The energetics of hydrogen bonds in model systems: implications for enzymatic catalysis.
Low-barrier or short, strong hydrogen bonds have been proposed to contribute 10 to 20 kilocalories per mole to transition-state stabilization in enzymatic catalysis. The proposal invokes a large increase in hydrogen bond energy when the pKa values of the donor and acceptor (where Ka is the acid constant) become matched in the transition state (delta pKa=0). This hypothesis was tested by investigating the energetics of hydrogen bonds as a function of delta pKa for homologous series of compounds under nonaqueous conditions that are conducive to the formation of low-barrier hydrogen bonds. In all cases, there was a linear correlation between the increase in hydrogen-bond energy and the decrease in delta pKa, as expected from simple electrostatic effects. However, no additional energetic contribution to the hydrogen bond was observed at delta pKa=0. These results and those of other model studies suggest alternative mechanisms by which hydrogen bonds can contribute to enzymatic catalysis, in accord with conventional electrostatic considerations.
Shan
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Department of Biochemistry, Stanford University, CA 94305-5307,USA.
Loh
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Herschlag
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D002384:Catalysis; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010636:Phenols / Q000737:chemistry; D010795:Phthalic Acids / Q000737:chemistry; D013816:Thermodynamics
D004798:Enzymes; D010636:Phenols; D010795:Phthalic Acids; C032279:phthalic acid