title: Theoretical modeling of hydroxyl-radical-induced lipid peroxidation reactions.
abstract: The OH-radical-induced mechanism of lipid peroxidation, involving hydrogen abstraction followed by O2 addition, is explored using the kinetically corrected hybrid density functional MPWB1K in conjunction with the MG3S basis set and a polarized continuum model to mimic the membrane interior. Using a small nonadiene model of linoleic acid, it is found that hydrogen abstraction preferentially occurs at the mono-allylic methylene groups at the ends of the conjugated segment rather than at the central bis-allylic carbon, in disagreement with experimental data. Using a full linoleic acid, however, abstraction is correctly predicted to occur at the central carbon, giving a pentadienyl radical. The Gibbs free energy for abstraction at the central C11 is approximately 8 kcal/mol, compared to 9 kcal/mol at the end points (giving an allyl radical). Subsequent oxygen addition will occur at one of the terminal atoms of the pentadienyl radical fragment, giving a localized peroxy radical and a conjugated butadiene fragment, but is associated with rather high free energy barriers and low exergonicity at the CPCM-MPWB1K/MG3S level. The ZPE-corrected potential energy surfaces obtained without solvent effects, on the other hand, display considerably lower barriers and more exergonic reactions.
authors.affiliation: Departament de Química, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Tejero
authors.forename: Angels
authors.initials: A
authors.lastname: Gonzalez-Lafont
authors.forename: José M
authors.initials: JM
authors.lastname: Lluch
authors.forename: Leif A
authors.initials: LA
authors.lastname: Eriksson
mesh_terms: D017665:Hydroxyl Radical / Q000737:chemistry*; D015227:Lipid Peroxidation; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D008055:Lipids; D017665:Hydroxyl Radical; D010100:Oxygen