Computational hydrogen bond catalysis

Studies on solvent effects on the endo-exo selectivity of Diels-Alder reactions have revealed the importance of hydrogen bonding interactions besides the already mentioned solvophobic interactions and polarity effects. Further evidence of the significance of the former interactions comes from computer simulations" and the analogy with Lewis-acid catalysis which is known to enhance dramatically the endo-exo selectivity (Section 1.2.4). 

It should be clear from this brief review that low-barrier hydrogen bonds play an important role in many enzymatic reactions, in many cases contributing the energy of their formation to provide catalysis. I have not reviewed the extensive computational literature on low-barrier hydrogen bonds, but an early review will provide more information.10 Other short reviews on their role in enzymatic reactions have been published.4,15,58,59 I have not included references to early critics of the role of low-barrier hydrogen bonds, as I think their criticisms have been shown to be invalid. References to those articles are available in the reviews noted above. 

The EVB method proposed by Warshel [6] is an elegant and computationally very efficient method of describing the entire BO surface, thus allowing treatment of chemical reactions such as proton transfer in hydrogen bonds. It can also be used in vibrational analysis. In conjunction with the environment described at the molecular mechanics level it was the first QM/MM method. Vibrational analyses of hydrogen bonded systems and of enzymatic catalysis have a lot in common. 

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