Low-barrier hydrogen bonds:: Ab initio and DFT investigation

High-level ab initio and DFT molecular orbital calculations have been used to investigate the physical properties of a model low-barrier hydrogen bond (LBHB) system: formic acid-formate anion. Ln the gas phase, it is found that the hydrogen bond formed is extraordinarily short and strong [ca. 27 kcal/mol at B3LYP/6-31 + + G(d, p)], with a calculated enthalpy of activation for proton transfer from donor to acceptor that is less than the zero-point vibrational energy available to the system. Several perturbations to this system were studied, Forcing a mismatch of pK(a)s between donor and acceptor, via the use of substituents, causes the strength of the hydrogen bond to decrease. Microsolvation of the hydrogen-bonded complex does not affect the strength of the low-barrier hydrogen bond very much. Small variations in the structure of the LBHB results in a decrease in hydrogen-bond strength. Increasing the effective polarity of the cavity surrounding the LBHB was found to have a significant impact on the strength of the hydrogen bond. Implications for enzyme catalysis are discussed. (C) 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1345-1352, 1998.