Error message

  • Deprecated function: Unparenthesized `a ? b : c ? d : e` is deprecated. Use either `(a ? b : c) ? d : e` or `a ? b : (c ? d : e)` in include_once() (line 1439 of /home/science2016/public_html/includes/bootstrap.inc).
  • Deprecated function: Array and string offset access syntax with curly braces is deprecated in include_once() (line 3557 of /home/science2016/public_html/includes/bootstrap.inc).
  • Deprecated function: Unparenthesized `a ? b : c ? d : e` is deprecated. Use either `(a ? b : c) ? d : e` or `a ? b : (c ? d : e)` in include_once() (line 1439 of /home/science2016/public_html/includes/bootstrap.inc).
  • Deprecated function: Array and string offset access syntax with curly braces is deprecated in include_once() (line 3557 of /home/science2016/public_html/includes/bootstrap.inc).

Design and Synthesis of Imidazole-Based Ligand and Its Metal Complexes: Spectroscopic Characterization and Evaluation of Antibacterial, Antioxidant and Hemolytic Activities

Howraa A. Khudair1, Sawsan K. Abbas2, Suhad K. Abbas1
Affiliation: 
Department of Chemistry, College of Science, University of Kerbala, Karbala, Iraq1 2Department of Chemistry, College of Education for Pure Science, University of Kerbala, Karbala, Iraq suhad.k@uokerbala.edu.iq
DOI: 
https://doi.org/
AttachmentSize
PDF icon full_text.pdf1.49 MB

Keywords:

Abstract: 
In this study, new complexes containing a multi-substituted aryl imidazole ligand, namely (2-(1H-phenanthro[9,10-d] imidazol-2-yl) phenol, have been synthesized. Imidazole ligand L was synthesized via a condensation reaction between diketone (9,10-phenathroquinone), aromatic aldehyde (2-hydroxy benzaldehyde), and ammonium acetate in the presence of glacial acetic acid as a solvent and catalyst. Subsequently, metal complexes were prepared by reacting this ligand with transition metal salts, including Fe (II), Cu (II), Ni(II), and Co(II) chlorides, in an appropriate solvent like ethanol under controlled temperature and stirring conditions to ensure the formation of stable complexes. The structures of the ligands and their metal complexes were characterized utilizing different spectroscopic techniques, such as (UV-Vis), FT-IR, 1H NMR, 13C NMR spectroscopic, mass spectroscopy, magnetic susceptibilities, molar conductivity, and elemental analysis (C.H.N). It is observed that the synthesized complexes have tetrahedral and octahedral geometrical structures. The ligand and its complexes play important roles in supramolecular assemblies because they can also provide bidentate N-donor sites for chelating with metal ions to form a bridge ligand. The biological evaluation was performed using the agar well diffusion method to assess the antibacterial activity of both ligand and metal complexes against selected Gram-positive and Gram-negative bacterial strains. The results revealed that the free ligand and its metal complexes displayed significantly enhanced antibacterial activity compared to the reference drug. Antioxidant potential was assessed using the DPPH radical scavenging assay; metal complexes generally showed higher radical inhibition percentage. Hemolytic activity was evaluated on human red blood cells to determine cytocompatibility. The findings showed that the ligand and metal complexes exhibited low to moderate hemolytic activity, indicating acceptable biocompatibility for potential biomedical applications.
