Copper Complexes Research Articles

Anticancer Tetranuclear Cu(I) Complex Catalyzes a Click Reaction to Synthesize a Chemotherapeutic Agent in situ to Achieve Targeted Dual‐Agent Combination Therapy for Cancer

To develop next‐generation metal‐based drugs and dual‐drug combination therapy for cancer, we proposed to develop a copper (Cu) complex that exerts anticancer function by integrating chemotherapy, immunotherapy and catalyzes a click reaction for the in situ synthesis of a chemotherapeutic agent, thereby achieving targeted dual‐agent combination therapy. We designed and synthesized a tetranuclear Cu(I) complex (Cu4) with remarkable cytotoxicity and notable catalytic ability for the in situ synthesis of a chemotherapeutic agent via Cu(I)‐catalyzed azide‐alkyne 1,3‐cycloaddition (CuAAC). We also constructed an apoferritin (AFt)‐Cu4 nanoparticles (NPs) delivery system. AFt‐Cu4 NPs not only showed an enhanced performance of tumor growth inhibition, but also improved the targeting ability and reduced the systemic toxicity of Cu4 in vivo. Importantly, the anticancer effect was enhanced by combining the AFt‐Cu4 NPs with the resveratrol analogue obtained from the CuAAC reaction in situ. Finally, we revealed the anticancer mechanism of the Cu4/AFt‐Cu4 NPs, which involves both cuproptosis and cuproptosis‐induced systemic immune response.

A comprehensive review on the development of chiral Cu, Ni, and Zn complexes as pharmaceutical agents over the past decades: Synthesis, molecular structure and biological activity.

Chirality is a fundamental and widespread geometric structural property in living organisms that most biomacromolecules including nucleic acids, proteins and enzymes, possess. Consequently, the development of chiral drugs capable of binding specific targets have gradually gained wide attention in recent decades due to their selective effects on a broad spectrum of biological events ranging from cell metabolism to cell fate. In this context, the synthesis of chiral compounds as promising therapeutic candidates has assumed a major role in drug discovery. Among them, chiral metal complexes have attracted considerable interest due to their unique and intriguing structural features that could enable overcoming side effects and drug-resistance phenomena of metal-based drugs currently in the market such as cisplatin. In the current scenario, an in-depth overview of non-platinum chiral complexes needs to be presented and carried forward. Therefore, in this perspective article, an update of the scientific development of bioactive chiral copper, zinc and nickel complexes have been reported since they have not been thoroughly reviewed so far. Specifically, we focused the article mainly on metal complexes containing chiral ligands (type 2 chirality) as in literature they are more numerous than those with chirality at the metal center (type 1 chirality). Herein, not only their biological activity but also their mechanism of action is summarized. Furthermore, in the final section of the article we have highlighted copper-based complexes as those with a superior biological activity profile and greater prospects for development as a drug.

Novel copper complex inhibits the proteasome in skin squamous cell carcinoma induced by DMBA in mice

The proteasomal system is becoming a target for the treatment of several diseases, especially in cancer therapy. The present study aims to develop a novel copper complex that inhibits the proteasome in skin squamous cell carcinoma. New molecules based on the copper complex were synthesized for the first time to assess their potential as proteasome inhibitors, specifically targeting squamous cell carcinoma induced by 7,12-dimethylbenz(a)anthracene (DMBA) in mouse models. Fourier Transform Infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), and energy dispersive X-ray analysis (EDX) were carried out to characterize this new copper complex. Notably, the presence of a papilloma (skin tumor) was confirmed by histopathological analysis. Subsequent investigation included the quantification of proteasome levels using a sandwich ELISA test, and the catalytic activity of the 20S proteasome was determined by measuring the fluorescence emitted after the cleavage of 7-amino-4-methylcoumarin (AMC). Hence, X-ray crystallography indicates that all Cu atoms are five-coordinated in a square-pyramidal configuration and biological activity of copper Schiff base complex, which exhibits high proteasome inhibitory activities with particular selectivity of β5 subunit. The pharmacokinetic properties (ADMET) of the copper complex named Cu(L1) showed encouraging results with very low toxicity, distribution, and absorption. Structure–activity relationship (SAR) information obtained from Cu(L1) demonstrated its selectivity and potent inhibition for β5 subunit. In this regard, this copper complex has emerged as a novel therapy for skin cancer.

