The para-fluoro-thiol ligation in water

Abstract

The para-fluoro-thiol reaction (PFTR) is performed for the first time in aqueous media. A water-soluble model scaffold based on poly(N,N-dimethylacrylamide) and incorporating pentafluorostyrene units was synthesized by nitroxide-mediated copolymerization. The effect of pH, temperature, and stoichiometry on the solution-phase kinetics of the PFTR for side-chain modification is studied by ¹⁹F and ¹H NMR spectroscopy using mercaptoethanol as a model thiol. While the reaction can occur from pH 11 on, increasing pH greatly accelerates the reaction. Yields >90% are achieved at pH 12 and 40 °C in 24 h, while quantitative coupling is reached at pH 13 and 50 °C in less than 16 h. Grafting of a cysteine-containing peptide on tissue culture plates demonstrated by ToF-SIMS evidences the benefit of performing this reaction in aqueous media for surface functionalization of materials prone to degradation in organic solvents.