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Properties of water

Water is the most abundant substance in living systems, making up 70% or more of the weight of most organisms. The first living organisms doubtless arose in an aqueous environment, and the course of evolution has been shaped by the properties of the aqueous medium in which life began. The attractive forces between water molecules and the slight tendency of water to ionize are of crucial importance to the structure and function of biomolecules. Weak Interactions in Aqueous Systems Hydrogen bonds between water molecules provide the cohesive forces that make water a liquid at room temperature and that favor the extreme ordering of molecules that is typical of crystalline water (ice). Polar biomolecules dissolve readily in water because they can replace water-water interactions with more energetically favorable water-solute interactions. In contrast, nonpolar biomolecules interfere with water-water interactions but are unable to form water-solute interactions consequently, nonpolar molecules are poorly soluble in water. In aqueous solutions, nonpolar molecules tend to cluster together.Hydrogen bonds and ionic, hydrophobic (Greek,water-fearing), and van der Waals interactions are individually weak, but collectively they have a very significant influence on the three-dimensional structures of proteins, nucleic acids, polysaccharides, and membrane lipids. Hydrogen Bonding Gives Water Its Unusual Properties Water has a higher melting point, boiling point, and heat of vaporization than most other common solvents .These unusual properties are a consequence of attractions between adjacent water molecules that give liquid water great internal cohesion. A look at the electron structure of the H2O molecule reveals the cause of these intermolecular attractions.Each hydrogen atom of a water molecule shares an electron pair with the central oxygen atom. The geom-etry of the molecule is dictated by the shapes of the outer electron orbitals of the oxygen atom, which are similar to the sp3 bonding orbitals of carbon. These orbitals describe a rough tetrahedron, with a hydrogen atom at each of two corners and unshared electron pairs at the other two corners. The H-O-H bond angle is 104.5o, slightly less than the 109.5 o of a perfect tetrahedron because of crowding by the nonbonding orbitals of the oxygen atom. The oxygen nucleus attracts electrons more strongly than does the hydrogen nucleus (a proton); that is, oxygen is more electronegative. The sharing of electrons between H and O is therefore unequal; the electrons are more often in the vicinity of the oxygen atom than of the hydrogen. The result of this unequal electron sharing is two electric dipoles in the water molecule, one along each of the H-O bonds; each hydrogen bears a partial positive charge (+) and the oxygen atom bears a partial negative charge equal to the sum of the two partial positives (2 -). As a result, there is an electrostatic attraction between the oxygen atom of one water molecule and the hydrogen of another , called a hydrogen bond. Hydrogen bonds are relatively weak. Those in liquid water have a bond dissociation energy (the energy required to break a bond) of about 23 kJ/mol, compared with 470

kJ/mol for the covalent O-H bond in water or 348 kJ/mol for a covalent C-C bond. The hydrogen bond is about 10% covalent, due to overlaps in the bonding orbitals, and about 90% electrostatic. At room temperature, the thermal energy of an aqueous solution (the kinetic energy of motion of the individual atoms and molecules) is of the same order of magnitude as that required to break hydrogen bonds. When water is heated, the increase in temperature reflects the faster motion of individual water molecules. At any given time, most of the molecules in liquid water are engaged in hydrogen bonding, but the lifetime of each hydrogen bond is just 1 to 20 picoseconds (1 ps = 10-12s); upon breakage of one hydrogen bond, another hydrogen bond forms, with the same partner or a new one, within 0.1 ps. The sum of all the hydrogen bonds between H2O molecules confers great internal cohesion on liquid water. Extended networks of hydrogen-bonded water molecules also form bridges between solutes (proteins and nucleic acids, for example) that allow the larger molecules to interact with each other over distances of several nanometers without physically touching.The nearly tetrahedral arrangement of the orbitals about the oxygen atom allows each watermolecule to form hydrogen bonds with as many as four neighboring water molecules. In liquid water at room temperature and atmospheric pressure, however, water molecules are disorganized and in continuous motion, so that each molecule forms hydrogen bonds with an average of only 3.4 other molecules. In ice, on the other hand, each water molecule is fixed in space and forms hydrogen bonds with a full complement of four other water molecules to yield a regular lattice structure . Breaking a sufficient proportion of hydrogen bonds to destabilize the crystal lattice of ice requires much thermal energy, which accounts for the relatively high melting point of water. When ice melts or water evaporates, heat is taken up by the system: During melting or evaporation, the entropy of the aqueous system increases as more highly ordered arrays of water molecules relax into the less orderly hydrogenbonded arrays in liquid water or the wholly disordered gaseous state. At room temperature, both the melting of ice and the evaporation of water occur spontaneously;the tendency of the water molecules to associate through hydrogen bonds is outweighed by the energetic push toward randomness. Recall that the freeenergy change(G) must have a negative value for a process to occurspontaneously: G =H + T S where G represents the driving force, H the enthalpy change from making and breaking bonds, and S the change in randomness. Because H is positive for melting and evaporation, it is clearly the increase in entropy (S) that makes G negative and drives these transformations Water Forms Hydrogen Bonds with Polar Solutes Hydrogen bonds are not unique to water. They readily form between an electronegative atom (the hydrogen acceptor, usually oxygen or nitrogen with a lone pair of electrons) and a hydrogen atom covalently bonded to another electronegative atom (the hydrogen donor) in the same or another molecule Hydrogen atoms covalently bonded to carbon atoms do not participate in hydrogen bonding, because carbon is only slightly more electronegative than hydrogen and thus the C-H bond is only very weakly polar. The distinction explains why butanol (CH3(CH2)2CH2OH) has a relatively high boiling point of 117 oC, whereas butane (CH3(CH2)2CH3) has a

