Why Does Monoamine Oxidase (MAO) Catalyze the Oxidation of Some Tetrahydropyridines?

Results pertaining to the mechanism of the oxidation of the tertiary amine 1-methyl-4-(1-methyl-1-H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (MMTP, a close analog of the Parkinsonism inducing compound MPTP) by 3-methyllumiflavin (3MLF), a chemical model for the FAD cofactor of monoamine oxidase, are reported. MMTP and related compounds are among the few tertiary amines that are monoamine oxidase B (MAO-B) substrates. The MMTP/3MLF reaction is catalytic in the presence of O and the results under anaerobic conditions strongly suggest the involvement of radical intermediates, consistent with a single electron transfer mechanism.

Mechanism and Kinetics of the Reaction of Nitrate Radicals with Carboxylic Acids.

Rate constants for the reaction of nitrate radical (NO ⋅) with several carboxylic acids (RCO H) were measured in acetonitrile using laser flash photolysis, and found to be on the order of 10 -10  M s . No observable H/D kinetic isotope effect was observed at the carboxyl O-H group, α-C-H bond and (possibly) in the case of formic acid, the formylic C-H bond. This suggests that NO ⋅ does not abstract hydrogen from any of these positions despite the fact that all these processes are thermodynamically favorable.

Insight into Hydrogen Abstractions by Nitrate Radical: Structural, Solvent Effects, and Evidence for a Polar Transition State.

The role of a polarized transition state and solvent effects on nitrate radical reactions was examined with a previously under-reported class of substrates, ethers, for their atmospheric implications. Absolute rate constants for hydrogen abstraction from a series of alcohols, ethers, and alkanes by nitrate radical have been measured in acetonitrile, water, and mixtures of these two solvents. Across all of these classes of compounds, using a modified form of the Evans-Polanyi relationship, it is demonstrated that the observed structure/reactivity trends can be reconciled by considering the number of abstractable hydrogens, strength of the C-H bond, and ionization potential (IP) of the substrate.

Interplay between Structure and Mechanism in Reductive Dissociative Electron Transfers to α,β -Epoxyketones.

The electrochemical reduction of several α,β -epoxyketones was studied using cyclic (linear sweep) voltammetry, convolution voltammetry, and homogeneous redox catalysis. The results were reconciled to pertinent theories of electron transfer. α,β -Epoxyketones undergo dissociative electron-transfer reactions with C-O bond cleavage, via both stepwise and concerted mechanisms, depending on their structure.

Stereoelectronic and Resonance Effects on the Rate of Ring Opening of -Cyclopropyl-Based Single Electron Transfer Probes.

-Cyclopropyl--methylaniline () is a poor probe for single electron transfer (SET) because the corresponding radical cation undergoes cyclopropane ring opening with a rate constant of only 4.1 × 10 s, too slow to compete with other processes such as radical cation deprotonation. The sluggish rate of ring opening can be attributed to either (i) a resonance effect in which the spin and charge of the radical cation in the ring-closed form is delocalized into the phenyl ring, and/or (ii) the lowest energy conformation of the SET product () does not meet the stereoelectronic requirements for cyclopropane ring opening.

Evidence for a Proton-Coupled Electron Transfer Mechanism in a Biomimetic System for Monoamine Oxidase B Catalysis.

Mechanistic studies with 5-ethyl-3-methyllumiflavinium (Fl ) perchlorate, a biomimetic model for flavoenzyme monoamine oxidase B (MAO-B) catalysis, and the tertiary, allyl amine 1-methyl-4-(1-methyl-1 H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (MMTP) reveal that proton-coupled electron transfer (PCET) may be an important pathway for MAO catalysis. The first step involves a single-electron transfer (SET) leading to the free radicals Fl and MMTP , the latter produced by deprotonation of the initially formed and highly acidic MMTP . Molecular oxygen (O ) is found to play a hitherto unrecognized role in the early steps of the oxidation.

Does Metal Ion Complexation Make Radical Clocks Run Fast? An Experimental Perspective.

The rate constant for the β-scission of the cumyloxyl radical (k) was measured in the presence of various added electrolytes in acetonitrile and DMSO solvent. The results show that in CHCN, k increases in the presence of added electrolyte, roughly paralleling the size of the cation: Li > Mg ≈ Na > BuN > no added electrolyte. As suggested by Bietti et al.

Comparison of two extraction techniques, solid-phase microextraction versus continuous liquid-liquid extraction/solvent-assisted flavor evaporation, for the analysis of flavor compounds in gueuze lambic beer.

Lambic is a beer style that undergoes spontaneous fermentation and is traditionally produced in the Payottenland region of Belgium, a valley on the Senne River west of Brussels. This region appears to have the perfect combination of airborne microorganisms required for lambic's spontaneous fermentation. Gueuze lambic is a substyle of lambic that is made by mixing young (approximately 1 year) and old (approximately 2 to 3 years) lambics with subsequent bottle conditioning.

