Nonenzymatic pathway of PUFA oxidation. A first-principles study of the reactions of OH radical with 1,4-pentadiene and arachidonic acid

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Abstract

The oxidation of polyunsaturated hydrocarbons by ·OH radical can play an important role in lipid oxidation of polyunsaturated fatty acids (PUFA) such as arachidonic acid (AA). As a prototype of this oxidation, the reaction of 1,4-pentadiene with the -OH radical is studied using the QCISD(T)/cc-pVTZ// BH&HLYP/6-31G(d) level of theory. One of the prereaction complexes is shown to be a springboard for the indirect bisallylic hydrogen abstraction (A o), terminal (T0o), and nonterminal ·OH addition (NT0o) reactions. The enthalpies of the transition states of the Ao, T0o, and NT0o reactions are found to be lower than those of the reactants, so all these reactions are expected to be fast. The nonterminal adduct is found to be reactive via two low-lying consecutive reaction channels. The first channel is a five-membered ring closing (NT1o). The second channel is bond scission, which results in an allyl radical and a vinyl alcohol (NT2o). An analogous reaction pathway in which AA takes the place of 1,4-pentadiene was explored using the ONIOM(QCISD(T)/cc-pVTZ:BH&HLYP/6-31G(d))//BH&HLYP/6-31G(d) method. The results show that the formation of the five-membered ring (AA-NT1o) is energetically favored. Our results demonstrate for the first time a possible, ab initio-based mechanism for the nonenzymatic biosynthesis of isoprostane-like structures from AA without the presence of molecular oxygen. Furthermore, the energetically low-lying bond scission channel may explain the observed formation of short fatty acids and dieneols (tautomers of unsaturated aldehydes).

Original languageEnglish
Pages (from-to)1472-1479
Number of pages8
JournalJournal of chemical theory and computation
Volume4
Issue number9
DOIs
Publication statusPublished - Sep 9 2008

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ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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