The use of the density threshold value as a shape descriptor on the toxicity of benzene derivatives

Abstract

The Quantitative Structure Activity Relationship (QSAR) method, based on the three-dimensional (3D) shapes of formal molecular bodies and computed molecular descriptors, was used to calculate the octanol-water partition coefficient (logKow) of benzene derivatives to indicate their toxicity. The aim of this study is to use electron density threshold values as descriptors in predicting toxicology of benzene derivatives. Through Density Domain Analysis (DDA), a shape fragment database of benzene derivatives was constructed. Electron density threshold values were generated from molecular isodensity counter surfaces (MIDCO) of benzene molecules that were calculated at the ab initio HF/6-31G* level. Multiple linear regression analyses were performed, and two successful QSAR models were obtained. The analysis of variance (ANOVA) ratio for regression (F) and the significance of F (Fs) values was also used to evaluate the predictive power of the established QSAR models. The results indicate that the electron density threshold value, “a”, gives a specific description of the 3D shape of electron density clouds. These models were further analyzed by three 3D shape features as one local and two global descriptors based on the electron density threshold “a” value. The global and local properties of benzene derivatives were found to exhibit similar toxicity behaviors.