Synthesis, Characterization, and Catalysis of Planar Chiral Ferrocene‐based N‐Heterocyclic Carbene Ligands and Its Metal Complexes

This study presents the development of a novel planar chiral ferrocene‐based NHC ligand and its corresponding metal complexes. The key unit of the imidazolium backbone, planar chiral ortho‐isopropyl ferrocenyl amine, was synthesized starting from (R)‐Ugi's amine. Imidazolium was obtained through the sequential condensation of glyoxal with ferrocenyl amine, followed by the ring‐closure of 1,3‐diferrocenyldiimine with chloromethylethyl ether. Chiral imidazolylidene NHC (IFcPr) metal complexes were prepared by treating imidazolium with silver oxide or base followed by transmetalation with appropriate metal salts. The steric and electronic properties of the IFcPr ligand were assessed using %Vbur and TEP, respectively. These assessments indicated that the ligand was as bulky as the adamantyl NHC ligand and exhibited strong donor ability similar to that of a triazolylidene NHC ligand. The catalytic performance of the copper and palladium complexes was evaluated in the asymmetric borylation of ethyl cinnamate and Suzuki–Miyaura coupling reactions, respectively. The IFcPr‐Cu complex catalyzed the borylation of ethyl cinnamate with bis(pinacolato) diboron, followed by oxidation to yield the hydroxy ester with 58% yield and 30% ee. In contrast, the IFcPr‐Pd‐PEPPSI complex provided the axial chiral binaphthyl compound with 59% yield and 51% ee at a low catalyst loading (0.1 mol%, TON = 590).

N‐heterocyclic carbene copper complexes catalyze the C1 polymerization of substituted diazomethanes

AbstractThe C1 polymerization of substituted diazomethanes, including diazoethane and 2,2,2‐trifluoromethyl diazomethane, are reported. N‐heterocyclic carbene copper complexes were employed as catalysts for the polymerization reactions and afforded the corresponding persubstituted polymers containing methyl or trifluoromethyl units along the backbones of the polymer products. The polymers were characterized using size exclusion chromatography, a variety of spectroscopic and thermal techniques, and contact angle measurements. Polymers prepared using the C1 polymerization methodology described herein are more hydrophobic than related polymers that were obtained using a standard C2 polymerization method and the fluorinated polymers were determined to be more hydrophobic than their hydrogenated analogues. The relationship between fluorine content and wettability of persubstituted polymers was quantified.

Controlling the Size of Molecular Copper Clusters Supported by a Multinucleating Macrocycle.

The use of a nonrigid, pyridyldialdimine-derived macrocyclic ligand (3PDAI2) enabled the synthesis of well-defined mono-, di-, tri-, and tetra-nuclear Cu(I) complexes in good yields through rational synthetic means. Starting from mono- and diargentous 3PDAI2 complexes, transmetalation to Cu(I) proceeded smoothly with formation of AgX (X = Cl, I) salts to generate mono-, di-, and trinuclear copper complexes. Monodentate supporting ligands (MeCN, xylNC, PMe3, PPh3) were found to either transmetallate with or bind various di- and trinuclear clusters. The solution-phase dynamic behaviors of these species were studied through NMR spectroscopic investigations, and an in-depth study of the trinuclear systems revealed a rate dependence on the identity of the supporting ligand, indicating that ligand dissociation reactions were involved in the dynamic exchange processes. Synthetic investigations further found methods for the purposeful interconversion between the di- and trinuclear systems as well as the synthesis of a pseudotetrahedral tetracopper complex with two μ-Ph supporting ligands.

Copper(I) Complexes With Phenanthroline‐Functionalized NHC Ligands Achieve Effective Anticancer Activity via Mitochondrial and Endoplasmic Reticulum Stress

