title: Oxidation of caffeine and related methylxanthines in ascorbate and polyphenol-driven Fenton-type oxidations.
abstract: Caffeine and related methylxanthines were subjected to free radical mediated oxidation by incubation with Fe(3+)-EDTA/ascorbate and Fe(3+)-EDTA/polyphenolics. The reaction mixtures were analysed by reverse-phase HPLC, revealing the corresponding C-8 hydroxylated analogues as the major products of hydroxyl radical mediated attack. Further oxidation products of caffeine, analysed by liquid chromatography-mass spectrometry (LC-MS), were the N1-, N3- and N7-demethylated methylxanthine analogues theobromine, paraxanthine and theophylline, respectively. Isolable amounts of the imidazole ring operated 6-amino-5-(N-formylmethyl-amino)-1,3-dimethyl-uracil (1,3,7-DAU) derivative were also detected, which was characterised by 1H NMR and mass spectroscopy. The identified products indicate that the pertinent chemical reactions, i.e. C-8 hydroxylation, demethylations, and C8-N9 bond scission, are comparable to the primary metabolic pathways of caffeine in humans. The influence of pH, transition metals, hydrogen peroxide, free radical scavengers and metal chelators on caffeine oxidation was studied. This report illustrates that natural food-borne reactants can aid in identifying specific chemical markers of free radical induced damage. Furthermore, potentially anti-and pro-oxidative reactions can be elucidated which may be important in assessing the impact of nutrient additives and supplements on the shelf life and stability of foods and beverages.
authors.affiliation: Nestec Ltd., Nestle Research Centre, Lausanne, Switzerland.
authors.forename: R H
authors.initials: RH
authors.lastname: Stadler
authors.forename: J
authors.initials: J
authors.lastname: Richoz
authors.forename: R J
authors.initials: RJ
authors.lastname: Turesky
authors.forename: D H
authors.initials: DH
authors.lastname: Welti
authors.forename: L B
authors.initials: LB
authors.lastname: Fay
mesh_terms: D000818:Animals; D001205:Ascorbic Acid; D002110:Caffeine / Q000737:chemistry*; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004492:Edetic Acid; D005296:Ferrous Compounds; D017665:Hydroxyl Radical; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010636:Phenols; D011687:Purines; D013482:Superoxide Dismutase / Q000378:metabolism; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000737:chemistry*
chemical_list: D005296:Ferrous Compounds; D010636:Phenols; D011687:Purines; D014970:Xanthines; C055526:Fe(II)-EDTA; D019820:Xanthine; C008514:methylxanthine; D017665:Hydroxyl Radical; D002110:Caffeine; D004492:Edetic Acid; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D001205:Ascorbic Acid