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 been the subject of considerable controversy. Confusion has arisen about the relationship among bond strength, the "low-barrier" or "no-banier" nature of the hydrogen bonding, the role of pK(a), matching, the covalent or electrostatic nature of the bonding, and the role of solvation on the strengths of these types of hydrogen bonds. We have attempted to strip away the "Alice in Wonderland" quality of the definitions in this field by defining, through high-level calculations, when short-strong hydrogen bonds do and do not occur. The strengths and geometries of several types of hydrogen bonds involving anions have been investigated by ab initio quantum mechanical calculations. For a series of enols hydrogen-bonded to enolates, the strengths of the short, strong gas-phase hydrogen bonds are linearly related to the differences between the proton affinities (PA) of the two anions which share the proton. The bond strength is also related to the O ... O distance between them. There is bo discontinuity at Delta PA = 0, ana hydrogen-bonding becomes even stronger in a computational experiment when the PA of the II-bond acceptor exceeds that of the donor. "Low-barrier" hydrogen bonds with single-well minima after inclusion of zero-point energies occur when Delta PA is near 0, but no special stability accrues when the double-well minimum becomes single-well. The maleic/fumaric and mesaconic/citraconic systems studied by Drueckhammer have been investigated computationally. The influence of solvation on hydrogen-bond strength was studied using solvent cavity models. Small increases in dielectric constant from the gas-phase value (epsilon = 1) rapidly reduce the strengths of charged hydrogen bonds. Short, strong hydrogen bonds occur only with charged systems, and only then in nonpolar (epsilon < 10) environments; Alternative mechanisms are often available to account for enzymatic catalysis; the example of orotidine monophosphate decarboxylase is discussed.