Quantum Mechanical Calculations and Molecular Docking Simulation Studies of N-(5-chloro-2-oxobenzyl)-2-hydroxy-5-methylanilinium Compound

Abstract

Schiff bases were first synthesized by Hugo Schiff in 1864. The formation of a carbon-nitrogen double bond is what gives specificity to Schiff bases. This double bond is referred to as an imine (R-N=C-R). This double bond contributes to the high activity of Schiff bases, allowing for extensive research across various fields and disciplines. Neurodegenerative diseases are conditions that continuously and irreversibly affect neurons and nerve cells in the central nervous system, and they are among the leading causes of death in developed countries. Alzheimer’s disease, which is a type of neurodegenerative disease, currently has about 5 million new cases each year, and there is no definitive and complete treatment method for it. Individuals with this disease exhibit symptoms such as memory loss, inability to form new memories, and slowing of cognitive functions. Additionally, these patients show imbalances in neurotransmitters responsible for facilitating neural transmission between neurons, particularly an irreversible loss of cholinergic neurons, which are a significant part of the central nervous system. Disruption of homeostasis in the mechanisms of acetylcholinesterase (AChE) and monoamine oxidase (MAO) neurotransmitters is indicated among the causes of Alzheimer’s disease. In this study; the physical, chemical and biological properties of N-(5-chloro-2-oxobenzyl)-2-hydroxy-5-methylanilinium molecule were investigated by quantum mechanical calculation methods. In support of the X-ray results, the geometrical parameters (bond lengths, and bond angles) and quantum chemical properties of the title compound were theoretically realized by the density functional theory method with B3LYP/6-311G(d,p) basis set using Gaussian 03W program. Herein, Frontier orbitals, molecular electrostatic potential surface, nonlinear optical properties, natural bond orbital analysis, Mulliken charges, and Hirshfeld surface analysis of the title compound were also calculated to explain the intermolecular interactions. Additionally, molecular docking results were performed with AChE and MAO-B enzymes obtained from the Protein Data Bank (PDB). All these studies have shown that the structure has high stability and forms a strong bond with the relevant enzymes.

Keywords

• Quantum mechanical calculations
• Molecular docking
• Alzheimer’s disease
• AChE
• MOA-B.

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