Peptide-based metalloporphyrin catalysts: unveiling the role of the metal ion in indole oxidation

Over the last decades, much effort has been devoted to the construction of protein and peptide-based metalloporphyrin catalysts capable of promoting difficult transformations with high selectivity. In this context, mechanistic studies are fundamental to elucidate all the factors that contribute to catalytic performances and product selectivity. In our previous work, we selected the synthetic peptide-porphyrin conjugate MnMC6*a as a proficient catalyst for indole oxidation, promoting the formation of a 3-oxindole derivative with unprecedented selectivity. In this work, we have evaluated the role of the metal ion in affecting reaction outcome, by replacing manganese with iron in the MC6*a scaffold. Even though product selectivity is not altered upon metal substitution, FeMC6*a shows a lower substrate conversion and prolonged reaction times with respect to its manganese analogue. Experimental and theoretical studies have enabled us to delineate the reaction free energy profiles for both catalysts, indicating different thermodynamic limiting steps, depending on the nature of the metal ion.

Automated summary

In the past few decades, efforts have been made to construct protein and peptide-based metalloporphyrin catalysts for selective and difficult transformations. Mechanistic studies are crucial to understand the factors influencing catalytic performances and product selectivity. Our previous work demonstrated the efficiency of the synthetic peptide-porphyrin conjugate MnMC6*a as a catalyst for indole oxidation. In this study, we investigated the role of the metal ion by replacing manganese with iron and found that although product selectivity remained unchanged, FeMC6*a showed lower substrate conversion and prolonged reaction times compared to MnMC6*a.