Bioinorganic Chemistry

• Bioinorganic Chemistry focus upon the

function of inorganic “substances“ in living
systems.
• Bioinorganic chemistry is a field that examines
the role of metals in biology.
Chemical elements essential to life forms can be
divided into the following

(i) Bulk elements: C, H, N, O, P, S

(ii) Macrominerals and ions: Na, K, Mg, Ca, Cl, PO 3-, SO 2-

4 4

(iii) Trace elements: Fe, Zn, Cu

(iv) Ultratrace elements comprises of

(a) non-metals: F, I, Se, Si, As, B

(b) metals: Mn, Mo, Co, Cr, V, Ni, Cd, Sn, Pb, Li
 Concentration and physiological
effect

Effect

Conc
Lack of element Deficiency Optimal supply Excess Toxic dose
(Death) (Disease) (Disease) (Death)
Metals essential for life:

The role for most is uncertain

Na, K, Mg, Ca
V, Cr, Mn, Fe Co, Ni, Cu, Zn
Mo, W
Na, K: Charge carriers
Osmotic and electrochemical
gradients
Nerve function

Mg, Ca: Enzyme activators

Structure promoters
Lewis acids
Mg2+: chlorophyll, photosynthesis
Ca2+: insoluble phosphates
 Role:
Na+
• Extracellular fluid
• Osmotic balance „sodium pump”
• Acid-base balance
• Conformation of proteins
nucleic acids
• Electrical impulse of nerve system

Mg2+
3Na+ic + 2K+ec + ATP4- + H2O

3Na+ec + 2K+ic + ADP3- + HPO42- + H+

K+
• Enzyme activator
• Conformation of proteins
RNA (replication)
• Secretion of gastric acid
• Transmembrane potentials!
Fe, Cu, Mo: Electron-transfer
Redox proteins and enzymes
Oxygen carrying proteins
Nitrogen fixation

Zn: Metalloenzymes
Structure promoters
Lewis acid
Not a redox catalyst!
Cu(I), Cu(II)
Protection of DNA
Plants Electron transfer
Animals O2-carrying from O2-

Cu-proteins and enzymes

 Cytochrome oxidase O2 H2O
 Tyrosinase, phenol oxidase ox. of phenols
 Ceruloplasmin Fe(II) Fe(III)
 Blue proteins Electron transfer
 Superoxide dismutase Elimination of O2-
 Hemocyanin O2 transport
 Metalloporphyrins

They are bioinoganic compounds and

play a vital role in biological system
Structure of porhyrin or porphin
• It is a cyclic ligand made up
of four pyrrole rings.
• Linked together through
methene bridges
• It has conjugated double
bonds
 Metalloporphyrins

• Porphine has four N atoms are donor atoms.

• If two protons present in two NH groups are removed, then
all four N atoms can be coordinated to M2+ metallic ions
(M2+ = Mg2+, Fe2+, Ni2+ etc.) to form complexes known
as metalloporphyrins.
• Heme and chlorophyll are two important
metalloporphyrins.
Heme is one of several proteins that
contain iron.
 Hemoglobin
• Hemoglobin is composed of four parts or
subunits arranged in the form of a helix or spiral
that is attached to a heme group.
• Each heme group contains Fe2+, which is a
potential site for attaching an oxygen molecule.
• Binding of oxygen to iron in hemoglobin is quite
weak.
• Groups such as CN-, CO, H2S .. bind strongly to
Fe2+, which makes it impossible for O2 to attach.
 hemoglobin
• Molar mass of Hb is 64500.
• It is an octahedral complex of Fe(II)
• The four subunits are linked through salt bridges
present between the polypeptide chains.
• Made up of four globin protein subunits ( and ).
– Each protein partially encloses a heme group.
• Each heme group is in a porphyrin pocket.
– One axial position of the iron is bound to an imidazole
nitrogen from the protein.
– One axial position is available/vacant or has H2O bound
to it.
• Dissolved O2 can bind reversibly to this axial position.
• Hb which has not taken up O2 –
deoxyhemoglobin
• Hb which has taken up O2 – oxyhemoglobin
 Structure of heme prosthetic group

