UC Santa Barbara

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)(bpCO₂)]^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.