World Wide Web-Based Calculation of Substituent Parameters for QSAR Studies

Abstract

In the classical Hansch-Fujita correlation analysis¹ properties of molecules under study are quantified with help of hydrophobic, electronic and steric substituent parameters. In actual calculations these parameters are usually manually extracted from various data tables². This approach, however, has numerous disadvantages, most notably low quality of data for rare functional groups and unavailability of parameters for many important substituents. Therefore a web-based system enabling interactive calculation of important substituent parameters for any organic functional group was developed. Properties calculated include hydrophobic, electronic and steric ones. Hydrophobic properties are represented by octanol-water partition coefficient (π constant) and molar refractivity. Both these parameters are calculated according to the methodology of Ghose and Crippen³ based on the sum of atomic hydrophobicity contributions. Comparison of calculated and experimental² π constants for a set of 256 substituents yielded the following correlation (see also Fig. 1).