A refined model for prediction of hydrogen bond acidity and basicity parameters from quantum chemical molecular descriptors

摘要

Abraham's H-bonding parameters α_2~H and β_2~H have been described in terms of a minimal set of readily obtainable molecular descriptors. These parameters are basically equilibrium constants for complexation of acids with a reference base (α_2~H) or bases with a reference acid (β_2~H) measured in a non-hydrogen bonding solvent such as tetrachloromethane. The models were developed using partial least squares with a diverse dataset recently compiled by Platts et al., encompassing a wide range of hydrogen bond acids and bases in order to give a robust model. Although less accurate than the model of Platts et al. the descriptors used in this work avoid expensive supermolecule calculations, and allow prediction of hydrogen bonding characteristics from the isolated molecular wave function. These descriptors can then be generated for a large number of compounds, making them ideal for storage in a quantum isostere database (QID), the construction of which we initiated. The QID is a web-based tool developed to predict bioisosteric replacements in lead optimisation projects. The current descriptors provide hydrogen bonding characteristics of molecules of interest.