Redox-neutral, metal-free tryptophan labeling of polypeptides in hexafluoroisopropanol (HFIP).

Despite the unmet needs for chemical tools to study biological roles of tryptophan in living systems, there has been a lack of chemical modification methods for tryptophan residues that can be used in cellular environments. Driven by a preliminary computational study of our previous research, this work experimentally examined our hypotheses to translate the metal-catalyzed tryptophan modification method in hexafluoroisopropanol (HFIP) into a metal-free process. While one of the hypotheses merely confirmed the superiority of the thiophene-ethanol reagent developed in the previous report, the second hypothesis resulted in the identification of a trifluoroborate salt and an acidic ionic liquid as alternatives for the catalysis.