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

Abstract

Quantum chemical parameters such as LUMO energy, HOMO energy, ionization energy ( I ), electron affinity ( A ), chemical potential (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>μ</mml:mi></mml:math>), hardness (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>η</mml:mi></mml:math>) electronegativity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>χ</mml:mi></mml:math>), philicity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msup><mml:mi>ω</mml:mi><mml:mi>α</mml:mi></mml:msup></mml:mrow></mml:math>), and electrophilicity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>ω</mml:mi></mml:math>) 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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mrow><mml:mtext>pIGC</mml:mtext></mml:mrow><mml:mrow><mml:mn>50</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>) 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 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>ω</mml:mi></mml:math>) and energy of the lowest unoccupied molecular orbital (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>E</mml:mi><mml:mrow><mml:mtext>LUMO</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>). A comparison is made towards the toxicity predicting the ability of electrophilicity (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>ω</mml:mi></mml:math>) versus<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mi>E</mml:mi><mml:mrow><mml:mtext>LUMO</mml:mtext></mml:mrow></mml:msub></mml:mrow></mml:math>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<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mrow><mml:mtext>IGC</mml:mtext></mml:mrow><mml:mrow><mml:mn>50</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>from mg/L to molarity and by removing the racemates and the diastereoisomers from the data set.