boiling point of only -0.5 oC. Butanol has a polar hydroxyl group and thus can form intermolecular hydrogen bonds. Uncharged but polar biomolecules such as sugars dissolve readily in waterbecause of the stabilizing effect of hydrogen bonds between the hydroxyl groups or carbonyl oxygen of the sugar and the polar water molecules. Alcohols, aldehydes, ketones, and compounds containing N-H bonds all form hydrogen bonds with water molecules and tend to be soluble in water. Hydrogen bonds are strongest when the bonded molecules are oriented to maximize electrostatic interaction, which occurs when the hydrogen atom and the two atoms that share it are in a straight linethat is, when the acceptor atom is in line with the covalent bond between the donor atom and H. Hydrogen bonds are thus highly directional and capable of holding two hydrogen-bonded molecules or groups in a specific geometric arrangement. This property of hydrogen bonds confers very precise threedimensional structures on protein and nucleic acid molecules, which have many intramolecular hydrogen bonds. Water Interacts Electrostatically with Charged Solutes Water is a polar solvent. It readily dissolves most biomolecules, which are generally charged or polar compounds compounds that dissolve easily in water are hydrophilic (Greek, water-loving). In contrast, nonpolar solvents such as chloroform and benzene are poor solvents for polar biomolecules but easily dissolve those that are hydrophobicnonpolar moleculessuch as lipids and waxes. Water dissolves salts such as NaCl by hydrating and stabilizing the Na+ and Cl - ions, weakening the electrostatic interactions between them and thus counteracting their tendency to associate in a crystalline lattice. The same factors apply to charged biomolecules, compounds with functional groups such as ionized carboxylic acids (-COO-), protonated amines (-NH3+), and phosphate esters or anhydrides. Water readily dissolves such compounds by replacing solute -solute hydrogen bonds with solute-water hydrogen bonds, thus screening the electrostatic interactions between solute molecules.Water is especially effective in screening the electrostatic interactions between dissolved ions because it has a high dielectric constant, a physical property reflecting the number of dipoles in a solvent. The strength, or force (F), of ionic interactions in a solution depends upon the magnitude of the charges (Q), the distance between the charged groups (r), and the dielectric constant () of the solvent in which the interactions occur Entropy Increases as Crystalline Substances Dissolve As a salt such as NaCl dissolves, the Na+ and Cl- ions leaving the crystal lattice acquire far greater freedom of motion. The resulting increase in entropy (randomness) of the system is largely responsible for the ease of dissolving salts such as NaCl in water. Nonpolar Gases Are Poorly Soluble in Water

The molecules of the biologically important gases CO2, O2, and N2 are nonpolar. In O2 and N2, electrons are shared equally by both atoms. In CO2, each C=O bond is polar, but the two dipoles are oppositely directed and cancel each other . The movement of molecules from the disordered gas phase into aqueous solution constrains their motion and the motion of water molecules and therefore represents a decrease in entropy. The nonpolar nature of these gases and the decrease in entropy when they enter solution combine to make them very poorly soluble in water. Some organisms have water-soluble carrier proteins (hemoglobin and myoglobin, for example) that facilitate the transport of O2. Carbon dioxide forms carbonic acid (H2CO3) in aqueous solution and is transported as the HCO3- (bicarbonate) ion, either freebicarbonate is very soluble in water or bound to hemoglobin. Nonpolar Compounds Force Energetically Unfavorable Changes in the Structure of Water When water is mixed with benzene or hexane, two phases form; neither liquid is soluble in the other. Non-polar compounds such as benzene and hexane are hydrophobicthey are unable to undergo energetically favorable interactions with water molecules, and they interfere with the hydrogen bonding among water molecules. All molecules or ions in aqueous solution interfere with the hydrogen bonding of some water molecules in their immediate vicinity, but polar or charged solutes (such as NaCl) compensate for lost waterwater hydrogen bonds by forming new solute-water interactions. The net change in enthalpy (H) for dissolving these solutes is generally small. Hydrophobic solutes, however, offer no such compensation, and their addition to water may therefore result in a small gain of enthalpy; the breaking of hydrogen bonds between water molecules takes up energy from the system. Furthermore, dissolving hydrophobic compounds in water produces a measurable decrease in entropy. Water molecules in the immediate vicinity of a nonpolar solute are constrained in their possible orientations as they form a highly ordered cagelike shell around each solute molecule. These water molecules are not as highly oriented as those in clathrates, crystalline compounds of non-polar solutes and water, but the effect is the same in both cases: the ordering of water molecules reduces en tropy. The number of ordered water molecules, and therefore the magnitude of the entropy decrease, is proportional to the surface area of the hydrophobic solute enclosed within the cage of water molecules. The free-energy change for dissolving a nonpolar solute in wateris thus unfavorable: G =H + T S, where H has a positive value, S has a negative value, and G is positive.Amphipathic compounds contain regions that are polar (or charged) and regions that are nonpolar .. When an amphipathic compound is mixed with water, the polar, hydrophilic region interacts favorably with the solvent and tends to dissolve, but the nonpolar, hydrophobic region tends to avoid contact with the water. The nonpolar regions of the molecules cluster together to present the smallest hydrophobic area to the aqueous solvent, and the polar regions are arranged to maximize their interaction with the solvent. These stable structures of amphipathic compounds in water, called micelles, may contain hundreds or thousands of molecules. The forces that hold the nonpolar regions of the molecules together

are called hydrophobic interactions. The strength of hydrophobic interactions is not due to any intrinsic attraction between nonpolar moieties. Rather, it results from the systems achieving greatest thermodynamic stability by minimizing the number of ordered water molecules required to surround hydrophobic portions of the solute molecules. Many biomolecules are amphipathic; proteins, pigments, certain vitamins, and the sterols and phospholipids of membranes all have polar and nonpolar surfaceregions. Structures composed of these molecules are stabilized by hydrophobic interactions among the nonpolar regions. Hydrophobic interactions among lipids, and between lipids and proteins, are the most important determinants of structure in biological membranes.Hydrophobic interactions between nonpolar amino acids also stabilize the three-dimensional structures of proteins. Hydrogen bonding between water and polar solutes also causes some ordering of water molecules, but the effect is less significant than with nonpolar solutes. Part of the driving force for binding of a polar substrate (reactant) to the complementary polar surface of an enzyme is the entropy increase as the enzyme displaces ordered water from the substrate Properties of Acids and Bases

ACIDS Taste sour Reach with certain metals (Zn, Fe, etc.) to produce hydrogen gas cause certain organic dyes to change color react with limestone (CaCO3) to produce carbon dioxide React with bases to form salts and water BASES Taste bitter feel slippery or soapy react with oils and grease cause certain organic dyes to change color react with acids to form salts and water Define:
o o

1. 2. 3. 4. 5.

1. 2. 3. 4. 5.

