Hydrogen bonding parameters for QSAR: Comparison of indicator variables, hydrogen bond counts, molecular orbital and other parameters

Abstract

Hydrogen bonding is an important property in drug and xenobiotic interaction with biota, and numerous attempts have been made to quantify it for use in quantitative structure - activity relationships. These attempts are reviewed, and their ability to model hydrogen bond donor ability examined by correlating them with the melting points of a series of anilines, known to be very dependent on hydrogen bonding. The best model was found to be a two-parameter model involving the charge on the hydrogen bonding hydrogen(s) and the energy of the lowest unoccupied molecular orbital. These parameters were further tested successfully by using them to replace other hydrogen bonding parameters in a series of QSAR correlations.