Electrochemistry at the Edge of Reason: Chalcogen-Based Redox Systems in Biochemistry and Drug Design

Abstract

Abstract In Biology, numerous cellular signalling and control networks are centred around redox active chalcogen species, such as the thiol group of cysteine, the sulfide of methionine and the selenol(ate) of the unusual amino acid selenocysteine. These amino acids form part of peptides, proteins and enzymes, which they endow with a distinct (i.e. chalcogen) redox activity. Compared to the biological redox chemistry of metal ions (e.g. iron, copper, manganese), the redox behaviour of such chalcogen-based systems is considerably more diverse, complex and difficult to study. Not surprisingly, there have been few interactions between electrochemists and biological chalcogen redox chemists in the past. Nonetheless, electrochemistry provides several interesting leads: Impedance measurements enable cell biologists to ‘watch cells grow’ in real time and in a continuous manner, which forms the basis for innovative drug profiling. Voltammetry can be used to monitor the formation of (oxygen and nitrogen based) reactive species at the level of individual macrophages without the need of elaborate staining techniques. At the same time, Cyclic Voltammetry provides access to the redox properties of various cysteine proteins and enzymes, and hence may assist in unravelling some of the remaining mysteries of the cellular thiolstat. And finally, electrochemical methods are extraordinarily powerful and useful in the characterization and ultimately also the design of redox-modulating natural products and drugs, including potential antioxidants and anticancer agents.