Transformations of 2,6-diisopropylphenol by NO-derived nitrogen oxides, particularly peroxynitrite

To investigate the protective effect of the anesthetic 2,6-diisopropylpheno l, or propofol, in oxidative processes in which (NO)-N-. and peroxynitrite are involved, direct interactions were explored. The reactions of the highl y lipophilic propofol with (NO)-N-. in methanolic or aqueous buffered solut ions under air were shown to produce the same compounds as those detected w ith peroxynitrite, hut with very low yields and slow rates. In aqueous neut ral medium, peroxynitrite (ONOO-, ONOOCO2-, ONOOH) was able to nitrate and oxidize propofol: In addition to oxidation products, quinone and quinone di mer, the formation of the 1-nitropropofol derivative was detected, increasi ng with peroxynitrite or CO2 concentrations. Nitration reached 20% after th e addition of 25 mM bicarbonate to an equimolecular mixture of peroxynitrit e and propofol in methanol/ phosphate-buffered solution (1/4,v/v) at pH 7.4 . However, peroxynitrite either in methanol or in alkaline-buffered mixture (optimum pH 10-12) resulted in the rapid and almost complete transformatio n of propofol to an intermediate compound 1, which further decomposed to 4- nitrosopropofol. The transient compound 1 was obtained from either peroxyni trite or (NO)-N-. in the presence of oxygen. From mass spectrometry determi nation of compound 1 we propose the involvement of the nitrosodioxyl radica l ONOO., forming an adduct with the propofoxyl radical, to yield 4-nitrosod ioxypropofol and finally 4-nitrosopropofol. (C) 2000 Academic Press.