Search Results (659)

Copper–organic compounds are being investigated as antitumor candidates. Besides their efficacy as cytotoxic agents alone, the oxidative potential of electrochemical Cu²⁺-to-Cu¹⁺ transition emerges as an attractive approach for elimination of tumor cells otherwise resistant to chemotherapy. To minimize side effects of the potent oxidative burst upon Cu(II) reduction, the metal cations should be delivered to the tumor site. Taking advantage of the ability of bisphosphonates to accumulate in the bone, we synthesized a Cu(II) complex of zoledronic acid (ZA), an FDA-approved drug for prevention of bone destruction. The CuZA complex obtained upon precipitation of ZA and different copper salts (sulfate, chloride or perchlorate) were structurally identical, consisting of two organic moieties coordinated by three metal cations. Combined treatment with water-soluble formulations of CuZA and cysteine triggered rapid death in human cell lines. This effect was achievable with non-toxic concentrations of CuZA and cysteine alone. Importantly, the K562 chronic myelogenous leukemia cells that demonstrated an attenuated response to the 3d generation Bcr-Abl tyrosine kinase inhibitor in the medium conditioned by bone marrow-derived fibroblasts, were readily killed by CuZA–cysteine combination. Thus, oxidative burst upon metal reduction in CuZA complexes emerges as a promising method of eradication of tumor cells in the bone microenvironment. Full article

Introduction: Osteosarcoma (OS) is the most common primary malignant bone tumor in children and young adults, with poor prognosis due to relapse, metastasis, and chemoresistance. The search for novel metal-based therapeutics has highlighted copper complexes as promising candidates. Here, we report the in vitro and in vivo antitumor activity of a tetranuclear Cu(II)-hydrazone complex (Cu₄L₄) derived from (E)-5-chloro-N′-(2-hydroxy-3-methoxybenzylidene)thiophene-2-carbohydrazide. Results: Cytotoxic assays on MG-63 OS cells revealed potent activity with an IC₅₀ of 0.50 ± 0.04 µM, significantly surpassing its free ligand (IC₅₀ = 13.9 ± 1.6 µM) and cisplatin (IC₅₀ = 39.0 ± 1.8 µM). This tetranuclear complex outperforms mononuclear Cu-hydrazones analogs (e.g., 4-fold vs. CuHL1, 2-fold vs. CuHL2, 5-fold vs. CuHL3, 17-fold vs. CuHL4,), and Cu₄L₄ also exhibits reduced clonogenic survival, induces reactive oxygen species production, and promotes late apoptosis as a main mechanism, being the main mechanism of action involved in anticancer activity. In multicellular tumor spheroids, the complex maintained strong cytotoxicity (IC₅₀ = 4.11 ± 0.12 µM), impaired spheroid integrity, and markedly inhibited cell migration at sub-IC₅₀ concentrations. The tetranuclear architecture confers markedly enhanced antitumor activity relative to the corresponding mononuclear Cu–hydrazone complexes (e.g., 2-fold vs. CuHL1, 4-fold vs. CuHL2, 2-fold vs. CuHL3). In a xenograft model, sustained administration of Cu₄L₄ (2 mg/kg, i.p., twice weekly) inhibited tumor growth by 43.6%, reduced mitotic index, and increased necrotic area without significant systemic toxicity. Conclusions: Overall, Cu₄L₄ displayed potent and selective antitumor activity against OS cells in 2D, 3D, and in vivo models, underscoring copper–hydrazone complexes as promising scaffolds for the development of new therapies against OS. Full article

Carnosine (or β-alanyl-L-histidine) is an endogenous compound playing very important roles in human organisms as antiglycation and antioxidant agents, and, in addition, helping to mitigate illnesses such as cancer and neurodegenerative diseases. Aiming to explore the chelating ability of carnosine, based on its coordinating possibilities, we started to investigate the metal complexes of essential copper(II), zinc(II), and iron(II) ions coordinated to this dipeptide. Different compounds were isolated in the solid state by adding stoichiometric amounts of metal salts to carnosine at controlled pH or under a controlled atmosphere, with the formation of mono-, bi- and polynuclear species. These complexes were subsequently characterized mainly by spectroscopic techniques (UV–Vis, IR, EPR), in addition to elemental analysis. A binuclear species was isolated with copper(II) and had its structure determined by X-ray diffraction, improving previously reported data in the literature. Two insoluble correlated trinuclear species were isolated with zinc(II) ions, using perchlorate or chloride as counter-ions. In the case of iron, a mononuclear species was verified with Fe(II) ions, obtained under an inert atmosphere. Further, the antioxidant properties of free carnosine and the copper–carnosine complex were verified by their scavenging activity toward the ABTS^•+ radical, using Trolox as a reference, showing significant activity. The carnosine–metal complexes were also tested as potential antineoplastic agents, in comparison to the free ligand, after 24 h of incubation at 37 °C, using malignant HeLa, SKMEL 28 and SKMEL 147, and non-tumor fibroblast cells. Results indicated neglected or poor anti-proliferative properties of these metal complexes, when compared to other similar compounds described in the literature. Full article

