Binuclear Copper Complexes Research Articles

Competition between Cu-Br semi-coordinate bond and C-H∙∙∙Br, C-H∙∙∙S and S∙∙∙S interactions; new two thioalkylazothiophenol (SNS) copper (II) dimers [Cu(L)(µ-Br)

Two new copper dimers [Cu(L)(µ-Br)]2, HL = 2(RS)C6H4N = NC(COCH3)-SC6H5, where R = CH3 (1), C6H5 (2) were synthesized and characterized using a variety of physicochemical methods, including single crystal X-ray diffraction. The molecular structures of the two binuclear copper(II) complexes show that Cu∙∙∙Cu inter-nuclei distances are 3.662 \\AA and 3.392 \\AA in 1 and 2, respectively. Structural analysis of the two dimers supported by QTAIM analysis of electron density indicates the presence of competition between Cu∙∙∙Br semi-coordinate bond and CH∙∙∙Br and CH∙∙∙S hydrogen bonding interactions and S∙∙∙S chalcogen bonding interactions. In complex 1, CH∙∙∙Br and CH∙∙∙S hydrogen bonding interactions exist, in contrast, they are absent in 2. Cu∙∙∙Br semi-coordinate bonds are stronger in 2 as indicated by Cu∙∙∙Br bond distances; Cu∙∙∙Br bond distances are 2.955 and 2.858 Å in 1 and 2.746 Å in 2. There are two weaker S∙∙∙S interactions in 2 and one stronger interaction in 1 as indicated by S∙∙∙S interatomic distances. The two copper dimers and their ligands exhibited good anticancer efficacy against breast (MCF-7), lung (HCT115), and colon human (A549) cancer cell lines. Complex 1 demonstrated strong cancer cell death compared to complex 2. Additionally, the complexes exhibited higher activity than the ligands. Dimer 2 exhibits two quasi-reversible one-electron reduction waves at −0.05 V and −0.37 V. The comproportionating constant for forming the Cu(I/II) mixed-valence complex was 2.57 × 105. The absence of Intervalence transfer (IT) bands in the electronic absorption spectrum for the mixed-valence complex suggested that a single unpaired electron is localized on one copper center.

An immunogenic anti-cancer stem cell bi-nuclear copper(II)-flufenamic acid complex.

An asymmetric bi-nuclear copper(II) complex with both cytotoxic and immunogenic activity towards breast cancer stem cells (CSCs) is reported. The bi-nuclear copper(II) complex comprises of two copper(II) centres bound to flufenamic acid and 3,4,7,8-tetramethyl-1,10-phenanthroline. The bi-nuclear copper(II) complex exhibits sub-micromolar potency towards breast CSCs grown in monolayers and three-dimensional cultures. Remarkably, the bi-nuclear copper(II) complex is up to 25-fold more potent toward breast CSC mammospheres than salinomycin (a gold standard anti-breast CSC agent) and cisplatin (a clinically administered metallodrug). Mechanistic studies showed that the bi-nuclear copper(II) complex readily enters breast CSCs, elevates intracellular reactive oxygen species levels, induces apoptosis, and promotes damage-associated molecular pattern release. The latter triggers phagocytosis of breast CSCs by macrophages. As far as we are aware, this is the first report of a bi-nuclear copper(II) complex to induce engulfment of breast CSCs by immune cells.

Investigation on chloro-bridged binuclear copper(ii) complexes as potent metallodrug candidates against colon cancer via chemical and biological assessments

Synthesized binuclear copper(ii) complexes have been utilized for catechol oxidase mimicking activity, DNA/BSA interactions, molecular docking and pharmacological potential assessment against colon cancer and normal skin cells through in vitro method.

Synthesis, structural analysis, DFT study, and catalytic performance of a glycine-Schiff base binuclear copper(ii) complex

We report the synthesis of a binuclear copper(ii) complex with a Schiff base ligand from glycine, showing excellent catalytic performance in olefin cyclopropanation and C–S cross-coupling, with high yields, selectivity, and versatility.

Synthesis, characterization, crystal structure, hirshfeld surface analysis and chromotropic properties of halo- bridged copper(II) complexes

In this study, two novel chromotropic binuclear copper(II) complexes were introduced. The complexes were denoted as [LCu(μ-Cl)Cl]2, 1 and [LCu(μ-Br)Br]2, 2 with L representing the chelating ligand N,N-dimethyl-N'-(9-methylanthracenyl)ethylenediamine. To investigate the structures of these complexes, various analytical techniques were employed, including FT-IR, EPR, UV–Vis spectroscopy, TG-DTA, molar conductivity measurements, and elemental analysis. The geometrical property of [LCu(μ-Br)Br]2 was determined using X-ray crystallography, while the intermolecular interactions were studied through Hirshfeld surface analysis. The characterization data provided strong evidence supporting the proposed binuclear structure, wherein two copper (II) centers are connected by two halogen bridges. Remarkably, these complexes exhibit solvatochromism and thermochromism properties, displaying a diverse range of colors in solutions with varying polarities and/or temperatures. Experimental findings suggest that the observed chromotropism can be attributed to the substitution of solvent molecules with the coordinated halogens in the complexes.

