Reaction between the anesthetic agent propofol and the free radical DPPH˙ in semiaqueous media: Kinetics and characterization of the products

The reaction of the free radical diphenylpicrylhydrazyl (DPPH˙) with the anesthetic agent 2,6-diisopropylphenol (propofol, PPF) was investigated in buffered hydroalcoholic media. The kinetics was followed using a stopped-flow system. DPPH˙ was reduced to the hydrazine analogue DPPH–H with a measured stoichiometry (DPPH˙/PPF) of 2. The main product of the reaction, 3,5,3′,5′-tetraisopropyl-(4,4′)-diphenoquinone (PPFDQ) was isolated by chromatography and its structure was fully characterized. The reaction mechanism was inferred from the stoichiometry, kinetics, and product identification. The first step, which primarily determines the kinetics, is the reaction of DPPH˙ with PPF to produce DPPH–H and the PPF radical. The rate constant was found to be 31.8, 207, and 908 M− 1 s− 1 at pH 6.4, 7.4, and 8.4, respectively. The pH dependence is indicative of a higher reactivity of the phenolate form of PPF. Then, PPF radicals combine to form dipropofol, which is quickly oxidized to PPFDQ by the remaining DPPH˙. This reaction scheme is corroborated by numerical simulations of the kinetics. In the course of this study we also disclosed an unexpected effect, the photochemical degradation of PPFDQ. The need to compare antioxidants on a kinetics basis is again emphasized. In our hands, PPF presents a significantly weaker reactivity than Trolox.