LAUSR

Abstract Biological sensor molecules for oxidative stress often rely on the oxidation of thiols to sulfenic acid intermediates. How this transformation induces a physiological response often relies on the fate of sulfenic acid. Sulfenic acids will react with other biologically relevant nucleophiles such as amines, thiols, and thiolates. In the presence of excess oxidants, the sulfenic acid can be further oxidized. The free energy of reaction (ΔG) and free energies of activation (ΔG‡) were determined for the reactions of sulfenic acid with amines, thiols, and thiolates. The methods employed included B3LYP, B3P86, HF, M06-2X, and MP2, and the effect of water solvation on the reactions was estimated using the integral equation formulation of the polarizable continuum model (IEF-PCM). A front-side approach of the sulfenic acid for amines, thiols, and thiolates was observed. In addition to front-side attack, a back-side transition state was converged for the more nucleophilic thiolates in several cases.