Synthesis, spectroscopic investigation, molecular docking, ADME/T toxicity predictions, and DFT study of two trendy ortho vanillin-based scaffolds

Dhrubajyoti Majumdar; Amit Dubey; Aisha Tufail; Dipankar Sutradhar; Sourav Roy

doi:10.1016/j.heliyon.2023.e16057

Synthesis, spectroscopic investigation, molecular docking, ADME/T toxicity predictions, and DFT study of two trendy ortho vanillin-based scaffolds

Heliyon. 2023 May 10;9(6):e16057. doi: 10.1016/j.heliyon.2023.e16057. eCollection 2023 Jun.

Authors

Dhrubajyoti Majumdar^{1

2}, Amit Dubey^{3

4}, Aisha Tufail³, Dipankar Sutradhar⁵, Sourav Roy⁶

Affiliations

¹ Department of Chemistry, Tamralipta Mahavidyalaya, Tamluk, 721636, West Bengal, India.
² Department of Chemistry and Chemical Biology, Indian Institute of Technology (Indian School of Mines), Dhanbad, Jharkhand, 826004, India.
³ Computational Chemistry and Drug Discovery Division, Quanta Calculus, Greater Noida, Uttar Pradesh, 274203, India.
⁴ Department of Pharmacology, Saveetha Dental College, and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, 600077, India.
⁵ School of Advanced Sciences and Languages, VIT Bhopal University, Kothrikalan, Sehore, Madhya Pradesh, 466114, India.
⁶ Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore, 560 012, India.

Abstract

In this article, we have synthesized two contemporary ortho-vanillin-based Salen-type ligands (H₂L¹/H₂L²) characterized by modern spectroscopic tools. EDX analysis supports the elemental composition (C, N, O, and Br). SEM examined the morphology of the synthesized compounds. The molecular geometry was optimized in the gas phase using B3LYP-D3/6-311G (d, p) level. The global reactivity parameters, HOMO-LUMO energy gap (Δ), atomic properties, MESP, and ADME/T, vividly explore the chemical reactivity and toxicity of two Salen-type ligands. The DFT simulated IR/NMR characterized essential structural assignments, and UV-Visible spectra were employed to predict the optical properties. The article demonstrated in silico molecular docking against the Gm + ve Bacillus subtilis (6UF6), and Gm -ve Proteus Vulgaris establishes the ligand binding ability with essential amino acids through conventional H-bonding or other significant interactions. The docking simulation is compared for two compounds better than the control drugs and confirms the antimicrobial activity. The theoretical drug-like properties have been explored in-depth by ADME/T using the SWISSADME database. The analysis estimated the molecule's lipophilicity, the consensus P0/W, and water solubility. Thus, using various pharmaco-logical parameters, toxicity explains where the electron-withdrawing Br group plays a more toxic effect in H₂L² than in H₂L¹.

Keywords: ADME/T; DFT; Molecular docking; Molecular dynamics; Salen ligand; Toxicity.