Applied Chemical Engineering

Cr (III), Mn (II), Co (II), and Ni (II) complexes with a bidentate Mannich base: Synthesis, bioevaluation, and docking studies of the free ligand

Marwa Jassim Al-Muhamadawi

Department of Chemistry, College of Science, Mustansiriyah University, Baghdad, 10045, Iraq

Rehab Abdul Mahdi Al-Hassani

Department of Chemistry, College of Science, Mustansiriyah University, Baghdad, 10045, Iraq

DOI: https://doi.org/10.59429/ace.v8i4.5766

Keywords: 5-chloro-2-mercapto-oxazole; benzaldehyde; mannich base ligand; mannich base complexes; coordination complexes; FTIR; UV-Vis spectroscopy; transition metals; molecular docking

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Abstract

The design and synthesis of novel coordination compounds have attracted considerable interest in the field of inorganic chemistry field, particularly as a result of Mannich base ligands’ capability of forming stable complexes with metal ions often result in an enhancement of the chemical and physical characteristics.   In the present study, a new Mannich base ligand was synthesized by condensing benzaldehyde, di-benzylamine, and 5-chloro-2-mercapto-oxazole. The ligand has been thoroughly characterized using elemental analysis (CHNS), Fourier-transform infrared spectroscopy (FTIR), ultraviolet–visible spectroscopy (UV–Vis), proton and carbon nuclear magnetic resonance spectroscopy (¹H NMR and ¹³C NMR), and mass spectrometry. As a result, the ligand’s coordination complexes with ions of Co (II), Cr (III), Mn (II), and Ni (II) had been synthesized and characterized through FT-IR, magnetic susceptibility measurements, UV-Vis spectroscopy, molar conductivity, and elemental analyses for the purpose of elucidating their electronic and structural features. FTIR spectra had confirmed the ligand’s bidentate coordination mode across all metal complexes. The electronic spectra and magnetic moment data indicated that the resulting complexes are of a variety of geometries according to the center of the metal. Molar conductivity measures have revealed that all complexes exhibited non-electrolytic behavior in the solutions suggesting high structural integrity and stability level. In addition to that, molecular docking studies were performed on the free ligand using the gold program to evaluate its possible interactions with the targeted enzyme’s active site. The docking analyses showed that ligand has the ability to effectively interact with residues of key amino acids within the enzyme’s active site, which results in the formation of stable binding conformations in addition to extensive bonding of hydrogen bonds, which support its possible biological activities. Additionally, the biological activities of the synthesized ligand and the biological activities of its metal complexes were assessed in vitro against bacterial strains, which include Escherichia coli and Staphylococcus aureus, in addition to some fungal species, like Penicillium spp. and Aspergillus flavus. The MICs (i.e., minimum inhibitory concentrations) were determined to assess the compounds’ anti-microbial potency. Standard antibiotics, Fluconazole and Ampicillin, have been used as reference drugs. Results showed that metal complexes exhibited an improved anti-microbial activity compared with the reference drugs and free ligands, which has highlighted their potential for a wider range of pharmaceutical applications.

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References

[1]. Smith J., Petrovic P., Rose M., De Souz C., Muller L., Nowak B., Martinez J., Placeholder Text: A Study, The Journal of Citation Styles, 2021, 3:2000

[2]. Tamilvendan D., Rajeswari S., Ilavenil S., Chakkaravarthy K., Venkatesa Prabhu G., Syntheses, spectral, crystallographic, antimicrobial, and antioxidant studies of few Mannich bases, Medicinal Chemistry Research, 2012, 21:4129

[3]. Kalia S., Jasrotia R., Singh V.P. (eds.). Magnetic Nanoferrites and Their Composites: Environmental and Biomedical Applications. Elsevier; 2023.

[4]. Afsah E.M., Elmorsy S.S., Abdelmageed S.M., Zaki Z.E., Synthesis of some new mixed azines, Schiff and Mannich bases of pharmaceutical interest related to isatin, Zeitschrift für Naturforschung B, 2015, 70:393

[5]. Biersack B., Ahmed K., Padhye S., Schobert R., Recent developments concerning the application of the Mannich reaction for drug design, Expert Opinion on Drug Discovery, 2018,13:39

[6]. Waheed E.J., Al-Khazraji A., Ahmed A.A., Versatile applications of mannich base ligands and their metal complexes: a review article, Journal of Applied Sciences and Nanotechnology, 2023,3:42

[7]. Khazaal A.Q., Mahmood Z.F., Hammood S.A., Analyzing the characteristics and biological activities of methanolic extracts from Stachys byzantina leaves, Iraqi Journal of Agricultural Sciences, 2024, 55:1894

[8]. Etheb A.M., Al-Jeboori M.J., Synthesis, structural characterisation and biological activity of new Mannich compounds derived from cyclohexanone moiety, HIV Nursing, 2022, 22:3659

[9]. Saleh H.A., Abdul Rahman A.S.A., Al-Jeboori M.J., Synthesis, structural characterisation and biological evaluation of new semicarbazone metal complexes derived from Mannich-base, Biochemical & Cellular Archives, 2021, 21:1

[10]. Subrahmanian S., Thirumoorthy K., Singh R.R., Prasad M., Mannich metal complex: Synthesis, reaction mechanism and computational studies, Journal of Molecular Structure, 2022, 1268:133625.

[11]. Manhee T.Q., Alabdali A.J., Synthesis, characterization, and anticancer activity of Ni(II), Cu(II), Pd(II), and Au(III) complexes derived from a novel Mannich base, Vietnam Journal of Chemistry, 2024, 62:201.

[12]. Aldeen S.W.A., Abbass N.M., Metal complexes of Metronidazole Benzoate with some metal ions: synthesis and characterization and study apart from their biological applications,2023.

[13]. Kadhim H.M., Kadhim Y.M., Fawzi H.A., Abdul Khalik Z.M., Jawad A.M., Ghédira K., Bioassay-guided isolation and active compounds identification of the antidiabetic fractions of Centaurea calcitrapa extract and the predicted interaction mechanism, Molecules, 2025, 30:2394.

[14]. Shimanouchi T., Matsuura H., Ogawa Y., Harada I., Tables of molecular vibrational frequencies, Journal of Physical and Chemical Reference Data, 1978, 7:1323.

[15]. Karaağaç D., Spectroscopic and thermal studies of cyano bridged hetero-metallic polymeric complexes derived from ligands containing N and S donor atoms, Bulletin of the Chemical Society of Ethiopia, 2020, 34:365.

[16]. Koucký F., Dobrovolná T., Kotek J., Císařová I., Havlíčková J., Liška A., Hermann P., Transition metal complexes of the (2,2,2-trifluoroethyl) phosphinate NOTA analogue as potential contrast agents for 19F magnetic resonance imaging, Dalton Transactions, 2024, 53:9267.

[17]. Al-Jeboori M.J., New metal complexes derived from Mannich-base ligand: synthesis, spectral characterisation and biological activity, J. Global Pharma Tech, 2019, 11:548.