxylic acid groups are facing out:
This is also known as a lipid bilayer. The word “lipid” is derived from the Greek
word “lipos”, meaning “fat”. It could also be called a “fatty bilayer”, but lipid
bilayer has become the established term.
But why is this arrangement so important? Because an identical structure also oc-
curs in cells, including those that are found in your body and mine. The lipid bilayer
has the convenient property of preventing the water-soluble substances in its interior
from reaching the outside. In order to accomplish this, they would first have to pass
through the bilayer – which they cannot do because they are not soluble in the fatty
layer. As a result, they are trapped inside the cell, which enables a cell to exist in the
first place.
However, the lipid bilayers in the cells of your body have a significantly more
complex structure. For example, almost all of them contain a substance I intro-
duced to you earlier: cholesterol. Cholesterol performs important functions, such as
ensuring increased stability of the lipid bilayer. An average human body contains
about 140 g of it!
Moreover understanding the lipid bilayer gets more complicated when taking an
even closer look at a cell in your body. All cells need minerals like sodium ions or
potassium ions to be able to exist. But how do they get into the cell? Sodium and po-
tassium are charged ions, which means their solubility in water is very high and thus
their chance of crossing a lipid bilayer is virtually zero. This brings us right back to
the problem we started with!
Things get even more complicated when considering that sodium ions and potas-
sium ions have completely different roles in your body, which is also responsible for
closely monitoring the concentration of sodium and potassium in different parts of
your body. When you are given an IV at the hospital, it should be based on 0.9% so-
dium chloride solution (known as an isotonic saline). If you were given a potassium
chloride solution instead, you would, unfortunately, after the IV most likely be dead.
As you can see, the question of how to get “salt into oil” is rather interesting. In
the 1970s, the discovery that compounds like the one shown below are basically
capable of locking up sodium ions caused quite a stir in the scientific community:
Compounds like these have been dubbed crown ethers. Ethers are specific chemical
compounds, which I will not go into right now. But they are called “crown” ethers
because, when seen from the side, their structure looks a bit like a crown:
As I have mentioned, these compounds bind sodium, with the sodium being located
inside the crown. Since the oxygen atoms in crown ether have free electron pairs,
several hydrogen bonds can form, as shown in the following figure:
Now what can be done with these compounds and the sodium bound in them? Very
easy: They can be dissolved in “oil”! Crown ethers dissolve very well in non-polar
compounds. The figure shown above and the previous image make clear how this
works: The crown ether is polar on the inside, making the sodium feel “right at
home”. But, towards the outside, only the carbon–hydrogen bonds are visible. They
harmonise particularly well with non-polar liquids and ensure solubility.
Hence, the situation is the opposite of that seen in a micelle. The sodium can
“enter” the crown ether, which then dissolves in the non-polar solvent. The crown
ether then serves as a kind of molecular lift for the sodium.
Interestingly, (only) crown ether with ten carbon atoms, as shown above, takes
sodium along. If the crown ether is slightly larger, as shown below, it no longer
binds sodium:
Why? This is because sodium is too small for hydrogen bonds to form. Instead, this
compound binds sodium’s “big brother”, potassium. This means that crown ethers
are capable of distinguishing between sodium and potassium! These and other
spectacular findings prompted the Nobel committee to award the 1987 Nobel Prize
in chemistry to three scientists who, along with their doctoral candidates and
teams, had been instrumental in studying crown ethers and similar compounds.
But how does your body transport sodium and potassium into a cell and distin-
guish between them? This question is again not that easy to answer. It has been
discovered that the body does this by using the so-called ion channels in which so-
dium and potassium are also distinguished by their size in a way that is very similar
to how this happens in crown ethers. Potassium channels transport only potassium,
and sodium channels only sodium. The ion channels are more or less integrated
into the lipid bilayer, acting as a kind of tunnel between the interior of the cell and
its surroundings. It has been discovered that the structure of certain potassium
channels and the structure of crown ethers do share some similarities, although the
former are obviously far more complex. In 2003, another Nobel Prize was awarded
for insights into the structure of certain ion channels.
To conclude this chapter, I would like to introduce you to valinomycin, a mole-
cule found in bacteria:
As you can see, valinomycin bears a certain resemblance to crown ethers because it
is also ring-shaped and has lots of inward-facing oxygen atoms. Just like the previ-
ously shown crown ether, it binds potassium very well, as opposed to sodium,
which is hardly bound at all. What is valinomycin used for? It is used for the
purpose of transporting potassium into cells, specifically hostile cells. Valinomycin

is known as an antibiotic and is used in nature by certain bacteria to defend against
other bacteria. Valinomycin has the ability to “store” potassium while also being
able to penetrate the lipid bilayer of bacterial cells. By freely introducing potassium
into hostile bacteria, valinomycin disrupts the processes in these bacteria so much
that they are killed! The word antibiotic means exactly the same thing: against life.
That is also the reason why crown ethers are quite toxic.
7 Recognise your vis-à-vis
I would like to take a step back and briefly discuss the structure of carboxylic
acids, which were introduced in the previous chapter. I will be using acetic acid
as an example. You are all familiar with acetic acid. Acetic acid is found in vinegar
and is responsible for giving vinegar its sour taste. Chemically, acetic acid looks
like this:
It is a fairly simple compound. Unlike fatty acids, it also dissolves in water because
of its short carbon chain. The exact three-dimensional structure of acetic acid is as
follows:
Acetic acid is structurally divided into two parts. The left part, consisting of a
carbon atom attached to three hydrogen atoms, has the tetrahedral structure we
discussed earlier.
The right part, by contrast, has a different structure. There is a double
bond between oxygen and carbon. This is basically nothing unusual; we have
already seen this in CO2 in Chapter 1. However, as a result of this double bond,
the other bonds now have a bit more space, slightly expanding and flattening
the entire structure. This is mainly due to the fact that with one centre and
three bonds, this is the arrangement where all bonds have the greatest distance
to each other. The double bond and the two other bonds on the carbon atom
lie in the same plane, producing an angle of (approximately) 120°, as would be
expected:
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46 7 Recognise your vis-à-vis
120°
Tetrahedral Flat
When examining acetic acid, it becomes apparent that acetic acid forms hydrogen
bonds with itself, which looks like this:
The two flat ends fit together very well, as you can see. But what is important about
this structure is that the pairing of the two acetic acid molecules is not random but
strategic. The hydrogen bond is used to transmit directional information from one
acetic acid molecule to the other. This directional information specifically refers to
the arrangement in a line – with each second carbon atom facing outwards.
That does not seem like that much (yet)? It really isn’t. Determining the direc-
tion in acetic acid any more specifically is difficult because the molecule is rela-
tively small. In addition, it needs to be considered that a single bond in carbon can
be freely rotated like an axle. That is why the following structure
cannot really be distinguished from the one below:

Using the bond between the carbon atoms, the molecule was simply “turned
around” like a wheel on an axle.
The following, considerably more complex molecule makes things better:
This molecule is slightly larger, but not that difficult to understand for our pur-
poses. It consists of four parts:
Part A is simply a carbon atom with three hydrogen atoms, like in acetic acid. This
part is not relevant. Part B is similar to something I showed you in Chapter 5. It re-
sembles a benzene ring, with one of the carbon atoms having been replaced by a
nitrogen atom. This structure is called pyridine and is also very stable. It is impor-
tant to note that, first, nitrogen has a free electron pair that can form hydrogen
bonds and, second, that this pyridine ring is flat just like the benzene ring.
Part C is a nitrogen atom that is attached to part D. Part D is again a carboxylic
acid group, similar to those in fats, whose structure I showed you in the previous
chapter. In fat, however, this part was attached to an oxygen atom, as indicated by
the arrows in the figure below:
This is now a nitrogen atom. The combination of part C + D is also called an amide.
But the only thing that matters for our purposes is that the nitrogen atom still has a
bond with a hydrogen atom, so part D itself is not particularly relevant right now.
What does this molecule do? It also forms two hydrogen bonds with itself:
You can tell right away that the transmitted directional information is now consider-
ably larger. The second molecule can only attach to the first when it turns around
and the Parts “D” are not on the same side, but part from each other. Hence, the first
molecule determines the direction in which the second can attach to it.
Systems like these have spawned an entire field of research called molecular rec-
ognition. This term stems from the fact that the individual molecules recognise each
other – and, when done correctly, attach to each other the way you want them to.
This can then be taken advantage of to the point of creating molecular architecture.
In the next chapter, I will talk in more detail about some other benefits and
uses of molecular recognition and why even our existence depends largely on the
fact that molecular recognition exists. But first, I would like to show you another
slightly more complex molecule, which also involves molecular recognition. It was
introduced by Prof. E. W. “Bert” Meijer from the Eindhoven University of Technol-
ogy in 1998 and looks like this:
Again, “R” stands for a carbon chain, which, however, is not important in this
case. This molecule now forms no less than four hydrogen bonds with itself in the
following way:
This number of hydrogen bonds in a compound was a world record for a “syntheti-
cally” produced molecule at the time, so this molecule caused quite a stir. But there is
a small trick to it, which needs to be explained. Just like in acetic acid, this molecule
can be rotated at many positions – including the one shown in the following figure:
Rotating the molecule at this position produces the following structure:
It is instantly apparent that things are now getting a bit difficult for hydrogen
bonds. So why does the molecule not rotate around this axis? Because in addi-
tion to the four hydrogen bonds, there is a fifth running through the molecule
itself:
This additional hydrogen bond holds the molecule in place!

8 Jerry Donohue and the DNA
At this point, I would like to bring up a molecule that shows how essential hydrogen
bonds are in nature. It is DNA, or deoxyribonucleic acid. Do not expect me to explain
what DNA means. The name is not essential to understanding DNA, so I won’t go
into it any further. In biology, DNA is the molecule in which genetic information is
stored, making it the most essential molecule without which “nothing works”. DNA
has the following structure:
But this is only a small section. DNA molecules that can be isolated in nature are
much, much bigger. After all, DNA can store the entire genetic material of a human
being, for example. Now if you think that DNA looks pretty complicated, I agree
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52 8 Jerry Donohue and the DNA
with you – but I will try to simplify things a little bit. DNA is usually divided into
what are called the backbone and the bases. The backbone provides the framework
along which the bases are arranged, and is not that important for this chapter. The
bases are the essential part of DNA. Similar to how information on a computer is
stored as a series of zeros and ones, DNA stores information as a series of bases.
But instead of using just one and zero, there are four different bases, namely ade-
nine (A), thymine (T), cytosine (C) and guanine (G). The backbone and the bases
are structured as follows:
Base #3: Adenine (A)
Base #2: Cytosine (C)

