Oxidation and Peroxygenation of C–H Bonds by Artificial Cu Peptides (ArCuPs): Improved Catalysis via Selective Outer Sphere Modifications

Abstract

We report the construction of de novo designed artificial Cu peptides (ArCuPs) that support the oxidation and peroxygenation of C–H bonds of abiotic substrates via electrochemically generated Cu–oxygen species. Selective alteration of outer sphere steric at the d layers above and below the Cu site allows facilitated access of substrates, where a more pronounced effect on catalysis is observed when space is created at the d layer below the Cu site via Ile to Ala mutation. Independent spectroscopic studies revealed that the rate of formation of the Cu–oxygen species and the spectroscopic feature of the most active variant is distinct compared to the other ArCuPs. Systematic alteration of outer sphere hydrophobicity led to a correlated tuning of the T2 Cu site redox potentials by ∼80 mV. The enhanced activity of the ArCuP variant is attributed to a combination of steric effect that allows easy access of substrates, the nature of Cu–oxygen species, and stability of this construct compared to others, where Ile to Ala mutation unexpectedly leads to a higher thermostability that is further augmented by Cu binding.