title: The Reaction of Thiyl Radical with Methyl Linoleate: Completing the Picture.
abstract: Cis lipids can be converted by thiols and free radicals into trans lipids, which are therefore a valuable tell-tale for free radical activity in the cell's lipidome. Our previous studies have shown that polyunsaturated lipids are isomerized by alkanethiyl radicals (S•) in a cycle propagated by reversible double-bond addition and terminated by radical H-abstraction from the lipid. A critical flaw in this picture has long been that the reported lipid abstraction rate from radiolysis studies is faster than addition-isomerization, implying that the "cycle" must be terminating faster than it is propagating! Herein, we resolved this longstanding puzzle by combining a detailed product analysis, with reinvestigation of the time-resolved kinetics, DFT calculations of the indicated pathways, and reformulation of the radical-stasis equations. We have determined thiol-coupled products in dilute solutions arise mainly from addition to the inside position of the bisallylic group, followed by rapid intramolecular H•transfer, yielding allylic radicals (LZZ+ S•⇄ SL•→ SL'•) that are slowly reduced by thiol (SL'•+ SH → SL'H + S•). The first-order grow-in rate of the L-H•signal (kexp280nm) may therefore be dominated by the addition-H-translocation rather than slower direct H•-abstraction. Steady-state kinetic analysis of the new mechanism is consistent with products and the rates and trends for polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and mixtures, with and without physiological [O2]. Implications of this new paradigm for the thiol-ene reactivity fall in an interdisciplinary research area spanning from synthetic applications to metabolomics.
authors.affiliation: ISOF, Consiglio Nazionale delle Ricerche , Via P. Gobetti 101, 40129 Bologna, Italy.
authors.forename: Chryssostomos
authors.identifier: 0000-0003-2626-2925
authors.initials: C
authors.lastname: Chatgilialoglu
authors.affiliation: ISOF, Consiglio Nazionale delle Ricerche , Via P. Gobetti 101, 40129 Bologna, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ferreri
authors.affiliation: ISOF, Consiglio Nazionale delle Ricerche , Via P. Gobetti 101, 40129 Bologna, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Guerra
authors.affiliation: Department of Chemistry, United Arab Emirates University , P.O. Box 15551, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Abdelouahid
authors.initials: A
authors.lastname: Samadi
authors.affiliation: James Cook University , Cairns 4878 QLD, Australia.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Bowry
mesh_terms: D005609:Free Radicals / Q000737:chemistry; D008041:Linoleic Acids / Q000737:chemistry*; D015394:Molecular Structure; D011789:Quantum Theory; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D005609:Free Radicals; D008041:Linoleic Acids; D013438:Sulfhydryl Compounds; C005575:methyl linoleate