Synthesis, Crystal Structure, Hirshfeld Surface Analysis, and DFT Calculations of the Novel Binuclear Copper(I) Complex Containing 2-Benzimidazolethiole and Triphenylphosphine Ligands.

The reaction of 2-benzimidazolethiole (2-BIT) with copper dichloride in the presence of two equivalents of triphenylphosphine led to a binuclear complex of the type [Cu(µ-S-2-BIT)2(Ph3P)2Cl2]: dichloridobis(μ-1,3-dihydro-2H-benzimidazole-2-thione)bis(triphenylphosphi ne)-di-copper. The Cu(I) compound has been fully identified by elemental analysis, molar conductivity, FT-IR, UV/Vis, and single-crystal X-ray diffraction (XRD). The XRD study reveals that the complex has distorted tetrahedral geometry around the Cu(I)center, which contains two bridge sulfur atoms. The Hirshfeld surface mappedover dnorm, shape index, and curvature revealed important H...H, H... C/C...H, and H... Cl/Cl...H intermolecular interactions as the main contributors to crystal packing. The natural bond orbital (NBO) was applied to understand the strength of nucleophilic and electrophilic attack between ligands and Cu(I)ions. Furthermore, density functional theory (DFT) was employed to demonstrate the molecular reactivity and stability of the ligands and coppercomplex.

Deciphering non-covalent interactions in unprecedented binuclear copper complex: Spectroscopic, Hirshfeld surface and DFT investigation

Binuclear Cu(II) complex derived from taurine and 2‑hydroxy-4-methoxybenzaldehyde adduct was synthesised and characterised by X-ray crystallography, spectroscopic, Hirshfeld surface and DFT studies. The complex crystallises in monoclinic system with I 2/a space group. A theoretical study of the Cu (II) complex is performed with unrestricted density functional method at the level of B3LYP/ LANL2DZ/6–311 G (d, p) and a comparison between the experimental and simulated results were conducted. As predicted by the experiment, the computed results support distorted pyramidal geometry at metal centre. Non-covalent interactions primarily H-bonding and π-π stacking close contacts were observed at the intramolecular and intermolecular levels of the complex. An analysis of the FMO parameters reveals less reactivity and stability of complex. A high HOMO energy value and interatomic charge transfer has taken place with the Schiff base ligand. Furthermore, MEP used for predicting reactive sites clearly shows this complex is void of electrophilic reaction site. This complex has been subjected to NBO analysis to determine its hyperconjugation and therefore stability. The NBO analysis revealed the delocalization of charge within the molecule. Based on Hirshfeld surface analysis, there is evidence for a wide range of interactions and a significant contribution from several non-covalent interactions to crystal packing.

Comparative analysis of EPR parameters in X-, Q-, W-bands for exchange-coupled copper(II) dimers

In this work, binuclear, polymeric binuclear, and molecular 16-nuclear copper(II) complexes [Py2Cu2(Piv)4] (1), {[(EtOH)2Cu2(Chda)2]·EtOH}n (2) and [K2(H2O)6(Py)8Cu16(OH)2(Chda)16]·EtOH·MeCN·3H2O (3) (piv is pivalate, Chda is 1,1-cyclohexanediacetate) have been studied by EPR spectroscopy in the X-, Q- and W-bands. Polynuclear copper(II) complexes are formed by binuclear fragments bonded by bridging carboxylate anions. In compounds 1–3, only pairwise interactions between copper ions are observed, despite the fact that in 2 and 3 there may be additional interactions between copper ions belonging to different dimers.

