The thermodynamics of thiol sulfenylation

► Reduction potentials for sulfenylation were calculated at low computational cost. ► For analogous reactions, the reaction energy correlates with the free energy. ► Polar residues thermodynamically drive the oxidation of thiolate. ► A hydrophobic environment thermodynamically drives the thiol oxidation. ► In human peroxiredoxin, Arg127 determines the sulfenylation thermodynamics