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.
Highlights
The derivatives of hydrazide-hydrazone moiety with heterocyclic systems possess a range of biological activities; namely, anti-microbial, antimycobacterial, antitubercular, anticonvulsant, anticholinesterase [1], antiplatelet, and more importantly antitumor [5,7]
Self-assembly of transition metals with multifunctional polydentate ligands has resulted in a successful paradigm of single-step synthesis of a new class of clusters of well-defined aesthetical architectures bearing spectacular electronic, catalytic, photophysical, photochemical, and magnetic properties [10–12]
The geometry optimization revealed the planarity of the L1 and L2 molecules
Summary
Polytopic ligands containing hydrazide-hydrazone moiety (-CO-NHN=CH-) are important for new drug development [1–6] because their polyfunctional nature offers multifarious synthetic ways to derivatize such organic molecules towards suitable and effective drug–receptor interaction. Transition metal complexes derived from such types of ligands have been widely studied since they demonstrate significant biological and pharmacological properties [8–11]. Self-assembly of transition metals with multifunctional polydentate ligands has resulted in a successful paradigm of single-step synthesis of a new class of clusters of well-defined aesthetical architectures bearing spectacular electronic, catalytic, photophysical, photochemical, and magnetic properties [10–12]. The foremost synthetic challenge in this field is to design and synthesize new polytopic ligands with appropriate donor groupings placed strategically in place for metal coordination. Pyrrole, thiophene, and their organic and metal cluster derivatives are recognized to present a wide range of biological activities [20–33]. The design and synthesis of novel ligands containing the thiophene and pyrrole rings have attracted great interest
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