New binuclear copper(I) complexes with dual bioactivity: Synthesis, structural characterization and biological assays against bacteria and cancer

Novel binuclear heteroleptic copper(I) complexes based on mixed DPPE /thiocarbamoyl-pyrazoline ligands were synthesized and structurally characterized. Accordingly, the X-ray studies the three prepared complexes belong to the monoclinic crystalline system. All complexes 1, 2, and 3 possess similar structural behavior around the Copper(I) atoms which presented a distorted tetrahedral coordination geometry determined by using the τ4 (tau four) parameter analysis. The complete characterization of the prepared compounds also included HRMS-ESI(+), NMR and elemental analyses, MID infrared, and UV–Vis spectroscopies. TD-DFT studies were also performed to support the assignments and interpretation of the main absorption bands observed in the UV–Vis experiments. The binuclear CuI complexes were assayed against a panel of antibiotic-resistant (MDR) bacteria (S. aureus) and S. pseudointermedius (MDR isolated from dog skin) showing promising MIC (7.8 to 62.5 µg/mL) and MBC (15.6 to 62.5 µg/mL) values. Additionally, the binuclear complexes were also tested as anticancer agents against tumoral cells B16F10 and 4 T1 (metastatic murine melanoma and murine mammary carcinoma respectively) showing very low IC50 (0.16 to 0.6 µM) values.

Synthesis, crystal structure and protein binding studies of a binuclear copper(I) complex with triphenylphosphine based dithiocarbazate

A binuclear copper(I) complex with general formula [Cu(L)]2 where L = N’-(diphenylphosphanyl-benzylidine)-hydrazinecarbodithioic acid methyl ester have been synthesized and characterized by elemental analysis, FT-IR, NMR and UV–Vis spectroscopy, mass spectrometry and single crystal X-ray diffraction. The complex crystallizes in the monoclinic space system, space group P21/c. The coordination geometry around the copper(I) atom was best described as distorted square planar geometry. The binding interaction between the copper(I) complex and bovine serum albumin (BSA) was studied by absorption and fluorescence spectroscopy at room temperature. The Stern-Volmer quenching constant (Ksv), binding constant (Kb), and number of binding sites (n) were determined.

Synthesis, structural characterization of dinuclear copper(II) complexes based on Schiff base derived ligands and their impacts on DNA-binding affinities

Two binuclear copper (II) complexes ([Cu2(L1)2(Py)4] (1) and [Cu2(L2)2(Py)4] (2) where H2L1 (3-((2-hydroxybenzylidene)amino)benzoic acid and H2L2 (3-((2-hydroxy-5-nitrobenzylidene)amino)benzoic acid) have been synthesized and characterized by analytical and different spectroscopic technique. The X-ray diffraction analysis of both 1 and 2 complexes revealed that the geometry around the copper (II) centres are distorted square pyramidal. The crystal lattice in both 1 and 2 are stabilized by several types of intermolecular hydrogen bonds and π…π interactions. The intermolecular interactions on the crystal packing of 1 and 2 have been further studied by Hirshfeld surface analysis and corresponding 2D fingerprint plots. The interaction of 1 and 2 with calf thymus DNA (ct-DNA) have also been evaluated using absorption and fluorescence techniques and the result indicates that both 1 and 2 can bind to ct-DNA via an intercalative mode. The binding constant using absorption spectra between 1 with ct-DNA and 2 with ct-DNA have been found to be (10.3 ± 0.02) × 104 M−1 and (6.91 ± 0.01) × 104 M−1 respectively. Molecular docking studies also support the partial insertion of both 1 and 2 into the DNA backbone. Importantly, in Cu(II) complex 2, the Schiff base ligand possessing a significant electron withdrawing –NO2 group exhibits less interaction with ct-DNA compared to 1, containing less or no electron withdrawing character Schiff base.

Docking Studies, Cytotoxicity Evaluation and Interactions of Binuclear Copper(II) Complexes with S-Isoalkyl Derivatives of Thiosalicylic Acid with Some Relevant Biomolecules.

The numerous side effects of platinum based chemotherapy has led to the design of new therapeutics with platinum replaced by another transition metal. Here, we investigated the interactions of previously reported copper(II) complexes containing S-isoalkyl derivatives, the salicylic acid with guanosine-5'-monophosphate and calf thymus DNA (CT-DNA) and their antitumor effects, in a colon carcinoma model. All three copper(II) complexes exhibited an affinity for binding to CT-DNA, but there was no indication of intercalation or the displacement of ethidium bromide. Molecular docking studies revealed a significant affinity of the complexes for binding to the minor groove of B-form DNA, which coincided with DNA elongation, and a higher affinity for binding to Z-form DNA, supporting the hypothesis that the complex binding to CT-DNA induces a local transition from B-form to Z-form DNA. These complexes show a moderate, but selective cytotoxic effect toward colon cancer cells in vitro. Binuclear complex of copper(II) with S-isoamyl derivative of thiosalicylic acid showed the highest cytotoxic effect, arrested tumor cells in the G2/M phase of the cell cycle, and significantly reduced the expression of inflammatory molecules pro-IL-1β, TNF-α, ICAM-1, and VCAM-1 in the tissue of primary heterotopic murine colon cancer, which was accompanied by a significantly reduced tumor growth and metastases in the lung and liver.

