The Energetics of Hydrogen Bonds in Model Systems: Implications for Enzymatic Catalysis

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Science  05 Apr 1996:
Vol. 272, Issue 5258, pp. 97-101
DOI: 10.1126/science.272.5258.97


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 (ΔpKa = 0). This hypothesis was tested by investigating the energetics of hydrogen bonds as a function of ΔpKa 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 ΔpKa, as expected from simple electrostatic effects. However, no additional energetic contribution to the hydrogen bond was observed at ΔpKa = 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.

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