CHEM 2713 Biochemistry I 12/26/2018 S.A. McFarland©2008

Free energy changes Enthalpy & entropy determine spontaneity of a reaction at a given temperature Enthalpy (ΔH) – relative strengths of the bonds broken in reactants(s) vs. bonds formed in product(s) Entropy (ΔS) – relative degree of disorder in reactant(s) vs. product(s) Spontaneity favors strong bonds and high disorder in the product(s) 12/26/2018 S.A. McFarland©2008

Spontaneity does not mean certainty Spontaneity does not relate whether the reaction is kinetically feasible! ΔGo = -693 cal (2900 J) Will your diamond turn to graphite? Thermodynamics say yes, but kinetics say no! 12/26/2018 S.A. McFarland©2008

Spontaneity does not mean certainty Conversion of diamond to graphite has a high activation barrier ΔG = -693o cal (2900 J) Diamond (sp3 bonds) Graphite (sp2 bonds) 12/26/2018 S.A. McFarland©2008

Enzymes serve as biological catalysts A catalyst lowers the activation barrier for a reaction, allowing a kinetically unfavorable reaction to proceed Enzymes serve as biological catalysts Biological reactions have activation barriers; this adds another element of control in biological systems 12/26/2018 S.A. McFarland©2008

ATP hydrolysis is highly exergonic This property allows ATP to be used a storage form of energy Phosphoanhydride bond is thermodynamically unstable but kinetically stable. Kinetic stability is essential for the role of ATP as an energy storage molecule Otherwise, ATP would have a fleeting existence and would not be available when energy is required 12/26/2018 S.A. McFarland©2008

Central role of ATP in metabolism ATP is the chemical intermediate that links energy-releasing to energy-requiring cellular processes Its role in the cell is analogous to that of money in an economy ATP is earned/produced in exergonic reactions and spent/consumed in endergonic ones 12/26/2018 S.A. McFarland©2008

Equations to review ΔGo = ΔHo – TΔSo ΔG = ΔGo + RT ln Q ΔGo = -RT ln Keq ln Keq = - ΔHo/R(1/T) + ΔSo/R ΔGo’ = free energy change under biochemical standard conditions Activity of pure water is 1, [H2O] = 1 pH is 7 Standard state refers to naturally occurring mixture (where the substance can undergo acid-base reactions) 12/26/2018 S.A. McFarland©2008

Chapter 2: Water Most abundant substance in living systems (70% or more of the weight of most organisms) All aspects of cell structure and function are adapted to the physical and chemical properties of water Attractive forces between H2O molecules and the slight tendency of H2O to ionize are of crucial importance to the structure and function of biomolecules 12/26/2018 S.A. McFarland©2008

Water exhibits very strong intermolecular dipole- dipole forces: hydrogen bonding (H-bonding) 12/26/2018 S.A. McFarland©2008

Structure of a single water molecule 12/26/2018 S.A. McFarland©2008

Water is polar Summation of individual dipoles determine overall polarity 12/26/2018 S.A. McFarland©2008

Water is polar H2O molecules exhibit cohesive forces known as hydrogen bonds H-bonding is a special kind of dipole-dipole interaction H-bonding is possible when H is attached to O, N, or F Individual H-bonds are weaker than covalent and ionic bonds, but collectively strong H-bonding gives water its relatively high melting and boiling points (and high heats of fusion and vaporization) 12/26/2018 S.A. McFarland©2008

Hydrogen bonding in ice In ice, each H2O molecule forms the maximum of four H-bonds, creating a crystalline solid In liquid H2O at room temp. and atmospheric pressure, each H2O molecule H-bonds with an average of 3.4 other H2O molecules Crystalline lattice of ice results in a structure that is less dense than liquid H2O, thus ice floats on H2O 12/26/2018 S.A. McFarland©2008

Putting H-bonds in perspective 12/26/2018 S.A. McFarland©2008

Van der Waals forces H-bonding is a special type of (a) 12/26/2018 S.A. McFarland©2008

Water forms H-bonds with polar solutes 12/26/2018 S.A. McFarland©2008

Common H-bonds in biological systems H-bonds are not unique to water Note that H atoms covalently bound to C do not make H-bonds C is only slightly more electronegative than H; the C-H bond is only weakly polar 12/26/2018 S.A. McFarland©2008

Some biologically important H-bonds 12/26/2018 S.A. McFarland©2008

Hydrogen bonds Strongest when two electronegative atoms are oriented 180o H-bonds are highly directional Capable of holding two H-bonded molecules or groups in a specific geometric arrangement Confers very precise 3-D structures on protein and nucleic acid molecules, which have many intramolecular H-bonds 12/26/2018 S.A. McFarland©2008

Water interacts with charged solutes Disrupts electrostatic solute-solute interactions Water has a high dielectric constant, a physical property reflecting the number of dipoles in a solvent: ε (H2O) is 78.5; ε (PhH) is 4.6 Ionic interactions are much weaker in more polar environments (solute-solvent interactions strong) When crystalline NaCl dissolves in H2O, entropy increases ΔG = ΔH – TΔS: ΔH has a small positive value and TΔS has a large positive value 12/26/2018 S.A. McFarland©2008

Nonpolar gases are poorly soluble in water CO2, O2, and N2 are nonpolar Dissolution of such gases in not favored by enthalpy or entropy Poor solubility in water requires other methods of transport O2 carried by hemoglobin CO2 carried as HCO3- 12/26/2018 S.A. McFarland©2008

Transfer is entropically driven Entropy (ΔS) increases when hydrocarbons move from water to a nonpolar solvent 12/26/2018 S.A. McFarland©2008

Orientation of water around a nonpolar solute Increased ordering of water reduces entropy of system Fewer ways for water to form H-bonds (orient) around a nonpolar molecule relative to the number of ways H-bonds can form in bulk water 12/26/2018 S.A. McFarland©2008

Aggregation of nonpolar molecules in water Nonpolar substance is excluded from the aqueous phase Hydrophobic effect: water’s tendency to minimize its contacts with hydrophobic molecules 12/26/2018 S.A. McFarland©2008

Amphipathic compounds in aqueous solution 12/26/2018 S.A. McFarland©2008

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Model of a micelle Twenty molecules of the detergent octyl glucoside 12/26/2018 S.A. McFarland©2008

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In summary Individually weak, collectively strong 12/26/2018 S.A. McFarland©2008

Pure water is slightly ionized Hydration of dissociating protons virtually instantaneous 12/26/2018 S.A. McFarland©2008

Pure water has high ionic mobility Movement of hydronium and hydroxide ions in an electric field is anomalously fast 12/26/2018 S.A. McFarland©2008

Draw a molecule with an alcohol (acidic form), a phosphoryl group (basic form), and an ester. Show two of these molecules interacting via a hydrogen bond. 12/26/2018 S.A. McFarland©2008