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

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.

Graphical abstract

Scheme 1

Synthetic outlines for the contemporary ligands (H₂L¹/H₂L²).

Fig. 1

Experimental (top) and DFT computed (bottom) IR plot of H₂L¹.

Fig. 2

Experimental (top) and DFT computed (bottom) IR plot of H₂L².

Fig. 3

Theoretical ¹H NMR (top) and ¹³C NMR (bottom) curve for H₂L¹.

Fig. 4

Theoretical ¹H NMR (top) and ¹³C NMR (bottom) curve for H₂L².

Fig. 5

HOMO-LUMO map with energy gap for H₂L.¹.

Fig. 6

HOMO-LUMO map with energy gap for H₂L².

Fig. 7

MESP profile (A) and optimized structure (B) of H₂L¹.

Fig. 8

MESP profile (A) and optimized structure (B) of H₂L².

Fig. 9

RMSD Calculations A. For H₂L¹ (Before docking pose) (Grey Ball Stick structure) superimpose over H₂L¹ (After docking pose) (Pink Ball Stick structure) with Gram-positive bacterium, Bacillus subtilis. B. H₂L¹ (Before docking pose) (Grey Ball Stick structure) superimpose over H₂L¹ (After docking pose) (Blue Ball Stick structure) with Gram-negative bacterium, Proteus Vulgaris. RMSD Calculations A. For H₂L² (Before docking pose) (Grey Ball Stick structure) superimpose over H₂L² (After docking pose) (Violet Ball Stick structure) with Gram-positive bacterium, Bacillus subtilis. B. H₂L² (Before docking pose) (Grey Ball Stick structure) superimpose over H₂L² (After docking pose) (Brown Ball Stick structure) with Gram-negative bacterium, Proteus Vulgaris. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)