Abstract
Background: Local anesthetics are widely used to decrease sensitivity to pain in specific regions of the body, while performing medical tasks. Many studies have probed the mechanism of action of local anesthetics but still, many questions remain. (2R-(-)2-(2, 6-dimethylphenylaminocarbonyl)- 1-methyl piperidinium chloride (DAMP), is an extensively used amide-type local anesthetic.
Objective: This study aims at revealing the various electrophysical and chemical properties of the title compound. This study will be useful for future research by pharmacologists. Methods: Density Functional Theory (DFT) computations were executed using Gaussian’09 program package and were optimized with the B3LYP /6-311+G (d, p) basis set. Natural Bond Orbital (NBO) analysis was carried out with version 3.1. Normal Coordinate Analysis (NCA) was used to systematically calculate the harmonic vibrational wavenumbers. Molecular docking simulations were carried out to understand the pharmacokinetic behavior of the drug. Results: The presence of strong N-H…Cl intra molecular hydrogen bonding was evidently revealed from the FT-IR spectrum due to the shifting of NH stretching wavenumber. Stability of the molecule arising from hyper conjugative interactions exhibits the bioactivity of the molecule by natural bond orbital analysis. The title molecule binds to the inner pore and blocks voltage - gated sodium channels in peripheral neurons. Conclusion: A detailed molecular picture of DAMP and its interactions were obtained by modeling analysis, IR, Raman, and UV-Vis spectroscopy. The geometrical parameters agree well with the XRD data. NBO analysis indicates the bioactivity of the molecule. The HOMO-LUMO energy gap indicates the possibility of intramolecular charge transfer of the molecule. From the ligand docking studies, it is concluded that the title molecule binds to the inner pore and blocks voltage-gated sodium channels in peripheral neurons.Keywords: DFT, NCA, NBO, cyclo-voltammetry, molecular docking, computations.
Graphical Abstract
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