title: Catalytic chain-breaking pyridinol antioxidants.
abstract: The synthesis of 3-pyridinols carrying alkyltelluro, alkylseleno, and alkylthio groups is described together with a detailed kinetic, thermodynamic, and mechanistic study of their antioxidant activity. When assayed for their capacity to inhibit azo-initiated peroxidation of linoleic acid in a water/chlorobenzene two-phase system, tellurium-containing 3-pyridinols were readily regenerable by N-acetylcysteine contained in the aqueous phase. The best inhibitors quenched peroxyl radicals more efficiently than alpha-tocopherol, and the duration of inhibition was limited only by the availability of the thiol reducing agent. In homogeneous phase, inhibition of styrene autoxidation absolute rate constants k(inh) for quenching of peroxyl radical were as large as 1 x 10(7) M(-1) s(-1), thus outperforming the best phenolic antioxidants including alpha-tocopherol. Tellurium-containing 3-pyridinols could be quantitatively regenerated in homogeneous phase by N-tert-butoxycarbonyl cysteine methyl ester, a lipid-soluble analogue of N-acetylcysteine. In the presence of an excess of the thiol, a catalytic mode of action was observed, similar to the one in the two-phase system. Overall, compounds bearing the alkyltelluro moiety ortho to the OH group were much more effective antioxidants than the corresponding para isomers. The origin of the high reactivity of these compounds was explored using pulse-radiolysis thermodynamic measurements, and a mechanism for their unusual antioxidant activity was proposed. The tellurium-containing 3-pyridinols were also found to catalyze reduction of hydrogen peroxide in the presence of thiol reducing agents, thereby acting as multifunctional (preventive and chain-breaking) catalytic antioxidants.
authors.affiliation: Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, SE-751 23 Uppsala, Sweden.
authors.forename: Sangit
authors.initials: S
authors.lastname: Kumar
authors.forename: Henrik
authors.initials: H
authors.lastname: Johansson
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kanda
authors.forename: Lars
authors.initials: L
authors.lastname: Engman
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Helena
authors.initials: H
authors.lastname: Bergenudd
authors.forename: Mats
authors.initials: M
authors.lastname: Jonsson
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Pedulli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Amorati
authors.forename: Luca
authors.initials: L
authors.lastname: Valgimigli
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D000975:Antioxidants; D002384:Catalysis; D016166:Free Radical Scavengers / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000737:chemistry*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry; D019163:Reducing Agents / Q000737:chemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013691:Tellurium / Q000737:chemistry*
chemical_list: D000473:Alkanes; D000975:Antioxidants; D016166:Free Radical Scavengers; D016566:Organoselenium Compounds; D011728:Pyridones; D019163:Reducing Agents; D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D013691:Tellurium