title: On the complex•OH/•O--induced free radical chemistry of arylalkylamines with special emphasis on the contribution of the alkylamine side chain.
abstract: A full account of the•OH-induced free radical chemistry of an arylalkylamine is given taking all the possible reaction pathways quantitatively into consideration. Such knowledge is indispensable when the alkylamine side chain plays a crucial role in biological activity. The fundamental reactions are investigated on the model compound N-methyl-3-phenypropylamine (MPPA), and extended to its biologically active analog, to the antidepressant fluoxetine (FLX). Pulse radiolysis techniques were applied including redox titration and transient spectral analysis supplemented with DFT calculations. The contribution of the amine moiety to the free radical-induced oxidation mechanism appeared to be appreciable.•O-was used to observe hydrogen atom abstraction events at pH 14 giving rise to the strongly reducing α-aminoalkyl radicals (∼38% of the radical yield) and to benzyl (∼4%), β-aminoalkyl (∼24%), and aminyl radicals (∼31%) of MPPA. One-electron transfer was also observed yielding aminium radicals with low efficiency (∼3%). In the•OH-induced oxidation protonated α-aminoalkyl (∼49%), β-aminoalkyl (∼27%), benzyl radicals (∼4%), and aminium radicals (∼5%) are initially generated on the side chain of MPPA at pH 6, whereas hydroxycyclohexadienyl radicals (∼15%) were also produced. These initial events are followed by complex protonation-deprotonation reactions establishing acid-base equilibria; however, these processes are limited by the transient nature of the radicals and the kinetics of the ongoing reactions. The contribution of the radicals from the side chain alkylamine substituent of FLX totals up to ∼54% of the initially available oxidant yield.
authors.affiliation: a Centre for Energy Research, Hungarian Academy of Sciences , Institute for Energy Security and Environmental Safety , Budapest , Hungary.|b Department of Organic Chemistry and Technology , Budapest University of Technology and Economics , Budapest , Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Szabó
authors.affiliation: a Centre for Energy Research, Hungarian Academy of Sciences , Institute for Energy Security and Environmental Safety , Budapest , Hungary.
authors.forename: Viktória
authors.initials: V
authors.lastname: Mile
authors.affiliation: b Department of Organic Chemistry and Technology , Budapest University of Technology and Economics , Budapest , Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Tóth
authors.affiliation: c Compound Profiling Laboratory , Gedeon Richter Plc , Budapest , Hungary.
authors.forename: György T
authors.initials: GT
authors.lastname: Balogh
authors.affiliation: d Research Centre for Natural Sciences, Hungarian Academy of Sciences , Institute of Organic Chemistry , Budapest , Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Földes
authors.affiliation: a Centre for Energy Research, Hungarian Academy of Sciences , Institute for Energy Security and Environmental Safety , Budapest , Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Takács
authors.affiliation: a Centre for Energy Research, Hungarian Academy of Sciences , Institute for Energy Security and Environmental Safety , Budapest , Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Wojnárovits
mesh_terms: D000588:Amines / Q000737:chemistry*; D004579:Electron Transport; D005609:Free Radicals / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D011675:Pulse Radiolysis; D014867:Water / Q000737:chemistry*
chemical_list: D000588:Amines; D005609:Free Radicals; D014867:Water; D017665:Hydroxyl Radical
keywords: Arylalkylamine; amine oxidation; hydroxyl radical; radical kinetics; time-resolved transient spectroscopy