Acid - a substance that produces protons, H+ Base - a substance that produces hydroxide ions, OH-

II. Reaction of acids and bases with water:


Acids and bases form ions in solution: HCl(aq) H+(aq) + Cl-(aq) H3O+ - hydronium ion H+ and H3O+ are equivalent in aq. solution

When we look at the reactions of acids - can be generalized using hydrogen ion

1. Reaction with zinc yields hydrogen gas 2. Reaction with limestone - produce CO2(g) 3. Acids react with bases to produce a salt

Similarly for bases, produce hydroxide ions

III. Neutralization and Salts


Neutralization - one type of double replacement reaction Acid + Base Salt + water Net ionic equation shows what drives the neutralization reaction

example: Molecular: HCl(aq) + NaOH(aq) NaCl(aq) + H2O(l) Total Ionic: H+(aq) + Cl-(aq) + Na+(aq) + OH-(aq) Na+(aq) + Cl-(aq) + H2O(l) Net Ionic: H+(aq) + OH-(aq) H2O(l)

SALT - a salt is formed from the anion of the acid and the cation of the base usually present as spectator ions. - not always NaCl

IV. Types of Acids


Monoprotic - a solution that produces one mole of H+ ions per mole of acid HCl , HNO3 Diprotic - a solution that produces two moles of H+ ions per mole of acid H2SO4 Triprotic - a solution that produces three moles of H+ ions per mole of acid H3PO4 Polyprotic - two ore more H+ per mole of acid

V. Polyprotic acids:

can be Partially neutralized acid salt - an ionic compound containing the anion with one or more hydrogens that can be neutralized with a base

VI. Strengths of Acids and Bases:

STRONG ACIDS

Acids that are essentially 100% ionized in aqueous solutions ex: HCl, HNO3, HClO4 produce the maximum concentration of H+ [acid] = [H+] WEAK ACIDS o Acids that are partially ionized ( usually less than 5%) in equilibrium.
o o o o

HF + H2O(l) H3O+(aq) + F-(aq) The forward and the reverse reaction are occurring simultaneously most found as HF. STRONG BASES o those compounds that completely ionize in water to produce OH- ions o NaOH(s) Na+(aq) + OH-(aq) o Concentration of base = concentration of hydroxide ions WEAK BASES
o o o o

NH3(aq) + H2O(l) NH4+(aq) + OH-(aq) equilibrium lies far to the left (mostly reactants present)

VII. Equilibrium of Water


H2O(l) + H2O(l) H3O+(aq) + OH-(aq) Autoionization - produces positive and negative ions from the dissociation of the molecules of a liquid. Experimentally, found concentration of ions = 1.0 x 10-7 M at 25 C [H3O+][OH-] = Kw at 25 C (1.0 x 10-7)(1.0 x 10-7) = 1.0 x 10-14 Kw = ION PRODUCT - gives us the concentrations of hydronium and hydroxide ions in pure water and acidic and basic solutions [H3O+] = [OH-] = 1.0 x 10-7 M [H3O+] > 1.0 x 10-7, [OH-] <1.0 x 10-7 [H3O+] < 1.0 x 10-7, [OH-] >1.0 x 10-7

Neutral Acidic Basic

Ionization of Water, Weak Acids, and Weak Bases lthough many of the solvent properties of water can be explained in terms of the uncharged H2O molecule, the small degree of ionization of water to hydrogen ions (H+) and hydroxide ions (OH-) must also be taken into account. Like all reversible reactions, the ionization of water can be described by an equilibrium constant.

When weak acids are dissolved in water, they contribute H+ by ionizing; weak bases consume H+ by becoming protonated. These processes are also governed by equilibrium constants. The total hydrogen ion concentration from all sources is experimentally measurable and is expressed as the pH of the solution. To predict the state of ionization of solutes in water, we must take into account the relevant equilibrium constants for each ionization reaction. We therefore turn now to a brief discussion of the ionization of water and of weak acids andbases dissolved in water Water molecules have a slight tendency to undergo reversible ionization to yield a hydrogen ion (a proton) and a hydroxide ion, giving the equilibrium H2O==============H+ + OHAlthough we commonly show the dissociation product of water as H+, free protons do not exist in solution; hydrogen ions formed in water are immediately hydrated to hydronium ions (H3O+). Hydrogen bonding between water molecules makes the hydration of dissociating protons virtually instantaneous:The ionization of water can be measured by its electrical conductivity; pure water carries electrical current as H+ migrates toward the cathode and OH-toward the anode. The movement of hydronium and hydroxide ions in the electric field is anomalously fast compared with that of other ions such as Na+, K+, and Cl-. This highionic mobility results from the kind of proton hopping. No individual proton moves very far through the bulk solution, but a series of proton hops between hydrogen-bonded water molecules causes the net movement of a proton over a long distance in a remarkably short time. As a result of the high ionic mbility of H+ (and of OH-, which also moves rapidly by proton hopping, but in the opposite direction), acid-base reactions in aqueous solutions are generally exceptionally fast. As noted above, proton hopping very likely also plays a role in biological proton-transfer reactions .Because reversible ionization is crucial to the role of water in cellular function, we must have a means of expressing the extent of ionization of water in quantitative terms. The position of equilibrium of any chemical reacion is given by its equilibrium constant, Keq (some5times expressed simply as K). For the generalized eaction A + B----------- C + D an equilibrium constant can be defined in terms of the oncentrations of reactants (A and B) and products (C nd D) at equilibrium: Keq = [C} [D] [A] [B]

The equilibrium constant is fixed and characteristic for any given chemical reaction at a specified temperature. It defines the composition of the final equilibrium mixture, regardless of the starting amounts of reactants and products. Conversely, we can calculate the equilibrium constant for a given reaction at a given temperature if the equilibrium concentrations of all its reactants and products are known. The Ionization of Water Is Expressed by an Equilibrium Constant The degree of ionization of water at equilibrium (Eqn21) is small; at 25 C only about two of every 109 molecules in pure water are ionized at any instant. The equilibrium constant for the reversible ionization of water is Keq = [H+] [OH-] [H2O] In pure water at 25 oC, the concentration of water is 55.5 M (grams of H2O in 1 L divided by its gram molecular weight: (1,000 g/L)/(18.015 g/mol)) and is essentially constant in relation to the very low concentrations of H+ and OH-,namely, 1 x 10-7M. Accordingly, we can substitute 55.5 M in the equilibrium constant expression to yield Keq = [H+] [OH-] 55.5 which, on rearranging, becomes (55.5 M)(Keq) == [H+] [OH-] Kw where Kw designates the product (55.5 M)(Keq), the ion product of water at 25 C.The value for Keq, determined by electrical-conductivity measurements of pure water, is 1.8 x 10-16M at 25 C. Substituting this value for Keq gives the value of the ion product of water Kw = [H+] [OH-] = (55.5 M)( 1.8 x 10-16M) =1 x 10-14 M2 Thus the product [H+] [OH-] in aqueous solutions at 25 C always equals 1 x 10-14 M2. When there are exactly equal concentrations of H+ and OH-, as in pure water, the solution is said to be at neutral pH. At this pH, the concentration of H+ and OH- can be calculatedfrom the ion product of water as follows: Kw [H+] [OH-]= [H+]2 Solving for [H+] gives

