A Comparative Study of Two Quantum Chemical Descriptors in Predicting Toxicity of Aliphatic Compounds towards Tetrahymena pyriformis

Abstract

Quantum chemical parameters such as LUMO energy, HOMO energy, ionization energy ( I ), electron affinity ( A ), chemical potential ( μ ), hardness ( η ) electronegativity ( χ ), philicity ( ω α ), and electrophilicity ( ω ) of a series of aliphatic compounds are calculated at the B3LYP/6-31G(d) level of theory. Quantitative structure-activity relationship (QSAR) models are developed for predicting the toxicity ( pIGC 50 ) of 13 classes of aliphatic compounds, including 171 electron acceptors and 81 electron donors, towards Tetrahymena pyriformis . The multiple linear regression modeling of toxicity of these compounds is performed by using the molecular descriptor log P (1-octanol/water partition coefficient) in conjunction with two other quantum chemical descriptors, electrophilicity ( ω ) and energy of the lowest unoccupied molecular orbital ( E LUMO ). A comparison is made towards the toxicity predicting the ability of electrophilicity ( ω ) versus E LUMO as a global chemical reactivity descriptor in addition to log P . The former works marginally better in most cases. There is a slight improvement in the quality of regression by changing the unit of IGC 50 from mg/L to molarity and by removing the racemates and the diastereoisomers from the data set.