Proton Shuttle Mechanism for the Oxidation of Formaldehyde by Aldehyde Oxidase: An Electronic Structure Description of Formal Hydride Transfer and “Inhibited” Species

International Journal of Applied Chemistry

© 2019 by SSRG - IJAC Journal

Volume 6 Issue 1

Year of Publication : 2019

Authors : Tadege Belay, Dr.Abebe Berhane

10.14445/23939133/IJAC-V6I1P108

How to Cite?

Tadege Belay, Dr.Abebe Berhane, "Proton Shuttle Mechanism for the Oxidation of Formaldehyde by Aldehyde Oxidase: An Electronic Structure Description of Formal Hydride Transfer and “Inhibited” Species," SSRG International Journal of Applied Chemistry, vol. 6,  no. 1, pp. 49-63, 2019. Crossref, https://doi.org/10.14445/23939133/IJAC-V6I1P108

Abstract:

The mechanism(s) of molybdoenzymes such as aldehyde oxidase and xanthine oxidase is of interest since these enzymes are more frequently being linked to major metabolic pathways of drugs. Aldehyde oxidase(AO) enzyme is known to oxidize aldehydes. One of the aldehydes, formaldehyde, is known to inhibit xanthine oxidase as it turns over. However, there is no reported data whether it behaves the same when it reacts with aldehyde oxidase. Therefore, the research is intended to probe the most plausible proton shuttle mechanism for the oxidation of formaldehyde that precedes through either a concerted or stepwise mechanism. Density Functional Theory of the B3LYP correlation functional formalism (DFT-B3LYP) methods were used to generate several parameters from the electronic structure calculations. Accordingly, the higher percentage (%) contribution to HOMO and energy barrier (kcal/mol) (0.099, -7.185040E+04) makes formaldehyde as the favored substrate for aldehyde oxidase. In addition, the transition state structures for the active site bound to formaldehyde (ACT-FA) was confirmed by one imaginary negative frequency(-328.44S-1). Similarly, the wave function and bonding description support a stepwise formal hydride transfer mechanism (Path IC) for the oxidation of formaldehyde.

Keywords:

Aldehyde oxidase (AO), formaldehyde (FA), proton shuttle, oxidative hydroxylation, DFT-B3LYP

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