Permanent-Charge Generation Derivatization for the Analysis of Thiols by “Soft” Ionization Mass Spectrometry Methods

A new method is proposed for the permanent-charge generation derivatization of thiols of different structures by a reaction with haloalkanes and dibromides. It was shown that 1,4-dibromobutane and 1,2-xylylene dibromide are the most effective alkylating agents, providing the formation of a stable five-membered ring with a positively charged sulfur atom. Such cations are readily detected by electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry. Sulfonium cations were further studied by tandem mass spectrometry using collision-induced dissociation (CID). Typical and specific CID directions for cyclic cations formed from thiols of different structures are revealed. They can be used to identify and quantify thiol analytes by the selected reaction monitoring method.