On the complex OH/O-induced free radical chemistry of arylalkylamines with special emphasis on the contribution of the alkylamine side chain

László Szabó, Viktória Mile, Tünde Tóth, György T. Balogh, Tamás Földes, E. Takács, László Wojnárovits

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)124-140
Number of pages17
JournalFree Radical Research
Volume51
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

Fingerprint

Fluoxetine
Free Radicals
Pulse Radiolysis
Oxidation
Radiolysis
Bioactivity
Titration
Oxidants
Discrete Fourier transforms
Spectrum analysis
Antidepressive Agents
Oxidation-Reduction
Amines
Hydrogen
Electrons
Atoms
Kinetics
hydroxide ion
hydroxycyclohexadienyl radical

Keywords

  • amine oxidation
  • Arylalkylamine
  • hydroxyl radical
  • radical kinetics
  • time-resolved transient spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

On the complex OH/O-induced free radical chemistry of arylalkylamines with special emphasis on the contribution of the alkylamine side chain. / Szabó, László; Mile, Viktória; Tóth, Tünde; Balogh, György T.; Földes, Tamás; Takács, E.; Wojnárovits, László.

In: Free Radical Research, Vol. 51, No. 2, 01.02.2017, p. 124-140.

Research output: Contribution to journalArticle

Szabó, László ; Mile, Viktória ; Tóth, Tünde ; Balogh, György T. ; Földes, Tamás ; Takács, E. ; Wojnárovits, László. / On the complex OH/O-induced free radical chemistry of arylalkylamines with special emphasis on the contribution of the alkylamine side chain. In: Free Radical Research. 2017 ; Vol. 51, No. 2. pp. 124-140.
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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.",
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AU - Balogh, György T.

AU - Földes, Tamás

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KW - hydroxyl radical

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