References: 

[1] Jeenat, A.; Ruby, A.; Chandrabhan, V. Imidazole and its derivatives as corrosion inhibitors. In Organic Corrosion Inhibitors: Synthesis, Characterization, Mechanism, and Applications; Wiley, 2021; pp 95–122. https://doi.org/10.1002/9781119794516.ch6
[2] Liu, H.; Yang, Ch.; Li, T.; Ma, S.; Wang, P.; Wang, G.; Su, Sh.; Ding, Y.; Yang, L.; Zhou, X.; et al. Design, Synthesis and Bioactivity Evaluation of Novel 2-(Pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents. Molecules 2023, 28, 2442. https://doi.org/10.3390/molecules28062442
[3] Gujjarapp, R.; Kabi, A.K.; Sravani, S.; Garg, A.; Vodnala, N.; Tyagi, U.; Kaldhi, D.; Velayutham, R.; Singh, V.; Gupta, S.; et al. Overview on Biological Activities of Imidazole Derivatives. In Nanostructured Biomaterials. Materials Horizons: From Nature to Nanomaterials; Swain, B.P., Ed.; Springer: Singapore, 2022; pp 135–227. https://doi.org/10.1007/978-981-16-8399-2_6
[4] Kedimar, N.; Rao, P.; Rao, S. A. Imidazole-Based Ionic Liquid as Sustainable Green Inhibitor for Corrosion Control of Steel Alloys: A Review. J. Mol. Liq. 2024, 411, 125789. https://doi.org/10.1016/j.molliq.2024.125789
[5] Tolomeu, H. V.; Fraga, C. A. M. Imidazole: Synthesis, Functionalization and Physicochemical Properties of a Privileged Structure in Medicinal Chemistry. Molecules 2023, 28, 838. https://doi.org/10.3390/molecules28020838
[6] Siwach, A.; Verma, P. K. Synthesis and Therapeutic Potential of Imidazole Containing Compounds. BMC Chemistry 2021, 15, 12. https://doi.org/10.1186/s13065-020-00730-1
[7] Sağlık, B. N.; Işık, A.; Çevik, U. A.; Özkay, Y. Synthesis, Characterization, and Molecular Docking Study of Some Novel Imidazole Derivatives as Potential Antifungal Agents. J. Heterocycl. Chem. 2018, 56, 142–152. https://doi.org/10.1002/jhet.3388
[8] Sawsan, K. A; Mohammed, T.J; Hayder ,R A, Alanood ,A. A. Synthesis, Antibacterial Evaluation and molecular docking of 2,4,5-Tri-imidazole Derivatives. Mor. J. Chem. 2024, 12, 1222–1239. https://doi.org/10.48317/IMIST.PRSM/morjchem-v12i3.48221
[9] Li, Z.; Bhowmik, S.; Sagresti, L.; Brancato, G.; Smith, M.; Benson, D. E.; Li, P.; Merz, K. M., Jr. Simulating Metal-Imidazole Complexes. J. Chem. Theory Comput. 2024, 20, 6706–6716. https://doi.org/10.1021/acs.jctc.4c00581
[10] Taheri, B.; Taghavi, M.; Zarei, M.; Chamkouri, N.; Mojaddami, A. Imidazole and Carbazole Derivatives as Potential Anticancer Agents: Molecular Docking Studies and Cytotoxic Activity Evaluation. Bull. Chem. Soc. Ethiop. 2020, 34, 235–246. https://doi.org/10.4314/bcse.v34i2.14
[11] Serdaliyeva, D.; Nurgozhin, T.; Satbayeva, E.; Khayitova, M.; Seitaliyeva, A.; Ananyeva, L. Review of Pharmacological Effects of Imidazole Derivatives. J. Clin. Med. Kazakh. 2022, 19, 11–15. https://doi.org/10.23950/jcmk/12117
[12] Bouchal, B.; Abrigach, F.; Takfaoui, A.; Ichou, F.; Kabouche, Z.; Kabouche, A.; Bendahou, M. Identification of Novel Antifungal Agents: Antimicrobial Evaluation, SAR, ADME–Tox and Molecular Docking Studies of a Series of Imidazole Derivatives. BMC Chem. 2019, 13, 100. https://doi.org/10.1186/s13065-019-0623-6
[13] Sawsan, K. A; Lamyaa, S M; Jihan, H. A. Synthesis and Biological Evaluation of New 2,4,5-Trisubstituted and 1,2,4,5-Tetrasubstituted Imidazole Derivatives as Antioxidant and Antimicrobial Agents. Chem. Data Collect. 2025, 58, 101194. https://doi.org/10.1016/j.cdc.2025.101194
