The tert-butoxyl radical mediated hydrogen atom transfer reactions of the Parkinsonian proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and selected tertiary amines.
Previous studies have shown that the hydrogen atom transfer (HAT) reactions of tert-butoxyl radical from the Parkinsonian proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) occur with low selectivity at the allylic and non-allylic alpha-C-H positions. In this paper, we report a more comprehensive regiochemical study on the reactivity of the tert-butoxyl radical as well as on the associated primary kinetic deuterium isotope effects for the various hydrogen atom abstractions of MPTP. In addition, the results of a computational study to estimate the various C-H bond dissociation energies of MPTP are presented. The results of the present study show the allylic/non-allylic selectivity is approximately 73:21. The behavior of the tert-butoxyl radical mediated oxidation of MPTP contrasts with this reaction as catalyzed by monoamine oxidase B (MAO-B) that occurs selectively at the allylic alpha-carbon. These observations lead to the conclusion that the tert-butoxyl radical is not a good chemical model for the MAO-B-catalyzed bioactivation of MPTP.
Suleman
N Kamrudin
NK
Division of Natural Sciences, University of Guam, University Drive, Mangilao, GU 96923. nsuleman@uguam.uog.edu
Flores
Joey
J
Tanko
James M
JM
Isin
Emre Mehmet
EM
Castagnoli
Neal
N
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000737:chemistry* / Q000378:metabolism; D000588:Amines / Q000737:chemistry* / Q000378:metabolism; D002244:Carbon / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D003903:Deuterium / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008995:Monoamine Oxidase / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000473:pathology; D013329:Structure-Activity Relationship; D020122:tert-Butylhydroperoxide / Q000737:chemistry* / Q000378:metabolism
D000588:Amines; D009498:Neurotoxins; D002244:Carbon; D006859:Hydrogen; D020122:tert-Butylhydroperoxide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003903:Deuterium; D008995:Monoamine Oxidase