A Simple Computational Tool for Accurate, Quantitative Prediction of One-Electron Reduction Potentials of Hypoxia-Activated Tirapazamine Analogues.

A Simple Computational Tool for Accurate, Quantitative Prediction of One-Electron Reduction Potentials of Hypoxia-Activated Tirapazamine Analogues. J Pharm Pharm Sci. 2020;23:231-242 Authors: Elsaidi HR, Wiebe LI, Kumar P Abstract The reduction potentials of bioreductively-activated drugs represent an important design parameter to be accommodated in the course of creating lead compounds and improving the efficacy of older generation drugs.  Reduction potentials are traditionally reported as single-electron reduction potentials, E(1), measured against reference electrodes under strictly defined experimental conditions.  More recently, computational chemists have described redox properties in terms of a molecule's highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), in electron volts (eV).  The relative accessibility of HOMO/LUMO data through calculation using today's computer infrastructure and simplified algorithms make the calculated value (LUMO) attractive in comparison to the accepted but rigorous experimental determination of E(1).  This paper describes the correlations of eV (LUMO) to E(1) for three series of bioreductively-activated benzotriazine di-N-oxides (BTDOs), ring-substituted BTDOs, ring-added BTDOs and a selection of aromatic nitro compounds. The current computational approach is a closed-shell calculation with a single optimization.  Gas phase geometry optimization was followe...
Source: J Pharm Pharm Sci - Category: Drugs & Pharmacology Authors: Tags: J Pharm Pharm Sci Source Type: research