Noncytotoxic catalytic enzyme functional mimics including cyanide poisoning antidotes

Abstract

Functional mimics of enzymes have a long history with bioinorganic chemists. Early motivation for creating these mimics was strongly based on the study of the enzyme reaction mechanisms. In more recent times, interest in functional mimics has expanded to catalytic metallodrugs, where the mimics are deliberately designed for specific catalytic reactions intended for therapeutic purposes. In vivo, noncytotoxic catalysis targets reactions designed to activate prodrugs. Natural or de novo proteins were developed for artificial enzyme catalysis of Diels-Alder reactions, or as artificial oxygenase mimics. Novel sulfur-rich catalytic superoxide dismutase (SOD) mimics were discovered as antioxidants. Detoxification of elevated levels of cyanide where the natural rhodanese enzyme becomes inefficient in turnover rates and bioavailability is particularly attractive for sulfur-rich molybdenum clusters. This brief overview includes metal catalysts performing abiotic reactions in vivo disguised by attachment to cell surfaces, as artificial enzymes, and interesting new sulfur-rich complexes performing SOD reactions or neutralizing cyanide.