Prediction of hydrogen bond basicity from computed molecular electrostatic properties: implications for comparative molecular field analysis

Computed molecular electrostatic properties have been evaluated as predictors of hydrogen bond basicity for a set of heterocycles with nitrogen as the hydrogen bond acceptor. The properties were (a) the electrostatic potential local minimum, Vmin, in the region of the nitrogen lone pair, (b) the electrostatic potential, Vβ(r), and (c) the magnitude of the electric field strength, |Fβ(r)|, at points along the lone pair axis, defined by the distance r from nitrogen. Vmin was found to be an excellent predictor of hydrogen bond basicity. The ability of the other parameters to fit the data was maximised at r= 1.4 Å for Vβ(r) and at r= 2.5 Å for |Fβ(r)| which has implications for Comparative Molecular Field Analysis.