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Published April 5, 1996 | public
Journal Article

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 pK_a values of the donor and acceptor (where K_a is the acid constant) become matched in the transition state (ΔpK_a = 0). This hypothesis was tested by investigating the energetics of hydrogen bonds as a function of ΔpK_a 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 ΔpK_a, as expected from simple electrostatic effects. However, no additional energetic contribution to the hydrogen bond was observed at ΔpK_a = 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.

Additional Information

© 1996 American Association for the Advancement of Science. Received 7 November 1995; accepted 14 February 1996. We thank J. Brauman, J. Klinman, and J. Kirsch for discussions and helpful suggestions, the Bordwell group for technical help, and the Herschlag lab for comments on the manuscript. This work is supported by grants from the Lucille P. Markey Charitable Trust and the Chicago Community Trust to D.H. D.H. is a Lucille P. Markey Scholar and a Searle Scholar.

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