scholarly journals Path Integral Calculation of the Hydrogen/Deuterium Kinetic Isotope Effect in Monoamine Oxidase A-Catalyzed Decomposition of Benzylamine

Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4359 ◽  
Author(s):  
Mateusz Z. Brela ◽  
Alja Prah ◽  
Marek Boczar ◽  
Jernej Stare ◽  
Janez Mavri
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Path Integral ◽  
Kinetic Isotope Effect ◽  
Monoamine Oxidase A ◽  
Kinetic Isotope ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Hydrogen Deuterium ◽  
Rate Limiting

Monoamine oxidase A (MAO A) is a well-known enzyme responsible for the oxidative deamination of several important monoaminergic neurotransmitters. The rate-limiting step of amine decomposition is hydride anion transfer from the substrate α–CH2 group to the N5 atom of the flavin cofactor moiety. In this work, we focus on MAO A-catalyzed benzylamine decomposition in order to elucidate nuclear quantum effects through the calculation of the hydrogen/deuterium (H/D) kinetic isotope effect. The rate-limiting step of the reaction was simulated using a multiscale approach at the empirical valence bond (EVB) level. We applied path integral quantization using the quantum classical path method (QCP) for the substrate benzylamine as well as the MAO cofactor flavin adenine dinucleotide. The calculated H/D kinetic isotope effect of 6.5 ± 1.4 is in reasonable agreement with the available experimental values.

scholarly journals How Do Aromatic Nitro Compounds React with Nucleophiles? Theoretical Description Using Aromaticity, Nucleophilicity and Electrophilicity Indices

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4819
Author(s):  
Kacper Błaziak ◽  
Witold Danikiewicz ◽  
Mieczysław Mąkosza
Keyword(s):  
Kinetic Isotope Effect ◽  
Theoretical Description ◽  
Reaction Conditions ◽  
Kinetic Isotope ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Leaving Group ◽  
Aromatic Nitro ◽  
Rate Limiting ◽  
Reaction Direction

In this study, we present a complete description of the addition of a model nucleophile to the nitroaromatic ring in positions occupied either by hydrogen (the first step of the SNAr-H reaction) or a leaving group (SNAr-X reaction) using theoretical parameters including aromaticity (HOMA), electrophilicity and nucleophilicity indices. It was shown both experimentally and by our calculations, including kinetic isotope effect modeling, that the addition of a nucleophile to the electron-deficient aromatic ring is the rate limiting step of both SNAr-X and SNAr-H reactions when the fast transformation of σH-adduct into the products is possible due to the specific reaction conditions, so this is the most important step of the entire reaction. The results described in this paper are helpful for better understanding of the subtle factors controlling the reaction direction and rate.

Nuclear quantum effects in enzymatic reactions: simulation of the kinetic isotope effect of phenylethylamine oxidation catalyzed by monoamine oxidase A

2020 ◽  
Vol 22 (13) ◽  
pp. 6838-6847 ◽  
Author(s):  
Alja Prah ◽  
Peter Ogrin ◽  
Janez Mavri ◽  
Jernej Stare
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Quantum Effects ◽  
Monoamine Oxidase A ◽  
Computational Techniques ◽  
Nuclear Motion ◽  
Enzymatic Reactions ◽  
Kinetic Isotope ◽  
Nuclear Quantum Effects

By using computational techniques for quantizing nuclear motion one can accurately reproduce kinetic isotope effect of enzymatic reactions, as demonstrated for phenylethylamine oxidation catalyzed by the monoamine oxidase A enzyme.

scholarly journals Deuterium Kinetic Isotope Effect Studies of a Potential in Vivo Metabolic Trapping Agent for Monoamine Oxidase B

2018 ◽  
Vol 9 (12) ◽  
pp. 3024-3027 ◽  
Author(s):  
Lindsey R. Drake ◽  
Allen F. Brooks ◽  
Anthony J. Mufarreh ◽  
Jonathan M. Pham ◽  
Robert A. Koeppe ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Isotope Effect ◽  
Kinetic Isotope Effect ◽  
Monoamine Oxidase B ◽  
Kinetic Isotope ◽  
Trapping Agent

Primary kinetic isotope effect in the gas phase photochlorination of ethyl chloride-1-d1

1984 ◽  
Vol 62 (5) ◽  
pp. 899-906 ◽  
Author(s):  
Jan Niedzielski ◽  
T. Yano ◽  
E. Tschuikow-Roux
Keyword(s):  
Activation Energy ◽  
Gas Phase ◽  
Isotope Effect ◽  
Ground State ◽  
Rate Constants ◽  
Kinetic Isotope Effect ◽  
Kinetic Isotope ◽  
Primary Reference ◽  
Hydrogen Deuterium ◽  
Increasing Temperature

The abstraction of hydrogen/deuterium from CH3CHDCl by ground state chlorine atoms produced photolytically from Cl2 has been investigated at temperatures betwen 280 and 368 K. The relative rates for the internal competition[Formula: see text]are found to conform to an Arrhenius rate law:[Formula: see text]These data, taken together with the external competition results for the C2H5Cl/CH3CHDCl system, in conjunction with the competitive results using CH4 as a primary reference, have yielded the rate constants (cm3 s−1):[Formula: see text]The relatively weak primary kinetic isotope effect, kH/kD, decreases with increasing temperature from 1,855 at 280 K to 1.66 at 365 K. The results are compared with those obtained based on the BEBO method. While both the trend and the magnitude of the kinetic isotope effect are satisfactorily predicted, the activation energy is not.

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