[H+] = Kw = 1 x 10-14 M2 M2 [H+] = [OH-] = 10-7 M As the ion product of water is constant, whenever [H+ ] is greater than 1x 10-7 M, , [OH-] must become less than 1x 10-7 M and vice versa. When [H+] is very high,as in a solution of hydrochloric acid, [OH-] must be very low. From the ion product of water we can calculate [H+] if we know [OH-], and vice versa . VIII. pH Scale - another way of writing concentrations. The pH Scale Designates the H+ and OH- Concentrations The ion product of water, Kw, is the basis for the pH scale. It is a convenient means of designating the concentration of H+(and thus of OH-) in any aqueous solution in the range between 1.0 M H+ and 1.0 M OH-. The term pH is defined by the expression pH = -log[h+] , pOH = -log[OH-] The symbol p denotes negative logarithm of. For a precisely neutral solution at 25 0C, in which the concentration of hydrogen ions is 1 x 10-7M, the pH can be calculated as follows: pH = log 1.0 1 x 10-7 = log ( 1.0 x 10 7) = log 1 + log10 7= 0 + 7= 7 Solutions having a pH greater than 7 are alkaline or basic; the concentration of OH- is greater than that of H+. Conversely, solutions having a pH less than 7 are acidic. X. Brnsted-Lowry Acids and Bases

acid - a proton (H+) donor base - a proton (H+) acceptor NH3(aq) + H2O(aq) NH4+(aq) + OH- (aq)

NH3 and NH4+ are conjugate acid-base pairs H2O and OH- are conjugate acid-base pairs

Amphiprotic - a compound or ion that can either donate or accept H+ ions. H2O, HSO4- , HPO42-, HSO3- etc.

XI. Predicating acid base reactions in water:


Acid-Base reactions always yield conj. acid-base Strong Acid weak conj. base Strong Base weak conj. acid Weak Acid strong conj. base Weak Base strong conj. acid The strength of the reactant compared to the strength in the product determines which direction the equilibrium lies. Three predictions can be made: o The reactant may Not react at all, leaving essentially all reactants (negligible) o The reactants may Slightly react, leaving mostly reactants (limited) o The reactants may react (essentially) completely, leaving little or no reactants (favorable)

Weak Acids and Bases Have Characteristic Dissociation Constants. Hydrochloric, sulfuric, and nitric acids, commonly called strong acids, are completely ionized in dilute aqueous solutions; the strong bases NaOH and KOH are also completely ionized. Of more interest to biochemists is the behavior of weak acids and basesthose not completely ionized when dissolved in water. These are common in biological systems and play important roles in metabolism and its regulation. The behavior of aqueous solutions of weak acids and bases is best understood if we first define some terms. Acids may be defined as proton donors and bases as proton acceptors. A proton donor and its corresponding proton acceptor make up a conjugate acid-basepair. Acetic acid (CH3COOH), a proton donor, and the acetate anion (CH3COO-), the corresponding proton acceptor, constitute a conjugate acid-base pair, related by the reversible reaction CH3COOH ===============H+ + CH3COOEach acid has a characteristic tendency to lose its proton in an aqueous solution. The stronger the acid, the greater its tendency to lose its proton. The tendency of any acid (HA) to lose a proton and form its conjugate base (A-) is defined by the equilibrium constant (Keq) for the reversible reaction HA ==========H+ + A-, which is Keq = [H+] [A-] = Ka

[HA] Equilibrium constants for ionization reactions are usually called ionization or dissociation constants, oftendesignated Ka.. Stronger acids, such as phosphoric and carbonic acids, have larger dissociation con-stants; weaker acids, such as monohydrogen phosphate(HPO4 2-), have smaller dissociation constants. pKa = log 1 = - log Ka Ka The stronger the tendency to dissociate a proton, the stronger is the acid and the lower its pKa. Titration Curves Reveal the pKa of Weak Acids Titration is used to determine the amount of an acid in a given solution. A measured volume of the acid is titrated with a solution of a strong base, usually sodium hydroxide (NaOH), of known concentration. The NaOH is added in small increments until the acid is consumed (neutralized), as determined with an indicator dye or a pH meter. The concentration of the acid in the original solution can be calculated from the volume and concentration of NaOH added. A plot of pH against the amount of NaOH added (a titration curve) reveals the pKa of the weak acid. Consider the titration of a 0.1 M solution of acetic acid (for simplicity denoted as HAc) with 0.1 M NaOH at 25 oCTwo reversible equilibria are involved in the process: H2O ========H+ + OHHAc ============H+ + AcThe equilibria must simultaneously conform to their characteristic equilibrium constants, which are, respectively, Kw = Kw = [H+] [OH-] = 1 x 10-14 M2 Ka = [H+] [Ac-] = 1.74 x 105 M [HAc] At the beginning of the titration, before any NaOH is added, the acetic acid is already slightly ionized, As NaOH is gradually introduced, the added OH combines with the free H+in the solution to form H2O,to an extent that satisfies the equilibrium relationship As free H+ is removed, HAc dissociates further to satisfy its own equilibrium constant . The net result as the titration proceeds is that more and more HAc ionizes, forming Ac-, as the NaOH is added. At the midpoint of the

