Synthesis, molecular structure, supramolecular and biological evaluation of benzimidazole-based Schiff bases
5 affiliations
- 1Department of Chemistry, Jahangirnagar University Dhaka 1342 Bangladesh [email protected].
- 2Hajee Mohammad Danesh Science & Technology University (HSTU) Dinajpur Bangladesh.
- 3Department of Pharmacy, Jahangirnagar University Dhaka 1342 Bangladesh.
- 4Department of Chemistry, University of Manitoba Winnipeg Manitoba R3T 2N2 Canada.
- 5Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf Universitätsstr. 1 D-40225 Düsseldorf Germany.
Abstract
Benzimidazole-based Schiff bases, (Z)-2-(((1H-benzo[d]imidazol-2-yl)imino)methyl)phenol monohydrate (HL1·H₂O) and (Z)-1-(((1H-benzo[d]imidazol-2-yl)imino)methyl)naphthalen-2-ol monohydrate (HL2·H₂O) were synthesized and characterized by IR, UV-vis, EI-mass, ¹H NMR spectroscopy, and single-crystal X-ray diffraction studies. Molecular structure determination suggested the presence of crystal water in the unit cell of each compound. The structure adopted a usual enol-imine form, with an intramolecular hydrogen bond between the phenolate-oxygen and the imine-nitrogen atoms. Supramolecular packing indicated that the structure was assembled and stabilized by several significant intermolecular non-covalent interactions between symmetrically related lattice water and the molecules, as supported by quantitative Hirshfeld surface analyses. DSC analyses revealed an irreversible phase transition from solid-crystal to isotropic liquid. Computational modeling by DFT/TD-DFT supported the experimental results of the molecular and electronic structures of the compounds. Molecular orbital (MO) calculations revealed a relatively lower HOMO-LUMO energy gap for HL2 (ΔE g = 2.41 eV) compared with HL1 (2.65 eV), suggesting the former had enhanced charge delocalization due to the extended π-electrons conjugation system, in parallel with molecular electrostatic potential (MEP) surface maps. Biological activities were assessed using cytotoxicity, antioxidant, α-amylase, and antibacterial tests. HL1 possessed more pronounced cytotoxic effects on cervical cancer (HeLa) cells (IC₅₀ = 75.53 ± 3.10 µM) than HL2 (IC₅₀ = 462.61 ± 5.24 µM). DPPH radical-scavenging studies revealed moderate antioxidant activity for HL2 (IC₅₀ = 168 ± 4 µM) and weaker activity for HL1 (IC₅₀ = 233 ± 5 µM) compared with the standard ascorbic acid (IC₅₀ = 106 ± 1 µM). HL1 showed moderately the inhibit α-amylase enzyme (IC₅₀ = 399 ± 2.7 µM), while no inhibitory activity for HL2 was noted. Both compounds were moderately active against selected bacterial strains in a concentration-dependent manner. Computational analyses on Escherichia coli BepA metalloprotease (6SAR) and human DNA topoisomerase IIα (5GWK) using molecular docking exhibited favorable predicted protein-ligand interactions, involving hydrogen-bonding, hydrophobic and π-stacking interactions. HL1 had a more favorable predicted binding affinity towards BepA metalloprotease, whereas HL2 had a more favorable predicted binding affinity towards human DNA topoisomerase IIα, which was associated with enhanced hydrophobic interactions.
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BibTeX
@article{enamullah2026synthesis,
title = {{Synthesis, molecular structure, supramolecular and biological evaluation of benzimidazole-based Schiff bases}},
author = {Mohammed Enamullah and Imdadul Haque and Taslima Akter and Tarek Aziz and Amelia Kacperkiewicz and David E Herbert and Takin Haj Hassani Sohi and Christoph Janiak},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra07753f},
url = {https://europepmc.org/article/PMC/PMC13717624},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Synthesis, molecular structure, supramolecular and biological evaluation of benzimidazole-based Schiff bases
AU - Mohammed Enamullah
AU - Imdadul Haque
AU - Taslima Akter
AU - Tarek Aziz
AU - Amelia Kacperkiewicz
AU - David E Herbert
AU - Takin Haj Hassani Sohi
AU - Christoph Janiak
PY - 2026
DA - 2026/10/29
JO - RSC advances
DO - 10.1039/d6ra07753f
UR - https://europepmc.org/article/PMC/PMC13717624
AB - Benzimidazole-based Schiff bases, (Z)-2-(((1H-benzo[d]imidazol-2-yl)imino)methyl)phenol monohydrate (HL1·H₂O) and (Z)-1-(((1H-benzo[d]imidazol-2-yl)imino)methyl)naphthalen-2-ol monohydrate (HL2·H₂O) were synthesized and characterized by IR, UV-vis, EI-mass, ¹H NMR spectroscopy, and single-crystal X-ray diffraction studies. Molecular structure determination suggested the presence of crystal water in the unit cell of each compound. The structure adopted a usual enol-imine form, with an intramolecular hydrogen bond between the phenolate-oxygen and the imine-nitrogen atoms. Supramolecular packing indicated that the structure was assembled and stabilized by several significant intermolecular non-covalent interactions between symmetrically related lattice water and the molecules, as supported by quantitative Hirshfeld surface analyses. DSC analyses revealed an irreversible phase transition from solid-crystal to isotropic liquid. Computational modeling by DFT/TD-DFT supported the experimental results of the molecular and electronic structures of the compounds. Molecular orbital (MO) calculations revealed a relatively lower HOMO-LUMO energy gap for HL2 (ΔE g = 2.41 eV) compared with HL1 (2.65 eV), suggesting the former had enhanced charge delocalization due to the extended π-electrons conjugation system, in parallel with molecular electrostatic potential (MEP) surface maps. Biological activities were assessed using cytotoxicity, antioxidant, α-amylase, and antibacterial tests. HL1 possessed more pronounced cytotoxic effects on cervical cancer (HeLa) cells (IC₅₀ = 75.53 ± 3.10 µM) than HL2 (IC₅₀ = 462.61 ± 5.24 µM). DPPH radical-scavenging studies revealed moderate antioxidant activity for HL2 (IC₅₀ = 168 ± 4 µM) and weaker activity for HL1 (IC₅₀ = 233 ± 5 µM) compared with the standard ascorbic acid (IC₅₀ = 106 ± 1 µM). HL1 showed moderately the inhibit α-amylase enzyme (IC₅₀ = 399 ± 2.7 µM), while no inhibitory activity for HL2 was noted. Both compounds were moderately active against selected bacterial strains in a concentration-dependent manner. Computational analyses on Escherichia coli BepA metalloprotease (6SAR) and human DNA topoisomerase IIα (5GWK) using molecular docking exhibited favorable predicted protein-ligand interactions, involving hydrogen-bonding, hydrophobic and π-stacking interactions. HL1 had a more favorable predicted binding affinity towards BepA metalloprotease, whereas HL2 had a more favorable predicted binding affinity towards human DNA topoisomerase IIα, which was associated with enhanced hydrophobic interactions.
SN - 2046-2069
ER -