Prediction and Measurement of Redox Properties of Drugs and Biomolecules

Abstract

Selective activation of drugs via redox processes is now firmly established, both at the clinical level with the widespread use of drugs such as metronidazole or chlorpromazine, and at the experimental stage with the search, for example, for hypoxic-specific chemotherapeutic agents active against solid tumours. Ionizing radiation by definition initiates redox processes, so the study of radiation-drug interactions has much to learn from, and contribute to, research with redox-active drugs not involving radiation. Quantitative measures of ease of reduction or of oxidation, of both drugs and biomolecules, are central to our understanding of molecular mechanisms and the search for new drugs. This paper outlines the basis for such measurements, emphasising the value of applying experience from wider fields to provide a framework for reliable prediction of redox properties. Since conventional measures of redox processes involving the transfer of two or more electrons are widely available in electrochemistry and bioenergetics, the redox couples discussed here are restricted to those involving only one electron, with a free radical as reductant or oxidant. Such radicals are increasingly recognised to be obligate intermediates in the activation of many drugs.