titration, at which exactly 0.5 equivalent of NaOH has been added, one-half of the original acetic acid has undergone dissociation, so that the concentration of the proton donor, [HAc], now equals that of the proton acceptor, [Ac-]. At thismidpoint a very important relationship holds: the pH of the equimolar solution of acetic acid and acetate is exactly equal to the pKa of acetic acid . As the titration is continued by adding further increments of NaOH, the remaining nondissociated aceticacid is gradually converted into acetate. The end point of the titration occurs at about pH 7.0: all the acetic acid has lost its protons to OH- to form H2O and acetate. The most important point about the titration curve of a weak acid is that it shows graphically that a weak acid and its aniona conjugate acid-base paircan act as a buffer. XII. Buffer solutions Buffers Are Mixtures of Weak Acids and Their Conjugate Bases Buffers are aqueous systems that tend to resist changes in pH when small amounts of acid (H+) or base (OH-) are added. A buffer system consists of a weak acid (the proton donor) and its conjugate base (the proton acceptor). As an example, a mixture of equal concentrations of acetic acid and acetate ion, found at the midpoint of the titration curve, is a buffer system. The titration curve of acetic acid has a relatively flat zone extending about 1 pH unit on either side of its midpoint pH of 4.76. In this zone, an amount of H+ orOH- added to the system has much less effect on pH than the same amount added outside the buffer range. This relatively flat zone is the buffering region of the acetic acidacetate buffer pair. At the midpoint of the buffering region, where the concentration of the proton donor (acetic acid) exactly equals that of the proton acceptor (acetate), the buffering power of the system is maximal; that is, its pH changes least on addition of H+ or OH-. The pH at this point in the titration curve of acetic acid is equal to its pKa. The pH of the acetate buffer system does change slightly when a small amount of H+ or OH- is added, but this change is very small compared with the pH change that would result if the same amount of H+ or OH- were added to pure water or to a solution of the salt of a strong acid and strong base, such as NaCl, which has no buffering power. Buffering results from two reversible reaction equilibria occurring in a solution of nearly equal concentrations of a proton donor and its conjugate proton acceptor. Whenever H+ or OH- is added to a buffer, the result is a small change in the ratio of the relative concentrations of the weak acid and its anion and thus a small change in pH. The decrease in concentration of one component of the system is balanced exactly by an increase in the other. The sum of the buffer components does not change, only their ratio. Each conjugate acid-base pair has a characteristic pH zone in which it is an effective buffer The titration curves of acetic acid, H2PO4 -, and NH4+ have nearly identical shapes, suggesting that these curves reflect a fundamental law or relationship.This is indeed the case. The shape of the titration curve of any weak acid is described by the HendersonHasselbalch equation, which is important for understanding buffer action and acid-base

balance in the blood and tissues of vertebrates. This equation is simply a useful way of restating the expression for the dissociation constant of an acid. For the dissociation of a weak acid HA into H+ and A-, the Henderson-Hasselbalch equation can be derived as follows: Ka = [H+] [A-] [HA] [H+] = Ka [HA] [A-] Then take the negative logarithm of both sides: -log[H+] =- log Ka- log [HA] [A-] Substitute pH for -log [H+] and pKa for -log Ka : pH = pKa - log [HA] [A-] Now invert -log [HA]/[A-], which involves changing its sign, to obtain the HendersonHasselbalch equation: pH = pKa + log [A-] [HA Stated more generally pH = pKa + log [proton acceptor] [proton donor] Weak Acids or Bases Buffer Cells and Tissues against pH Changes The intracellular and extracellular fluids of multicellular organisms have a characteristic and nearly constant pH. The organisms first line of defense against changes in internal pH is provided by buffer systems. The cytoplasm of most cells contains high concentrations of proteins, which contain many amino acids with functional groups that are weak acids or weak bases. For example,the side chain of histidine has a pKa of 6.0;proteins containing histidine residues therefore buffer effectively near neutral pH. Nucleotides such as ATP, as well as many low molecular weight metabolites, contain ionizable groups that can contribute buffering power to the cytoplasm. Some highly specialized organelles and extracellular compartments have high concentrations of compounds that contribute buffering capacity: organic acids buffer the vacuoles of plant cells; ammonia buffers urine. Two especially important biological buffers are the hosphate and bicarbonate systems. The phosphate buffer system, which acts in the cytoplasm of all cells, consists of H2PO4-as proton donor and HPO42-as proon acceptor: H2PO4-=========== H+ + HPO42The phosphate buffer system is maximally effective at pH close to its pKa of 6.86 and thus tends to resist pH changes in the range between about 5.9 and 7.9. It is therefore an effective buffer in biologal fluids; in mammals, for example, extracellular fluds and most cytoplasmic compartments have a pH in the range of 6.9 to 7.4.Blood plasma is buffered in part by the bicarbonate

system, consisting of carbonic acid (H2CO3) as proton donor and bicarbonate (HCO3-) as proton acceptor: H2CO3======== H+ + HCO3K1 = [H+ ] [HCO3-] [H2CO3] This buffer system is more complex than other conjugate acid-base pairs because one of its components, carbonic acid (H2CO3), is formed from dissolved (d) carbon dioxide and water, in a reversible reaction: CO2(d) + H2O ======= H2CO3 K2= [H2CO3] [CO2(d)] [H2O] Carbon dioxide is a gas under normal conditions, and the concentration of dissolved CO2 is the result of equilibration with CO2 of the gas (g) phase: [CO2(g)]========= [CO2(d)] K2= [CO2(d)] [CO2(g)] The pH of a bicarbonate buffer system depends on the concentration of H2CO3 and HCO3-, the proton donor and acceptor components. The concentration of H2CO3in turn depends on the concentration of dissolved CO2,which in turn depends on the concentration of CO2 inthe gas phase, called the partial pressure of CO2. Thus the pH of a bicarbonate buffer exposed to a gas phase is ultimately determined by the concentration of HCO3 in the aqueous phase and the partial pressure of CO2 in the gas phase .Human blood plasma normally has a pH close to 7.4.Should the pH-regulating mechanisms fail or be overwhelmed, as may happen in severe uncontrolled diabetes when an overproduction of metabolic acids causes acidosis, the pH of the blood can fall to 6.8 or below, leading to irreparable cell damage and death. In otherdiseases the pH may rise to lethal levels. Although many aspects of cell structure and function are influenced by pH, it is the catalytic activity of enzymes that is especially sensitive. Enzymes typically show maximal catalytic activity at a characteristic pH, called the pH optimum .On either side of the optimum pH their catalytic activity often declines sharply. Thus, a small change in pH can make a large difference in the rate of some crucial enzyme-catalyzed reactions. Biological control of the pH of cells and body fluids is therefore of central importance in all aspects of metabolism and cellular activities.

Chemical Bonding
Chemical compounds are formed by the joining of two or more atoms. A stable compound occurs when the total energy of the combination has lower energy than the separated atoms. The bound state implies a net attractive force between the atoms ... a chemical bond. The two extreme cases of chemical bonds are: Covalent bond: bond in which one or more pairs of electrons are shared by two atoms.

Ionic bond: bond in which one or more electrons from one atom are removed and attached to another atom, resulting in positive and negative ions which attract each other. Other types of bonds include metallic bonds and hydrogen bonding. The attractive forces between molecules in a liquid can be characterized as van der Waals bonds

Covalent Bonds
Covalent chemical bonds involve the sharing of a pair of valence electrons by two atoms, in contrast to the transfer of electrons in ionic bonds. Such bonds lead to stable molecules if they share electrons in such a way as to create a noble gas configuration for each atom. Hydrogen gas forms the simplest covalent bond in the diatomic hydrogen molecule. The halogens such as chlorine also exist as diatomic gases by forming covalent bonds. The nitrogen and oxygen which makes up the bulk of the atmosphere also exhibits covalent bonding in forming diatomic molecules.

