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 H 2 O 2 , it is critical to assess the underlying CO release mechanism(s). In this context, a quantitative mechanistic investigation of the H 2 O 2 oxidation of the water-soluble model complex fac -[Mn(CO) 3 (Br)(bpCO 2 )] 2– , ( A , bpCO 2 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 H 2 O 2 oxidation of A via pH-dependent kinetics that are first-order both in [ A ] and in [H 2 O 2 ]. 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.

A Novel H2O2 Generator for Tumor Chemotherapy-Enhanced CO Gas Therapy

Carbon monoxide (CO) gas therapy is a promising cancer treatment. However, gas delivery to the tumor site remains problematic. Proper tunable control of CO release in tumors is crucial to increasing the efficiency of CO treatment and reducing the risk of CO poisoning. To overcome such challenges, we designed ZCM, a novel stable nanotechnology delivery system comprising manganese carbonyl (MnCO) combined with anticancer drug camptothecin (CPT) loaded onto a zeolitic imidazole framework-8 (ZIF-8). After intravenous injection, ZCM gradually accumulates in cancerous tissues, decomposing in the acidic tumor microenvironment, releasing CPT and MnCO. CPT acts as a chemotherapy agent destroying tumors and producing copious H2O2. MnCO can react with the H2O2 to generate CO, powerfully damaging the tumor. Both in vitro and in vivo experiments indicate that the ZCM system is both safe and has excellent tumor inhibition properties. ZCM is a novel system for CO controlled release, with significant potential to improve future cancer therapy.