title: Nonenzymatic Pathway of PUFA Oxidation. A First-Principles Study of the Reactions of OH Radical with 1,4-Pentadiene and Arachidonic Acid.
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 (AO), 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).
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, 6725 Szeged, Hungary, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo náméstí 2, 16610 Prague 6, Czech Republic, and Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6.
authors.forename: Milan
authors.initials: M
authors.lastname: Szori
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, 6725 Szeged, Hungary, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo náméstí 2, 16610 Prague 6, Czech Republic, and Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6.
authors.forename: Imre G
authors.initials: IG
authors.lastname: Csizmadia
authors.affiliation: Department of Chemical Informatics, Faculty of Education, University of Szeged, Boldogasszony sgt. 6, 6725 Szeged, Hungary, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo náméstí 2, 16610 Prague 6, Czech Republic, and Department of Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 3H6.
authors.forename: Bela
authors.initials: B
authors.lastname: Viskolcz