Effects of Ligand-Constraints on the Reactivity of Biomimetic Thiolate-Ligated Transition Metal Complexes

Abstract

The addition of steric constraints to thiolate-ligated transition metal complexes was explored herein, with particular focus on the addition of a tertiary amine to the backbone to form complexes [FeII(S2Me2N2NMe(Pr,Pr))] and [CoII(S2Me2N2NMe(Pr,Pr))]. The coordination environment of these complexes serves as a biomimetic model applicable to cysteinate-ligated enzymes cysteine dioxygenase (CDO), nitrile hydratase (NHase), and Isopenicillin-N-synthase (IPNS). The dioxygen reactivity of these complexes was investigated and multiple dioxygen derived intermediates were isolated and characterized in both the Fe and Co systems. The intermediates included a hydroxy-sulfenate -FeIII species, [FeIII(S-O)SMe2N2NMe(Pr,Pr))(OH)], applicable to the proposed CDO mechanism, which indicated the formation of an unobserved peroxythiolate species [FeII(S-OO)SMe2N2NMe(Pr,Pr))]. Sulfur oxygenation processes are of particular interest in studying both CDO, which transforms cysteine to cysteine sulfinic acid, and NHase, which contains two oxygenated cysteines in its coordination sphere. Two singly-oxygenated sulfenate species [FeIII(η2-SMe2O)(SMe2N2NMe(Pr,Pr)]+ and [CoIII(η2-SMe2O)(SMe2N2NMe(Pr,Pr))]+ were crystallographically characterized from the addition of oxo-atom donor PhIO. The kinetics of both the dioxygen reactivity and oxo-atom donor addition were explored, and revealed a spin-state dependence for the formation of [FeIII(η2-SMe2O)(SMe2N2NMe(Pr,Pr)]+. In order to study the effects of steric constraints on the reactivity of thiolate-ligated transition metal complexes, the Fe/Co sterically constrained complexes and products were compared to their predecessor analogues that contained a secondary amine in the coordination sphere. To further explore and isolate the effect of the thiolate in the inner coordination sphere, DFT calculations of a thiolate-ligated Mn-alkylperoxo species and an alkoxide-ligated Mn-alkylperoxo species were carried out. The alkoxide-ligated RO-MnIII-OOR complex was an order of magnitude more stable than its thiolate-ligated RS-MnIII-OOR derivative. The highest occupied molecular orbital of the thiolate-ligated derivative possesses significant sulfur character and π-backdonation from the thiolate competes with π-backdonation from the peroxo π*(O−O). DFT-calculated Mulliken charges show that the Mn ion Lewis acidity of alkoxide-ligated RO-MnIII-OOR (+0.451) is greater than that of thiolate-ligated RS-MnIII-OOR (+0.306), thereby facilitating π-backdonation from the antibonding peroxo π*(O−O) orbital and increasing its stability. This helps to explain why the photosynthetic oxygen-evolving Mn complex, which catalyzes O−O bond formation as opposed to cleavage, incorporates O- and/or N-ligands as opposed to cysS-ligands.