The proposed work focuses on (a) understanding how natural multimetallic clusters operate as active sites in metalloenzymes, and (b) using synthetic multimetallic clusters for productive chemical synthesis. Many metalloenzymes feature multimetallic clusters as active sites for catalyzing multielectron/multiproton transformations of gaseous small molecules, including cases of environmental significance to human health like atmospheric regulation of carbon dioxide and nitrous oxide. In many cases, these multimetallic clusters have unusual compositions and geometries, and so the chemical reactivity patterns have not been mapped out in laboratory settings. This proposal aims to achieve that for several multimetallic active sites, including the tetrametallic active site of nitrous oxide reductase and the heterobimetallic active site of carbon monoxide dehydrogenase, using synthetic model studies based on the PI’s established expertise in this area. Additionally, lessons about how these natural multimetallic clusters operate will be applied to develop synthetic multimetallic catalysts for C-C and C-X bond-forming reactions of relevance to pharmaceutical synthesis. The benefits of developing this catalytic paradigm for synthetic organic chemistry include emergence of reactivity and selectivity patterns that are complementary to established mononuclear catalyst systems, as well as the advancement of a bio-inspired tool to design earth-abundant metal catalysts that improve the sustainability of synthetic technologies in the pharmaceutical industry.