Backb
one
Base #1: Cytosine (C)
The backbone, which always repeats itself anyway, is therefore simply “ignored” in
practice and only the bases are listed (e.g. CCA – which would be the molecule
shown above). Readers of the German newspaper Frankfurter Allgemeine Zeitung
may remember that on 27 June 2000, an entire page was filled with such a DNA
sequence. When abbreviating the backbone as “R” (for residue), DNA is shortened
as follows, depending on the base:
Adenine Cytosine
Guanine Thymine
This makes things a bit easier to read, so I will stick with it. But I would like to go
into some more detail about the chemical structure of these four bases. These
compounds are called bases because, when isolated in water, they react as bases,
similar to the way soda lye does. But that does not really matter for the role of the
bases in DNA. By itself, DNA (as its name implies) is actually even acidic, which is
the exact opposite. But this term has still become established in scientific lan-
guage, so I will stick with it.
When looking at adenine, for example, you will see that it also contains alternat-
ing single and double bonds similar to those in benzene (Chapter 5) and pyridine
(Chapter 7). In the figure below, the double bonds are highlighted:
Just like in benzene and pyridine, they add great stability to this molecule. More-
over, it basically becomes flat. The fact that there are not just bonds between
carbon atoms but also quite a few between carbon and nitrogen atoms does not
make much of a difference. Something similar is true of the other three bases.
I would now like to take you back to the year 1953 to the laboratory in Cam-
bridge, where James Watson and Francis Crick were attempting to understand the
structure of DNA, called the “double helix” – of course, the two did not know at the
time that the double helix actually was the correct structure. Apart from the fact
that DNA is so incredibly important for biology, I believe one of the reasons why the
story of how the structure of DNA was discovered has become so well known is that
it is a bit like a great movie.5 According to popular opinion, it features all the impor-
tant characters of a classic movie:
– The two youthful heroes facing challenge with little money but great enthusi-
asm are James Watson and Francis Crick. When they published the correct
structure, James Watson was just 25 years old! Watson at least presented him-
self and Crick that way in his book The Double Helix, published in 1968, spark-
ing a not insignificant amount of criticism.
– The seemingly unbeatable and superior opponent is Linus Pauling, then recog-
nised as the greatest chemist of his time, who operated a giant lab in the United
States.
– The tragic hero Rosalind Franklin provided the decisive X-ray images of DNA
that made the discovery possible in the first place, but died before she could
receive the Nobel Prize.
– The “supporter” of the two heroes is Maurice Wilkins, who, presumably by chance,
made said X-ray images available to Watson and Crick, but not to Pauling.
As in a classic thriller, the two heroes already seem to have lost the race when
Linus Pauling publishes a proposal for the structure of DNA in early 1953. But after
reading this publication, they realise that the proposed structure cannot be correct.
This is generally explained by the fact that Linus Pauling did not see Rosalind
Franklin’s DNA X-ray images. But it still seems like there is a jinx on it. They feel
like they are on the right track, but somehow it all just does not fit together.
Feel free to try what Watson and Crick did. Your task is to figure out the
arrangement of the bases in DNA. The following information will help you:
– The structure of DNA is always made up of at least two DNA molecules, also
called strands. The structure proposed by Linus Pauling was based on three
strands. However, Watson and Crick believed that there were only two.
– Research by Erwin Chargaff had shown that the number of adenine units is
equal to the number of thymine units and the number of cytosine units is equal
to the number of guanine units, leading Watson and Crick to deduce that ade-
nine and thyme as well as cytosine and guanine must somehow be connected.
5 By that I mean movies in general – not the existing TV movie made in 1986 on the same subject.
– Based on Rosalind Franklin’s X-ray images and their own experiments,6 Watson
and Crick assumed that the bases of DNA are positioned “on the inside”, that
is, opposite each other. From this, they deduced that there must be hydrogen
bonds between adenine and thymine as well as between cytosine and guanine.
With adenine coming from one DNA strand and thymine from the other, the
same must be true of cytosine and guanine.
So what do these hydrogen bonds look like? Now that is your task. Adenine and thy-
mine as well as guanine and cytosine should naturally be arranged in such a way
that the backbone, “R”, is always in the same position, meaning the “Rs” of the
adenine–thymine pair are pointing in the same direction as those of the guanine–
cytosine pair. Moreover, the recognition pattern of adenine/thymine should be a dif-
ferent one than that of guanine/cytosine. The molecules are shown again below, with
all usable H atoms being highlighted and all usable free electron pairs being marked
by arrows. A hydrogen bond always forms between an electron pair and an H atom.
Of course, the individual molecules can be turned around and also be mirrored.
Adenine Cytosine
Thymine Guanine
Did you try it? Seriously? And you were able to produce a structure? If that is true:
Congratulations! This makes you an even greater scientific genius than Watson and
Crick put together!
6 They largely consisted of constructions made from cardboard and wire. A model that two of them
built is on display in London’s Science Museum.
After all, the honest answer is: It does not fit. There is no solution. And that
was Watson and Crick’s problem for a long time.
But things changed when Jerry Donohue entered the story. Like in every movie,
there is also the role of the “best supporting actor”, for which there is even an
Oscar given out every year. And “supporting” was precisely what Jerry Donohue
did. We also know the exact date: 27 February 1953.
On that day, there was a conversation between Watson and Donohue.7 Like
Watson, Donohue had come to Cambridge as a researcher visiting from America and
was working in the same laboratory. Watson was doing experiments, unsuccessfully
trying to figure out the structure of DNA. On said 27 February 1953, Donohue gave him
the crucial tip. Watson had assumed the chemical structure of the bases to be like the
structures published in a book by author James N. Davidson in 1950, which is exactly
how the bases in this chapter have been depicted so far. Donohue informed him that
those structures were not necessarily correct; on the contrary, they were most likely
even wrong. More recent research had shown that the structure of two of the four
bases, namely guanine and thymine, should differ from Davidson’s as follows:
Guanine according to Davidson Alternative structure
Thymine according to Davidson Alternative structure
7 The sources I have read about this are somewhat conflicting. Sometimes it is Watson who talked
with Donohue, sometimes Crick, and sometimes even both of them. The exact content of the con-
versation also varies slightly from source to source. But it is undisputed that, without Donohue’s
help, Pauling would probably have discovered the structure first.
Now give it another try! It only took Watson and Crick one more day to complete a
first experimental model of their double helix structure on 28 February 1953. The
correct structures as well as the usable hydrogen atoms and electron pairs are
shown again below:
Adenine Cytosine
Thymine Guanine
Well? Did you find an arrangement this time? If you did, it should look something
like this, because this is how the hydrogen bonds in DNA are arranged:
Thymine Cytosine
Adenine Guanine
By the way, it is not that easy to explain why the structure of guanine and thymine is
different from the one originally proposed. In any case, it made a lot of sense to assume
that guanine and thymine looked the way James Davidson described them. That is
why without Donohue’s tip, the realisation that these structures could be wrong would
probably have come too late for Watson and Crick or may never have come at all.
About 1 month later, on 2 April 1953, the two submitted their now-famous man-
uscript to Nature, a scientific magazine. This manuscript was published on 25 April
1953 and is considered one of the most important scientific publications of the last
century. In this publication, they expressed their gratitude to Jerry Donohue for
“constant advice and criticism”, but that is not the most famous excerpt from this
article, which goes as follows: “It has not escaped our notice that the specific pair-
ing we have postulated immediately suggests a possible copying mechanism for the
genetic material.” And that is correct, as we know today. The hydrogen bonds and
the resulting molecular recognition between the bases ensure that whenever there
is, for example, adenine in a DNA strand, thymine will be inserted at the same posi-
tion into a second, newly forming DNA strand during replication – and vice versa;
wherever there is cytosine, guanine will be inserted – and vice versa.
DNA replication involves the formation of what is called a complimentary strand.
This works exactly like a negative in “analogue” photography, where a fixer and a
developer are used to produce photographs – some of the older readers among you
may remember how this used to be done. In a negative, all the dark areas are actually
light and vice versa, just like in a complementary strand, where thymine originally
was adenine, cytosine was guanine and so on. When this new DNA strand is copied
again, the original one is recreated, just like in “analogue” photography, where the
negative produces a picture on photo paper through exposure.
All of this is only possible because of hydrogen bonding – truly a “bond for
life”! Considering how important this is, I will explain it in a bit more detail. This is
what the hydrogen bonds in DNA look like:
Thymine Cytosine
Adenine Guanine
Everything fits perfectly. It is not only important that adenine/thymine and gua-
nine/cytosine fit, but also that combinations like adenine/cytosine and guanine/
thymine do not. Because that would result in the following structure:
Cytosine Thymine
Adenine Guanine
It is instantly apparent that hydrogen bonding is not possible between adenine and
cytosine or between thymine and guanine, because in both possible pairs, hydro-
gen atoms would be directly opposite to each other. An adenine/guanine pair is
also not possible – due to the fact alone that the structure does not offer enough
space for it. The opposite is the case with cytosine/thymine, because the distances
are too large. But the hydrogen bonds would not fit either. Feel free to give it a try.
Hence, only adenine matches with thymine and only guanine with cytosine,
making the copying mechanism unambiguous. Well, maybe not that unambiguous,
because it has been known to happen in the body that the wrong base is inserted
by mistake. This is estimated to happen in about 0.1% of all cases, but it depends
on various factors. However, the DNA copying mechanism in your body has to be
far more precise, because otherwise there is always the risk of unexpected and un-
desired consequences – such as developing cancer. That is why there is a veritable
“proofreading machinery” to ensure that the error rate is reduced even further. But
the accuracy must not be too high either, because otherwise there would be no evo-
lution and we would all still be bacteria floating around on the Earth.
Watson, Crick and Wilkins received the Nobel Prize in medicine in 1962. By the
way, Linus Paul also won a Nobel Prize the same year, but he was awarded the
Nobel Peace Prize in recognition of his efforts to end nuclear testing. Interestingly,
he received the prize in 1963 retroactively for 1962. He had already received a scien-
tific Nobel Prize, the one in chemistry, in 1954. Jerry Donohue returned to America
where he went on to become a highly respected professor, without ever working

with DNA again.
I would like to mention one more thing. It has been discovered that the hydro-
gen bonds in DNA described by Watson and Crick are not the only ones found in
nature. For example, there is another arrangement known as Hoogsteen base pair-
ing, named after Karst Hoogsteen, a Dutch biochemist. However, this only works
with one of these four bases, guanine. Under favourable conditions, it forms a
structure that looks as follows:
Although this structure almost looks like a piece of art, it has turned out to be rather
common8 and the presence of such structures, called G-quadruplexes or G-tetrads,
has important control functions in specific genes. For this reason, they are the sub-
ject of intense research.
8 There is almost always another potassium atom at the centre, like in some of the crown ethers
from Chapter 6. This structure has been found to add further stability. For the sake of simplicity,
potassium is not shown in the figure.
9 How to make hydrogen bonds visible
All the hydrogen bonds I have introduced to you so far seemed to come “out of
nowhere”. I simply told you that they exist and where they are located. But that
kind of approach is, of course, not an option in science, where you cannot just
claim that there are hydrogen bonds between molecules of A and B. You also have
to prove it. So I will now explain to you how to do this.
There are several ways to prove the presence of hydrogen bonds. You are
already familiar with one of them: X-ray analysis, as was used by Rosalind Franklin
to analyse DNA. However, this method is comparatively complex. An easier method
is proton nuclear magnetic resonance spectroscopy, abbreviated as 1H-NMR.
Explaining how this works in detail is rather complicated, so I am not even going to
attempt it. But this measuring technique is one of the most commonly used
methods in organic chemistry for the structural analysis of substances. It delivers
(at least) one signal for each hydrogen atom in a compound, depending on
the atom’s “chemical environment”. The signal also depends on the number
of hydrogen atoms, with two hydrogen atoms producing a signal twice as
strong as that of one. The number of hydrogen atoms present can therefore be
directly derived from the signal. When the measurement is performed properly and
the signals are then read correctly, 1H-NMR can determine the structure of a
molecule.
All of this also applies to the following molecule, which I will call “A”:
The important hydrogen atom, which we will be focusing on below, is highlighted.

