SHORT, STRONG HYDROGEN-BONDS IN THE GAS-PHASE AND IN SOLUTION - THEORETICAL EXPLORATION OF PKA MATCHING AND ENVIRONMENTAL-EFFECTS ON THE STRENGTHS OF HYDROGEN-BONDS AND THEIR POTENTIAL ROLES IN ENZYMATIC CATALYSIS

Short, strong hydrogen bonds are common in charged systems in the gas phase, but the importance of such bonding in enzymatic catalysis has b een the subject of considerable controversy. Confusion has arisen abou t the relationship among bond strength, the ''low-barrier'' or ''no-ba nier'' nature of the hydrogen bonding, the role of pK(a), matching, th e covalent or electrostatic nature of the bonding, and the role of sol vation on the strengths of these types of hydrogen bonds. We have atte mpted to strip away the ''Alice in Wonderland'' quality of the definit ions in this field by defining, through high-level calculations, when short-strong hydrogen bonds do and do not occur. The strengths and geo metries of several types of hydrogen bonds involving anions have been investigated by ab initio quantum mechanical calculations. For a serie s of enols hydrogen-bonded to enolates, the strengths of the short, st rong gas-phase hydrogen bonds are linearly related to the differences between the proton affinities (PA) of the two anions which share the p roton. The bond strength is also related to the O ... O distance betwe en them. There is bo discontinuity at Delta PA = 0, ana hydrogen-bondi ng becomes even stronger in a computational experiment when the PA of the II-bond acceptor exceeds that of the donor. ''Low-barrier'' hydrog en bonds with single-well minima after inclusion of zero-point energie s occur when Delta PA is near 0, but no special stability accrues when the double-well minimum becomes single-well. The maleic/fumaric and m esaconic/citraconic systems studied by Drueckhammer have been investig ated computationally. The influence of solvation on hydrogen-bond stre ngth was studied using solvent cavity models. Small increases in diele ctric constant from the gas-phase value (epsilon = 1) rapidly reduce t he strengths of charged hydrogen bonds. Short, strong hydrogen bonds o ccur only with charged systems, and only then in nonpolar (epsilon < 1 0) environments; Alternative mechanisms are often available to account for enzymatic catalysis; the example of orotidine monophosphate decar boxylase is discussed.