 Four Pyrrole groups [A to D]

linked by methene bridges

 Fe+2 coordinated by porphyrin N

atoms and N from Histidine

 A molecule of O2 acts as 6th

ligand
 Hemoglobin
• Cooperativity
– The function of hemoglobin is to bind O2 at high oxygen
pressure and carry it through the blood to needed areas
(and myoglobin for storage).
Hb + 4O2  Hb(O2)4
Hb(O2)4 + 4Mb  4Mb(O2) + Hb
• As one iron binds an oxygen molecule in Hb, the
molecular shape changes to make binding of
additional oxygen molecules easier. In a similar
fashion, initial removal of oxygen triggers the release
of the remaining oxygens.
 Hemoglobin (III)
• In nonoxygenated hemoglobin, the Fe(II) is about 70
pm out of the plane of the porphyrin nitrogens.
• Bonding O2 or CO in the sixth position causes the
iron to be come planar.
– Fe(II) becomes diamagnetic
• Oxygen bonds at an angle of ~130 degrees
• Explain these structural changes upon bonding.
 Hemoglobin
• At low partial pressures of
O2, Mb has a much greater
affinity for O2.
[Mb(O 2 )]
K Mb 
[Mb][O 2 ]

[Hb (O 2 ) 4 ]
K Hb 
[Hb ][O 2 ]2.8
• The Bohr effect.
– Increased acidity favors the
release of O2 from Hb(O2)4
 Myoglobin
• Made up of one heme unit connected to a
polypeptide chain.
• The polypeptide chain in Mb is coordinated to
iron atom of the heme group through N-atom
of histidine.
• Molar mass is about 17000.
Metalloporphyrins
• Porphine ligand is a ring system. It is made of
four pyrole rings.
• These pyroles are linked together by methene
bridges .
• It has conjugated double bonds.
 Porphyrins and Related Complexes in
Bioinorganic Molecules
• A porphine ring has a square planar geometry with a
“pocket” in the center.
• A metalloporphyrin complex can result by
incorporating a metal atom into the pocket.
– Axial sites are available for other ligands.
• Structure, specificity, and reactivity are changed by
differing the side chains, metal ions, and surrounding
species.
 Porphyrins
Porphine has four N atoms are donor atoms.
If two protons present in two NH groups are removed,
then all four N atoms can be coordinated to M2+
metallic ions (M2+ = Mg2+, Fe2+, Ni2+ etc.) to form
complexes known as metalloporphyrins.
Heme and chlorophyll are two important
metalloporphyrins.
The porphyrins can accept two hydrogen ions to form+2 diacids or donate
two protons to form -2 dianions

Porphyrins are found in many metalloenzyme

Enzyme Function

Fe-porphyrin Cytochrome electron transfer

Fe-porphyrin Hemoglobi dioxygen carrier

n
Myoglobi
n
Mg-porphyrin Chlorophyll photosynthesis
 Structure of heme

Heme B group of hemoglobin. An iron (Fe) atom in the middle is shown in red,
complexed to four interior nitrogen atoms shown in blue.
 Hemoglobin and myoglobin
O2 does not easily diffuse in muscle and O2 is toxic to biological systems, so living
systems have developed a way around this.

