Catalytic activation of copper (II) salts on the reaction of peroxynitrite with propofol in alkaline medium

We report here on the role of copper (II) salts on the acceleration of peroxynitrite (ONOO−) decomposition and ONOO− reaction with the anaesthetic agent propofol (2,6-diisopropylphenol) in alkaline medium. We observed a strong acceleration of the ONOO− decomposition in alkaline medium in the presence of copper (I and II) salts. After 18 h of ONOO− reaction with propofol, we observed nitrosated, nitrated, and oxidized (quinone and diphenylquinone) derivatives of propofol, but in the presence of Cu(II) (20% molar vs ONOO−), the yields of quinone and nitrosopropofol strongly increased. We also observed that the temperature and the atmosphere influenced the effects of Cu(II) on ONOO− reactions with propofol: low temperatures promoted nitrosation and high temperatures promoted oxidation; O2 atmosphere increased the general reactivity and the yield of nitrated and oxidized products. We highlighted the influence of Cu(II) salts on the radical character of the reaction by direct EPR technique. The exact mechanism of the Cu(II) catalysis remains unexplained, but we suggest the formation of a copper complex with propofol or, more probably, the oxidation of ONOO− into ONOO by copper ions promoting the formation of quinone and nitrosopropofol according to a previously reported mechanism [M. Cudic, C. Ducrocq, Transformations of 2,6-diisopropylphenol by NO-derived nitrogen oxides, particularly peroxynitrite, Nitric Oxide 4 (2000) 147-156].