ABSTRACTCopper complexes exhibit promising anticancer properties, which can be further promoted by suitable ligands. In this study, we synthesized and investigated the anticancer effects of three copper(I) complexes with N‐heterocyclic carbene (NHC) ligands derived from phenanthroline‐functionalized imidazole salts. The synthesis of these NHC‐copper(I) complexes (Cu1‐Cu3) was meticulously characterized using NMR and elemental analysis; their crystal structures were further delineated by X‐ray diffraction. Our findings illustrate the unique geometric configurations of these complexes: Cu1 features a dinuclear arrangement with off‐linear geometry; Cu2 and Cu3 are characterized by a bi‐copper core stabilized by two phenanthroline‐modified carbene ligands. Crucially, in vitro cytotoxic evaluations revealed that these complexes possess suitability anticancer activity. Among them, Cu2 exhibited enhanced cytotoxicity activity, achieving a half‐maximal inhibitory concentration (IC50) of 4.36 ± 0.25 μM in colon cancer cell line HCT‐116, markedly surpassing the efficacy of cisplatin. Subsequent investigations elucidated that Cu2 notably increases intracellular reactive oxygen species (ROS) levels and induces mitochondrial membrane depolarization and endoplasmic reticulum stress, leading to oxidative stress‐mediated apoptosis of colon cancer cells.

Synthesis, characterization and bioactive evaluation of cobalt(II) and copper(II) complexes of {4-[5-(5-sulfanylidene-2,5-dihydro-1H-1,2,4-triazol-3-yl) furan-2-yl] phenyl} acetic acid

A new triazole derivative was synthesized by three steps. The first step involve adding 2-carboxyaledhyed furan to the 4-amino phenyl acetic acid after converting the substituted aromatic amine to the diazanium salt. In the first stage, [4-(5-formylfuran-2-yl) phenyl] acetic acid is the title of product. The second step is adding the thiosemicarbazide to the [4-(5-formylfuran-2-yl) phenyl] acetic acid which it gives the (4-{5-[(2-carbamothioylhydrazinylidene) methyl] furan-2-yl} phenyl) acetic acid. A final compound with the title {4-[5-(15-sulfanylidene-2,5-dihydro-1H-1,32,4-triazol-3-yl) furan-22-yl] phenyl} acetic acid was produced as a result of adding sodium acetate and chloro ethyl acetate to the product from the second step in the presence of triethyl amine which is used as a ligand to prepare cobalt(II) and copper(II) complexes. The structures of synthesized compounds were identified through the utilization of diverse measures, these measurements were (UV-Vis spectrum, LC-MS technique, FT-IR spectrophotometer, conductivity measurements, GC-mass spectra and atomic absorption) and melting point measurement. The results confirmed that the complexes have octahedral geometry. The biological activity data for the synthesized compounds revealed that the ligand and its complexes had antibacterial activity. KEY WORDS: Synthesis, Triazole derivatives, Cobalt(II) complex, Copper(II) complex, Biological evaluation Bull. Chem. Soc. Ethiop. 2024, 38(6), 1595-1607. DOI: https://dx.doi.org/10.4314/bcse.v38i6.8

EPR study of a copper impurity center in a single crystal of 6-chlorouracil

Single crystals of 6-chlorouracil containing traces of copper were gamma-irradiated at room temperature and studied using EPR spectroscopy. The ionizing radiation induced the conversion of copper impurities, initially present in the host lattice as Copper(I) complexes, into paramagnetic copper(II) complexes. These complexes exhibited intricate EPR spectra characteristic of Copper(II) complex with two ligated nitrogen atoms. Using EPR spectroscopy, the binding site of Cu(II) ions in a single crystal of 6-chlorouracil was determined. It was proposed that planar coordination bonding to the cupric Cu(II) ion, having two pairs of oxygen and nitrogen atoms as ligands, served to bridge neighboring 6-chlorouracil molecules, thereby replacing a pair of hydrogen bonds with stronger Cu-coordination bonding. The spectroscopic parameters, including g tensor, A(63Cu), and A(14N) tensors, closely resemble those previously reported for copper(II) planar centers in similar systems. However, a small deviation in the principal axes of the g and A(63Cu) tensors from axial symmetry suggests a subtle distortion from the ideal planar geometry of the complex. The theoretically derived spectroscopic parameters further corroborate the proposed structure of the complex.