[14] Patel, H. M.; Noolvi, M. N.; Sethi, N. S.; Gadad, A. K.; Cameotra, S. S. Synthesis and Antitubercular Evaluation of Imidazo[2,1-b][1,3,4]thiadiazole Derivatives. Arab. J. Chem. 2013, 10, 717–724. https://doi.org/10.1016/j.arabjc.2013.01.001
[15] Selwin Joseyphus, R.; Reshma, R.; Arish, D.; Elumalai, V. Antimicrobial, Photocatalytic Action and Molecular Docking Studies of Imidazole-Based Schiff Base Complexes. Results Chem. 2022, 4, 100583. https://doi.org/10.1016/j.rechem.2022.100583
[16] Volpi, G.; Laurenti, E.; Rabezzana, R. Imidazopyridine Family: Versatile and Promising Heterocyclic Skeletons for Different Applications. Molecules 2024, 29, 2668. https://doi.org/10.3390/molecules29112668
[17] Hiremath, A. F.; Pradeep Kumar, M. R.; Rajagopal, K.; Barua, R.; Rab, S. O.; Alshehri, M. A.; Bin Emran, T. Imidazole-Based Metal Complex Derivatives: A Comprehensive Overview of Synthesis and Biological Applications. Med. Chem. 2024, 31, 1015–1050. https://doi.org/10.2174/0115734064332208241015154509
[18] Loginova, N. V.; Harbatsevich, H. I.; Osipovich, N. P.; Ksendzova, G. A.; Koval’chuk, T. V.; Polozov, G. I. Metal Complexes as Promising Agents for Biomedical Applications. Curr Med Chem. 2020, 27, 5213–5249. https://doi.org/10.2174/0929867326666190417143533
[19] Ndagi, U.; Mhlongo, N.; Soliman, M. E. Metal Complexes in Cancer Therapy—An Update from Drug Design Perspective. Drug Des. Devel. Ther. 2017, 11, 599–616. https://doi.org/10.2147/DDDT.S119488
[20] Lateef, H. M. A.; El-Dabea, T.; Khalaf, M. M.; Abu-Dief, A. M. Recent Overview of Potent Antioxidant Activity of Coordination Compounds. Antioxidants 2023, 12, 213. https://doi.org/10.3390/antiox12020213
[21] Boros, P.; Dyson, P. J.; Gasser, G. Classification of Metal-Based Drugs according to Their Mechanisms of Action. Chem 2020, 6, 41–60. https://doi.org/10.1016/j.chempr.2019.10.013
[22] Mondal, R.; Guin, A.K.; Chakraborty, G.; Paul, N.D. Metal–Ligand Cooperative Approaches in Homogeneous Catalysis Using Transition Metal Complex Catalysts of Redox Noninnocent Ligands. Org. Biomol. Chem. 2022, 20, 296–328. https://doi.org/10.1039/D1OB01153G
[23] Gulcin, İ.; Alwasel, S. H. Metal Ions, Metal Chelators and Metal Chelating Assay as Antioxidant Method. Processes 2022, 10, 132. https://doi.org/10.3390/pr10010132
[24] Sánchez-López, E.; Gomes, D.; Esteruelas, G.; Bonafé, F.; Cianciosi, D.; Estrela, J. M.; Espinosa, A.; Ettcheto, M.; Cano, A.; López-Torres, M.; et al. Metal-Based Nanoparticles as Antimicrobial Agents: An Overview. Nanomaterials 2020, 10, 292. https://doi.org/10.3390/nano10020292
[25] Gautam, S.; Das, D.K.; Kaur, J. Transition Metal-Based Nanoparticles as Potential Antimicrobial Agents: Recent Advancements, Mechanistic, Challenges, and Future Prospects. Nanoscale Res. Lett. 2023, 18, 261. https://doi.org/10.1186/s11671-023-03861-1
[26] Nguyen, V.-T.; Huynh, T.-K.-C.; Gia-Thien-Thanh Ho, G.-T.-C.; Nguyen, T.-H.-A.; Dao, D.Q.; Mai, T.V.T.; Huynh, L.K.; Hoang, T.K.D. Metal Complexes of Benzimidazole-Derived as Potential Anti-Cancer Agents: Synthesis, Characterization, Combined Experimental and Computational Studies. R. Soc. Open Sci 2022, 9, 220659. https://doi.org/10.1098/rsos.220659
[27] Silverstein, R. M.; Webster, F. X.; Kiemle, D. J. Spectrometric Identification of Organic Compounds, 8th ed.; Wiley: Hoboken, NJ, 2014.