ORAChromatography and total phenolics content of peanut root extracts.

A large number of compounds have been reported in peanut plants. Many of these compounds are phytoalexins, which are produced by plants experiencing environmental stress and often exhibit antioxidant activity. It is difficult to determine which of the many compounds has the greatest impact on total antioxidant capacity in a mixture.

Simultaneous degradation of disinfection byproducts and earthy-musty odorants by the UV/H2O2 advanced oxidation process.

Advanced treatment technologies that control multiple contaminants are beneficial to drinking water treatment. This research applied UV/H(2)O(2) for the simultaneous degradation of geosmin, 2-methylisoborneol, four trihalomethanes and six haloacetic acids. Experiments were conducted in de-ionized water at 24 ± 1.

Reaction of benzophenone triplet with aliphatic amines. What a potent neurotoxin can tell us about the reaction mechanism.

A photochemical model study of benzophenone triplet ((3)BP) with the MAO-B substrate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP (1)] and two of it's derivatives, 1-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine (2) and (±)-[trans-2-phenylcyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine (3) were performed. Literature precedent and calculations reported herein suggest that the barrier to ring opening for aminyl radical cations derived from N-cyclopropyl derivatives of tertiary amines (such as MPTP) will be low. The LFP results reported herein demonstrate that pathways for the reaction of (3)BP with 1, 2, and 3 are very similar.

How solvent modulates hydroxyl radical reactivity in hydrogen atom abstractions.

The hydroxyl radical (HO*) is a highly reactive oxygen-centered radical whose bimolecular rate constants for reaction with organic compounds (hydrogen atom abstraction) approach the diffusion-controlled limit in aqueous solution. The results reported herein show that hydroxyl radical is considerably less reactive in dipolar, aprotic solvents such as acetonitrile. This diminished reactivity is explained on the basis of a polarized transition state for hydrogen abstraction, in which the oxygen of the hydroxyl radical becomes highly negative and can serve as a hydrogen bond acceptor.

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.

Activation/driving force relationships for cyclopropylcarbinyl --> homoallyl-type rearrangements of radical anions.

By using direct and indirect electrochemical methods, rate constants (ko) for cyclopropane ring opening of radical anions derived from the one-electron reduction of trans-1-benzoyl-2-phenylcyclopropane, trans-1-benzoyl-2-vinylcyclopropane, 2-methylenecyclopropyl phenyl ketone, spiro[anthracene-9,1'-cyclopropan-10-one], 3-cyclopropylcyclohex-2-en-1-one, and 3-(1-methylcyclopropyl)cyclohex-2-en-1-one were determined. Qualitatively, rate constants for ring opening of these (and other cyclopropyl- and cyclobutyl-containing radical anions) can be rationalized on the basis of the thermodynamic stability of the radical anion, the ability of substituents on the cyclopropyl group to stabilize the radical portion of the distonic radical anion, and the stability of the enolate portion of the distonic radical anion. On the basis of this notion, a thermochemical cycle for estimating deltaG(o) for ring opening was presented.

Chemistry of the t-butoxyl radical: evidence that most hydrogen abstractions from carbon are entropy-controlled.

Absolute rate constants and Arrhenius parameters for hydrogen abstractions (from carbon) by the t-butoxyl radical ((t) BuO.) are reported for several hydrocarbons and tertiary amines in solution. Combined with data already in the literature, an analysis of all the available data reveals that most hydrogen abstractions (from carbon) by (t) BuO.

Synthesis of Succinimido[3,4-b]indane and 1,2,3,4,5,6-Hexahydro-1,5-methano-3-benzazocine-2,4-dione by Sequential Alkylation and Intramolecular Arylation of Enolates Derived from N,N,N'N'-Tetramethylbutanediamides and N,N,N'N'-Tetramethylpentanediamides.

The tricyclic title compounds, 4 and 5, were synthesized by initial alkylation of the lithium monoenolates of N,N,N',N'-tetramethylbutanediamide (6) and N,N,N',N'-tetramethylpentanediamide (19) with 2-iodobenzyl chloride in liquid NH(3) at -60 degrees C to afford 2-(2-iodobenzyl)-N,N,N',N'-tetramethylbutanediamide (9) and 2-(2-iodobenzyl)-N,N,N',N'-tetramethylpentanediamide (20) in yields of 88 and 87%, respectively. Treatment of 9 with KNH(2) in liquid NH(3) resulted in formation and intramolecular arylation of the less-substituted alpha-enolate to produce trans-1,2-bis(N,N-dimethylcarboxamido)indane (10a) in 60% yield. Selective hydrolysis of 10a with aqueous Na(2)O(2) gave trans-1-(N,N-dimethylcarboxamido)indane-2-carboxylic acid (17), which was then converted to bridged succinimide 4 by transformation to trans-1-(N,N-dimethylcarboxamido)indane-2-carboxamide (10c) followed by cyclization of this mixed primary/tertiary amide by means of NaH in refluxing THF.