Nitrosation, Thiols, and Hemoglobin: Energetics and Kinetics

[Image: see text] Nitrosothiols are powerful vasodilators. Although the mechanism of their formation near neutral pH is an area of intense research, neither the energetics nor the kinetics of this reaction or of subsequent reactions have been addressed. The following considerations may help to guide experiments. (1) The standard Gibbs energy for the homolysis reaction RSNO → RS(•) + NO(•)(aq) is +110 ± 5 kJ mol(–1). (2) The electrode potential of the RSNO, H(+)/RSH, NO(•)(aq) couple is −0.20 ± 0.06 V at pH 7. (3) Thiol nitrosation by NO(2)(–) is favorable by 37 ± 5 kJ mol(–1) at pH 7. (4) N(2)O(3) is not involved in in vivo nitrosation mechanisms for thermodynamic — its formation from NO(2)(–) costs 59 kJ mol(–1) — or kinetic — the reaction being second-order in NO(2)(–) — reasons. (5) Hemoglobin (Hb) cannot catalyze formation of N(2)O(3), be it via the intermediacy of the reaction of Hb[FeNO(2)](2+) with NO(•) (+81 kJ mol(–1)) or reaction of Hb[FeNO](3+) with NO(2)(–) (+88 kJ mol(–1)). (6) Energetically and kinetically viable are nitrosations that involve HNO(2) or NO(•) in the presence of an electron acceptor with an electrode potential higher than −0.20 V. These considerations are derived from existing thermochemical and kinetics data.