Barrett Jacob A, Li Zhi, Garcia John V, Wein Emily, Zheng Dongyun, Hunt Camden, Ngo Loc, Sepunaru Lior, Iretskii Alexei V, Ford Peter C
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
Department of Chemistry and Environmental Sciences, Lake Superior State University, Sault Sainte Marie, MI 49783, USA.
R Soc Open Sci. 2021 Nov 10;8(11):211022. doi: 10.1098/rsos.211022. eCollection 2021 Nov.
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 HO, it is critical to assess the underlying CO release mechanism(s). In this context, a quantitative mechanistic investigation of the HO oxidation of the water-soluble model complex -[Mn(CO)(Br)(bpCO)], (, bpCO = 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 HO oxidation of via pH-dependent kinetics that are first-order both in [] and in [HO]. 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.
过氧化氢与金属羰基化合物反应的动力学很少受到关注。鉴于有报道称，在羰基锰与内源性过氧化氢反应时，缺氧肿瘤细胞中会释放出治疗水平的一氧化碳，因此评估潜在的一氧化碳释放机制至关重要。在此背景下，在生理相关条件下对水溶性模型配合物[Mn(CO)(Br)(bpCO)]（bpCO = 2,2'-联吡啶-4,4'-二羧酸二价阴离子）的过氧化氢氧化进行了定量机理研究。表征此类途径对于评估氧化还原介导的一氧化碳释放作为抗癌策略的可行性至关重要。目前的实验研究表明，在过氧化氢氧化时，通过与[HO]均呈一级反应的pH依赖性动力学，大约会释放出2.5当量的一氧化碳。采用密度泛函计算来评估所提出反应机制中的关键中间体。根据这些途径与一氧化碳释放基团进行生理一氧化碳递送的相关性对其进行了讨论。
