S-Nitrosoglutathione exhibits greater stability than S-nitroso-N-acetylpenicillamine under common laboratory...

S-Nitrosothiols (RSNOs) such as S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP) are susceptible to decomposition by stimuli including heat, light, and trace metal ions. Using stepwise isothermal thermogravimetric analysis (TGA), we observed that NO-forming homolytic cleavage of the S-N bond occurs at 134.7 ± 0.8 °C in GSNO and 132.8 ± 0.9 °C in SNAP, contrasting with the value of 150 °C that has been previously reported for both RSNOs. Using mass spectrometry (MS), nuclear magnetic resonance (NMR), and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), we analyzed the decomposition products from TGA experiments. The organic product of GSNO decomposition was glutathione disulfide, while SNAP decomposed to form N-acetylpenicillamine disulfide as well as other products, including tri- and tetrasulfides. In addition, we assessed the relative solution stabilities of GSNO and SNAP under common laboratory conditions, which include variable temperature, pH, and light exposure with rigorous exclusion of trace metal ions by chelation. GSNO exhibited greater stability than SNAP over a 7-day period except in one instance. Both RSNOs demonstrated an inverse relationship between solution stability and temperature, with refrigeration considerably extending shelf life. A decrease in pH from 7.4 to 5.0 also enhanced the stability of both RSNOs. A further decrease in pH from 5.0 to 3.0 resulted in decreased stability for both RSNOs, and is notably the only occasion in which SNAP proved more stable than GSNO. After 1 h of exposure to overhead fluorescent lighting, both RSNOs displayed high susceptibility to light-induced decomposition. After 7 h, GSNO and SNAP decomposed 19.3 ± 0.5% and 30 ± 2%, respectively.