Synthesis of Novel Tritopic Hydrazone Ligands: Spectroscopy, Biological Activity, DFT, and Molecular Docking Studies

Sharmin Akther Rupa; Md Rassel Moni; Md Abdul Majed Patwary; Md Mayez Mahmud; Md Aminul Haque; Jamal Uddin; S M Tareque Abedin

doi:10.3390/molecules27051656

Synthesis of Novel Tritopic Hydrazone Ligands: Spectroscopy, Biological Activity, DFT, and Molecular Docking Studies

Molecules. 2022 Mar 2;27(5):1656. doi: 10.3390/molecules27051656.

Authors

Sharmin Akther Rupa¹, Md Rassel Moni¹, Md Abdul Majed Patwary¹, Md Mayez Mahmud², Md Aminul Haque³, Jamal Uddin⁴, S M Tareque Abedin⁵

Affiliations

¹ Department of Chemistry, Comilla University, Cumilla 3506, Bangladesh.
² Faculty of Pharmaceutical Science, Tokushima University, Tokushima Shi 770-0026, Japan.
³ Department of Chemistry, Jagannath University, Dhaka 1100, Bangladesh.
⁴ Department of Natural Sciences, Center for Nanotechnology, Coppin State University, Baltimore, MD 21216, USA.
⁵ Department of Chemistry, Jahangirnagar University, Savar 1342, Bangladesh.

Abstract

Polytopic organic ligands with hydrazone moiety are at the forefront of new drug research among many others due to their unique and versatile functionality and ease of strategic ligand design. Quantum chemical calculations of these polyfunctional ligands can be carried out in silico to determine the thermodynamic parameters. In this study two new tritopic dihydrazide ligands, N’2, N’6-bis[(1E)-1-(thiophen-2-yl) ethylidene] pyridine-2,6-dicarbohydrazide (L1) and N’2, N’6-bis[(1E)-1-(1H-pyrrol-2-yl) ethylidene] pyridine-2,6-dicarbohydrazide (L2) were successfully prepared by the condensation reaction of pyridine-2,6-dicarboxylic hydrazide with 2-acetylthiophene and 2-acetylpyrrole. The FT-IR, 1H, and 13C NMR, as well as mass spectra of both L1 and L2, were recorded and analyzed. Quantum chemical calculations were performed at the DFT/B3LYP/cc-pvdz/6-311G+(d,p) level of theory to study the molecular geometry, vibrational frequencies, and thermodynamic properties including changes of ∆H, ∆S, and ∆G for both the ligands. The optimized vibrational frequency and (1H and 13C) NMR obtained by B3LYP/cc-pvdz/6-311G+(d,p) showed good agreement with experimental FT-IR and NMR data. Frontier molecular orbital (FMO) calculations were also conducted to find the HOMO, LUMO, and HOMO−LUMO gaps of the two synthesized compounds. To investigate the biological activities of the ligands, L1 and L2 were tested using in vitro bioassays against some Gram-negative and Gram-positive bacteria and fungus strains. In addition, molecular docking was used to study the molecular behavior of L1 and L2 against tyrosinase from Bacillus megaterium. The outcomes revealed that both L1 and L2 can suppress microbial growth of bacteria and fungi with variable potency. The antibacterial activity results demonstrated the compound L2 to be potentially effective against Bacillus megaterium with inhibition zones of 12 mm while the molecular docking study showed the binding energies for L1 and L2 to be −7.7 and −8.8 kcal mol−1, respectively, with tyrosinase from Bacillus megaterium.

Keywords: DFT; FMO; molecular docking; polydentate; tritopic; vibrational frequencies.

MeSH terms

Hydrazones*

Substances

Hydrazones