This molecule A forms two hydrogen bonds with a second molecule B, which looks
as follows9:
9 The two molecules A and B were not chosen at random, but I will get to this later in Chapter 11.
https://doi.org/10.1515/9783110628012-009
62 9 How to make hydrogen bonds visible
Producing this result:
This will hopefully make it easier for you to understand that the hydrogen bond
changes the “chemical environment” of the highlighted hydrogen atom. The
bound hydrogen atom now produces a different signal when performing a mea-
surement. When measuring only molecule A shown at the top, a different signal
would therefore be expected than when analysing a mixture of the two molecules
A and B.
A measurement is performed in the same way. First, the molecule A shown at the
top is measured alone, usually in an amount of a few milligrams. Several mixtures of
A and B are then analysed while gradually increasing the amount of B. What would
now be expected?
When only the molecule A shown at the top was measured, a signal would be
expected for the highlighted hydrogen atom, looking something like this:
Of course, the other hydrogen atoms also produce signals, but let us ignore those
for now. Assuming a mixture of A and B in a ratio of 5:1 is analysed, the highlighted
hydrogen atom would be expected to produce two signals: one signal for the hydro-
gen atoms that are now bound by the hydrogen bond between A and B, and a sec-
ond – slightly stronger – signal from the highlighted hydrogen atoms that are still
free. This signal is stronger because there is five times as much A as there is B,
which is why not all molecules of A can be bound. Altogether, the following signal
is expected:
This actually happens, but only when the sample is cooled to a very low temperature.
At normal temperatures, such as 20 °C (68 °F), however, the hydrogen bonds are con-
stantly moving back and forth and the signals become “blurred”. Two signals are
only visible when preventing this movement by strong cooling. But this is not done
in practice, because it is very complicated and also not necessary. What is really seen
is still only one signal, but slightly shifted (a bit to the left, in this example) – the
“average”, so to speak.
When analysing a mixture of A and B containing a higher percentage of B, the visi-

ble signal is even further shifted to the left. The spectrum below shows such a series
of measurements using various mixtures of A and B, in which the amount of A was
kept constant while varying the amount of B:
The use of the ppm measuring scale and the odd fact that this scale increases to the
left, which is the exact opposite of how it normally works, is due to the measuring
technique. Please do not let this bother you.
The spectrum shows very clearly how the signal of the highlighted hydrogen
atom travels further to the left, the higher the percentage of molecule B. The per-
centage of B is shown on the far right. Well, anyone who is used to reading these
kinds of spectra will see right away that it is very clear. When looking at such a
series of measurements for the first time, it may not be instantly noticeable. I will
therefore explain the above figure in a bit more detail:
Shown at the very bottom are the signals that are measured when analysing the
first molecule A alone, indicated by an arrow in the figure below:
Shown above that are the signals that are produced when adding 20% (“0.2 eq.” = 0.2
equivalents, i.e. 20%) of B. On the far right, highlighted in grey in the figure below, a
few weak signals are starting to appear; these are the signals of the new molecule B –
as could be expected:
In addition, a new signal has appeared on the far left. It is the shifted signal of the
highlighted hydrogen atom shown in the figure at the very beginning of this
chapter:
By the way, if you look very carefully, it can also be spotted in the first spectrum on
the far right in the first “forest” of signals at 8.0 ppm:
So, what happened? By adding 20% of molecule B, the signal of the highlighted
hydrogen atom has shifted from the original 8 to about 8.7. This is a strong indication
that the presence of molecule B does indeed change the “chemical environment” of
this hydrogen atom, meaning a hydrogen bond involving this hydrogen atom has
formed. As you can see, the other signals do not change. This is therefore a strong
indication that these hydrogen atoms are not involved in the hydrogen bond that has
formed. This information is of course also important to determine the exact location
of the hydrogen bond.
The signals above that are produced when adding 40% of the second molecule B,
indicated by an arrow in the figure below. The signal on the far left has been shifted
even further to the left.
Above that is the signal at 60% B – with the signal being even further to the left
and so on.
When adding a surplus of the second molecule B, indicated by “2 eq.” for twofold
surplus up to “10 eq.” for tenfold surplus, nearly every single molecule A is now
bound by hydrogen bonds. However, the other signals do not change. This is not sur-
prising, because these hydrogen atoms do not form hydrogen bonds. But as the con-
centration increases, the signals of the second molecule B are gaining the “upper
hand”. That is also why the signal of the highlighted hydrogen atom is dropping
slightly, as can be seen clearly in the next figure:
Hence, the shifting of the signal can be used to determine the presence of a hydrogen
bond and to identify which hydrogen atoms in the individual molecules are involved
in it. Another advantage of this method is that it can determine not only the presence
of a bond but also its strength by evaluating the individual measurements more
closely. In addition, such a measurement does not take very long, only about one
day, and requires only a small amount of substance. So it is no wonder that virtually
all chemists worldwide use this method to examine hydrogen bonds.
You may be wondering: Why is a tenfold surplus of the second molecule B neces-
sary to bind all of the first (A)? Shouldn’t it be enough to just add the same amount?
It depends on the strength of the bond and the fact that what we are dealing
with here is called equilibrium. I will go into this very briefly – and then I will also
tell you how to take advantage of such equilibria in chemistry.
When analysing the concentration of the free first molecules of A, the concen-
tration of the free second molecules of B and the concentration of the bound mole-
cules – also called a duplex – in our system, it becomes apparent that, regardless of
the conditions, the following equation applies:
A*B = K *AB
In this equation, A stands for the concentration of the free molecules of A, B for the
concentration of the free molecules of B and AB for the concentration of the duplex.
K is a constant. This constant K indicates the strength of the bond between the mol-
ecules. It is extremely dependent on the specific conditions, such as temperature
and solvent. When trying to bind as many molecules of A as possible which in the
equations means to make A as small as possible, it is helpful to rearrange the equa-
tion a little bit:
K * AB
A=
B
You can see that A automatically becomes smaller as the concentration of B

increases. When trying to bind as many molecules of A as possible, it is therefore
necessary to add as much of the bonding partner B as is reasonably possible. That
is exactly what was done in the above measurement. You can see that it is very
reasonable to add a tenfold surplus of B to really bind almost all molecules of A.
Thinking in terms of equilibria takes some getting used to, because it somewhat
contradicts everyday experience – but a lot of things can be done with it. To illustrate
this point, I would like to take a look at another very simple (but completely
hypothetical) equilibrium. Let us assume there are 10,000 people living in a small
city, 9,900 of whom are Schalke 04 supporters and the remaining 100 are Borussia
Dortmund supporters.10 The relationship between them would be a chemical equilib-
rium, producing the following equation:
Schalke = 99 × Dortmund
This means there is a ratio of one Dortmund supporter to 99 Schalke supporters,

two Dortmund supporters to 198 Schalke supporters and so on.
Let us suppose that despite this difficult starting situation, Borussia Dortmund
was interested in converting all residents of that town into Dortmund supporters.
How could Borussia go about it?
In real life, it would be difficult, of course, because a Schalke 04 supporter
would never betray her or his club and defect to the other side, no matter how
well Borussia may be playing. But in chemistry, there is a surprisingly simply so-
lution: Borussia Dortmund would convince the Dortmund supports to move away
from that city!
So, what would happen then? Since the equilibrium always (!) applies, a few
Schalke supporters would now automatically become Dortmund supporters. When
all Dortmund supporters have moved away, there would only be 9,900 people left
in that city, but since the equilibrium continues to apply, 9,801 people would now
support Schalke and 99 Dortmund, meaning 99 of the original Schalke supporters
have now changed their minds. The above-described relationship between Dort-
mund and Schalke supporters also applies the other way round: There automati-
cally must be a ratio of one Dortmund supporter to 99 Schalke supporters, so in a
population of 9,900 people, there must be 99 Dortmund supporters, regardless of
whether they were previously Schalke supporters or not.
Now, if Borussia Dortmund were to carry out another “moving-away” campaign,
there would be 9,702 people left in the city. According to the equilibrium, 9,605 of
them would be Schalke supporters and 97 Dortmund supporters.
10 For those readers who are not familiar with Schalke 04 and Borussia Dortmund: They are Ger-
man football clubs that share a healthy rivalry. Alternatively, you could think of Manchester United
and Manchester City.
As you can see, a respectable 100 + 99 + 97 = 296 of all (original) residents of

the city have converted to being Dortmund supporters, meaning the percentage of
people who go into every season dreaming of celebrating a championship in Borsig-
platz, the birthplace of Borussia Dortmund, has now almost tripled.
If Borussia Dortmund were to keep going this way, the club’s management
could succeed in turning all residents of the city into Dortmund supporters, even
though 99% of the mood is always set against them. However, there would ulti-
mately be no residents left in the city. Well, you can’t have everything.
What does that mean for chemistry? Let us suppose the equilibrium between
Schalke and Dortmund would be like that between the starting product and the
end product in a chemical reaction, where we would, of course, only be interested
in the end product (no offense, Schalke supporters). Even with a very unfavoura-
ble starting situation where only 1% of our desired product exists, we can still
carry out 100% of the reaction – if we can manage to successfully remove the end
product from the reaction (and ensure that the starting product does not react
otherwise, which is sometimes a problem). Once this has happened, the starting
product reacts with an automatic response, forming more of the end product.
Many chemical reactions can only be carried out for this single reason and would
otherwise not work at all.
10 “Now let’s step on the accelerator”
. . . says the boy called “the professor” in the classic “Emil and the Detectives” by
Erich Kästner to the other boys when they talk about recovering Emil’s money and
supporting him in fighting evil Mr Grundeis. In other words: Let’s get going –
quickly!
In chemistry, there are comparably helpful accelerators, which are useful when
it comes to setting things in motion at an accelerated rate. However, these are usually
called catalysts. Those catalysts that are likely to be known to (almost) all readers are
catalytic converters, that is, porous metallic structures used in cars. I do not mean
those; the function of these catalytic converters is really difficult to explain and is not
dealt with in this book, since they do not form hydrogen bonds. The catalyst I would
like to address in this chapter looks like this:
It has been found that it can accomplish truly amazing things. However, we should
start with some background information.
In Chapters 4–7, I showed you that methane and other carbon compounds have
the so-called tetrahedral structure. This has unexpected consequences. Look at the
two-molecule models below:
What exactly A, B, C and D stand for does not play a role here; it only matters that
they are all different.
Each of the two molecules has one A, one B and so on. Only A and B have been
switched. A is highlighted to make this more visible. But are the two molecules
identical? You can try to rotate them until they are congruent.
I tell you right away: It doesn’t work. These two molecules are almost identical,
but not quite. They are like an image and its reflexion or like your left and right
hand. They are also almost identical, but just almost.
https://doi.org/10.1515/9783110628012-010
72 10 “Now let’s step on the accelerator”
This fact is called chirality and the corresponding molecules are referred to as
chiral, from Greek chiros = hand. It simply results from the mathematical properties
of a tetrahedron and was recognised (independently of each other) by Jacobus van’t
Hoff and Joseph le Bel as early as 1874.
Since the two aforementioned molecules differ only in the spatial arrangement
of A, B, C and D, they have the same name. To yet distinguish between the two chi-
ral forms, a system was developed in which one form is designated as the R form
and the other as the S form. There are clear rules to determine which form is R and
which is S. For historical reasons, there is unfortunately another system in which
the two forms are designated with D and L, with different rules for distinguishing
between them.
Chirality would not be that important if it did not have unexpected impacts in
real life. An example of that is carvone, which looks like this:
Carvone (D) or (S) carvone (L) or (R) carvone
On the left, carvone is shown in the way molecules have so far been depicted; next
to it, you can see the two chiral forms of carvone in a sort of three-dimensional (3D)
view. The D or S carvone is shown in the middle, and the L or R carvone on the
right. The two chiral forms differ only in the arrangement of the group below the
ring, which points to the left in the first case (in D and S carvone) and to the right in
the second case (in L and R carvone).
D carvone smells of caraway and is also the substance that accounts for the pri-
mary smell of caraway on your spice rack. By contrast, L carvone smells of mint.
This minor difference is sufficient for the olfactory sensors in your nose to associate
the two molecules with different smells, although they otherwise have a completely
identical structure.
“Well, it’s no big deal when substances smell different”, you might say. But the
whole thing can have even more far-reaching consequences. I would like to demon-
strate this by comparing two types of sugar (please do not bother too much about
the structural complexity, only the difference matters!):
Just like carvone above, the two sugars are shown in a 3D view. The sugar on the
left is grape sugar (also called glucose), and the one on the right is galactose, a sub-
unit of lactose, or milk sugar, which is contained in milk, as the name implies. The
two sugars differ only in the arrangement of a single alcohol group, which is
highlighted. The alcohol group points “downwards” in glucose and “upwards” in
galactose.11
What consequences does this difference have, which appears to be minor at
first glance? Very significant ones – perhaps even for you personally.
Glucose can be eaten by all people – however, there are many people who do
not tolerate lactose. This is also referred to as lactose intolerance. About 75% of all
people worldwide are affected by it, among Chinese even 95% and among Thais
98%! Only in Central and Northern Europe, the United States and Russia can the
majority of people eat lactose, that is, tolerate larger amounts of milk.
Lactose intolerance is even associated with the settlement history of Africa and
other regions. The reason for this is that in certain regions there are people who do
tolerate lactose well or at all, although other people in surrounding areas com-
monly do not. It is assumed that the ancestors of these first people had an advan-
tage due to their genetic make-up, as they were able to drink the milk of their riding
animals, such as camels, while travelling through deserts or other inhospitable
areas and thus populated regions that were inaccessible to other people who did
not have this option.
This is already a huge effect of chirality – given that glucose and galactose dif-
fer only in the arrangement of a single group. In many medicines, too, only one
form is effective (i.e., R or S, D or L); the other is inactive or sometimes even toxic.
You see, chirality is indeed important.
The question of what exact structure a molecule has, that is, what the exact chi-
ral form looks like and, of course, how it can be produced in a targeted manner has
kept chemistry busy since the discovery by van’t Hoff and Le Bel, and many Nobel
Prizes, among them the very first in chemistry to van’t Hoff in 1901, have been
awarded for discoveries and synthesis methods in this field.
To make life easier, chemists have also introduced a shorthand notation for chi-
ral molecules. A bold line indicates that this residue projects forwards, a dashed line
11 “Upwards” was deliberately put in quotation marks, because the real spatial arrangement is yet
a bit different. This description was chosen for the sake of clarity.
that this residue projects backwards and a solid line that this residue projects neither
forwards nor backwards, but lies in the plane of the paper. This looks like this:
Chiral molecule The same molecule in the exact