Polar Covalent Bonds


Covalent bonds in which the sharing of the electron pair is unequal, with the electrons spending more time around the more nonmetallic atom, are called polar covalent bonds. In such a bond there is a charge separation with one atom being slightly more positive and the other more negative, i.e., the bond will produce a dipole moment. The ability of an atom to attract electrons in the presense of another atom is a measurable property called electronegativity

Ionic Bonds

In chemical bonds, atoms can either transfer or share their valence electrons. In the extreme case where one or more atoms lose electrons and other atoms gain them in order to produce a noble gas electron configuration, the bond is called an ionic bond. Typical of ionic bonds are those in the alkali halides such as sodium chloride, NaCl.

Metallic Bonds
The properties of metals suggest that their atoms possess strong bonds, yet the ease of conduction of heat and electricity suggest that electrons can move freely in all directions in a metal. The general observations give rise to a picture of "positive ions in a sea of electrons" to describe metallic bonding. There are many, much weaker, non-covalent interactions that are responsible for the 3dimensional configuration that the biological polymers adopt. These interactions also play a very important role in the flexibility of the macromolecules, their interactions with each other and with other molecules in the cell. The various non-covalent interactions can be classified as:

Ionic interactions Van der waals interactions Hydrogen bonds Hydrophobic interactions

Covalent bonds and noncovalent interactions The glue that holds macromolecules together: a Covalent bonds

b Noncovalent interactions: ionic bonds hydrogen bonds van der Waals interactions hydrophobicity-driven interactions Covalent bonds Formed when two different atoms share electrons in the outer atomic orbitals a Each atom can make a characteristic number of bonds (e.g., carbon is able to form 4 covalent bonds) Covalent bonds in biological systems are typically single (one shared electron pair) or double (two shared electron pairs) bonds Non- covalent bonds Several types: hydrogen bonds, ionic bonds, van der Waals interactions, hydrophobic bonds Noncovalent bonds require less energy to break than covalent bonds The energy required to break noncovalent bonds is only slightly greater than the average kinetic energy of molecules at room temperature Noncovalent bonds are required for maintaining the threedimensional structure of many macromolecules and for stabilizing specific associations between macromolecules .Multiple noncovalent bonds can confer binding specificity The hydrogen bond underlies waters chemical and biological properties ionic bonds ionic bonds result from the attraction of a positively charged ion (cation) to a negatively charged ion (anion) The atoms that form the bond have very different electronegativity values and the electron is completely transferred to the more electronegative atom. Ions in aqueous solutions are surrounded by water molecules, which interact via the end of the water dipole carrying the opposite charge of the ion Van der Waals interactions are caused by transient dipoles-- When any two atoms approach each other closely, a weak nonspecific attractive force (the van der Waals force) is created due to momentary random fluctuations that produce a transient electric dipole When any two atoms approach each other closely, they create a weak, nonspecific attractive force that produces a van der Waals interaction, named for Dutch physicist Johannes Diderik van der Waals (18371923), who first described it. These nonspecific interactions result from the momentary random fluctuations in the distribution of the electrons of any atom, which give rise to a transient unequal distribution of electrons, that is, a transient electric dipole. If two noncovalently bonded atoms are close enough together, the transient dipole in one atom will perturb the electron cloud of the other. This perturbation generates a transient dipole in the second atom, and the two dipoles will attract each other weakly. Similarly, a polar covalent bond in one molecule will attract an oppositely oriented dipole in another. Van der Waals interactions, involving either transient induced or permanent electric dipoles, occur in all types of molecules, both polar and nonpolar. In particular, van der

Waals interactions are responsible for the cohesion between molecules of nonpolar liquids and solids, such as heptane, CH3(CH2)5CH3, that cannot form hydrogen bonds or ionic interactions with other molecules. When these stronger interactions are present, they override most of the influence of van der Waals interactions. Heptane, however, would be a gas if van der Waals interactions could not form. The strength of van der Waals interactions decreases rapidly with increasing distance; thus these noncovalent bonds can form only when atoms are quite close to one another. However, if atoms get too close together, they become repelled by the negative charges in their outer electron shells. When the van der Waals attraction between two atoms exactly balances the repulsion between their two electron clouds, the atoms are said to be in van der Waals contact (Figure 2-15). Each type of atom has a van der Waals radius at which it is in van der Waals contact with other atoms. The van der Waals radius of an H atom is 0.1 nm, and the radii of O, N, C, and S atoms are between 0.14 and 0.18 nm. Two covalently bonded atoms are closer together than two atoms that are merely in van der Waals contact. For a van der Waals interaction, the internuclear distance is approximately the sum of the corresponding radii for the two participating atoms. Thus the distance between a C atom and an H atom in van der Waals contact is 0.27 nm, and between two C atoms is 0.34 nm. In general, the van der Waals radius of an atom is about twice as long as its covalent radius. For example, a CH covalent bond is about 0.107 nm long and a CC covalent bond is about 0.154 nm long.

Figure 2-15
Two oxygen molecules in van der Waals contact. Transient dipoles in the electron clouds of all atoms give rise to weak attractive forces, called van der Waals interactions. Each type of atom has a characteristic van der Waals radius at (more...) The energy of the van der Waals interaction is about 1 kcal/mol, only slightly higher than the average thermal energy of molecules at 25 C. Thus the van der Waals interaction is even weaker than the hydrogen bond, which typically has an energy of 12 kcal/mol in aqueous solutions. The attraction between two large molecules can be appreciable, however, if they have precisely complementary shapes, so that they make many van der Waals contacts when they come into proximity. Van der Waals interactions, as well as other noncovalent bonds, mediate the binding of many enzymes with their specific substrates (the substances on which an enzyme acts) and of each type of antibody with its specific antigen (Chapter 3). Hydrophobic bonds cause nonpolar molecules to adhere to one another Nonpolar molecules (e.g., hydrocarbons) are insoluble in water and are termed Hydrophobic.Since these molecules cannot form hydrogen bonds with water, it is energetically favorable for such molecules to interact with other hydrophobic molecules

This force that causes hydrophobic molecules to interact is termed a hydrophobic Bond Nonpolar molecules do not contain ions, possess a dipole moment, or become hydrated. Because such molecules are insoluble or almost insoluble in water, they are said to be hydrophobic (Greek, water-fearing). The covalent bonds between two carbon atoms and between carbon and hydrogen atoms are the most common nonpolar bonds in biological systems. Hydrocarbonsmolecules made up only of carbon and hydrogenare virtually insoluble in water. A large triacylglycerol (or triglyceride) such as tristearin, a component of animal fat, is also insoluble in water, even though its six oxygen atoms participate in some slightly polar bonds with adjacent carbon atoms (Figure 2-16). When shaken in water, tristearin forms a separate phase similar to the separation of oil from the water-based vinegar in an oil-and-vinegar salad dressing.

