QSPR of antioxidant phenolic compounds using quantum chemical descriptors

Abstract

Accelerated systemic free radical production poses a serious problem to healthy living. Since long, phenolic antioxidants have been studied for their ability to react with these toxic radicals. The present work deals with a series of substituted phenolic derivatives with a wide range of antioxidant property data. Quantitative structure–property relationship models have been developed correlating the antioxidant properties of these molecules with quantum chemical descriptors such as Mulliken charges of the common atoms and quantum topological molecular similarity indices of the common bonds. Models were developed based on the training set compounds, and were subsequently validated externally using the test set molecules. The results infer that substituents having a positive mesomeric effect increase the electron density over the phenolic oxygen and reduce the aromatic delocalisation of the lone pair of electron on the phenolic oxygen, thereby enabling effective interaction of the phenolic proton with the free radicals. Moreover, in addition to the mesomeric effect, the inductive effect of the different substituents also plays a crucial role for maintaining the overall charge distribution on the phenolic nucleus. On the basis of the predictive power and interpretability of the models, they may be further utilised for the design of more potent antioxidant molecules.

Keywords:

• QTMS
• QSPR
• phenolic derivatives
• antioxidants

Acknowledgements

This research work was supported in the form of a major research project to K.R. and a senior research fellowship to I.M. by the Indian Council of Medical Research (ICMR), New Delhi.