Steric Parameters Useful for the Study of Quantitative Structure-Activity Relationships : Calculation by Means of a Through-Space Interaction Model

Abstract

Various steric parameters used for the analysis of quantitative structure-activity relationships (QSAR) were examined in relation to CNDO/2 molecular orbital calculations. The through-space interaction energies ε^T_H and ε^T_X (see text for physical significance) among the atoms consisting of the outside part of [C(R₁R₂R₃)·C(OH)(OH₂)(OC₂H₅)]⁺ were calculated and employed as an index describing the steric effect. The structure was considered to be the transition state intermediate in the acid hydrolysis of C (R₁R₂R₃)·COO-C₂H₅. The correlation of ε^T_H or ε^T_X with steric parameters commonly used in QSAR studies was examined in detail. The characteristics of such steric parameters as E^C_S, E_S, molar volume, molar refractivity, parachor, ε^T_H and ε^T_X and discussed in relation to their usefulness for QSAR studies.