Three‐Dimensional, Quantitative‐Structure‐Property‐Relationship Study of Aqueous Solubility for Phenylsulfonyl Carboxylates Using Comparative‐Molecular‐Field Analysis and Comparative‐Molecular‐Similarity‐Indices Analysis

Abstract

With both the comparative‐molecular‐field analysis (CoMFA) and the comparative‐molecular‐similarity‐indices analysis (CoMSIA), the paper describes two five‐component, three‐dimensional, quantitative‐structure‐property‐relationship (3D‐QSPR) models for the aqueous solubility logS W (S W, mol·L‐1) of 52 phenylsulfonyl carboxylates. Two models yield the leave‐one‐out cross‐validated correlation coefficient q 2 values 0.851 and 0.821, and the conventional correlation coefficient r 2 values 0.963 and 0.929, respectively. The achievement of high q 2 and r 2 values of the CoMFA model indicates the significance of correlation of steric and electrostatic fields with the aqueous solubility. The key features in the CoMFA contour maps are critical to trace the important properties and gain insight to the solvation mechanism of tested compounds. The quality of CoMSIA model is slightly lower than that of CoMFA in terms of q 2 and r 2 values. Not requiring molecular superposition, CoMSIA may be faster than CoMFA in data processing.