shorthand notation
The catalyst I described at the very beginning of this chapter is called proline. It has
the advantage that it is commonly found in nature and is inexpensive, which is an
undeniable benefit in chemistry. More specifically, this catalyst is also chiral – and
the form that is mostly used in practice is the so-called S proline or L proline, which
has the following structure12:
The highlighted part on the right, which is, by the way, a carboxylic acid – you
might remember it – projects forwards. At this position, a hydrogen atom projects
backwards as usual, which was left out in the above figure for the sake of simplic-
ity. When adding it, the catalyst looks like this:
This catalyst accelerates a whole range of reactions, including the following

reaction:
12 Of course, R or D proline could theoretically be used as well, but it is not that common in nature
and is therefore more expensive.
This reaction or this type of reaction in general is called “aldol reaction“ and was
described as early as 1872 by Russian chemist Alexander Borodin (who was also a
famous classical composer of what is referred to as the Russian School).
You may have never heard of this reaction, but every chemistry student who
has ever visited a lecture in organic chemistry is familiar with it. After all, this reac-
tion is one of the most important reactions in this field of chemistry. To give you an
example, the synthesis of the medicine atorvastatin, which is marketed by the com-
pany Pfizer under the names “Sortis” and “Lipitor” and used to be the best-selling
medicine in the world for some time, involves two aldol reactions. Atorvastatin has
the following structure:
Atorvastatin
The two alcohol functional groups highlighted in grey are produced in two succes-
sive aldol reactions.
What makes the aldol reaction interesting is that the two reactants A and
B are not chiral, but the product C very well is, namely, at the highlighted
position:
This fact and the significance of the aldol reaction as such have challenged many
chemists to find a method that not only delivers the product but also delivers only
one chiral form of it straightaway. This does not happen automatically. When the
reaction is carried out “just like that”, it produces equal amounts of the product in
S and R form. But if the exact chiral form is important, half of the product is basi-
cally wasted. If you want one of the chiral forms to be produced in excess, the reac-
tion needs to be adapted, for example, by using an additional aid.
Around 2000, Benjamin List (back then at the Skaggs Institute in San Diego,
today at the Max Planck Institute for Carbon Research in Mülheim an der Ruhr)
found out that L proline was such an aid. When adding L proline to the above reac-
tion, more than 90% of the reaction product will be produced in one form, namely,
the following, in which the resulting alcohol projects forwards:
(But only in one form!)
This really was a great success, as most of the previously available methods re-
quired reagents that were much larger, more complex and, most importantly, ex-
pensive. By contrast, one kilogram of L proline costs well below 100 euros, even in
high-purity form, which is a true discount price.
How exactly does this reaction work? This has been extensively investigated
and the following mechanism is assumed to be most likely: Proline first reacts with
molecule A above to form the following molecule and water:
As you can see, the nitrogen atom here forms four bonds – the scientific correct
term would be that the nitrogen is “tetravalent” – and is additionally positively
charged. This is also why this molecule is not very stable and immediately reacts
again in such a way that the H atom highlighted in the figure below is donated as a
so-called proton, forming a double bond. As a result, the nitrogen atom again forms
three bonds (or to say it correctly, it becomes “trivalent”) and everything is alright
again. As usual, however, the nitrogen atom still has an electron pair, which will be
important later on.
This resulting molecule, which I will call “D”, has three important properties. The
first one is that it reacts with molecule B from the original equation, which is this
one:
faster than molecule A. This property is the most important one, because other-
wise A and B would also react “just like that” – and nothing would be gained. The
second property, resulting from proline now being “integrated”, is that it is chiral,
but in such a way, and this is the third property, that exactly this chiral site, as it
is a carboxylic acid, can form a hydrogen bond with molecule B. When taking a
closer look at the structure in 3D view, you will notice that the carboxylic acid
group in molecule D on one side of the double bond is quite precisely located
above it.
This entails that in the following reaction molecule B approaches “from below” –
first, because “from above” the carboxylic acid group is simply in the way and sec-
ondly, because a hydrogen bond forms between the oxygen atom of B and the hy-
drogen atom in the carboxylic acid group of D, which “holds” molecule B “in
place”. This looks something like this:
The two molecules then react with each other to form a new molecule in a spatially
precisely defined way, since the arrangement of the carboxylic acid group and the
hydrogen bond spatially controls the reaction. The next reaction has three steps. I
will explain them one after the other, but in reality, and this is important, they all
take place simultaneously.
In the first step, one bond of the carbon–oxygen double bond in molecule
B “folds over” towards the hydrogen atom of molecule D. The carboxylic acid
group, in turn, detaches from the hydrogen atom and thereby becomes nega-
tively charged:
In addition, one double bond of molecule D “folds over” towards molecule B13:
This happens at the same time as the bond “folds over” towards the hydrogen
atom; consequently, the resulting alcohol projects forwards and the hydrogen
atom, which is located on the same carbon atom, backwards. For the sake of sim-
plicity, this is no longer shown in the figures below. The free electron pair of the
nitrogen atom also “folds over” downwards:
13 The proline group in the following figures is shown slightly tilted to make the resulting alcohol
more visible. In a realistic arrangement, it would be covered by the carboxylic acid group.
The result is the following molecule shown again below, in which – this is impor-
tant and therefore I would like to repeat it – the newly created alcohol group then
projects forwards:
The nitrogen atom in this molecule is now again “tetravalent” and positively
charged. At the same time, the carboxylic acid group is negatively charged, because
the hydrogen atom was donated to the resulting alcohol group. As a result, it in-
stantly reacts with the water created at the beginning to form the following two
molecules:
These are exactly the desired reaction product C and proline! This means that the
proline is fully recovered during the reaction and can “step on the accelerator” in a
second reaction, or, in chemical terms, act as a catalyst. It does not even have to be
available in the same amount as the two other molecules. This is not the case in
practice either. It is usually used in a percentage of about 10–20%.
Of course, it is essential for the reaction that proline with as high a chiral purity
as possible is used, since proline virtually transfers its chirality to the product in
the course of the reaction. However, this is not a problem, since high-purity proline
is cheaply available. So, the “trick” is to use the cheap availability of chiral proline
for other reactions as well to easily synthesise new chiral compounds that cannot
be simply obtained from nature or other sources in chiral form. Unfortunately, as it
is often the case in life, such tricks work extremely rarely, and this is why the above
reaction attracted so much attention.
As already described in the first chapter, proline is also referred to as an or-