Figure 2-16
The chemical structure of tristearin, or tristearoyl glycerol, a component of natural fats. It contains three molecules of the fatty acid stearic acid, CH3(CH2)16COOH, esterified to one molecule of glycerol, HOCH2CH(OH)CH2OH. (more...) The force that causes hydrophobic molecules or nonpolar portions of molecules to aggregate together rather than to dissolve in water is called the hydrophobic bond. This is not a separate bonding force; rather, it is the result of the energy required to insert a nonpolar molecule into water. A nonpolar molecule cannot form hydrogen bonds with water molecules, so it distorts the usual water structure, forcing the water into a rigid cage of hydrogen-bonded molecules around it. Water molecules are normally in constant motion, and the formation of such cages restricts the motion of a number of water molecules; the effect is to increase the structural organization of water. This situation is energetically unfavorable because it decreases the randomness (entropy) of the population of water molecules. The role of entropy in chemical systems is discussed further in a later section. The opposition of water molecules to having their motion restricted by forming cages around hydrophobic molecules or portions thereof is the major reason molecules such as tristearin and heptane are essentially insoluble in water and interact mainly with other hydrophobic molecules. Nonpolar molecules can also bond together, albeit weakly, through van der Waals interactions. The net result of the hydrophobic and van der Waals interactions is a very powerful tendency for hydrophobic molecules to interact with one another, and not with water. Small hydrocarbons like butane (CH3CH2CH2CH3) are somewhat soluble in water, because they can dissolve without disrupting the water lattice appreciably. However, 1butanol (CH3CH2CH2CH2OH) mixes completely with water in all proportions. The

replacement of just one hydrogen atom with the polar OH group allows the molecule to form hydrogen bonds with water and greatly increases its solubility. Simply put, like dissolves like. Polar molecules dissolve in polar solvents such as water, while nonpolar molecules dissolve in nonpolar solvents such as hexane.

Multiple Noncovalent Bonds Can Confer Binding Specificity


Go to: Besides contributing to the stability of large biological molecules, multiple noncovalent bonds can also confer specificity by determining how large molecules will fold or which regions of different molecules will bind together. All types of these weak interactions are effective only over a short range and require close contact between the reacting groups. For noncovalent bonds to form properly, there must be a complementarity between the sites on the two interacting surfaces. Figure 2-17 illustrates how several different weak bonds can bind two protein chains together. Almost any other arrangement of the same groups on the two surfaces would not allow the molecules to bind so tightly. Such multiple, specific interactions allow protein molecules to fold into a unique three-dimensional shape (Chapter 3) and the two chains of DNA to bind together (Chapter 4).

Figure 2-17
The binding of a hypothetical pair of proteins by two ionic bonds, one hydrogen bond, and one large combination of hydrophobic and van der Waals interactions. The structural complementarity of the surfaces of the two molecules gives rise to this (more...)

Phospholipids Are Amphipathic Molecules


Go to: Multiple noncovalent bonds also are critical in stabilizing the structure of biomembranes, whose primary components are phospholipids. Because the essential properties of biomembranes derive from phospholipids, we first examine the chemistry of these compounds and then see how they associate into the sheetlike structures that are the foundation of biomembranes. All phospholipids contain one or more acyl chains derived from fatty acids, which consist of a hydrocarbon chain attached to a carboxyl group (COOH). Fatty acids are insoluble in water and salt solutions; they differ in length and in the extent and position of their double bonds. Table 2-2 lists the principal fatty acids found in cells. Most fatty acids have an even number of carbon atoms, usually 16, 18, or 20.

Table 2-2
Some Typical Fatty Acids Found in Cells. Fatty acids with no double bonds are said to be saturated; those with at least one double bond are unsaturated. Unsaturated fatty acid chains normally have one double bond, but some have two, three, or four. Two stereoisomeric configurations, cis and trans, are possible around each double bond:

A cis double bond introduces a rigid kink in the otherwise flexible straight chain of a fatty acid (Figure 2-18). In general, the fatty acids in biological systems contain only cis double bonds.

Figure 2-18
The effect of a double bond. Shown are space-filling models and chemical structures of the ionized form of palmitic acid, a saturated fatty acid, and oleic acid, an unsaturated one. In saturated fatty acids, the hydrocarbon chain is linear; (more...) Phospholipids consist of two long-chain fatty acyl groups linked (usually by an ester bond) to small, highly hydrophilic groups. Consequently, unlike tristearin, phospholipids do not clump together in droplets but orient themselves in sheets, exposing their hydrophilic ends to the aqueous environment. Molecules in which one end (the head) interacts with water and the other end (the tail) is hydrophobic are said to be amphipathic (Greek, tolerant of both). The tendency of amphipathic molecules to form organized structures spontaneously in water is the key to the structure of cell membranes.

In phosphoglycerides, a principal class of phospholipids, fatty acyl side chains are esterified to two of the three hydroxyl groups in glycerol

but the third hydroxyl group is esterified to phosphate. The simplest phospholipid, phosphatidic acid, contains only these components:

where R1 and R2 are fatty acyl groups. In most phospholipids, however, the phosphate group is also esterified to a hydroxyl group on another hydrophilic compound. In phosphatidylcholine, for example, choline is attached to the phosphate (Figure 2-19). In other phosphoglycerides, the phosphate group is linked to other molecules, such as ethanolamine, the amino acid serine, or the sugar inositol. The negative charge on the phosphate as well as the charged groups or hydroxyl groups on the alcohol esterified to it interact strongly with water.

Figure 2-19
Phosphatidylcholine, a typical phosphoglyceride, has a hydrophobic tail and a hydrophilic head in which choline is linked to glycerol by phosphate. Either or both of the fatty acyl side chains in a phosphoglyceride may be saturated or (more...)

The Phospholipid Bilayer Forms the Basic Structure of All Biomembranes


Go to: When a suspension of phospholipids is mechanically dispersed in aqueous solution, they can assume three different forms: micelles, bilayer sheets, and liposomes (Figure 2-20).