An Insight Into Experimental and Theoretical Investigation of Structure, Photophysical Property by ESIPT Processes and Biological Activities of Schiff Base Copper Complex

ABSTRACTA novel Schiff base (BSSMO) and its copper complex have been synthesized, and their structure was delineated using single crystal XRD studies. Computational techniques were used to design and evaluate BSSMO‐based luminophores, revealing a significant intramolecular hydrogen bond within the molecule. Understanding ESIPT is crucial for optimizing photophysical and luminophore properties of organic molecules, especially for advancing optoelectronic devices. The study also explored the mechanisms of GSIPT and ESIPT for these BSSMO‐based luminophores using transition state theory, charge distribution, molecular orbital analysis, and quantum theory of atoms in molecules. Results advocated that BSSMO‐L2 exhibits higher absorption compared with BSSMO‐L1 and the same trend is observed in emission spectral studies. However, the intensity of enol emissions in BSSMO‐L2 is lower than that of keto (BSSMO‐L3) emissions and the S1 (Keto form) emission of BSSMO‐L3 shows significantly larger values, making it attractive for optoelectronic devices. The findings offer valuable insights for the development of ESIPT emitters with distinct photophysical properties. The in silico antidiabetic study of BSSMO‐L2 explores the interaction with PPAR‐γ protein, revealing a moderate affinity and stable complex, enhancing its bio‐potential for future applications. The in vitro anticancer study of Cu‐BSSMO‐L2 complex shows a potential anticancer effect through mitochondrial and extrinsic death receptor mediated pathways. These insights contribute to the design of novel benzenesulfonamide‐based bioactive molecules.

Synthesis of some metal ion complexes of new imidazole derivative, characterization, and biological activity

Imidazole complexes with high biological activity for some metal complexes prepared by a new imidazole ligand from the reaction of a 1,3-oxazole derivative with hydroxylamine and utilizing this ligand in the preparation of some metal ion complexes. Many of the techniques available for all prepared compounds, such as elemental analysis (CHNS), (FT-IR), (UV-Vis) spectra, and 1H-NMR spectra, will be used in the diagnosis of these complexes, and the forms of the complexes will be deduced from the results obtained. The outcomes demonstrated that the octahedral geometries of all the produced complexes, except for the copper and palladium complexes, which were square planer shapes. The antimicrobial activity of both the ligand and its metal ionic complexes against various microbes was evaluated. KEY WORDS: Imidazole, Oxazole, Spectral data, Bioactivity Bull. Chem. Soc. Ethiop. 2024, 38(6), 1681-1690. DOI: https://dx.doi.org/10.4314/bcse.v38i6.14

Synthesis, Characterization, and Biological Evaluation of Novel [M(η6-arene)2]+ (M = Re, 99mTc) Hosted Terpyridines and Copper Complexes Thereof.

We report the synthesis, characterization, and in vitro biological activities of [Re(η6-arene)2]+-terpyridine conjugates and their CuII complexes. The terpyridine (terpy) chelators were attached to the [Re(η6-arene)2]+ scaffold via secondary amine linkers allowing for heteroleptic mono- and homoleptic bis-terpyridine-substituted chelators. Complexation with CuCl2 afforded the respective square pyramidal [Cu(terpy)Cl2] complexes hosted on the [Re(η6-arene)2]+ scaffold. The chelator conjugates and their respective complexes were found to be remarkably cytotoxic against malignant HT29 and A549 human cancer cell lines in vitro with IC50 values in the low micromolar range. Mitochondrial respiration disruption was identified as a possible mode of action of these novel drug candidates. Crucially, the [Re(η6-arene)2]+ hosts delivered water solubility of the otherwise insoluble [Cu(terpy)Cl2] motif. Importantly, the homoleptic [99mTc(η6-arene)2]+-terpyridine conjugate is available in a single step, which enables the presented system to be used as a theranostic approach to modern medicinal inorganic chemistry.

Research on synthesis of imidazopyridine-sulfide-aryl derivatives: copper complex immobilized on Fe3O4 nanoparticles catalyzed one-pot C–H bond sulfenylation of imidazopyridines

This research report the development of an eco-friendly, magnetic nanocatalyst, Fe3O4@SiO2-ABHA-CuCl, for the efficient synthesis of diaryl sulfides incorporating imidazo[1,2-a]pyridine scaffolds. The catalyst was successfully prepared by immobilizing CuCl on magnetic Fe3O4 nanoparticles modified with 4-amino-3-hydroxybenzoic acid. Characterization revealed spherical nanoparticles with a size range of 15-30 nm. The catalyst exhibited excellent catalytic activity in promoting C–H bond sulfenylation of imidazopyridines using the green solvent PEG-400. Remarkably, the catalyst demonstrated exceptional recyclability over eight consecutive cycles without significant loss of activity. Comprehensive analysis confirmed the preservation of the catalyst's magnetic properties and structural integrity after repeated use.

