Understanding How Highly Covalent Nickel-Thiolate Interactions Modulate the Reactivity of Model Metalloenzymes

Metal-thiolate interactions are prevalent across biology in electron transfer (ET) proteins and reductive nickel enzymes, including hydrogenases, carbon monoxide dehydrogenase (CODH), acetyl coenzyme A synthase (ACS), and others. The covalent nature of metal-thiolate bonds has been extensively investigated in the context of ET rates and reduction potentials. In this work, we will discuss how such covalency can promote substrate binding and redox catalysis. Protein-based models with at least one highly covalent metal-thiolate bond have been developed to mimic CODH and ACS. Both the basicity and polarizability of the thiolate ligand contribute to substrate binding, and a detailed electronic structure investigation of these species will be presented. The divergent reactivity towards small molecule substrates and the importance of the thiolate ligand for driving multielectron redox chemistry will be related to the high degrees of selectivity, activity, and efficiency seen in native metalloenzymes, with potential applications in catalyst design.