Quantitative study of electrostatic and steric effects on physicochemical property and biological activity

The physicochemical properties and biological activities are highly dependent on the electrostatic and steric effects of compounds. The characterization of these structural features will help to elucidate the quantitative structure–property/activity relationship (QSPR/QSAR). In this paper, two novel structural descriptors, lone-pair electrons index (LEI) and molecular volume index (MVI) were developed to quantify the molecular electrostatic and steric effects, respectively. One of the most attractive traits of these two descriptors is that the calculation is very easy, especially for LEI, which only takes the heteroatoms into account. Four data sets on diverse physicochemical properties and biological activities were selected as examples to evaluate the utility of these descriptors. One or two-variable multiple linear regression (MLR) models against the four data sets obtained such correlation results as follows: correlation coefficient R = 0.9998 and standard deviation s = 0.095 for the partition coefficient of halide benzenes; R = 0.9689 and s = 0.248 for the toxicity of heterocyclic nitrogen-containing compounds to miracidium; R = 0.9645 and s = 0.209 for the antifungal activity of benzyl alcohols to aspergillus niger; R = 0.9530 and s = 0.206 for the toxicity of substituted phenols against tetrahymena pyriformis. Leave-one-out cross validation was also carried out to evaluate the stability of each model and good results were obtained.