Cisplatin’s chemotherapy is hindered by drug resistance and toxicity, making copper complexes a potential alternative. A novel copper(II) complex, [CuLBr], was synthesized from a tetradentate vicinal dioxime ligand (H₂L) and characterized. [CuLBr] features a distorted square pyramidal geometry with a CuN₄Br chromophore. DFT calculations showed a narrowed HOMO-LUMO gap and increased electrophilicity, enhancing its chemical reactivity. [CuLBr] exhibited potent biomimetic catalytic activity, functioning as an efficient superoxide dismutase mimic and catalase mimic. Biophysical studies (UV-Vis, fluorescence, and viscosity) demonstrated a strong, spontaneous affinity of [CuLBr] for calf thymus DNA and Human Serum Albumin, suggesting groove-binding and static quenching mechanisms. In vitro assays revealed superior anticancer activity against HepG-2, HCT-116, and MDA-MB-231 cell lines, with greater selectivity than the free ligand and doxorubicin. Molecular docking studies reveal a high binding affinity of [CuLBr] with key proteins, including ferredoxin-1 and VEGF. This may suggest potential dual mechanisms of action, involving the induction of cuproptosis and the inhibition of tumor angiogenesis. These findings position [CuLBr] as an effective multi-metal-based anticancer agent with advantageous selectivity. Full article

This study presents the synthesis and electrochemical characterization of meso-tetracyanobutadiene (TCBD)-functionalized diphenylporphyrin (DPP) complexes incorporating copper (Cu) and nickel (Ni) metals. These push–pull metallo diphenylporphyrin–TCBD complexes were synthesized via a [2 + 2] cycloaddition–retroelectrocyclization reaction between 5-bromo-15-formyl-10,20-diphenylporphyrin metal(II) complexes (M = Cu, Ni) and tributyl(phenylethynyl)stannate, followed by tetracyanoethylene (TCNE) addition. The resulting TCBD-functionalized porphyrins were obtained in moderate yields (70–75%) and thoroughly characterized by ¹H and ¹³C NMR, UV-Vis spectroscopy, MALDI-TOF-MS, and single-crystal XRD. Although the single-crystal X-ray structure of NiDPP was solved, DFT calculations were used to determine the structures of the donor–acceptor MDPP-TCBD systems and to visualize their electronic structures. HOMO on the porphyrin π system and LUMO on the TCBD entity were observed, and energy level diagrams clearly laid out the electron donor and acceptor parts of the molecular systems. As expected, these novel donor–acceptor porphyrinoid assemblies exhibited enhanced push–pull properties in both the ground and excited states. Femtosecond transient absorption studies revealed that both NiDPP-TCBD and CuDPP-TCBD populate the charge-transfer state upon photoexcitation, with lifetimes of 383.1 ps and 484.7 ps, respectively, in benzonitrile. The charge-transfer states populated the triplet or doublet states (in the case of CuDPP) before returning to the ground state. Full article

Developments in electric vehicle (EV) technology are pushing on-board chargers (OBCs) toward higher power density and efficiency, making high-frequency transformer loss prediction a critical design bottleneck. However, the accuracy of commonly used analytical winding-loss models varies strongly with frequency, conductor type (Litz/solid), window fill factor, and winding layout (e.g., interleaved), which can render single-model-based optimization unreliable. In this study, six analytical copper-loss models from the literature were independently reimplemented in a unified Python 3.11.5 workflow with a standardized interface to enable fair comparison under identical geometry and operating conditions. The models were benchmarked against 2D finite-element simulations on test scenarios with increasing physical complexity, including high fill-factor Litz windings and interleaved arrangements. The results confirm a regime-dependent behavior: no single model consistently outperforms others across the full design space, and model dispersion increases in geometrically stressed and higher-frequency regions. To manage this uncertainty, variance maps were generated and model disagreement was quantified using the coefficient of variation (CV). Finally, a reliability-oriented multi-objective optimization framework based on NSGA-II was developed, where a SmartTransformerRouter selects a reference loss estimate per candidate and CV is incorporated via constraints/penalties, with optional FEM triggering in high-uncertainty regions. Full article