[28] Nourah, A.; Abd El-Lateef, H. M.; Mohamed, M.; Khalaf, M. M.; Abdou, A. Fe(III) and Ni(II) Imidazole-Benzimidazole Mixed-Ligand Complexes: Synthesis, Structural Characterization, Molecular Docking, DFT Studies, and Evaluation of Antimicrobial and Anti-Inflammatory Activities. Dalton Trans. 2025, 54, 12345–12360. https://doi.org/10.1039/D5DT00551E
[29] Ravera, E.; Gigli, L.; Czarniecki, B.; Lang, L.; Kümmerle, R.; Parigi, G.; Piccioli, M.; Neese, F.; Luchinat, C. A Quantum Chemistry View on Two Archetypical Paramagnetic Pentacoordinate Nickel (II) Complexes Offers a Fresh Look on Their NMR Spectra. Inorg. Chem. 2021, 60, 2068–2075. https://doi.org/10.1021/acs.inorgchem.0c03635
[30] Bera, R.; Ansari, M.; Alam, A.; Das, N. Riptycene, Phenolic-OH, and Azo-Functionalized Porous Organic Polymers: Efficient and Selective CO2 Capture. ACS Appl. Polym. Mater. 2019, 1, 959–968. https://doi.org/10.1021/acsapm.9b00213
[31] Asma, F.; Salah Eddine, H.; Yassmine, C.; Hanane, Z. Phytochemical Screening, Antibacterial and Antioxidant Activities of Ocimum basilicum L. Cultivated in Biskra, Algeria. Chem. Chem. Technol. 2023, 17, 397–406. https://doi.org/10.23939/chcht17.02.397
[32] Brand-Williams, W.; Cuvelier, M. E.; Berset, C. Use of a Free Radical Method to Evaluate Antioxidant Activity. LWT—Food Sci. Technol. 1995, 28, 25–30 https://doi.org/10.1016/S0023-6438(95)80008-5
[33] Amić, D.; Stepić, V.; Lucić, B.; Marković, Z.; Dimitrić Marković, J. M. PM6 Study of Free Radical Scavenging Mechanisms of Flavonoids: Why Does O–H Bond Dissociation Enthalpy Effectively Represent Free Radical Scavenging Activity? J. Mol. Model. 2013, 19, 2593–2603. https://doi.org/10.1007/s00894-013-1800-5
[34] Foti, M. C.; Daquino, C.; Geraci, C. Electron-Transfer Reaction of Cinnamic Acids and Their Methyl Esters with the DPPH Radical in Alcoholic Solutions. J. Org. Chem. 2004, 69, 2309. https://doi.org/10.1021/jo035758q
[35] Mohammed, S. A.; Mousa, H. M.; Alwan, A. H. Determination of Hemolytic Cytotoxicity and Antibacterial Activity of Conocarpus lancifolius Aqueous Leaves Extract. IOP Conf. Ser.: Mater. Sci. Eng. 2019, 571, 012045. https://doi.org/10.1088/1757-899X/571/1/012045