Two binuclear copper(II) complexes incorporated with 3-phenylpentanedioic acid: crystal structure and bioactivity characteristics

Two binuclear copper(II) complexes incorporated with 3-phenylpentanedioic acid: crystal structure and bioactivity characteristics

Binuclear Copper(I) Complexes for Near-Infrared Light-Emitting Electrochemical Cells.

Two binuclear heteroleptic CuI complexes, namely Cu-NIR1 and Cu-NIR2, bearing rigid chelating diphosphines and π-conjugated 2,5-di(pyridin-2-yl)thiazolo[5,4-d]thiazole as the bis-bidentate ligand are presented. The proposed dinuclearization strategy yields a large bathochromic shift of the emission when compared to the mononuclear counterparts (M1-M2) and enables shifting luminescence into the near-infrared (NIR) region in both solution and solid state, showing emission maximum at ca. 750 and 712 nm, respectively. The radiative process is assigned to an excited state with triplet metal-to-ligand charge transfer (3 MLCT) character as demonstrated by in-depth photophysical and computational investigation. Noteworthy, X-ray analysis of the binuclear complexes unravels two interligand π-π-stacking interactions yielding a doubly locked structure that disfavours flattening of the tetrahedral coordination around the CuI centre in the excited state and maintain enhanced NIR luminescence. No such interaction is present in M1-M2. These findings prompt the successful use of Cu-NIR1 and Cu-NIR2 in NIR light-emitting electrochemical cells (LECs), which display electroluminescence maximum up to 756 nm and peak external quantum efficiency (EQE) of 0.43 %. Their suitability for the fabrication of white-emitting LECs is also demonstrated. To the best of our knowledge, these are the first examples of NIR electroluminescent devices based on earth-abundant CuI emitters.

The Bulk Breast Cancer Cell and Breast Cancer Stem Cell Activity of Binuclear Copper(II)-Phenanthroline Complexes.

Mononuclear copper(II)-phenanthroline complexes have been widely investigated as anticancer agents whereas multinuclear copper(II)-phenanthroline complexes are underexplored. Here the synthesis and characterisation of two new binuclear copper(II)-phenanthroline complexes 1 and 2 is reported, comprising of 2,9-dimethyl-1,10-phenanthroline or 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, terminal chloride ligands, and bridging chloride or hydroxide ligands. The binuclear copper(II) complex containing 2,9-dimethyl-1,10-phenanthroline 1 displays nanomolar toxicity towards bulk breast cancer cells and breast cancer stem cells (CSCs) grown in monolayers, >50-fold greater than cisplatin (an anticancer metallodrug) and salinomycin (a gold-standard anti-CSC agent). Spectacularly, 1 exhibits >100-fold greater potency toward three-dimensionally cultured mammospheres than cisplatin and salinomycin. Mechanistic studies show that 1 evokes breast CSC apoptosis by elevating intracellular reactive oxygen species levels and damaging genomic DNA (possibly by an oxidative mechanism). To the best of our knowledge, this is the first study to probe the anti-breast CSC properties of binuclear copper(II)-phenanthroline complexes.

Synthesis, crystal structure and Hirshfeld surface analysis of binuclear Cu(II) complexes from o/p-hydroxybenzoic acid with ethanol and water solution of monoethanolamine

The new paddlewheel-like binuclear copper complexes of general formulae [Cu2(o-HBA)4(DMFA)2] (1),[Cu2(o-HBA)4(H2O)2]DMFA (2) and {[Cu2(o-HBA)2(p-HBA)2(H2O)2]EtOH}{[Cu2(o-HBA)4(H2O)2]}, (3) (o/p-HBA = ortho/para-hydroxybenzoic acid, DMFA = Di-methylforamide) have been obtained by the reaction in ethanol, water and water: ethanol solution of MEA (monoethanolamine) and freshly prepared copper hydroxide with o-HBA (for 1 & 2) and o/p-HBA (for 3) respectively. Each ligand was bonded through two oxygen atoms to the metals from a carboxylic acid group and solvent (DMFA/water) was bonded with each Cu (II) atom at axial position by oxygen atoms. Complex-3 was followed in a somewhat different manner by linking two dinuclear Cu(II) complexes through water molecules using hydrogen bonds. Hirshfeld analysis of both complexes was determined and the results indicated that percentage of interaction, the H···H contacts were about 43, 38.5 and 40.5% for complexes 1, 2 and 3 respectively and the percentage of other interactions was significantly lower than these.

