Kinetics and thermodynamics of 1-hydroxyethyl radical reaction with unsaturated lipids and prenylflavonoids

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Natália E C De Almeida, Inara De Aguiar, Andressa De Zawadzki, Daniel R. Cardoso

Hydroxyalkyl radicals have been reported to induce lipid oxidation as the key aspect of the pathogenesis of alcoholic fatty liver disease and are responsible for the alkylation and cleavage of DNA during the metabolism of a wide range of genotoxic compounds. However, relevant kinetic data for the oxidation of unsaturated lipids by 1-hydroxyethyl radical (HER) has not been reported. In this study, the rate constants for the reaction of unsaturated fatty acid methyl esters and sterols with HER have been determined using a competitive kinetic approach employing the spin-trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) as the competitive substrate. Polyunsaturated fatty acid methyl ester is shown to react with HER with an apparent second-order rate constant ranging from (3.7 ± 0.1) × 106 L mol-1 s-1 for methyl linoleate to (2.7 ± 0.2) × 107 L mol-1 s-1 for methyl docosahexanoate at 25.0 ± 0.2 °C in ethanol. The apparent second-order rate constant for polyunsaturated fatty acid methyl ester oxidation by HER is dependent on the number of bisallylic hydrogen atoms rather than on the bond dissociation energy value for the weakest C - H bond as determined by ab initio density functional theory calculations. Sterols displayed higher reactivity compared to unsaturated fatty acid methyl esters with apparent second-order rate constants of (2.7 ± 0.1) × 106 and (5.2 ± 0.1) × 107 L mol-1 s-1 at 25.0 ± 0.2 °C in ethanol for cholesterol and ergosterol, respectively. Similar experiments with prenylflavonoids as potential herbal chemopreventive agents for preventing alcoholic liver diseases yield apparent second-order rate constants close to the diffusion control with kapp values of (1.5 ± 0.2) and (3.6 ± 0.1) × 109 L mol-1s-1 for 6-prenylnarigerin and xanthohumol at 25.0 ± 0.2 °C in ethanol solution, respectively. Polyunsaturated lipids were revealed to be highly reactive oxidizable substrates toward HER-induced oxidation in biological systems leading to damage of membranes and sensitive structures.

Original languageEnglish
JournalJournal of Physical Chemistry B
Issue number49
Pages (from-to)14278-14287
Number of pages10
Publication statusPublished - 2014
Externally publishedYes

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