Physiological roles of:

– Hemoglobin
Found in red blood cells
Carries O2 from lungs to tissues and removes CO2 and H+ from blood to
lungs
Lower affinity for O2 than myoglobin
Tetrameter - two sets of similar units (22)
– Myoglobin
 Store of O2 in muscle, high affinity for O2
Transports O2 in rapidly respiring muscle
Monomer - single unit
Diving animals have large concentration of myoglobin to keep O2
supplied to muscles
 Hemoglobin (I)
• Made up of four globin protein subunits ( and
).
– Each protein partially encloses a heme group.
• Each heme group is in a porphyrin pocket.
– One axial position of the iron is bound to an imidazole
nitrogen from the protein.
– One axial position is available/vacant or has H2O
bound to it.
• Dissolved O2 can bind reversibly to this axial position.
http://www.umass.edu/microbio/chime/hemoglob/
 Hemoglobin (II)

• In hemoglobin, the Fe(II) does not become

oxidized to Fe(III) or Fe(IV).
– Occurs readily in simpler systems (see Figure on the
next page).
• There needs to be reversible binding of the O2
without oxidation. A free heme also oxidizes in
an aqueous environment.
– Why doesn’t oxidation occur in hemoglobin by O2
or H2O?
Hemoglobin (Figures)
 Hemoglobin (III)
• In nonoxygenated hemoglobin, the Fe(II) is about 70
pm out of the plane of the porphyrin nitrogens
(show with Chime).
• Bonding O2 or CO in the sixth position causes the
iron to be come planar.
– Fe(II) becomes diamagnetic
• Oxygen bonds at an angle of ~130 degrees (show
with Chime).
Explain these structural changes upon bonding.
 Hemoglobin(IV)
• There is a considerable amount of 
backbonding from the metal to the O2.
– Can be described as Fe(III)-O2-
• Why is the O2 bent? The energy changes very
little with this angle.
– suggestions
 Hemoglobin (V)
• Cooperativity
– The function of hemoglobin is to bind O2 at high oxygen
pressure and carry it through the blood to needed areas
(and myoglobin for storage).
Hb + 4O2  Hb(O2)4
Hb(O2)4 + 4Mb  4Mb(O2) + Hb
• As one iron binds an oxygen molecule in Hb, the
molecular shape changes to make binding of
additional oxygen molecules easier. In a similar
fashion, initial removal of oxygen triggers the release
of the remaining oxygens.
 Biological Role of Sodium
Sodium is important in the body, as it helps maintain body fluid
homeostasis. People with disorders that do not have enough sodium in the
body can take medication such as serum sodium in order to maintain a healthy
amount of sodium in the body. Sodium is also crucial in osmotic pressure, as
the body adjusts to when there is too little or too much sodium in the
body. Sodium is also the main cation in outside cells containing fluid in
mammalian bodies, and very little sodium inside the cells, consisting of
approximately 90% of the body's total sodium content.
Biological Role of Magnesium and calcium
Magnesium and calcium are ubiquitous and essential to all known living organisms.

They are involved in more than one role, with, for example, Mg/Ca ion pumps

playing a role in some cellular processes, magnesium functioning as the active

center in some enzymes, and calcium salts taking a structural role

 Hemoglobin and Myoglobin
• Oxygen transfer and storage agents in the
blood and muscle tissue.
– Hemoglobin transports oxygen (O2) from the
lungs/gills to tissues and muscles.
– Myoglobin stores oxygen (O2) in the muscles
and tissues.
Oxygen commonly transfers from the
hemoglobin to the myoglobin for later use.
 Hemoglobin
• Made up of four globin protein subunits ( and ).
– Each protein partially encloses a heme group.
• Each heme group is in a porphyrin pocket.
– One axial position of the iron is bound to an imidazole
nitrogen from the protein.
– One axial position is available/vacant or has H2O bound
to it.
• Dissolved O2 can bind reversibly to this axial position.
http://www.umass.edu/microbio/chime/hemoglob/
 Hemoglobin
• In hemoglobin, the Fe(II) does not become
oxidized to Fe(III) or Fe(IV).
– Occurs readily in simpler systems (see Figure on
the next page).
• There needs to be reversible binding of the O2
without oxidation. A free heme also oxidizes in
an aqueous environment.
– Why doesn’t oxidation occur in hemoglobin by O2
or H2O?