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

Abstract

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, V_min, in the region of the nitrogen lone pair, (b) the electrostatic potential, V_β(r), and (c) the magnitude of the electric field strength, |F_β(r)|, at points along the lone pair axis, defined by the distance r from nitrogen. V_min 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 V_β(r) and at r= 2.5 Å for |F_β(r)| which has implications for Comparative Molecular Field Analysis.