Metal complexes of ferrocenyl-substituted Schiff base: Preparation, characterization, molecular structure, molecular docking studies, and biological investigation

doi:10.1016/j.jorganchem.2020.121113

Journal of Organometallic Chemistry

Volume 917, 21 June 2020, 121113

https://doi.org/10.1016/j.jorganchem.2020.121113 Get rights and content

Highlights

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Organometallic Schiff base ligand (L) and its metal complexes were synthesized and characterized using different tools.
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Molecular docking studies of ferrocene, Schiff base and its complexes with the active site of 3HB5 receptor also studied.
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The result of biological activity of the ligand and its complexes was recorded.

Abstract

The organometallic Schiff base ligand (L) was synthesized by reacting 2-acetylferrocene with 1,8-naphthalenediamine in 1:1 molar ratio. The reaction of Schiff base with some transition metal ions mains to mono-species of chelates. The ligand and its metal complexes were characterized using elemental analysis (C, H, N and M), molar conductivity, FT-IR, UV–Vis, ¹H NMR, SEM and mass spectrometry. Also, their TG and DTG studies were investigated. All complexes had an octahedral geometry. From the spectral analyses data, the Schiff base ligand acted as NN-bidentate ligand. In addition, computational studies of the ligand (L) have been carried out by using the DFT method. From the optimized structure, the energy gap, HOMO, LUMO energy values, electronegativity and electrophilic index were calculated. The antibacterial and antifungal activities of the synthesized complexes have been screened in vitro against different bacteria and fungi species. The effect of these complexes on the proliferation of human breast cancer (MCF-7) cell line was studied and then compared with the parent free organometallic Schiff base. It was found that [Fe(L)(H₂O)₂Cl₂]Cl.3H₂O complex showed the lowest IC₅₀ value (11.3 μM). Docking studies were used to investigate the interaction between ferrocene, Schiff base and its metal complexes with the active site of the 3HB5 receptor.

Graphical abstract

Introduction

Cyclometalated complexes of a large variety of ligands that contain N, S or O as the heteroatom, have been widely investigated. The cyclometallated compounds containing a metal-carbon bond that stabilized by the intramolecular coordination of one or two neutral atoms are well known. These π-donor ligands and their metal complexes have great interest because of their important applications in many areas including homogeneous catalysis, design of new metallomesogens, organic synthesis, antitumoral medicines and resolution of racemic ligands [1]. The synthesis of half-sandwich metal-containing compounds is being investigated due to their crucial effect in the radiopharmaceutical industry. Some of these compounds are made from cyclopentadiene that attached to a targeting biomolecule such as a small molecule or a tumor-specific peptide that binds to a central nervous system receptor [2,3]. The bio-organometallic chemistry is a new field that gaining a lot of research interest where cyclopentadiene ligated transition metal compounds give a link between organometallic chemistry with molecular biotechnology, biology and medicine [4]. Scientists utilized organometallic compounds that can be used in treating breast cancer, which is the most common cancer among women, affecting about one in eight females [5]. Many of metal-containing compounds can be used as good reducing agents. For example, ferrocene, this is readily oxidized by hydroxyl radicals to stable ferrocenium. These hydroxyl radicals (^•OH) are reduced to (^–OH). This redox reaction can help in removing these deleterious compounds. This fact proposes that the ferrocene group may be useful in the therapeutic center if its pharmacokinetic response, solubility and distribution in the body could be suitably tailored [6]. The ferrocenyl group shows a special affinity towards proteins, amino acids, carbohydrates and DNA. So, it was widely used in the medicinal designs and biological researches. The ferrocene-related organometallic medicines have pharmacological functions of mainly ascribe to the effects of the cytotoxicity, redox property and lipophilicity of the ferrocene moiety on biological targets [[7], [8], [9]]. In continuation of our interest in organometallic ferrocene Schiff base ligands and their coordination chemistry [10], this article was interested in the synthesis of novel organometallic Schiff base ligand (L) by condensation of 2-acetylferrocene with 1,8-naphthalenediamine, then its coordination behavior with different transition metal ions was studied. The prepared ligand (L) and its metal complexes were characterized using different techniques. The biological and anticancer activities of these compounds were investigated. Also, the molecular and electronic structure of the organometallic Schiff base ligand was optimized theoretically and different quantum chemical parameters were calculated. Furthermore, molecular docking was studied to explain the mode of binding of the ferrocene, organometallic Schiff base (L) and its Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes with the receptor of breast cancer mutant oxidoreductase (PDB ID: 3HB5).

Section snippets

Characterization of the organometallic Schiff base ligand (L)

The organometallic Schiff base ligand (L) was synthesized by the reaction between 2-acetylferrocene and 1,8-naphthalenediamine in 1:1 molar ratio. The results of an elemental analysis for the ligand were in good agreement with the calculated values that confirmed its molecular formula as C₂₂H₂₀FeN₂. The synthesized ligand was stable in air and soluble in DMF and DMSO. The IR spectral analysis provides some important information concerning the skeleton of the synthesized ligand. The most

Conclusion

This paper represented a simple method for synthesis of a new organometallic Schiff base ligand (L) and its Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes. Both the Schiff base ligand (L) and its metal complexes were characterized by using different spectroscopic techniques for determination of their geometry.

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From IR spectral analysis: the prepared Schiff base ligand behaved as a neutral bidentate ligand in all metal complexes. It formed coordinate bonds with the

Materials and reagents

Chemicals of the highest purity were used in the preparation and in all analyses. The chemicals used included 2-acetylferrocene, 1,8-naphthalenediamine, hexahydrate of Cr(III), Fe(III), Co(II) and Ni(II) chlorides, di-hydrate of Mn(II) and Cu(II) chlorides and anhydrous Zn(II) and Cd(II) chlorides and they were supplied from Strem Chemicals Inc., Sigma-Aldrich, Sigma-Aldrich, Sigma-Aldrich, Sigma-Aldrich, BDH, BDH, BDH, BDH, and Merck, respectively. Solvents that used were ethanol (95%),

Declaration of competing interests

he authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Citation Excerpt :
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Metal complexes of ferrocenyl-substituted Schiff base: Preparation, characterization, molecular structure, molecular docking studies, and biological investigation

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Characterization of the organometallic Schiff base ligand (L)

Conclusion

Materials and reagents

Declaration of competing interests

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