Synthesis, structural, DNA/protein binding and cytotoxic studies of copper(I) ∝-diimine hydrazone complexes
Introduction
α-Diimine ligands have long been recognized for their ability to stabilize organometallic complexes [1]. They are obtained when a diketone reacts with two equivalents of an alkyl or arylamine, which is usually catalysed by a Lewis or Bronsted acid. The backbone as well as the aryl substituent is altered via these synthetic pathways, allowing for adjustment of the steric and electrical effects at the metal core. Aryl bis(imino)acenaphthenes (Ar-BIAN) are a type of α-diimine ligand that was initially discovered in the 1960s and has been studied extensively as a reliable ligand for catalytically active transition metal centres since the early 1990s [2]. Ar-BIAN compounds that have been functionalized are known to be oxidatively and thermally stable ligands for transition metal centres. The acenaphthene ring's vast π -system, paired with the sterically modular aniline, yields a wide range of π -acceptor frameworks with precise steric, optical, and electrical characteristics [3], [4]. As a result, Ar-BIAN ligands have been used to make a variety of transition metal molecular compounds that could be useful in light sensitization applications due to the well-studied MLCT (metal-to-ligand charge transfer) transition from the transition metal's d-orbitals to the Ar-BIAN ligand's π* orbitals [5], [6], [7].
Ar-BIAN ligand’s low-lying π* orbitals have been used successfully as “capacitors” for multielectron reductions in redox noninnocent ligands [8], [9], [10]. As a result, transition metal Ar-BIAN complexes have been reported as catalysts for organic reactions such as cycloaddition of azides and alkynes [11], [12], as well as olefin polymerization, work that Brookhart and co-workers pioneered using Ni(II) and Pd(II) Ar-BIAN complexes [13]. Cu(II) Ar-BIAN complexes have recently been studied as catalysts for styrene reverse atom transfer radical polymerization (ATRP). Furthermore, Cu(I) Ar-BIAN complexes have been used as light harvesters that can absorb in the near-infrared region [5], [7], [14]. The fluorescence emission behavior of acenapthaquinone-derived compounds and their complexes has been extensively studied for photophysical characteristics [15], [16] and bioimaging applications [17], [18], [19]. However, the biological application of the complexes encompassing acenapthaquinone derivatives is scarcely reported.
Transition metal complexes, on the other hand, are important in nucleic acid chemistry because of their many applications, including sequence specific binding, structural probes, and therapeutic agents, despite the fact that many medication compounds are organic in nature [20], [21], [22], [23], [24]. Despite its wide usage as a chemotherapeutic treatment, Cisplatin, a well-known metallo-drug for cancer, has a number of side effects, including nausea, kidney failure, and liver failure, all of which are typical of heavy metal toxicity [25], [26]. As a result, the researchers are looking for better non-platinum based metal complex candidates, such as copper, cobalt, nickel, zinc, ruthenium and iron which have fewer side effects [27]. DNA and proteins are the most common cellular targets for cytotoxicity because interactions with tiny molecules cause DNA damage in cancer cells by preventing them from dividing uncontrollably, resulting in cell death [28], [29], [30]. Transition metal complexes are currently being used to treat a variety of tumours with great effectiveness [31]. Copper complexes are being considered and proposed as better possibilities for cancer therapy since they have shown to play a vital function in biological systems while having no or minimal adverse effects [32], [33], [34]. As a result, non-platinum based metal complexes that can interact with DNA and also have antioxidant capabilities have received a lot of attention. Proteins have also recently garnered the attention of the scientific community as a prime molecular target [35]. Interactions between proteins and metal complexes are becoming increasingly important in the quest for novel therapeutic compounds [36], [37]. Since serum albumins, such as bovine serum albumin (BSA), are the most important proteins in plasma, they transport a variety of endo and exogenous substances. It is critical to look at drug-protein interactions because most of the drugs bound to serum albumins are usually transported as a protein complex [38].
Hence, in the course of our recent findings [39] on the biological applications of transition metal complexes containing various ligands, in this work, α-diimine ligands were synthesized from acenapthaquinone/phenanthrenequinone and hydrazone. The ligands were used to synthesize new copper(I) complexes. The new complexes were subjected to biological activities such as DNA and BSA binding as well as cytotoxicity studies after characterization. In vitro cytotoxicity of ligands and corresponding complexes was screened in one cancer and one normal cell lines along with well-known anticancer agent.
Section snippets
Methods
All chemicals used were analar quality. All the reactions including the preparation of metal complexes were carried out in oven or flame dried glassware using magnetic stirrer with anhydrous solvents using standard techniques [40]. Thin-layer chromatography (TLC) was carried out on Merck 1.05554 aluminum sheets pre-coated with silica gel 60 F254 and the spots were visualized with UV light at 254 nm. Column chromatography purifications were executed using silica mesh (100–200). The melting
Synthesis and characterization
The α-diimine hydrazone ligands L1-3 were synthesized from the reaction of acenaphthenequinone or 9, 10-phenanthrenequinone with 2-hydrazino benzothiazole or 2-hydrazino quinoline in ethanol (Scheme 1. The reaction between [Cu(CH3COO)(PPh3)2] and α-diimine hydrazone ligands (L1-4) in chloroform–methanol leads to the formation of the new complexes (Scheme 2). The ligands and their copper complexes were characterized by micro analyses, FT-IR, UV–Vis, 1H NMR, 13C NMR and mass spectroscopic
Conclusions
A series of copper(I) complexes (1–4) with α-diimine hydrazone ligands were synthesized and characterized by analytical, spectral and single crystal X-ray diffraction techniques. Based on the characterization results, a tetrahedral geometry was tentatively proposed around the copper centre. The results of DNA binding from absorption studies reveal that the DNA binding ability was in the order of 4 > 3 > 1 > 2. These observed results demonstrated that their effective interactions with DNA base
CRediT authorship contribution statement
S. Gayathri: Formal analysis, Investigation. P. Viswanathamurthi: Conceptualization, Funding acquisition, Methodology, Validation, Supervision, Project administration, Writing – original draft, Writing – review & editing. V. Thuslim: Investigation. M. Sathya: Investigation. M. Ranjani: Investigation. R. Prabhakaran: Formal analysis, Validation. J. Haribabu: Formal analysis, Investigation. Cesar Echeverria: Validation.
Declaration of Competing Interest
The 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.
Acknowledgements
The authors thank SAIF, Indian Institute of Technology, Chennai SAIF, Department of Chemistry, Gandhigram Rural Institiue, Gandhigram (spectral studies), CIMF, Periyar University, Salem (single crystal X-ray) for their help in characterization studies and the University Grants Commission (UGC), India [SAP grant No. 540/20/DRS-I/2016(SAP-I)] for financial assistance. J. H. thanks the Fondo Nacional de Ciencia y Tecnologia (FONDECYT, Project No. 3200391 and 11170840).
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