Protein phosphorylation and dephosphorylation reactions of intracellular molecules catalyzed by enzymes such as kinases and phosphatases are essential reactions in a lot of cellular functions such as intracellular signal transduction in living systems. The design and synthesis of artificial enzyme mimics are important research topics in bioorganic and bioinorganic chemistry. In this paper, we report on the construction of artificial phosphatases via the supramolecular self-assembly of compounds such as an amphiphilic bis(Zn²⁺-cyclen) (cyclen = 1,4,7,10-tetraazacyclododecane) complex, barbital derivatives modified with benzocrown ethers and boronophenyl groups, and a copper(II) ion in a two-phase solvent system. We have developed a hypothesis whereby a mono(4-nitrophenyl)phosphate (MNP) substrate coordinates to the Cu₂(µ-OH)₂ core in supramolecular complexes and is activated either by Lewis acidic units such as alkali metal (Li⁺, Na⁺ and K⁺)-benzocrown ether complexes or by boronophenyl moieties. The findings suggest that supramolecular phosphatase functionalized with a benzo-12-crown-4-Li⁺ complex shows a higher level of activity in the MNP hydrolysis of a two-phase solvent system compared with that of our previous supramolecular phosphatases in terms of hydrolysis activity and catalytic turnover. Full article

Copper(II) compounds exhibit interesting magnetic properties due to halide–halide, copper–halide, and intermolecular hydrogen bond interactions. In this study, seven new copper(II) bromide complexes were synthesised, six of which contain Dabco (1,4-diazabicyclo[2.2.2]octane) as a ligand. Single-crystal X-ray diffraction data were refined using both conventional spherical-atom models and a non-spherical-atom approach implemented in NoSpherA2. Magnetic properties were investigated by temperature-dependent magnetic susceptibility and field-dependent magnetisation measurements, analysed using a molecular field approximation. Crystallographic analysis shows that NoSpherA2 significantly improves the description of hydrogen atom positions, yielding C–H and N–H bond lengths closer to neutron diffraction values than conventional refinement. Magnetic measurements indicate that interactions between mononuclear copper(II) centres are determined primarily by the nature of intermolecular exchange pathways rather than copper–copper separations alone. Despite comparable Cu···Cu distances, complexes lacking N–H···Br hydrogen bonds exhibit only weak antiferromagnetic interactions, whereas stronger coupling, effective up to 150 K, is observed when such hydrogen bonds connect neighbouring complexes. These results highlight the importance of hydrogen-bond topology and three-dimensional connectivity in governing magnetic behaviour in mononuclear copper(II) systems. Full article

This paper reports the synthesis, structural characterization, and biological evaluation of a novel series of Cu^I and Cu^II complexes supported by an amantadine-functionalized bis(pyrazol-1-yl)acetate ligand (L^Ad) as potential anticancer agents for the treatment of glioblastoma (GBM). Comprehensive spectroscopic and structural investigations, including SR-XPS, XANES/EXAFS, and DFT modeling, confirmed the successful coordination of L^Ad to copper centers in both oxidation states, affording well-defined molecular architectures with distinct coordination geometries. Among the synthesized compounds, the Cu^I complexes bearing triphenylphosphine co-ligands (compounds 4 and 5) exhibited the strongest cytotoxicity against U87 MG and LN18 GBM cell lines, showing IC₅₀ values lower than those of cisplatin. These complexes induced a pronounced redox imbalance through reactive oxygen species (ROS) overproduction and glutathione (GSH) depletion, leading to G2/M cell cycle arrest and cell death. Flow cytometry and Western blot analyses demonstrated that cell death occurs via caspase-dependent apoptosis in LN18 cells, as evidenced by PARP cleavage, downregulation of Bcl-xL, release of cytochrome c, and mitochondrial translocation of Bax. Altogether, these findings highlight the potential of lipophilic amantadine-functionalized Cu^I complexes as promising anticancer candidates targeting glioma cells through mitochondrial dysfunction and redox-mediated pathways. Full article