Copper(II) complex of pentadentate N5 ligand as catalyst for 2-aminophenol oxidation

Exploring the catalytic activity of the copper(II) complex of pentadentate ligand in oxidizing o-aminophenol (OAP) has not been extensively studied. To scrutinize the least explored domain, we synthesized and characterized the copper(II) complex of pentadentate ligand, 3-(bis(pyridin-2-ylmethyl)amino)-N-(quinolin-8-yl)propanamide. Further, the complex was allowed to react with OAP to form 2-aminophenoxazin-3-one (APX) via oxidative coupling reaction, the resultant product is a functional analogue of phenoxazinone synthase (PHS), an active enzyme, relevant to the industrial production of a widely recognized antibiotic called Actinomycin D. Furthermore, kinetic studies were performed to comprehend the path of the reaction which unveiled the formation of the complex-substrate adduct. It is worth noticing that the complex displayed an impressive turnover number of 6.4 × 104 h−1 under atmospheric conditions in methanol. To the best of our knowledge, the present complex is the first copper(II) complex with pentadentate N5 ligand showing PHS mimicking catalytic activity.

Copper and Photocatalytic Synergistic Strategies for Radical Cyclization Reactions

AbstractThe rapid development of photo‐synergistic transition metal catalytic systems has provided a green paradigm to complement thermal transition metal catalytic methods. However, the most commonly used iridium or ruthenium complexes involve expensive in nature, in contrast to the abundant copper elements in the earth's crust, which are highly valued for their unique electronic structure and light‐absorbing properties. Recently, the application of copper and photocatalytic synergistic strategies in radical cyclization reactions has progressed considerably, leading to a renaissance in the synthesis of functional natural products, drugs and their analogues, but summary work addressing this aspect has not been reported. In this review, we briefly analyze the effect of ligand choice on copper complexes and some inorganic copper salts and even on light sources. We then summarize the copper and photocatalytic synergistic strategies in radical cyclization reactions and classify them into three categories, C, N and O radicals, according to the class of the central atom of the radical in each work, and in each category will be elaborated in turn from coordination cyclization via Cu catalysts, direct radical cyclization and other cyclization mode. For individual more complex reactions, the mechanisms are explored and briefly discussed.

Synthesis, characterization, and biological activity of a fresh class of sonochemically synthesized Cu2+ complexes

The synthesis and characterization of metal complexes have garnered significant attention due to their versatile applications in scientific and biomedical fields. In this research, two novel copper (Cu) complexes, [Cu(L)(L′)(H2O)2] (1) and [Cu(L)(Im)H2O] (2), where L = pyridine-2,6-dicarboxylic acid, L′ = 2,4-diamino-6-hydroxypyrimidine, and Im = imidazole, were investigated concerning their sonochemical synthesis, spectroscopic analysis, and biological activity. The complexes’ structural characterization was achieved using analytical techniques, including single-crystal X-ray structure determination, FTIR, PXRD, TGA and DTA, SEM, TEM, and EDS. Complex (1) displayed a six-coordinated Cu2+ ion, while complex (2) exhibited a five-coordinated Cu2+ ion. The crystal structures revealed monoclinic (C2/c) and triclinic (P-1) space groups, respectively. Both complexes showcased zero-dimensional (0D) supramolecular networks, primarily driven by hydrogen bonding and π–π stacking interactions, which played pivotal roles in stabilizing the structures and shaping the unique supramolecular architecture. Both complexes demonstrated significant antioxidant activity, suggesting their capability to neutralize free radicals and mitigate oxidative stress-related diseases. Hemolysis percentages were less than 2%, per the ASTM F756-00 standard, indicating non-hemolytic behavior. Low cytotoxicity was observed against fibroblast and MCF-7 cell lines. They do not exhibit antibacterial activity against Escherichia coli and Staphylococcus aureus. These findings suggest that the synthesized Cu2+‒complexes hold considerable promise for applications in drug delivery and cancer treatment. This research contributes to the advancement of supramolecular chemistry and the development of multifunctional materials for diverse scientific and medical applications.

Rational Design of a Hetero-multinuclear Gadolinium(III)-Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer.

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)-Cu(II) thiosemicarbazone complex (Gd-2Cu) and then constructed a Gd-2Cu@AFt nanoparticle (NP) delivery system. Gd-2Cu/Gd-2Cu@AFt NPs not only had significant T1-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu@AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo. Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.

