Investigation of the reaction of peroxynitrite with propofol at acid pH: Predominant production of oxidized, nitrated, and halogenated derivatives

Abstract

We reported here the reaction, in acidic conditions, of peroxynitrite (ONOO −) with the anaesthetic agent propofol (2,6-diisopropylphenol, PPF). The most interesting finding is that peroxynitrite is able to nitrate and to oxidize propofol leading to 4-nitropropofol, quinone, and diphenylquinone as the major products. More surprisingly, we also found that peroxynitrite is capable of halogenating propofol in the presence of halide ions, suggesting the formation of nitrosyl chloride (NOCl) or nitryl chloride (NO 2Cl) from the reaction of peroxynitrite with chloride ions. A significant enhancement of the halogenation yield is observed with a simultaneous decrease of the yields of the other products in the presence of methanol or hydrogen peroxide. Increased halogenation of PPF probably results from the formation of peroxynitrate (O 2NOO −), that further oxidizes chloride ions in hypochlorous acid (HOCl) or molecular chlorine (Cl 2). Spontaneous decay of peroxynitrate is relatively slow in acidic medium, thus explaining the decrease of the yields of the other products. By direct EPR techniques, we also observed that this reaction occurs via a radical pathway.