QSAR study of aromatic organochalcogens with glutathione peroxidase - like antioxidant activity

Abstract

The molecular orbital energies and atomic Electron Densities (ED) of compounds that mimic the action of Glutathione Peroxidase (GPx), such as derivatives of alpha-(phenylselenenyl) keton (Ph-Se-R-1) and aromatic organochalcogens [Y-Ph-(X)(1-2)-Ph-Y], were calculated by ab initio Hartree-Fock/3-21G (d)(gas) basis set. Single and multiple linear regression models for two types of aromatic chalcogens were obtained with R-2 > 0.75 and q(pre)(2) > 0.63. For the a-(phenylselenenyl) keton and derivatives that react with Glutathione (GSH) via mixed selenenyl-sulfide compounds (R-Se-S-G), a high correlation was obtained between the calculated LUMO (Ph-Se-R-1) energies and experimentally measured GPx like antioxidant activities. Thus, it is recommended to use the LUMO (Ph-Se-R-1) energies of novel derivatives (Ph-Se-R-1) of alpha-(phenylselenenyl) keton in the prediction of GPx like catalytic antioxidant activities. For the aromatic organochalcogens [Y-Ph-(X)(1-2)-Ph-Y] that react with GSH mainly via chalcogen-oxide intermediates, the Electrochemical Oxidation Potential (Epa) values on the glassy carbon electrode in aqueous media, the HOMO [Y-Ph-(X)(1-2)-Ph-Y] energies, and the ED on chalcogens [ED(X)] were selected as good predictors of GPx like catalytic antioxidant activities.