Elucidating Potential Energy Surfaces for Singlet O2 Reactions with Protonated, Deprotonated, and Di-Deprotonated Cystine Using a Combination of Approximately Spin-Projected Density Functional Theory and Guided-Ion-Beam Mass Spectrometry

The reactivity of cystine toward electronically excited singlet O2 (a1Δg) has been long debated, despite the fact that most organic disulfides are susceptible to oxidation by singlet O2. We report a combined experimental and computational study on reactions of singlet O2 with gas-phase cystine at different ionization and hydration states, aimed to determine reaction outcomes, mechanisms, and potential energy surfaces (PESs). Ion–molecule collisions of protonated and di-deprotonated cystine ions with singlet O2, in both the absence and the presence of a water ligand, were measured over a center-of-mass collision energy (Ecol) range from 0.1 to 1.0 eV, using a guided-ion-beam scattering tandem mass spectrometer. No oxidation was observed for these reactant ions except collision-induced dissociation at high energies. Guided by density functional theory (DFT)-calculated PESs, reaction coordinates were established to unravel the origin of the nonreactivity of cystine ions toward singlet O2. To account for mixed open- and closed-shell characters, singlet O2 and critical structures along reaction coordinates were evaluated using broken-symmetry, open-shell DFT with spin contamination errors removed by an approximate spin-projection method. It was found that collision of protonated cystine with singlet O2 follows a repulsive potential surface and possesses no chemically significant interaction and that collision-induced dissociation of protonated cystine is dominated by loss of water and CO. Collision of di-deprotonated cystine with singlet O2, on the other hand, forms a short-lived electrostatically bonded precursor complex at low Ecol. The latter may evolve to a covalently bonded persulfoxide, but the conversion is blocked by an activation barrier lying 0.39 eV above reactants. At high Ecol, C–S bond cleavage dominates the collision-induced dissociation of di-deprotonated cystine, leading to charge-separated fragmentation. Cross section for the ensuing fragment ion H2NCH­(CO2–)­CH2SS• was measured as a function of Ecol, and the mechanism of charge-separated fragmentation was discussed. It was also found that the reaction of deprotonated cystine with singlet O2 follows a similar mechanism as that of di-deprotonated cystine, but with an even higher activation barrier (0.72 eV).