Copper Complexes with Protein-Based N-Donor Ligands as cis-Selective Nascent Cyclopropanases.

In this study, we aimed to develop protein-based metal ligands to catalyze cis-selective cyclopropanation using the TM1459 cupin protein superfamily. Copper complexes with TM1459 mutants containing the 3-His metal-binding site exhibited excellent diastereoselectivity in cyclopropanation reactions with styrene and ethyl diazoacetate. Further mutations in the secondary coordination sphere increased the cis-preference with t-butyl diazoacetate as the substrate with up to 80 : 20 (cis:trans ratio) and high enantioselectivity (90 % ee).

Copper Imidazolin-imine Coordination Compounds as Precursors for a Cu/Al Complex.

The reactions of [(CF3SO3Cu)2(C6H6)] with the sterically hindered imidazolin-2-imine ligands DippImTMS (1,3-Bis(2,6-diisopropylphenyl)-2-(trimethylsilylimino)imidazoline) or DippImH (1,3-bis(2,6-diisopropylphenyl) imidazolin-2-imine) lead to the formation of the linear copper(I) complexes [Cu(DippImTMS)(OTf)] (1) and [Cu(DippImH)2][OTf] (2), respectively. The triflate counteranion in 2 can be easily exchanged to the weakly coordinating [BArF] giving [Cu(DippImH)2][BArF] (3) (BArF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate). Substitution of the N-heterocyclic imine (NHI) ligand in 3 by AlCp* (Cp* = pentamethylcyclopentadienyl) gives the tetrahedral [Cu(AlCp*)4][BArF] (5). The reaction between lithiated imidazolin-2-iminate DippImLi and CuCl results in the triangular cluster [Cu3(DippIm)2Cl] (4). All products have been fully characterized by 1H- and 13C NMR, mass spectrometry, as well as SC-XRD.

Novel copper-drugs bearing dipodal bis-mercaptobenzimidazoles: Synthesis, crystal structures, in vitro biological activities, DNA binding, DFT calculations and molecular docking

Three novel copper(II) complexes, 1–3, bearing dipodal bis-mercaptobenzimidazole derivatives based on ortho-, meta- or para-xylene (L1, L2, and L3) were successfully prepared and characterized by using various spectral techniques, including elemental analysis, FT-IR, 1H NMR, and UV–Vis spectroscopy, LC-MS spectrometry and TGA. The analysis revealed that the ligand/metal molar ratio in all copper(II) complexes is 1:1 and the ligand coordinates as a neutral N-donor onto metal center. Additionally, the crystal structures of L1, L2, L3, and copper(II) complex 2 were determined using single crystal X-ray diffraction (SC-XRD) analysis. Copper(II) complexes 1–3 displayed significant stability at pH range of 4–10. The antibacterial effect of ligands and complexes was tested against both gram-negative (Escherichia coli, E. coli ATCC 25922 PTCC 1399) and gram-positive (Staphylococcus aureus, S. aureus ATCC 6538 PTCC 1112) bacterial strains. It should be noted that the complexes showed enhanced antibacterial activity (up to 99 %) when compared to their free ligands. The in vitro studies of all synthesized compounds consisted of testing them against the human colorectal carcinoma cancer cell line (HCT-116) using the MTT assay. The findings revealed that the copper(II) complexes exhibited lower CC50 values (CC50 ranging from 0.045 mM to 0.135 mM) compared to their corresponding ligands (CC50 ranging from 0.150 mM to 0.240 mM) and carboplatin (CC50 = 0.165 mM), indicating higher anticancer activity of the complexes. Additionally, DAPI staining and fluorescence spectroscopy (at three different temperatures) were performed to further examine the impact of complexes 1–3 on inducing apoptosis and to explore their interaction with DNA, respectively. The results revealed a dynamic quenching mechanism, with hydrophobic forces playing a dominant role in the binding process. The viscosity measurements indicated that all complexes could interact in a groove binding manner with DNA. Density functional theory (DFT) calculations were employed to support the structural and vibrational studies and to predict the chemical reactivity. Docking simulations were conducted to evaluate their behavior of the synthesized compounds towards DNA (PDB: 1BNA). These results suggested that various elements, including NH groups, imidazole rings, thioetheric sulfur atom and sulfate moieties of ligands and complexes, are involved in groove binding with DNA.