ganic molecule. Findings like this have led to the development of an entire field of
chemistry called “organocatalysis”, that is, the use of organic molecules as cata-
lysts. These organocatalysts have by now produced spectacular results, which have
until recently been thought of as hardly possible.
One aspect of this success story is particularly interesting: Benjamin List was by
far not the first to recognise the potential of proline as a catalyst. As early as 1971,
two working groups separately published results regarding the use of proline as a
catalyst for chiral syntheses in a very similar type of reaction. Hence, it would have
been possible to recognise much earlier that proline was suitable for other reactions
as well. There are now more than 10 different types of reactions that are catalysed by
proline. Why did it take nearly 30 years – which is ages in modern chemistry – for
the potential of proline and organocatalysis to be discovered in the first place?
We can only speculate on that.
The most obvious question is, of course: Why was this field of research not es-
tablished by the original discoverers?
There is an answer to this question: Both original publications came from in-
dustrial chemists, one from researchers of Schering and the other from Hoffmann-
La Roche. They were actually aiming for something entirely different, namely, the
synthesis of pharmaceutically active ingredients. When they recognised that an im-
portant intermediate for these active ingredients was much easier to produce using
proline, they published this finding to subsequently continue working on other as-
pects of active ingredient synthesis, which was exactly what their employers paid
them for. So the original discoverers were not necessarily expected to further inves-
tigate this field.
But other chemists could have picked up the ball and continued playing – why
did they not?
Malicious gossip has it that there may be two major reasons for that: First, pub-
lications by industrial chemists are not always taken quite seriously by academic
scientists. On top of that, one of these two publications is not even an academic
paper, but a patent application – academics tend to look down on those.
Secondly, both publications were published in German. Unfortunately, however,
many academics, especially in the English-speaking world, think that foreign lan-
guage skills are unnecessary – “learning a different language is as flamboyant as
wearing a crown in a bus” is regrettably the attitude of many English and Americans.
Benjamin List is now a serious contender for the Nobel Prize. If he were to get
it, he might drink a toast to all the chemists before him who were too arrogant to
take German patent applications seriously and therefore did not beat him to it.
But like I said, it is all just speculation. Other discoveries that were later on rec-
ognised as revolutionary also had precursors that were not followed up on. Re-
search does not always move in a straight line. There are often discoveries where
people ask themselves later on why they were not discovered much earlier by
someone else. In any event, proline has by now become one of the most commonly
used catalysts in modern chemistry.
Now I would like to introduce you to another catalyst system that can be regarded
as more of a model system – but demonstrates very clearly how a catalyst works.
It involves the following reaction, in which a molecule, which I will again call
A, practically reacts with itself as follows:
Product
You will probably think that the reaction looks somewhat chaotic and complex, so I
will explain it in a bit more detail. This is a so-called Diels–Alder reaction, named
after the discoverers Otto Diels and Kurt Alder, who were awarded a Nobel Prize for
the discovery of this type of reaction in 1950. In this type of reaction, two parts of A,
namely, the two highlighted areas, react with each other to form a ring:
You can imagine that each of the three double bonds “folds over”, creating as many
as two new bonds, which are circled, and one double bond moves “one position
forward”:
By this reaction, a much more complex structure is obtained and that is why Diels–
Alder reactions became so popular in chemistry.
Andrew Hamilton (back then at the University of Pittsburgh, and now at Oxford
University) and his working group then investigated what happens when carrying
out this reaction, but adding either the molecule shown below, which is marked
with B, or the molecule C.
As you can see, the only difference between B and C is the number of carbon atoms
located on the central ring between the two “arms”, namely, two in B and only one
in C – or, in other words, the angle is 180° in B and 120° in C.
Now the following effect becomes apparent: With molecule C, the reaction takes
place 3.5 times faster than “just like that” – with molecule B, however, 10 times
slower. This means that this minor difference in the molecular structure has a tre-
mendous effect on the reaction!
How can this be explained? Actually, it is quite simple. Molecule A above forms
two times two hydrogen bonds with both molecule B and C – similar to those
shown in Chapter 9. With molecule B, this looks like this:
For the reaction to take place, however, the following highlighted areas of molecule
A have to be located in spatial proximity to each other, as already mentioned
above:
Owing to the fact that molecule A forms hydrogen bonds with molecule B via its two
carboxylic acid groups, it becomes slightly stretched and is kept in this position.
However, this makes a reaction practically impossible! The two highlighted areas are
simply too far apart from each other. For this reason, only the molecules that are cur-
rently unbound will enter into a reaction. But as these molecules are in the minority,
it takes much more time than in the absence of molecule B until they all react.
With molecule C, it is exactly the other way round. When A forms hydrogen
bonds with this molecule, it looks like this:
In this case, the hydrogen bonds push together the reactive areas of molecule A. It
is thus logical that the reaction is accelerated in the presence of molecule C, making
C a true catalyst!
I would like to briefly get back to proline. Proline is a so-called amino acid. This
means that proline has an amine group, basically meaning that a nitrogen atom is
present, as well as a (carboxylic) acid group. When many of these amino acids are
linked together via the so-called amide groups (which you already know from Chap-
ter 7), compounds with the following structure are created:
The figure above shows six amino acids, differing in the residues R. In this case,
proline was not among them, but it is commonly found in nature. When linking to-
gether 100 or more of these amino acids – it can be up to 30,000 (!) – giant mole-
cules referred to as “proteins” are created. You may have heard of them, for
example, in connection with meat that contains particularly high amounts of pro-
tein compared to pasta or rice.
However, proteins are much more important, as the name implies. This term
was used as early as 1839 by Dutch biochemist Gerardus Mulder, after having taken
up a suggestion from Swede Jöns Jakob Berzelius, one of the greatest chemists of all
times. He, in turn, derived the term protein from Greek – from “protos” meaning
the first/most important and “proteios” meaning fundamental.
And this is indeed true of proteins! Proteins have essential functions in the
human body. For instance, they are catalysts, the best ones known in chemistry
and biology. Proteins with a catalytic effect are also referred to as enzymes. There
are also other proteins, which I do not want to address in greater detail at this
point. Enzymes make sure that molecules in the human body are converted into
other molecules. Enzymes are so effective that they manage to accelerate reactions
not only a hundred-fold, which would already be pretty good, but often even a mil-
lion-fold. Without enzymes, we would not survive a single day.
How do enzymes do that? Basically, they often act similar to proline. They tem-
porarily bind to a type of molecules and make sure by forming hydrogen bonds that
other molecules react with them, the reactions being precisely controlled in terms
of space and time. Or they act like molecule C in Andrew Hamilton’s system and
make sure by forming hydrogen bonds that reactive areas of molecules get closer to
each other and thus react faster. Since proteins are much larger than proline, they
can virtually tailor themselves to specific reactions and form not only one but
several hydrogen bonds. Since proteins are so much larger than proline, I cannot
show that to you in a figure, because either I would need as much space as half a
dining table or the figure would be illegibly tiny. So you will have to try imagining
it or just believe me. For example, a protein called streptavidin forms as many as 15
hydrogen bonds with its target molecule called biotin. No wonder biotin and this
protein are “as thick as thieves”.14
By the way, if you would like to see enzymes, not just described in a book, but
as a substance in real life, you do not need to visit a chemical laboratory. Just look
at your detergent! The detergent industry is one of the major “users” of enzymes,
which are contained in every modern detergent in significant amounts. But to tell it
right away, enzymes are basically a white powder, whose excellent properties are
not apparent at the first glance.
The reason why enzymes are contained in detergents is easier to understand
when you briefly go back to Chapter 6 and once again have a look at the structure of
a fat. As discussed fats can be split up into glycerol and fatty acids using substances
like soda lye, which is referred to as saponification. Glycerol and the individual fatty
acids can be removed more easily from laundry, like a pair of jeans, than the fat it-
self, because they are much smaller and are also better soluble in water. You could
now be tempted to wash a stained pair of jeans with soda lye to saponify the fat. But
this would be a bad idea. You may have no fat anymore – but no jeans either, be-
cause even highly diluted soda lye causes quite large holes in jeans (as many chemis-
try students – including me – had to learn after a day of practical training in the
laboratory). No wonder soda lye is contained in many drain cleaners.
When adding an appropriate enzyme to the detergent, however, it will also
“split” the fat without destroying the jeans. For other types of soiling, such as albu-
min or red wine stains, there are also special enzymes that decompose the corre-
sponding substances. The detergent industry has taken advantage of these properties
of enzymes, ensuring that detergents have indeed improved significantly.
This progress has led to an unintentionally funny situation: Enzymes have a
maximum temperature at which they work best. Above this temperature, their struc-
ture changes and they no longer work properly.15 The optimum temperature usually
ranges between 30 and 40 °C, which is the body temperature of most mammals.
However, many users of washing machines are used to boil-wash laundry to
get it really clean, which is quite reasonable when using detergents that do not con-
tain enzymes. Since enzymes are produced industrially using genetic engineering
14 Experts do not quite agree as to the exact number, because it can be disputed which hydrogen
bonds point to biotin and which do not. A distinction is made between something like a “first cir-
cle” and “second circle”. In any case, it is at least eight, which is still quite a few.
15 You have certainly experienced this phenomenon in your laundry room, but with wool. Wool
also consists almost exclusively of proteins – and if woollen jumpers are washed too hot, the struc-
ture of these proteins also changes irrevocably: the jumper “shrinks”.
methods, which did not become commonly available until the mid-1980s, this is
not that long ago. When using detergents that contain enzymes, which nowadays
even the cheapest “no-name products” do, this has an adverse effect. At 95 °C (i.e.,
boil wash), normal enzymes are destroyed within a few minutes – so the effect of
the detergent does not improve, but deteriorates significantly! So, the next time you
use your washing machine, you had better set the temperature to 40 °C (or what is
suggested on the package of the detergent). Your laundry will thank you.
11 Substances that build themselves
In the previous chapter, I discussed about catalysts, that is, substances that accelerate
reactions like good Samaritans.
Of course, it would now be interesting to look into reactions where a catalyst
helps itself, meaning that it catalyses a reaction in which it forms as a product.
There is a whole range of such reactions. They are referred to as “autocatalytic”
(from Greek: auto = self) reactions. These reactions automatically become faster
over time, as more and more catalyst is produced.
It would be even more interesting if this reaction were not only autocatalytic,
but were to also involve “transmission of information”, meaning that the reaction
product is more complex than the starting substances. Reactions of this type are
not called autocatalytic, but self-replicating. What information can be transmitted?
In the simplest case, the directional information in terms of molecular recognition,
as already described in Chapter 7.
The reason why such reactions are extraordinarily interesting is that they – at
least in the opinion of all experts in this field – must have existed when life began
on the Earth.
It is largely unclear how life originated on the Earth. Something like the following
is widely agreed: 4.2 billion years ago, some kind of a primeval ocean, also referred
to as “primeval soup”, existed on the Earth. At the beginning, the primeval ocean
contained a whole smorgasbord of chemicals dissolved in it. But, basically, that was
it. There was no life.
Around 400 million years later, that is, 3.8 billion years ago, the first cells and
bacteria emerged, something you can certainly call life. However, even this point
in time is disputed; some researchers assume that life already existed as early as
4 billion years ago.
What happened in between? That’s the big question!
Somehow, because otherwise you and I would not even exist, a process or a
whole range of processes must have taken place within the primeval soup on the
Earth’s surface, which caused more complex molecules and then regular structures
to gradually come into being, culminating in something like cells and bacteria.
Nobody knows exactly what processes were involved.
But, of course, we want to know it, because the evolution of life out of simple
chemicals, virtually out of “nothing”, is something incredibly fascinating. The only
thing known with certainty in this entire field of research is that it has to work
somehow, as evidenced by your and my existence. Apart from that, practically
everything is subject to controversy, as you may have already noticed.
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90 11 Substances that build themselves
When taking a look at a cell, you will find that it is already a highly complex
system. Something like that does not just “fall from the sky”. The probability of a
cell developing spontaneously out of a primeval ocean is immeasurably small.
One thing life is characterised by is the ability to reproduce, that is, to copy or
to replicate, even though not always completely identically. After all, your children
do not look the same as you either – but this is another story. It is assumed that
before there were cells capable of replicating or copying, there must have been
much simpler reaction systems in which molecules copied and replicated – and
that before there was an evolution among living organisms, something like a
“chemical evolution” had taken place. These reaction systems are called self-
replicating.
Of course, it is very difficult for scientists investigating this subject to fully
reconstruct the processes that led to the evolution of life on the Earth. One reason
for this is that the Earth is already populated and organisms such as bacteria thus
intervene in possible processes all the time. We cannot just turn back time and
watch what happens (unfortunately). On the other hand, many of these processes
are most likely to have lasted very long, perhaps centuries, if not millennia. We
simply do not have so much time.
Therefore, scientists use simulations and model systems, for example, model
systems of self-replicating reactions. A schematic model of such a self-replicating
reaction system would look something like this:
The two molecules A and B react with each other to form the product C. However, A
and B each also have recognition sites, enabling them to mutually form hydrogen
bonds, similar to adenine and thymine in DNA or the molecules described in
Chapters 7 and 9. Of course, the product C also has both recognition sites, allowing
A and B to attach to product C. As a result, a complex of A, B and C forms, which is
marked with ABC on the top left of the above figure. A and B then react to form C.
As a result, a complex of two C molecules forms, which is marked with C2 on the
top right of the above figure. This reaction is accelerated by the formation of the
complex ABC, simply because as a result of this complex formation, A and B are
located in close proximity to each other, similar to the catalyst of Andrew Hamilton
in the previous chapter. C is thus also a catalyst – catalysing its own formation!
The complex C2 now breaks up, allowing molecule C to attach to A and B
again. However, there are now two molecules C, which is why two molecules C
can each attach to a molecule A and a molecule B two times. As a result, four mol-
ecules C form, then eight, then 16 and so on, resulting in what is called exponen-
tial growth.
Things get interesting if there are two replicators, that is, one from A, B and C –
and another from, let’s say, A, B’ and C’. A and B react to form C, but likewise A
and B’ react to form C’. Hence, the two compete for molecule A. Let us assume we
fill B and C as well as B’ und C’ into a vessel, but only add as much A that the two
replicators have to compete for A. When done correctly, one of these replicators
should prevail (at least this is how it has been demonstrated in theory), because it
would be faster than the other and would take away molecule A from the other.
This would then represent some kind of a chemical evolution.
At least since the 1980s, researchers have extensively looked for self-replicating
reactions, and in 1986 Günter von Kiedrowski from the University of Göttingen
presented the first reaction system of this kind. It is actually chemically very similar
to DNA. A chemical “sister” of DNA, RNA, which has a very similar chemical struc-
ture, is capable of not only self-replicating but also catalysing many reactions.
Sidney Altman was awarded the Nobel Prize in 1989 for this finding. In addition, it
was found that the primeval soup most likely contained molecules that could serve
as starting substances for RNA synthesis. Numerous models of the evolution of life
on the Earth now assume some kind of an “RNA world”, that is, a primeval ocean
dominated by RNA.
Following synthesis of the first DNA replicator, it was attempted to build not
only further replicators on the basis of DNA or RNA (although these may indeed
have once existed in nature), but also systems that are based on other reactions
and chemical structures. The reason for this is, first, that there is an interest in un-
derstanding the fundamental mode of action of replicators and, secondly, that
“synthetic” systems can be, as is hoped, better “tuned” to achieve desired effects.
By the way, the first synthetic replicator of this kind, which has nothing to do with
DNA anymore, was also presented by Günter von Kiedrowski, together with his
degree candidate Andreas Terfort in 1992.
I would like to introduce you to a more recent synthetic replicator, which was
synthesised in 2000 by Maik Kindermann in the laboratory of Günter von Kiedrowski,
now professor at the Ruhr University of Bochum. I chose this replicator for two
reasons: First, because it is not very large and therefore easier to explain and,
secondly, because self-replication is not that simple.
When taking another look at the above scheme, you will see where a major
snag is. If the two molecules C fit together so well, why would they separate? But
if the complex C2 does not break up, then C cannot act as a catalyst – it is virtually
rendered inactive. When Günter von Kiedrowski tested his first replicator, he
found that only part of the products C is actually active, another part is not. As he
had demonstrated in theoretical experiments, however, a real chemical evolution
requires replicators that work better. As big a sensation the first replicator might
have been, it is unfortunately not suitable to bring about a chemical evolution.
The replicator developed by Maik Kindermann comes very close to such an
ideal replicator and this is what makes it so interesting. It is shown in the figure
below:
As in the previous chapter, the actual reaction here is again a Diels–Alder reaction.
For a reaction to take place, the following highlighted areas have to be located in
close spatial proximity to each other:
Just like in the previous chapter, three double bonds “fold over” in this reaction:
When transferring this reaction to the general scheme shown above, the picture
looks like this:
As you can see, it is just two hydrogen bonds each that bind molecule A and B to
the product C – but that is enough! When taking a look at the structure of the com-
plex ABC on the top left of the above figure, you will see the essential thing: Similar
to how it works in Andrew Hamilton’s system from the previous chapter, product C
again makes sure that the reactive areas of A and B are located in close proximity to
each other so that the reaction between them can take place at an accelerated rate.
This reaction has also been examined using the 1H-NMR method, and the
course of the reaction can be clearly seen in the spectrum below:
This image shows a fragment of the entire spectrum, because there are naturally
many more hydrogen atoms in the respective molecules, but it clearly shows the
course of the reaction. The signals for product C are shown on the left and the sig-
nals of molecule A on the right. At the beginning, only very little C forms – but the
reaction then really gets going!
The fact that the system is indeed self-replicating can be recognised by the rate
at which product C forms. But it is also possible – as has been tested – to simply
modify molecule B, for example, to the effect that it does not form any hydrogen
bonds with A and the new product C, like this:
This reaction proceeds at a much slower rate than that of the replicator, because the
molecules do not form any bonds. The situation is similar when leaving molecule B
as it is, but modifying molecule A. Hence, it is the hydrogen bonds that matter.
Why is this replicator so close to the ideal growth? Of course, this has been
tested as well, and one of the reasons is that complex C2 is a bit “crooked”, meaning
that although two molecules C find each other and form hydrogen bonds, they do
not fit together perfectly:
As you can see in the above figure, the two recognition sites, marked with the grey
bars, do not fit together accurately, but form an angle. Therefore, the complex C2
breaks up relatively easily. Molecules A and B are much smaller and more mobile
and can thus attach to molecule C more easily – and this is exactly what is intended.
When taking another look at the molecules from Chapter 9, where I described
how hydrogen bonds can be measured, you will notice that these are quite similar
to the two molecules A and B. However, they do not react with each other and can
therefore be used as model substances to obtain certain data needed to properly
examine the replication system.
Is a molecular evolution known today? Unfortunately not. The big difficulty is
that replication systems are very hard to find and further conditions have to be met
for molecular evolution to take place. So far, nobody has figured out how to fit
everything together. Even if the replicator described above is modified only slightly,
self-replication does not take place anymore, sometimes not even a reaction.
So, there is still enough to do for researchers who want to know how life origi-
nated on the Earth.
12 Like Avalokiteśvara and Durga
In this chapter, I address an aspect in greater detail that I have previously “withheld”,
namely, the fact that most of the reactions described in earlier chapters do not take
place in a vacuum, but in a solution. This is only logical, given that the molecules
need to meet somehow, and this works best when they are dissolved in a liquid,
however, not in water. The reactions, for example those described in Chapter 11, do
not take place in water and the hydrogen bonds described in Chapters 7 and 9 cannot
be measured either.
Why is that? First, this is because some of the described molecules are not readily
soluble in water, but this is not the main reason. The main reason is that water forms
hydrogen bonds itself, preventing the molecules to find each other. And since water
is the solvent, there are naturally much more water molecules than other molecules
present. When applied to the Opera Ball analogy, this would mean that a male dancer
is trying to find a dance partner, but the men outnumber the women hundred to one.
Obviously, this makes dancing quite difficult.
This is why solvents that do not form hydrogen bonds such as chloroform are
mostly used to examine molecular recognition. But how can molecules find each
other in water as well (or in other solvents forming hydrogen bonds)? What can our
dancer do?
If he is a normal gentleman, there is relatively little he can do. The situation is
different if he happens to be like the bodhisattva Avalokiteśvara, a kind of “spiritual
being” in Buddhism. Avalokiteśvara has 11 heads and, most importantly, a thousand
arms! This makes it a lot easier to catch a lady. If that lady then happens to be like
the Hindu Goddess Durga, who can have up to 20 arms, depending on the situation,
things get even easier.
Exactly this phenomenon is found in DNA, for example. As explained earlier,
DNA recognises itself in water. However, even DNA requires a length of at least 10–20
bases and thus more than 20 hydrogen bonds – the exact number depends on the
concentration and other conditions – to actually form a double helix structure.
Otherwise, the DNA helix would be broken up by the water molecules or does not
form in the first place.
Giving their molecules many “arms” is exactly what several researchers and, most
notably, their working groups have attempted to do. I am going to address the results
of their work in this chapter. However, first I would like to answer the question why it
is interesting to examine molecular recognition in water in the first place.
The answer is simply because nearly all reactions in the human body also take
place in water. When intending to use molecular recognition systems, for example, to
develop new medicines or diagnostic agents, these have to be effective in water as
well. Therefore, many researchers have attempted to develop corresponding systems
that also work in water or similar solvents.
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98 12 Like Avalokiteśvara and Durga
One of these researchers is Carsten Schmuck from the University of Duisburg-

