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

Abstract EN

Quantum chemical parameters such as LUMO energy, HOMO energy, ionization energy (I), electron affinity (A), chemical potential (μ), hardness (η) electronegativity (χ), philicity (ωα), 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 (pIGC50) 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 (ELUMO).

A comparison is made towards the toxicity predicting the ability of electrophilicity (ω) versus ELUMO 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 IGC50 from mg/L to molarity and by removing the racemates and the diastereoisomers from the data set.