Cyclodesulfurization reaction catalyzed by artificial metalloenzymes containing cobalt protoporphyrin IX cofactors under green aqueous solvent conditions

Abstract

In this study, we report the development of an environmentally friendly artificial Vitreoscilla hemoglobin (VHb) for the synthesis of 3-amino-[1,2,4]-triazole and [4,3-a]pyridine. We employed a strategy that combines porphyrin substitution with axial ligand mutations to create a highly active VHb oxidase containing cobalt protoporphyrin IX (Co(ppIX)), while simultaneously introducing double mutations (H85Y, P54C). This artificial enzyme catalyzes the cyclization desulfurization reaction of the corresponding 2-hydrazinopyridine and isothiocyanate in PBS containing 10% DMSO (v/v) under aerobic conditions at room temperature. This method addresses the limitations of catalytic activity observed in natural hemoglobin and provides a novel pathway for the green synthesis of nitrogen-containing heterocycles. Furthermore, the porphyrin ligand substitution strategy broadens the application scope of artificial metalloenzymes in non-natural reactions.