Essen. For instance, he examined the following molecule,16 which he presented in
1999:
When adding this molecule to water, it actually finds itself and forms hydrogen
bonds with itself. Of course, the main reason for this is that there are as many as six
of it at a very short distance like this:
Another, much larger molecule with the same “basic architecture” was presented
by Prof. Schmuck in 2005 and referred to as a “molecular flytrap”. It looks like this:
16 This molecule is both negatively charged on one of the oxygen atoms and positively charged on
one of the nitrogen atoms, which is additionally “tetravalent”. Yet – for reasons I would like to just
skip for now – it is, unlike the molecules formed in the proline-catalysed reaction in Chapter 10,
very stable.
As you can see, it has a “central unit” and three “arms” – and binds the subsequent
molecule so strongly that it will (almost) never let go of it, even in water. You will at
least know it by name, because it is citric acid:
Citric acid
How does that work? The figure below shows the bond between one of the three
carboxylic acid groups of citric acid, which is present as the so-called citrate, meaning
that it is negatively charged, and the “flytrap”:
However, not only one of the carboxylic acid groups is bound to the “flytrap”, but
also all three, with the three arms “folding over” towards the citric acid. Schemati-
cally, you can imagine this as follows:
This threefold “clutch” ensures the incredibly strong attractive force, with the citric
acid being practically “trapped”. You may already recognise what such molecules
can be used for, namely, for detecting substances or “fishing” them out of solutions.
Some time earlier, in the 1990s, another researcher, George Whitesides from
Harvard University, published a strategy of arranging molecules so as to create
veritable molecular architectures with networks of hydrogen bonds. He took the
following two molecules as a basis:
When combining these two molecules, a kind of a two-dimensional network is

created with a pattern that is reminiscent of an Oriental carpet:
This network makes sure that these two molecules together form a solid – and do
not dissolve in virtually any liquid, rendering chemical reactions impossible. Prof.
Whitesides then slightly modified the two molecules by inserting some carbon
chains at relevant positions, simply marked with “R” as usual, and replacing a ni-
trogen atom by a carbon atom as follows:
The result is a network that still looks impressive, but is slightly smaller and thus
also soluble, making it suitable for chemical reactions:
Prof. Whitesides refers to this structure as a “rosette”, and presented a whole range
of such rosettes.
Jean-Marie Lehn17 from the College de France in Paris developed a very similar
system in 1996. However, he used only one instead of two different molecules,
namely, the following one:
17 He is one of the Nobel Prize winners who were distinguished for their research into crown
ethers, see Chapter 6.
It also forms a kind of hexagon with the following structure:

Steven C. Zimmerman from the University of Illinois chose yet another

approach. The starting molecules of his system, which he also published in 1996
together with his team, are these two:
The architecture of the molecules, the left one of which is straight and the right one
slightly bent, is not random. When combining these two molecules, they recognise
each other by the following hydrogen bonds, as shown on an example complex of
three molecules:
Of course, other molecules can attach on the left and right, creating a kind of
“molecular screw”, which looks something like this:
To conclude this chapter, I once again discuss two topics that were already
addressed in the previous chapters.
The first topic is DNA. As you remember, the information in DNA is transmitted
via the structure of the hydrogen bonds, where only adenine matches with thymine
and guanine with cytosine.
Unfortunately, DNA in the body is sometimes attacked, resulting in a change in
the molecular structure. This can have disastrous consequences for the copying
mechanism, which is, in turn, one of the main causes of cancer.
For example, if two thymines succeed each other in DNA, they may react with
each other in the presence of UV light as follows:
This often entails that these thymines are no longer recognised during a later copy-
ing process, entailing that a “bad copy” is produced at this position. Such bad cop-
ies are one of the main causes of skin cancer. Therefore, a UV protection cream
should be used when the skin is exposed to sunlight for extended periods of time,
as sunlight contains UV radiation. Such a protection cream absorbs most of this UV
component, thereby largely preventing this reaction.
Another important change is the reaction of guanine with environmental toxins,

or the like to form a compound named 8-oxoguanine, which looks like this:
Guanine 8-Oxoguanine
The area where the guanine has changed is highlighted. 8-Oxoguanine has the un-
pleasant property that it forms hydrogen bonds not only with cytosine but also with
adenine, given as follows:
As a disastrous consequence, it is no longer ensured that a cytosine is inserted

during a DNA copying process. Likewise, the new DNA may contain an adenine at this
position, which is a mistake. Unfortunately, 8-oxoguanine and guanine differ only
insignificantly, which makes it relatively difficult to detect 8-oxoguanine in DNA.
In 2011, Prof. Dr Shigeki Sasaki from Kyushu University in Fukuoka and his
team developed a “detector” for 8-oxoguanine, which I would like to introduce to
you. It looks like this:
As you can see, the molecule consists of two parts, namely, an adenine (bottom, the
molecule highlighted in light grey), to which a second molecule (for those interested:
diazaphenoxazine, the molecule highlighted in dark grey) is attached. This
detector can be inserted into a DNA strand to detect 8-oxoguanine.
To this end, a “detector DNA” is added to a test DNA that is suspected to contain
8-oxoguanine. This detector DNA is synthesised in such a way that, if the assumption
8-Oxoguanine
is correct, the 8-oxoguanine is located opposite this detector molecule in the DNA
double strand. The detector molecule now forms a very stable complex with the
8-oxoguanine, in which the detector molecule “wraps around” the 8-oxoguanine,
forming as many as five hydrogen bonds:
The presence of 8-oxoguanine can thus be verified on the basis of the hydrogen
bonds. This is already a good thing, but this detector can do even more. The detector
molecule has the pleasant property that it emits an intense blue-green light when
irradiated with the appropriate light. But this only applies as long as the molecule is
“free”. When the above complex of 8-oxoguanine and the detector molecule forms,
the electronic states of the detector molecule are slightly changed by the hydrogen
bonds, which entails that the molecule no longer emits any light.
Prof. Sasaki and his team were able to demonstrate that this “blackout” actually
only takes place if the detector molecule (in the “detector DNA”) is located opposite
an 8-oxoguanine (in the “test DNA”) in a DNA double strand. With any other base
opposite to it, the detector molecule continues to emit blue-green light. This makes it
possible to optically verify that hydrogen bonds have actually been formed between
8-oxoguanine and the detector.
Why is this so important? Simply because such optical methods allow for
detecting molecules in tiny concentrations. Other detection methods, such as 1H-NMR
described in Chapter 9, are more difficult and also require larger amounts of
substance.
Finally, I would get back to a molecule that I described earlier in Chapter 7,
namely, the system developed by E.W. “Bert” Meijer. You might remember what it
looked like:
It already has quite a few “arms”. Prof. Meijer and his working group have somewhat
modified, or rather extended this molecule, meaning that they slightly altered the res-
idue “R”, which simply consisted of a carbon chain in the molecule from Chapter 7:
As you can see, the old molecule has more or less been doubled. However, a closer
look reveals that this new molecule cannot bond to itself congruently, because the
recognition sites do not quite fit together:
First, the molecule would have to rotate around its own axis at the centre; second,
the two hydrogen atoms are always located exactly at the centre and the two other
binding sites on the outside. Of course, it is intended to be this way!
Now how does this molecule behave? It nevertheless recognises itself,
because the bonding with as many as four hydrogen bonds is extremely strong.
However, this results in an arrangement where the second molecule is slightly
displaced:
This means that only four of the eight possible binding sites (four on the left and
four on the right) are used, which is why binding sites are left over to which other
molecules can attach. In the end, a long chain is created:
Measurements have shown that this chain can consist of more than one hundred
molecules. The chain becomes so long that a structure with properties that are mac-
roscopically similar to plastics is created. The kind of plastics that plastic bags are
made of also consists of molecules forming very long chains, as already explained
in Chapter 5.
However, there is a significant difference between the chain of Prof. Meijer
and the plastics used in plastic bags, which is called polyethylene in chemistry. In
polyethylene, all bonds in the chain are covalent and are therefore difficult to
break. In Prof. Meijer’s chain, only some of the bonds are covalent, namely, those
within the chain molecule. The bonds between the molecules are hydrogen
bonds. Under the appropriate conditions, these are almost as strong as a proper
covalent bond, but when the conditions are altered, the hydrogen bonds break
apart and the chain collapses. This means that you can determine whether or not
a plastic structure is created merely by selecting the external conditions.
This plastic material is highly interesting. Another group of scientists, namely,
those headed by Christoph Weder from the University of Fribourg, went a step further
and extended this system by synthesising a molecule that has not only two but three
recognition sites. It looks like this:
It is again the highlighted recognition sites that are important – the rest
of the molecule is less interesting and was only selected because it is easy to
synthesise.
This molecule now forms a network with itself, which looks something like
this:
The interesting thing about it is that the network structure of this molecule causes a
sort of glass to form, that is, a solid you can look through. It is also relatively stiff
and can be picked up, for example, with pincers, without bending.
This fact alone would not be that spectacular, given that glass already exists.
Moreover, this molecule is not quite as stable as solid glass; for example, it can be
cut with a razor blade. But it can do something normal glass cannot.
When cutting real glass, for example, with a glass cutter, the resulting cuts
cannot be simply smoothened out again. However, this can easily be done with
Christoph Weder’s molecule. For instance, when you cut through the “Weder glass”
with a razor blade, the cut can be removed again within a few hours by heating up
the molecule or exposing it to UV light (which is also just heating, but more
targeted) and letting it cool down again. The “Weder glass” then becomes just as
smooth as before!
Why is that? The reason is that the hydrogen bonds break when exposed to heat.
When the material is cooled down, they are recreated, ensuring that the structure is
“as good as new” again:
Hence, the “Weder glass” is self-healing: a truly amazing property owed to