Two crystalline complexes, (2,2′-bipyridine)Cu(CH₃COO)₂·5H₂O (3) and (2,2′-bipyridine)Cu(CH₃COO)₂·CH₃CN (4), have been isolated and characterized by low-temperature single-crystal X-ray diffraction experiments. Crystals of phase 3 were studied previously at room temperature (296 K) under conditions leading to rapid desolvation and less distinct characterization of the waters of crystallization. With our redetermination of 3 at 100(2) K, we present a detailed description of ribbon-like structure formed by water molecules in crystals of (2,2′-bipyridine)Cu(CH₃COO)₂·5H₂O. Acetate oxygens are linked by hydrogen-bonding to two inequivalent waters separated by 4.72 Å; the other three water molecules are trapped in polymeric ribbons of anticooperative hydrogen-bonded six-membered rings fused with cooperative hydrogen-bonded four-rings. Water oxygens of the fused ring ribbons associate only with other water oxygens, and this water structure has a local density and pair distribution function which resembles that of liquid water. Crystals of 4 are monoclinic, with acetonitrile of solvation unassociated with the complex. In both 3 and 4, bipyridine planes interleave through π-aryl stacking. Full article

Copper(II) coordination complexes with coumarin-derived heterocyclic ligands are promising in inorganic therapeutics for anticancer and antimicrobial applications. To establish quantitative structure–activity relationships for lead design, we studied six copper(II) complexes (Cu1–Cu6)with four- and five-coordinate geometries using Density Functional Theory, Conceptual Density Functional Theory, and visualization analyses. Geometry optimization at M06/6-31G(d)+DZVP revealed distorted coordination environments from $d^9$ Jahn–Teller effects. Tridentate $N_{2}O$-chelatedcomplexes (Cu4–Cu6) showed greater aqueous stability ($\Delta G_{solv}=-43$ to $-50$ kcal·mol⁻¹) than four-coordinate analogs ($-29$ to $-31$ kcal·mol⁻¹). CDFT global descriptors contrasted reactivity: four-coordinate Cu1–Cu2 had higher electron affinity (>4.2 eV) and electrophilicity (>5.7 eV), suggesting propensity for redox cycling and for undergoing nucleophilic attack by DNA bases, whereas Cu4–Cu6 displayed increased chemical hardness (3.43–3.54 eV) and lower electrophilicity (≈3.8 eV), implying enhanced kinetic stability and bioavailability. Frontier orbital analysis indicated ligand-to-metal charge transfer via a LUMO delocalized over the $\pi$-conjugated coumarin, facilitating intercalation by $\pi$-$\pi$ stacking. The visualization showed strong covalent bonds (blue isosurfaces) stabilizing the metal and dispersive $\pi$ interactions (green surfaces) on the ligand, enabling solvent interactions and biomolecular recognition. Tridentate $N_{2}O$ coordination thus balances electronic stability and biological reactivity, making Cu4–Cu6 promising for further study. Full article

Salicyluric acid (SUA), the main metabolite of aspirin and a natural product, is known for its ability to chelate iron and other metal ions. In particular, the chelation and increased excretion of iron by SUA may contribute to the aspirin-induced iron deficiency anemia observed in long-term aspirin users. The redox activity of iron and copper complexes of drugs and also drug metabolites, such as SUA, is an important parameter of their overall toxicity profile, including the induction of ferroptosis, which has been associated with many diseases. In this context, the effect of SUA on iron- and copper-induced lipid peroxidation and also its localization within a model lipid membrane have been investigated. A combination of physicochemical methods, including Nuclear Magnetic Resonance (¹H NMR), molecular dynamics (MD), and Nuclear Overhauser Effect Spectroscopy (¹H NOESY), has been used to demonstrate that SUA does not promote the peroxidation of linoleic acid micelles in the presence of Fe(II) or Cu(II) ions. NMR experiments revealed that SUA incorporates into the lipid bilayer, which stabilizes the ligands and inhibits its metal chelation ability in comparison to the control. NOESY experiments and MD simulations further showed that SUA localizes shallowly within the membrane, interacting primarily with the head group and upper acyl chain regions of lipids. These findings provide crucial insights into the membrane redox reactivity and other behavior of SUA, explaining its lack of pro-oxidant activity and also highlighting its complex role in the pharmacological and toxicological effects on iron metabolism in long-term aspirin users. Full article