Mono- and binuclear complexes of copper(II) with dimethylaminomethyl derivatives of 2-naphthol and 6-quinolinol: synthesis and in vitro study of antitumor properties.

1-(Dimethylamino)methyl-6-quinolinol scaffold, a structural moiety of the molecule of anticancer drug topotecan, was modified into copper-containing products to study cytotoxic properties. New mononuclear and binuclear Cu(II) complexes with 1-(N, N-dimethylamino)methyl-6-quinolinol were synthesized for the first time. The same way Cu(II) complexes with 1-(dimethylamino)methyl-2-naphtol ligand were synthesized. The structures of mono- and binuclear Cu(II) complexes with 1-aminomethyl-2-naphtol were confirmed by X-ray diffraction. The obtained compounds were examined for in vitro cytotoxic activity against Jurkat, K562, U937, MDA-MB-231, MCF7, T47D, and HEK293 cells. The induction of apoptosis and the effect of novel Cu complexes on the cell cycle were investigated. The cells showed a higher sensitivity to mononuclear Cu(II) complex with 1-(N, N-dimethylamino)methyl-6-quinolinolligand. All synthesized Cu(II) complexes had higher antitumor activity than the drugs topotecan, camptothecin, and platinum containing cisplatin.

Synthesis and Crystal Structure of Chlorido-Bridged Binuclear Copper(I) Complexes with Carbodithioate-Type Ligands

The CuCl binuclear complexes were synthesized with phenyl-1H-pyrazole-1-carbodithioate (L1) and phenyl-3-methyl-1H-pyrazole-1-carbodithioate (L2) ligands. The complexes were isolated as crystalline material in a reasonable quantity. The complexes were crystallized in acetonitrile (MeCN) and characterized for their single crystal, using X-ray diffraction. The two units with the general formula LCuCl are bridged together via chlorido ligands, affording (LCuCl)2-type complexes. The complexes, [Cu2(μ-Cl)2(L1)2] 1 and [Cu2(μ-Cl)2(L2)2] 2 are monoclinic and triclinic with space group P21/n and Pi, respectively. The crystal packing is stabilized by C1(p)⋯C(p) and S⋯C(p) interactions extended in 2D fashion in complex 1, while complex 2 is stabilized by C(p)⋯S interactions extended in a 1D fashion. Structural features and secondary interactions present in both complexes discussed in this article.

Binuclear Cu complex catalysis enabling Li–CO2 battery with a high discharge voltage above 3.0 V

Li–CO2 batteries possess exceptional advantages in using greenhouse gases to provide electrical energy. However, these batteries following Li2CO3-product route usually deliver low output voltage (<2.5 V) and energy efficiency. Besides, Li2CO3-related parasitic reactions can further degrade battery performance. Herein, we introduce a soluble binuclear copper(I) complex as the liquid catalyst to achieve Li2C2O4 products in Li–CO2 batteries. The Li–CO2 battery using the copper(I) complex exhibits a high electromotive voltage up to 3.38 V, an increased output voltage of 3.04 V, and an enlarged discharge capacity of 5846 mAh g−1. And it shows robust cyclability over 400 cycles with additional help of Ru catalyst. We reveal that the copper(I) complex can easily capture CO2 to form a bridged Cu(II)-oxalate adduct. Subsequently reduction of the adduct occurs during discharge. This work innovatively increases the output voltage of Li–CO2 batteries to higher than 3.0 V, paving a promising avenue for the design and regulation of CO2 conversion reactions.

Employing Cu(II) complexes of N,O-donor ligand for catalysis in visible light driven cleavage of lignin C-C bonds

Transition metal complexes catalyzed visible-light assisted photoreactions are recently in huge demand for the development of environmentally friendly sustainable processes. To develop potential copper-containing photo-catalysts, a Schiff base ligand viz. 2-[((3-(dimethylamino)-2,2-dimethyl propyl)imino)(phenyl)methyl]phenol (HL) has been synthesized and characterized. Two binuclear copper complexes [Cu(L)Cl]2 (1) and [CuL(N3)]2 (2) have been obtained by reacting HL with Cu(II) salts. Under visible light irradiation, these catalysts can cleave the CC bonds of lignin in H2O as suggested by HPLC data. After completion of the reaction, the photo-catalysts could be recovered almost quantitatively and recycled for at least six times without much decrease in the catalytic efficiency. A plausible mechanistic pathway for the degradation reaction has been explored through ESI-MS spectrometry, NMR spectroscopy, UV-vis and computational study. The photocatalysts can degrade up to 95% of the authentic extracted lignocellulose sample into valuable chemicals. The catalysts have shown activity with sunlight as well towards degradation of lignin.