hydrogen bonds.
13 Conclusion and acknowledgements
At this point, I thank you for having made it this far – after all, I have guided you,
as promised, all the way from very simple molecules through DNA and enzymes to
current research.
This book is devoted only to one subject, namely, hydrogen bonding, but I
hope that you still did not get bored and that you have learnt what an important
role hydrogen bonds play in your life, even if you had not been quite aware of that
before.
In addition, I thank people who supported me in writing this book.
First of all, I thank Dr Maik Kindermann for allowing me to use parts of his
doctoral thesis is this book, including some figures. He also did the proofreading
of the original German version of this book.
Dr Malte Reimold, who possesses a perfect combination of scientific understanding
and graphic design skills, made sure that my raw templates became images and graphs
that are nice to look at.
Max Düren, Dr Stefan Höppner, Tianqiao Pan and, most importantly, Ute
Hüttermann provided me with valuable suggestions on how to make this book
easier to understand, especially for “non-scientists”, after having reviewed and
corrected the first German version of the this book.
I thank Mrs Berber-Nerlinger from the Oldenbourg Publishing House for the
copy-editing and her support in creating the first German version book. I thank
everyone at DeGruyter, namely, Ria Fritz, Maureen Pagel and Lena Stoll first for
suggesting the English version of this book and the support with the realization.
Prof. Dr Shigeki Sasaki and Prof. Dr Carsten Schmuck provided me with
research data and results as well as manuscripts of yet unpublished works.
Finally, I thank my wife, E. Hyun, for indulging me when I spent quite a few
weekends in an effort to further improve this book – as well as for reviewing this
book and giving me suggestions for improvement.
https://doi.org/10.1515/9783110628012-013
Bibliography
Below I have compiled a bibliography in case you would like to learn more about certain subjects
addressed in this book.
The majority of the basic information provided in Chapters 1 to 5 is taken from the “Hollemann-
Wiberg”: Hollemann, Wiberg, A Textbook of Inorganic Chemistry, 102nd edition, Berlin 2007.
For Chapters 6 to 12, I used my own textbook as well as the “Voet–Voet”:

Bräse, Bülle, Hüttermann, Organische und Bioorganische Chemie [Organic and Bioorganic
Chemistry], 2nd edition, Weinheim 2008.
Voet, Voet, Pratt, Beck-Sickinger, Hahn, Lehrbuch der Biochemie [A Textbook of Biochemistry], 2nd
edition, Weinheim 2010.
Chapter 1
If you are interested to learn more about the 112 chemical elements, I recommend that you read:
Ulf von Rauchhaupt, Die Ordnung der Stoffe: Ein Streifzug durch die Welt der chemischen Elemente
[The Order of Substances: A Ramble through the World of Chemical Elements], 2nd ed., Frankfurt,
2009 – it is however, so far only published in German.
“A cheerleader waves a cyanide wand, there’s a smell of peach blossom and bitter almond” in
Genesis, “Fly on a windshield/Broadway Melody of 1974”, from: The lamb lies down on Broadway
1974. If the song is to be believed, Howard Hughes (indirectly) “produces” potassium cyanide
himself, because that substance is contained in cigarette smoke.
Chapter 6
Fight Club, directed by: David Fincher, USA 1999, based on the novel by Chuck Palahniuk published
in 1996
For crown ethers, see the Nobel lecture of Charles Pedersen

Charles Pedersen, The Discovery of Crown Ethers (Nobel Lecture), Angew. Chem. 1988, 100,
1053–1059.
For ion channels, see the Nobel lecture of Roderick MacKinnon

Roderick MacKinnon, Potassium Channels and the Atomic Basis of Selective Ion Conduction (Nobel
Lecture), Angew. Chem. 2004, 116, 4363–4376.
Chapter 7
The molecule of “Bert” Meijer is published in
F. H. Beijer, R. P. Sijbesma, H. Kooijman, A. L. Spek and E. W. Meijer, Strong Dimerization of
Ureidopyrimidones via Quadruple Hydrogen Bonding, J. Am. Chem. Soc. 1998, 120, 6761–6769.
https://doi.org/10.1515/9783110628012-014
118 Bibliography
Chapter 8
The story of how DNA was discovered can be read in

J. D. Watson, The Double Helix. A Personal Account of the Discovery of the Structure of DNA,
Hamburg, 1997 (reprint).
J. D. Watson, A. Berry, DNA. The Secret of Life, New York 2003.
Jerry Donohue’s biography can be read on Wikipedia at http://en.wikipedia.org/wiki/Jerry_Donohue
The original publication by Watson & Crick:

J. D. Watson, F. H. C. Crick, A Structure for Deoxyribose Nucleic Acid, Nature 1953, 171, 737–738.
See also http://www.sns.ias.edu/~tlusty/courses/landmark/WatsonCrick1953.pdf
The (incorrect) structure according to Linus Pauling is published in:

L. Pauling, R. B. Corey, A Proposed Structure for the Nucleic Acids, PNAS 1953, 39 (2), 84–97.
Concerning the accuracy of the DNA copying mechanism, I recommend (if you understand German)
that you read the following article by Prof. Dr. Gottfried Schatz, published in the Neue Zürcher
Zeitung on 17 February 2011: http://www.nzz.ch/nachrichten/kultur/aktuell/schoepfer_zufall_1.
9562044.html
The G-quadruplex is described, among other publications, in

M. Gellert, M. N. Lipsett, D. R. Davies, Helix Formation by Guanylic Acid, PNAS, 1962, 48, 2013–2018.
Chapter 9
The described measurement is taken from the doctoral thesis of Dr. Maik Kindermann:
Maik Kindermann, Kleine organische Replikationssysteme und kristalline Filme durch Amidinium-
Carboxylat-Wechselwirkungen an der Luft-Wasser-Grenzschicht [Small Organic Replication
Systems and Crystalline Films through Amidinium-Carboxylate Interactions at the Air-Water
Interface], Doctoral Thesis, Bochum, 2001.
Chapter 10
Just for the sake of completeness:

Erich Kästner, Emil and the Detectives, Overlook Press, 2014 (first published in 1929).
If you are interested to learn how automotive catalytic converters and similar catalysts of this type
work, I recommend that you read the Nobel lecture of Gerhard Ertl:
Gerhard Ertl, Reactions at Surfaces: From Atoms to Complexity (Nobel Lecture), Angew. Chem.
2008, 120, 3478–3590.
Wikipedia has some articles worth reading, such as

Lactose intolerance: https://en.wikipedia.org/wiki/Lactose_intolerance
Aldol reaction: https://en.wikipedia.org/wiki/Aldol_reaction
Organocatalysis: https://en.wikipedia.org/wiki/Organocatalysis
Proline:https://en.wikipedia.org/wiki/Proline
For carvone, see

G. F. Russel, J. I. Hills, Odor Differences between Enantiomeric Isomers, Science, 1971, 172, 1043–1044.
Bibliography 119
The proline-catalysed aldol reaction was first described in

B. List, R. A. Lerner, C. F. Barbas, III., Proline-Catalyzed Direct Asymmetric Aldol Reactions, J. Am.
Chem. Soc. 2000, 122, 2395.
The mechanism is published in

Linh Hoang, K. N. Houk, S. Bahmanyar, B. List, Kinetic and Stereochemical Evidence for the
Involvement of Only One Proline Molecule in the Transition States of Proline-Catalyzed Intra-
and Intermolecular Aldol Reactions, J. Am. Chem. Soc. 2003, 125, 16–17.
The “precursor” reactions from 1971 are published in

U. Eder, G. Sauer, R. Wiechert, New Type of Asymmetric Cyclization to Optically Active Steroid CD
Partial Structures, Angew. Chem. 1971, 10, 492–493.
Z. G. Hajos, D. R. Parrish: Asymmetric Synthesis of Optically Active Polycyclic Organic Compounds,
German patent DE 2102623 (patent filed on 20 January 1971).
For the Diels-Alder reaction used by A. Hamilton, see

S. C. Hirst, A. Hamilton, Complexation Control of Pericyclic Reactions: Supramolecular Effects on
the Intramolecular Diels-Alder Reaction, J. Am. Chem. Soc. 1991, 113, 382–383.
For streptavidin-biotin, see

A. W. Hendrickson, A. Pähler, J. Smith, Y. Satow, E. A. Merritt, R. P. Phizackerley, Crystal Structure
of Core Streptavidin Determined from Multiwavelength Anomalous Diffraction of Synchrotron
Radiation, PNAS, 1989, 86, 2190–2194.
Chapter 11
A good introduction to the “origins of life” can be found, for example, in the doctoral thesis of
Dr. Kindermann (see above)
E. Szathmáry and J. Maynard Smith, The Major Transitions in Evolution. Oxford University Press,
New York 1995.
The first DNA-based replicator is published in

G. von Kiedrowski, A Self-Replicating Hexadeoxynucleotide, Angew. Chem. 1986, 86, 932–934.
The first fully synthetic replicator is published in

A. Terfort, G. von Kiedrowski, Self-Replication by Condensation of 3-Aminobenzamidines and
2-Formylphenoxyacetic Acids, Angew. Chem. 1992, 104, 626–628.
The replicator theory is published in

G. von Kiedrowski, Minimal Replicator Theory I: Parabolic Versus Exponential Growth, Bioorganic
Chemistry Frontiers 1993, 3, 113–146.
For RNA as a catalyst, see the Nobel lecture of Sidney Altman:

Sidney Altman, Enzymatic Cleavage of RNA by RNA (Nobel Lecture), Angew. Chem. 1990, 102,
735–744.
The “Kindermann replicator” is published in the doctoral thesis of Dr. Kindermann (see above) as
well as in
M. Kindermann, I. Stahl, M. Reimold, W.M. Pankau, G. von Kiedrowski, Systems Chemistry:
Kinetic and Computational Analysis of a Nearly Exponential Organic Replicator, Angew.
Chem. 2005, 117, 6908–6913.
120 Bibliography
Chapter 12
To learn more about Carsten Schmuck’s work, see

C. Schmuck, Highly Stable Self-Association of 5-(Guanidiniocarbonyl)-1H-Pyrrole-2-Carboxylate in
DMSO – The Importance of Electrostatic Interactions, Eur. J. Org. Chem. 1999, 2397–2403.
C. Schmuck, M. Schwegmann, A Molecular Flytrap for the Selective Binding of Citrate and Other
Tris-carboxylates in Water, J. Am. Chem. Soc. 2005, 127, 3373–3379.
To learn more about George Whitesides’ work, see

G. M. Whitesides, E. E. Simanek, J. P. Mathias, C. T. Seto, D. N. Chin, M. Mammen, D. M. Gordon,
Noncovalent Synthesis: Using Physical-Organic Chemistry to Make Aggregates. Acc. Chem.
Res. 1995, 28, 37.
To learn more about Jean-Marie Lehn’s work, see