Waste textiles may contain heavy metals, which can originate from dyes, mordants, or other chemical treatments used during manufacturing. To explore the impact of heavy metals on the adsorption properties of activated carbon derived from discarded textiles through pyrolysis and to mitigate heavy metal migration, this study investigated the adsorption behavior of copper-impregnated pyrolytic carbon toward typical pollutants—methylene blue and lead—in simulated dyeing wastewater. Aqueous copper nitrate was used to impregnate the waste pure cotton textiles (WPCTs) to introduce copper species as precursors for creating additional active sites. The study systematically examined adsorption mechanisms, single and binary adsorption systems, adsorption kinetics, adsorption isotherms, adsorption thermodynamics, and the influence of pH. Key findings and conclusions are as follows: Under optimal conditions, the copper-containing biochar (Cu-BC) demonstrated maximum adsorption capacities of 36.70 ± 1.54 mg/g for Pb(II) and 104.93 ± 8.71 mg/g for methylene blue. In a binary adsorption system, when the contaminant concentration reached 80 mg/L, the adsorption capacity of Cu-BC for Pb(II) was significantly enhanced, with the adsorption amount increasing by over 26%. However, when the Pb(II) concentration reached 40 mg/L, it inhibited the adsorption of contaminants, reducing the adsorption amount by 20%. SEM, XRD, Cu LMM, FTIR and XPS result analysis proves that the adsorption mechanism of methylene blue involves π–π interactions, hydrogen bonding, electrostatic interactions, and pore filling. For Pb(II) ions, the adsorption likely occurs via electrostatic interactions, complexation with functional groups, and pore filling. This study supplements the research content on the copper adsorption mechanism supported by biochar for heavy metal adsorption research and broadens the application scope of biochar in the field of heavy metal adsorption. Full article

Copper contamination in aquatic environments poses significant ecological and health risks, necessitating efficient and resilient treatment strategies. In this study, graphene oxide (GO) and magnetic graphene oxide (MGO) were synthesized and comprehensively evaluated for Cu(II) removal using an integrated multivariate approach combining kinetic and isotherm modelling, Response Surface Methodology (RSM), and advanced statistical analyses. Both adsorbents achieved high removal efficiencies (>90%) under optimized conditions, with Langmuir capacities of 59.2 mg g⁻¹ for GO and 40.1 mg g⁻¹ for MGO. Kinetic modelling confirmed reaction-controlled adsorption, while Freundlich isotherms highlighted heterogeneous surface binding. RSM identified pH as the dominant factor governing removal efficiency, with significant interactions among pH, Cu(II), and DOC reflecting competitive matrix effects. Principal Component Analysis (PCA) revealed that GO performance is strongly influenced by solution chemistry, whereas MGO exhibits reduced sensitivity due to modified physicochemical properties. FTIR analysis confirmed that adsorption proceeds primarily through electrostatic attraction and inner-sphere complexation, with Fe–O sites contributing to MGO’s enhanced affinity. Regeneration studies demonstrated superior reusability of MGO, which retained ~64% efficiency after five cycles compared to ~52% for GO. Collectively, these multivariate and mechanistic insights identify MGO as a more robust, versatile, and regenerable sorbent for Cu(II) removal under realistic water-matrix conditions. Full article

Background/Objectives: Leishmaniasis constitutes one of the most fatal parasitic diseases globally, adversely impacting the health of individuals residing in both intertropical and temperate zones. In these geographical areas, the administration of treatment is often inconsistent and largely ineffective with the available pharmaceuticals, as these exhibit more pronounced side effects than the therapeutic advantages they purport to provide. Methods: Consequently, the current investigation seeks to engage in molecular modeling of novel pharmacological candidates incorporating 1,2,3 disubstituted triazole moieties, coordinated with Cu^II metal centers, in pursuit of promising bioactive properties. Results: Two complexes were prepared and X-ray analysis revealed a comparable structural configuration surrounding the copper (II) atom. The planar square coordination geometry was elucidated through the assessment of the ${\tau }_4=0$ (tau four) parameters. The comprehensive characterization encompasses HRMS-ESI (+), NMR, elemental analyses, mid-infrared, and UV-vis spectroscopic techniques. Time-dependent density functional theory (TD-DFT) analyses will substantiate the findings obtained through UV-vis spectroscopy. Crucially, the biological assays against Leishmania (L.) amazonensis revealed that Complex 1 exhibited outstanding potency against the intracellular amastigote form, demonstrating a half-maximal inhibitory concentration (IC₅₀) of 0.4 µM. This activity was 6-fold higher than that of amphotericin B (IC₅₀ = 2.5 µM) and 33-fold higher than pentamidine (IC₅₀ = 13.3 µM). Furthermore, Complex 1 showed a promising selectivity index (SI = 9.7) against amastigotes, surpassing the reference drugs and meeting the criteria for a lead compound. While less active on promastigotes, both complexes demonstrated high stability in DMSO solution, a prerequisite for biological testing. Conclusions: These results unequivocally identify Complex 1 as a highly promising candidate for the development of new antileishmanial therapies, warranting further in vivo studies. Full article