Structural, molecular docking computational studies and in-vitro evidence for antibacterial activity of mixed ligand complexes

https://doi.org/10.1016/j.molstruc.2021.130481Get rights and content

Highlights

  • Molecular docking was used to predict the binding between 8-hydroxyquinoline, H2L1 and its mixed ligand complexes with receptors

  • The XRD patterns of the mixed ligand complexes were studied

  • The antimicrobial activity of 8-hydroxyquinoline, H2L1 and its mixed ligand complexes were investigated

  • Study of the cytological effect of the most active compounds: H2L1 and its M(II) and Cr(III) mixed ligand complexes

  • in-vitro activity and in-silico binding to some bacterial divisome proteins were tested

Abstract

A novel bis-bidentate azo dye ligand, formed by the diazotized reaction of 1,4-diaminobenzene and 8- hydroxyquinoline in 1:2 M ratio resulted the formation of 5,5′-{(1E, 1E`)-1,4-phenylenebis(diazene-2,1-diyl)}bis(quinoline-8-ol) (H2L1) as primary ligand and its Cu(II), Ni(II), Co(II), Mn(II), Cr(III), UO2(II) and Cd(II) complexes. Incorporating of 8-hydroxyquinoline (HL2) as co-ligand with the formed mixed-ligand complexes of the composition, [M2(L1)(L2)2(OH2)4] (M = Cu(II), Co(II), Ni(II), Mn(II), UO2(II), Cd(II) and [Cr2(L1)(L2)2(OH2)2(Cl2)] were synthesized and characterized. H2L1, HL2, and their mixed ligand complexes were screened against two local gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) and three local gram-negative bacteria (Klebsiella pneumoniae Escherichia coli and Pseudomonas sp). Antifungal activities were determined against Fusarium oxysporum Aspergillus niger, and Candida albicans. Cr(III), Mn(II) and UO2(II) mixed ligand complexes showed higher activity than H2L1 and HL2; their cytological effects on S. aureus and B. cereus along with the in-silico docking showed that these complexes represent antibacterials targeting FtsZ and DltA proteins; hence, affect cell divisions and gram-positive cell walls. The XRD patterns of the Mn(II) and UO2(II) mixed ligand complexes are polycrystalline natures.

Introduction

Azo compounds are known to be involved in a number of biological reactions, such as inhibition of DNA, RNA, and protein synthesis, nitrogen fixation [1], [2], [3], [4]. Azo dyes have high dyeing and good fastness properties and wide applications in dyeing of textile fibers, plastics, leather, paper and bio-medical studies.

It was found that a hydroxyl group in the quinoline ring confers special characteristics to the ligand, introducing changes in structural and spectroscopic properties of the complexes [5,6]. Also, nitrogen-containing heterocyclic compounds, in particular quinolines, have an important place among a large number of organic ligands. Due to the negatively charged group the charge density redistributed through the ring, reinforces the ligand bonds counteracting. In some cases, the weakening effect generated after the coordination of the metal. The proposed assignments are mainly based on comparisons with previously reported data for compounds of related ligands [7,8].

One of the main goals of present day inorganic coordination chemists and pharmaceutical investigations is the discovery and development of better drugs to fight diseases, and this has led to numerous studies on drug metal complexes [9].

Studies have shown that azo dye quinoline/quinoline may be considered a biologically important ligand manifested in the formation of chelate rings involving various coordination site [5,6]. In view of its biological and chemical properties, quinoline is a suitable ligand for the synthesis of complexes involving bioactive metals as cobalt, nickel and copper [10]. Quinoline has been used as a co-ligand to form mixed ligand complexes of ranitidine which is the most useful drug in the management of peptic and duodenal ulcer [11].

Azo dyes quinoline play important roles in coordination chemistry as they easily form stable complexes with most transition metal ions [12,13]. Many biologically important azo dyes quinoline have been reported in the literature possessing, antimicrobial, antibacterial, antifungal, anti-inflammatory, anticonvulsant, antitumor and anti HIV activities [5,6].

In the present work, we describe the synthesis, characterization and antimicrobial activities of 8-hydroxyquinoline (HL2), (5,5′-{(1E, 1E`)-1,4-phenylenebis(diazene-2,1-diyl)}bis(quinoline-8-ol)) (H2L1) and mixed ligand complexes. The in-vitro activity (in comparing with the standard antimicrobial drugs) and in-silico binding to some bacterial divisome proteins were tested. The cytological effect of H2L1 and mixed ligand complexes as well as HL2 was studied.

Section snippets

Preparation of H2L1 ligand and their mixed ligand complexes

1,4-Diaminobenzene (1 mmol) was dissolved in H2O (10 ml). 1 mol/l HCl (13.6 ml) and 10 % NaNO2 aqueous solution (3.1 ml) was added, and the solution were stirred at -5 °C for ~1 hr to complete diazotization. 8-Hydroxyquinoline (2 mmol) in 2 mol/l NaOH (4 ml) was added dropwise for 30 minutes and the stirring continued overnight. The pH was adjusted to ~ 9 and the precipitated dye was collected by filtration and dried under vacuum.

Mixed ligand complexes were prepared as described recently [10,14

Characterization of the ligand and the mixed ligand complexes

Elemental analysis exhibit show that all mixed-ligand complexes have (1:1:1) stoichiometry, all of them have a dark colored, stable, excellent yields, high melting point and soluble in DMF and DMSO solvent. The values of the molar conductance are very low showing the non-electrolytic nature of the mixed ligand complexes. The complex (1) depicts a broad band in the region 13,560 to 17,750 cm−1 with maximum at ~ 15,650 cm−1 in its spectrum, the broadness of the band may be due to tetragonal

Conclusion

Based on the above discussion and information available in the literature, the following conclusions may be drawn.

  • IR spectra show bonding of the metal ion through NO atoms of the two ligands and presence of water of bonding, confirmed by thermal analysis.

  • The XRD patterns of the mixed-ligand complexes (1, 3, 4 and 6) complexes show that these mixed ligand complexes are polycrystalline phases.

  • The proposed geometry for all the mixed-ligand complexes is octahedral.

  • Magnetic studies are indicative of

Funding

There are no funders to report for this submission.

Declaration of Competing Interest

None.

Acknowledgments

Acknowledgments and thanks to Dr. Ahmed Hassan Abu Hashim, Undersecretary of the Ministry of Health in Port Said for his encouragement and moral support during the scientific research.

The authors are grateful to Mr. Mohamed Marzouk El-Zahed, Assistant Lecturer of Microbiology at Botany and Microbiology Department, Faculty of Science, Damietta University, for his effort for detecting antimicrobial activities of the synthesized compounds.

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