Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible Light-Triggered Radical Photocages

27 July 2023, Version 2
This content is an early or alternative research output and has not been peer-reviewed by Cambridge University Press at the time of posting.


Described here is a photo-decaging approach to radical trifluoromethylation of biomolecules. This was accomplished by designing a quinolinium sulfonate ester that, upon absorption of visible light, achieves decaging via photolysis of the sulfonate ester to ultimately liberate free trifluoromethyl radicals that are trapped by π-nucleophiles in biomolecules. This photo-decaging process enables protein and protein-interaction mapping experiments using trifluoromethyl radicals that require only one second reaction times and low photo-cage concentrations. In these experiments, aromatic side chains are labelled in an environmentally dependent fashion, with selectivity observed for tryptophan (Trp), followed by histidine (His) and tyrosine (Tyr). Scalable peptide trifluoromethylation through photo-decaging is also demonstrated, where bespoke peptides harboring trifluoromethyl groups at tryptophan residues can be synthesized with five to seven minute reaction times and good yields.


Protein mapping

Supplementary materials

Supplementary file contains experimental procedures and characterization for photocage synthesis, protein trifluoromethylation, preparative scale peptide trifluoromethylation, mechanistic studies, computational analysis, and small molecule characterization.


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