A. Marsh, M. Silvestri, J.-M. Lehn, Self-Complementary Hydrogen Bonding Heterocycles Designed
for the Enforced Self-Assembly into Supramolecular Macrocycles, J. Chem Soc. Chem.
Commun. 1996, 13, 1527–1528
To learn more about Steven Zimmerman’s work, see

P. M. Petersen, W. Wu, E. E. Fenlon, S. Kim, S. C. Zimmerman, Synthesis of Heterocycles Containing
Two Cytosine or Two Guanine Base-Pairing Sites. Novel Tectons for Self-Assembly, Bioorg.
Med. Chem. 1996, 4, 1107.
To learn more about Shigeki Sasaki’s work, see

Y. Taniguchi, R. Kawaguchi, and S. Sasaki, Adenosine-1,3-Diazaphenoxazine Derivative for
Selective Base Pair Formation with 8-Oxo-2′-Deoxyguanosine in DNA, J. Am. Chem. Soc. 2011,
133, 7272–7275.
To learn more about “Bert” Meijer’s work, see

R. P. Sijbesma, F. H. Beijer, L. Brunsveld, B. J. B. Folmer, K. J. H. K. Hirschberg, R. F. M. Lange,
J. K. L. Lowe and E. W. Meijer, Reversible Polymers Formed from Self-Complementary
Monomers Using Quadruple Hydrogen Bonding, Science 1997, 278, 1601–1604.
To learn more about Christoph Weder’s work, see

Diederik W. R. Balkenende Christophe A., Monnier Gina L., Fiore, and Christoph Weder, Optically
responsive supramolecular polymer glasses; Nature Communications 2016, 7, 10995.
Index
1
H-NMR 61 Carvone 72
– in the Kindermann replicator 94 – Chirality 72
8-oxoguanine 107 Catalysts 71
– Autocatalysis 89
Acetic acid 45 – in aldol reactions 76
– Hydrogen bonds 46 – in Diels-Alder reactions 82
– Molecular recognition 46 – Proline 74
– Three-dimensional structure 45 – Proteins 86
Adenine 52 – Self-replication 89
– Hydrogen bonding with thymine 59 Cells 40
Alcohol 27 – Lipid bilayer 40
Alder, Kurt 82 Chargaff, Erwin 54
Aldol reaction 75 Chemical equilibria 68
– Chirality 75 Chemical evolution 91
Allyl alcohol 29 Chirality 72
Americium 2 – Lactose intolerance 73
Amino acids 86 – Nomenclature 72
Ammonia 16 Chlorine 4
– Boiling point 20 – Chloride 5
– Hydrogen bonds 20 – Chlorine gas 8
– Three-dimensional structure 23 – in sodium chloride 4
Antibiotics 43 – Structure of the chlorine molecule 8
Argon 2 Chlorine gas 8
Arrhenius, Svante 34 Cholesterol 32
Atorvastatin 75 – in the lipid bilayer 40
– Synthesis using aldol reactions 75 Citric acid 99
Autocatalysis 89 – Molecular recognition 99
– Self-replication 89 Covalent bond 7
Crick, Francis 54
Benzene 29 Crown ethers 40
Benzene rings 29 – Comparison with ion channels 42
Berkelium 2 – Comparison with valinomycin 42
Berzelius, Jöns Jakob 86 – Sodium 40
Biotin 87 – Toxicity 43
Borodin, Alexander 75 Curium 2
Borussia Dortmund 69 Cyanide ion 10
Butanol 32 Cytosine 52
– Hydrogen bonding with guanine 59
Calcium 9
Calcium oxide 9 Darmstadtium 2
– Structure 18 Detergents 87
Californium 2 – Enzymes 87
Carbon 2 Dichlorine monoxide 16
– as the basic element of organic chemistry 27 Diels, Otto 82
– in carbon dioxide 9 Diels-Alder reaction 82
Carbon dioxide 9 – in the Kindermann replicator 92
https://doi.org/10.1515/9783110628012-015
122 Index
DNA 51 Guanine 52
– 8-oxoguanine 107 – Correct structure 56
– Arrangement of hydrogen bonds 57 – G-tetrad 60
– Backbone 52 – Hydrogen bonding with cytosine 59
– Bases 52 – Structure according to Davidson 56
– Copying mechanism 58
– G-tetrad 60 Hamilton, Andrew 83
– Hoogsteen base pairing 60 Hassium 2
– Molecular recognition 57 Helium 2
– Reaction with UV light 106 Hoogsteen base pairing 60
– Self-recognition in water 97 Hoogsteen, Karst 60
– Story of how the structure of DNA was Hydrides 7
discovered 54 Hydrogen 1, 2
– Structure 51 – Origin of name 1
Donohue, Jerry 56 – Structure of the hydrogen molecule 7
Hydrogen bonding 13
Einsteinium 2 – Comparison with the Vienna Opera Ball 14
Electron pairs 8 – Definition 13
Electronegativity 11 – Detection by 1H-NMR 61
Elements 1 – in ammonia 20
Enzymes 87 – in proline-catalysed aldol reactions 78
– Proteins 87 – in self-replication 94
– Streptavidin 87 – in the Kindermann replicator 94
Equilibria 68, 69 – Role in the boiling point of water 18
– in chemistry 68 – Role in the density anomaly of water 25
Erbium 1 Hydrogen chloride 16
Ethanol 27 Hydrogen cyanide 10
– Three-dimensional structure 30 Hydrogen sulphide 16
Fats 35 Ice 24
– Saponification 35 – Structure 24
– Structure 35 Inorganic chemistry 2
Fatty acids 36 Ion channels 42
– Liposome 39 Ionic bond 4
– Micelles 37 Isotonic saline 40
– Soaps 37
– Structure 36 Kiedrowski, Günter von 91
Francium 1 Kindermann, Maik 91
Franklin, Rosalind 54 Kindermann replicator 91
Krypton 2
Gabriel, Peter 10
Galactose 73 Lactose intolerance 73
Gallium 1 Le Bel, Joseph 72
Germanium 1 Lehn, Jean-Marie 103
Glucose 73 Lipid bilayer 40
Glycerol 36 Lipitor See Atorvastatin
G-quadruplex See G-tetrad Liposomes 39
Grape sugar See Glucose – Structure 39
G-tetrad 60 List, Benjamin 76
Index 123
Meijer, E.W. “Bert” 48 – as amino acid 86

– “Switchable chain” 109 – Catalyst in aldol reactions 76
– Ureidopyrimidones 48 Propanol 28
Metallic bond 8 Propargyl alcohol 29
Methane 15 Proteins 86
– Boiling point 19 – Amino acids 86
– Natural gas 15 – as catalysts 86
– Tetrahedral structure 22 – Enzymes 87
Micelles 37 – Streptavidin 87
– as soaps 37 Proton nuclear magnetic resonance spectros-
Molecular flytrap 98 copy See 1H-NMR
Molecular recognition 48
– “Molecular flytrap” 99 Roentgenium 2
– in DNA 57
– in self-replication 94 Saponification 35
– in the Kindermann replicator 94 Sasaki,Shigeki 107
– Ureidopyrimidones 48 Schalke 04 69
Mulder, Gerardus 86 Schmuck, Carsten 98
Self-replication 89
Naphthalene 30 – Chemical evolution 91
Neon 2 – Origins of life on Earth 89
Nitrogen 2 Silver 1
– Structure of the nitrogen molecule 8 Soap 37
Noble gases 2 Sodium 4
– Crown ethers 40
Oganesson 2 – in sodium chloride 4
Organic chemistry 2 – Ion channels 42
– Organocatalysis 81 – Sodium ions 6
Organocatalysis 81 Sodium chloride 4
Oxygen 1 – Dissociation 34
– Boiling point 16 – Ionic bond 4
– in calcium oxide 9 – Solubility in water 33
– in carbon dioxide 9 – Structure 17
– Origin of name 1 – Structure in aqueous solution 33
Sortis See Atorvastatin
Pauling, Linus 54 States of matter 17
Periodic table of elements 3 – Gases 17
Phosphine 16 – Liquids 18
Polonium 1 – Solids 17
Potassium 10 Streptavidin 87
– Crown ethers 41 Sucrose 33
– in potassium cyanide 10 Sugar 32
– Ion channels 42 – Chirality 73
Potassium cyanide 10 – Solubility in water 33
– Cyanide ion 10
– Hydrogen cyanide 10 Terbium 1
Primeval ocean 89 Terfort, Andreas 91
Primeval soup 89 Tetrahedron 22
Proline 74 – Chirality 71
124 Index
– in ethanol 30 – Three-diemensional structure 23

Thymine 52 Watson, James 54
– Correct structure 56 Weder, Christoph 111
– Hydrogen bonding with adenine 59 Whitesides, George 101
– Structure according to Davidson 56 Wilkins, Maurice 54
Wöhler, Friederich 2
Urea 2
Ureidopyrimidones 48 Xenon 2
– Glass 111
– Polymer 109 Ytterbium 1
Yttrium 1
Valinomycin 42
van-der-Waals forces 19 Zimmerman, Steven C. 105
Van’t Hoff, Jacobus 72
vis vitalis 2 δ− 12
– in ammonia 19
Water 12 – in water 13
– as solvent 27 – Role in hydrogen bonding 13
– Boiling point 15 δ+ 12
– Density anomaly 21 – in ammonia 19
– Ethanol 31 – in water 13
– Melting point 15 – Role in hydrogen bonding 13

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The Hydrogen Bond

A Bond for Life

Library of Congress Control Number: 2019932010

Bibliographic information published by the Deutsche Nationalbibliothek

© 2019 Walter de Gruyter GmbH, Berlin/Boston

1 Before getting started 1

2 The “bond” in hydrogen bonding 11

3 The “water” in hydrogen bonding 15

4 The order in the ice 21

5 Dissolving like sugar in water 27

6 Soaps and cells 35

7 Recognise your vis-à-vis 45

8 Jerry Donohue and the DNA 51

9 How to make hydrogen bonds visible 61

10 “Now let’s step on the accelerator” 71

11 Substances that build themselves 89

12 Like Avalokiteśvara and Durga 97

13 Conclusion and acknowledgements 115

This book deals with what is called hydrogen bonding.

Atomic nucleus 2 electrons

1.1 An atom loses or gains electrons

An equivalent equation can be written for sodium. Previously, sodium’s outer-

Combining these two chemical equations produces the following equation:

1.2 Two atoms share electrons

1.3 Many atoms form what is called a “metallic bond”

No problem! Potassium donates its solitary electron, thereby reaching argon’s

As already mentioned in Chapter 1, the word “hydrogen” in hydrogen bond is derived

There is also a comparable compound of nitrogen and hydrogen. Nitrogen

Hydrogen sulphide Phosphine Hydrogen chloride

What happens when we replace hydrogen instead of oxygen? It is not much of an

Methane Ammonia Water

What is so miraculous about this?

Methane Ammonia Water

In the shorthand or bond line notation:

there are tens of thousands, sometimes even hundreds of thousands, of carbon

Allyl alcohol Propargyl alcohol

In the shorthand notation:

Allyl alcohol Propargyl alcohol

These hydrogen bonds cause salt to dissolve in water.

purpose of transporting potassium into cells, specifically hostile cells. Valinomycin

cannot really be distinguished from the one below:

Rotating the molecule at this position produces the following structure:

This additional hydrogen bond holds the molecule in place!

Base #3: Adenine (A)

Base #2: Cytosine (C)

Base #1: Cytosine (C)

Guanine according to Davidson Alternative structure

Thymine according to Davidson Alternative structure

where he went on to become a highly respected professor, without ever working

The important hydrogen atom, which we will be focusing on below, is highlighted.

Producing this result:

When analysing a mixture of A and B containing a higher percentage of B, the visi-

You can see that A automatically becomes smaller as the concentration of B

This means there is a ratio of one Dortmund supporter to 99 Schalke supporters,

As you can see, a respectable 100 + 99 + 97 = 296 of all (original) residents of

Carvone (D) or (S) carvone (L) or (R) carvone

Chiral molecule The same molecule in the exact

This catalyst accelerates a whole range of reactions, including the following

(But only in one form!)

As already described in the first chapter, proline is also referred to as an or-

One of these researchers is Carsten Schmuck from the University of Duisburg-

When combining these two molecules, a kind of a two-dimensional network is