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

Journal of Molecular Graphics and Modelling 24 (2006) 219–226 /locate/JMGM Quantitative study of electrostatic and steric effects on physicochemical property and biological activity Yi-Yu Cheng *, Hua Yuan Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310027, China Received 7 July 2005; received in revised form 18 August 2005; accepted 18 August 2005 Available online 22 September 2005 Abstract 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 heterocycli