Redox-mediated carbon monoxide release from a manganese carbonyl-implications for physiological CO delivery by CO releasing moieties

The dynamics of hydrogen peroxide reactions with metal carbonyls have received little attention. Given reports that therapeutic levels of carbon monoxide are released in hypoxic tumour cells upon manganese carbonyls reactions with endogenous H2O2, it is critical to assess the underlying CO release mechanism(s). In this context, a quantitative mechanistic investigation of the H2O2 oxidation of the water-soluble model complex fac-[Mn(CO)(3)(Br)(bpCO(2))](2-), (A, bpCO2(2-) = 2,2 '-bipyridine-4,4 '-dicarboxylate dianion) was undertaken under physiologically relevant conditions. Characterizing such pathways is essential to evaluating the viability of redox-mediated CO release as an anti-cancer strategy. The present experimental studies demonstrate that approximately 2.5 equivalents of CO are released upon H2O2 oxidation of A via pH-dependent kinetics that are first-order both in [A] and in [H2O2]. Density functional calculations were used to evaluate the key intermediates in the proposed reaction mechanisms. These pathways are discussed in terms of their relevance to physiological CO delivery by carbon monoxide releasing moieties.

Automated summary

This study quantitatively investigated the mechanism of hydrogen peroxide reactions with metal carbonyls to evaluate the CO release mechanism under physiological conditions. The results showed that approximately 2.5 equivalents of CO are released upon oxidation of the model complex A by H2O2, with kinetics dependent on pH. Density functional calculations were used to assess the key intermediates in the proposed reaction pathways and their relevance to physiological CO delivery by carbon monoxide releasing moieties.