The Outer-Coordination Sphere: Incorporating Amino Acids and Peptides as Ligands for Homogeneous Catalysts to Mimic Enzyme Function

Great progress has been achieved in the field of homogeneous transition metal-based catalysis; however, as a general rule these solution-based catalysts are still easily outperformed by their analogous enzyme counterparts, in terms of both rates and selectivity. This includes structural mimics of enzymatic active sites. This observation suggests that the features of the enzyme beyond the active site, i.e., the outer-coordination sphere, are important for enzymes' exceptional function. Directly mimicking the outer-coordination sphere requires the incorporation of amino acids and peptides as ligands for homogeneous catalysts. This effort has been attempted for many homogeneous catalysts which span the manifold of catalytic reactions including hydrogenation, hydroformylation, hydrogen production, oxygen activation, dioxygen transport, electron transfer, disproportionation of the superoxide anion radical, acylation, phosphorylation, esterification, ester hydrolysis, and hydrogen peroxide disproportionation. How much of the outer-coordination sphere to include in molecular catalysts and the preferential structural conformation of the appended section are long-standing questions. Synthetically incorporating an amino acid- or peptide-based outer-coordination sphere requires care to avoid unwanted side reactions with the large number of functional groups. Catalysis with amino acid or peptide containing catalysts requires careful consideration of solvent and pH to promote solubility, stabilize structure, optimize catalysis, and avoid catalyst degradation. This article reviews the current capability of synthesizing and characterizing this often challenging but very promising category of metal-based catalysts.