The type of structure formed by a pure phospholipid or a mixture of phospholipids depends on the length of the fatty acyl chains and their degree of saturation, on the temperature, on the ionic composition of the aqueous medium, and on the mode of dispersal of the phospholipids in the solution. In all three forms, hydrophobic interactions cause the fatty acyl chains to aggregate and exclude water molecules from the core. Micelles are rarely formed from natural phosphoglycerides, whose fatty acyl chains generally are too bulky to fit into the interior of a micelle.

Figure 2-20
Cross-sectional views of the three structures that can be formed by mechanically dispersing a suspension of phospholipids in aqueous solutions. Shown are a spherical micelle with a hydrophobic interior composed entirely of fatty acyl chains; (more...) Under suitable conditions, phospholipids of the composition present in cells spontaneously form symmetric sheetlike structures, called phospholipid bilayers, that are two molecules thick. Each phospholipid layer in this lamellar structure is called a leaflet. The hydrocarbon side chains in each leaflet minimize contact with water by aligning themselves tightly together in the center of the bilayer, forming a hydrophobic core that is about 3 nm thick. The close packing of these hydrocarbon side chains is stabilized by van der Waals interactions between them. Ionic and hydrogen bonds stabilize the interaction of the phospholipid polar head groups with each other and with water. At neutral pH, the polar head groups in some phospholipids (e.g., phosphatidylcholine) have no net electric charge, whereas the head groups in others have a net negative charge. Nonetheless, all phospholipids can pack together into the characteristic bilayer structure. A phospholipid bilayer can be of almost unlimited sizefrom micrometers () to millimeters (mm) in length or widthand can contain tens of millions of phospholipid molecules. Because of their hydrophobic core, bilayers are impermeable to salts, sugars, and most other small hydrophilic molecules. Like a phospholipid bilayer, all biological membranes have a hydrophobic core, and they all separate two aqueous solutions. The plasma membrane, for example, separates the interior of the cell from its surroundings. Similarly, the membranes that surround the organelles of eukaryotic cells separate one aqueous phasethe cell cytosolfrom anotherthe interior of the organelle. Several types of evidence indicate that the phospholipid bilayer is the basic structural unit of nearly all biomembranes (Chapter 5). Associated with membrane phospholipids are various proteins that help confer unique properties on each type of membrane.

Hydrogen bonding between water molecules is of crucial importance because all life requires an aqueous environment and water constitutes about 7080 percent of the weight of most cells. The mutual attraction of its molecules causes water to have melting and boiling points at least 100 C higher than they would be if water were nonpolar; in the absence of these intermolecular attractions, water on earth would exist primarily as a gas. The exact structure of liquid water is still unknown. It is believed to contain many transient, maximally hydrogen-bonded networks. Most likely, water molecules are in rapid motion, constantly making and breaking hydrogen bonds with adjacent molecules. As the temperature of water increases toward 100 C, the kinetic energy of its molecules becomes greater than the energy of the hydrogen bonds connecting them, and the gaseous form of water appears.

Properties of Hydrogen Bonds


Normally, a hydrogen atom forms a covalent bond with only one other atom. However, a hydrogen atom covalently bonded to a donor atom, D, may form an additional weak association, the hydrogen bond, with an acceptor atom, A:

In order for a hydrogen bond to form, the donor atom must be electronegative, so that the covalent DH bond is polar. The acceptor atom also must be electronegative, and its outer shell must have at least one nonbonding pair of electrons that attracts the + charge of the hydrogen atom. In biological systems, both donors and acceptors are usually nitrogen or oxygen atoms, especially those atoms in amino (NH2) and hydroxyl (OH) groups. Because all covalent NH and OH bonds are polar, their H atoms can participate in hydrogen bonds. By contrast, CH bonds are nonpolar, so these H atoms are almost never involved in a hydrogen bond. Water molecules provide a classic example of hydrogen bonding. The hydrogen atom in one water molecule is attracted to a pair of electrons in the outer shell of an oxygen atom in an adjacent molecule. Not only do water molecules hydrogen-bond with one another, they also form hydrogen bonds with other kinds of molecules, as shown in Figure 2-12. The presence of hydroxyl (OH) or amino (NH2) groups makes many molecules soluble in water. For instance, the hydroxyl group in methanol (CH3OH) and the amino group in methylamine (CH3NH2) can form several hydrogen bonds with water, enabling the molecules to dissolve in water to high concentrations. In general, molecules with polar bonds that easily form hydrogen bonds with water can dissolve in water and are said to be hydrophilic (Greek, water-loving). Besides the hydroxyl and amino groups, peptide and ester bonds are important chemical groups that interact well with water:

Figure 2-12
Water readily forms hydrogen bonds. In liquid water, each water molecule apparently forms transient hydrogen bonds with several others, creating a fluid network of hydrogenbonded molecules (a). The precise structure of liquid water (more...) Most hydrogen bonds are 0.260.31 nm long, about twice the length of covalent bonds between the same atoms. In particular, the distance between the nuclei of the hydrogen and oxygen atoms of adjacent hydrogen-bonded molecules in water is approximately 0.27 nm, about twice the length of the covalent OH bonds in water. The hydrogen atom is closer to the donor atom, D, to which it remains covalently bonded, than it is to the acceptor. The length of the covalent DH bond is a bit longer than it would be if there were no hydrogen bond, because the acceptor pulls the hydrogen away from the donor. The strength of a hydrogen bond in water (5 kcal/mol) is much weaker than a covalent OH bond (110 kcal/mol).

Hydrogen Bonds as a Stabilizing Force in Macromolecules


An important feature of all hydrogen bonds is directionality. In the strongest hydrogen bonds, the donor atom, the hydrogen atom, and the acceptor atom all lie in a straight line. Nonlinear hydrogen bonds are weaker than linear ones; still, multiple nonlinear hydrogen bonds help to stabilize the three-dimensional structures of many proteins. It is only because of the aggregate strength of multiple hydrogen bonds that they play a central role in the architecture of large biological molecules in aqueous solutions (see Figure 2-11). The strengths of the hydrogen bonds in proteins and nucleic acids are only 1 to 2 kcal/mol, considerably weaker than the hydrogen bonds between water molecules. The reason for this difference can be seen from Figure 2-13, which depicts the formation of a hydrogen bond between two amino acids in a protein. Initially, both the OH and NH2 groups in the protein are hydrogen-bonded to water, and the formation of a hydrogen bond between these groups involves disruption of their hydrogen bonds with water. Thus the net change in energy in forming this OHN hydrogen bond will be less than the 5 kcal/mol characteristic of hydrogen bonds between water molecules.

Figure 2-13
In order for a hydrogen bond (red dots) to form between a OH and an NH2 group in a protein (right), the hydrogen bonds between these groups and water must be disrupted (left).