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The reaction of copper(II) trimethylacetate, [Cu(Piv)2]n (Piv = (Me)3CCOO−), with 1,4-bis(R)-1,4-diaza-1,3-butadienes (R-DAD, R = 2,4,6-trimethylphenyl, Mes, or 2,6-diisopropylphenyl, dpp) in tetrahydrofuran afforded the coordination polymers [Cu2(Piv)4(Mes-DAD)]n (I) and [Cu2(Piv)4(dpp-DAD)]n (II). The structure of complexes in the crystal was determined by X-ray diffraction (CCDC nos. 2205866, 2205867). The products were shown to be 1D coordination polymers in which the binuclear {Cu2(Piv)4} moieties are linked into chains owing to the bridging function of 1,4-diaza-1,3-butadienes, which is unusual for this type of ligands. [ABSTRACT FROM AUTHOR]

Three Cu(II) complexes of 1,1,1-trifluoroacetylacetonate, viz. [Cu(TFACAC)2(MeOH)] (1), [Cu(TFACAC)2(py)] (2) and [Cu(TFACAC)2(DABCO)] (3) were synthesized and characterized by elemental analysis, IR, UV–Visible spectroscopy and cyclic voltammetry. Structures of complexes 1–3 were established by single crystal X-ray diffraction wherein 1 and 2 adapt square pyramidal geometry. Complex 1 crystallizes in triclinic space group P-1, with a = 8.5059(6) Å, b = 9.3025(7) Å, c = 10.9906(8) Å, α = 75.684(2)°, β = 73.191(2)°, γ = 64.992(2)°, and Z = 2. X-ray crystallographic studies revealed that in complex 1, both, TFACC ligands and coordinated methanol are disordered over two conformations giving a combination of two isomers with cis to trans isomer ratio of 0.538:0.462. In complex 3 DABCO is acting as a bridging ligand connecting two Cu(II) centers thereby forming a 1-D polymer chain with each copper in octahedral coordination. The cyclic voltammograms of 1 and 3 give a quasi-reversible Cu(II)/Cu(I) peak with E1/2 + 0.01 V and − 0.05 V respectively whereas complex 2 gives a one electron reversible Cu(II)/Cu(I) couple at E1/2 = − 0.25 V. Three Cu(II) complexes of (1,1,1-trifluoroacetylacetonato) ligand with methanol, pyridine and DABCO occupying the axial positions are reported. [ABSTRACT FROM AUTHOR]

A series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h, 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b, and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c were obtained by reacting of appropriate 2-iminocoumarin ligands L1a-h, L3a-b, and L5a-c with 3-fold molar excess of copper(II) chloride. The structure of these compounds was confirmed by IR spectroscopy, elemental analysis, and single-crystal X-ray diffraction data (2f, 2g, 2h, and 6c). All the synthesized complexes were screened for their activity against five human cancer cell lines: DAN-G, A-427, LCLC-103H, SISO, and RT-4 by using a crystal violet microtiter plate assay and relationships between structure and in vitro cytotoxic activity are discussed. The coordination of 2-iminocoumarins with copper(II) ions resulted in complexes 2a-h, 4a-b, and 6a-c with significant inhibitory properties toward tested tumor cell lines with IC50 values ranging from 0.04 μM to 15.66 μM. In comparison to the free ligands L1a-h, L3a-b, and L5a-c, the newly prepared Cu(II) complexes often displayed increased activity. In the series of copper(II) complexes of 2-imino-2H-chromen-3-yl-1,3,5-triazines 2a-h the most potent compound 2g contained a 4-phenylpiperazine moiety at position 6 of the 1,3,5-triazine ring and an electron-donating diethylamino group at position 7′ of the 2-iminocoumarin scaffold. Among the Cu(II) complexes of 3-(benzoxazol-2-yl)-2H-chromen-2-imines 4a-b and 3-(benzothiazol-2-yl)-2H-chromen-2-imines 6a-c the most active was benzoxazole-2-iminocoumarin 4b that also possessed a diethylamino group at position 7′ of the 2-iminocoumarin moiety. Moreover, compound 4b was found to be the most prominent agent and displayed the higher potency than cisplatin against tested cell lines. [ABSTRACT FROM AUTHOR]

Six novel Cu(II) complexes were prepared and thoroughly characterized crystallographically, spectrally and magnetically. Formation of 1D and 2D supramolecular networks through the hydrogen bonds were observed. Two of them exhibit solvent induced conformational polymorphs. Influence of solvent was indicated also by computational simulations. [Display omitted] Six novel copper(II) compounds with derivatives of methylsalicylate (MeSal–) and methoxysalicylate anions (MeOSal–) and 2-(hydroxymethyl)benzimidazole (2-MeBzim), were prepared and characterized by elemental analysis, X-ray analysis IR, UV–Vis and EPR spectroscopy. The synthesis in the presence of 3-methylsalicylate anion led to formation of two complexes with same composition [Cu(3-MeSal) 2 (2-MeBzim) 2 ] (1a and 1b) which provide a fortunate case of reproducible conformational polymorphism/isomerism. Using state-of-the-art metadynamic computational simulations, the hypothesis that their formation is due to the use of different solvents has been verified. [ABSTRACT FROM AUTHOR]

[Display omitted] • 2-Chloroquinoline-3-carboxaldehyde-4(N)-substituted thiosemicarbazone derivate of Cu(II) complexes. • DNA/BSA binding studies for the ligands and their corresponding complexes. • In vitro studies were carried out against human kidney cell (HEK) and HeLa cells. • AO/EtBr and DAPI staining studies were carried out for the compounds. Copper(II) metallates of 2-chloroquinoline-3-carboxaldehyde-4(N)-substituted thiosemicarbazone (CuQ1, CuQ2, CuQ3, CuQ4) were synthesized, characterized by Fourier-Transform Infrared (FT-IR), Ultraviolet–Visible (UV–Vis), Electron Paramagnetic Resonance (EPR) and Mass spectrometry. The true nature of the ligands and a representative complex was confirmed by X-ray single crystal analysis. During the complexation, the ligands underwent cyclisation to form thiadiazole and two units of thiadiazole were coordinated to copper ion through N2-nitrogen atom. The remaining sites were occupied with two chloride ions and a water molecule which led to a square pyramidal geometry around copper ion. Absorption and emission titration methods confirmed the partial intercalative mode of binding interaction between CT-DNA and the metal complexes. The interaction between complexes and BSA led to the formation of ground state fluorophore-quencher complex by following static quenching mechanism. In vitro cytotoxic effect of the ligands and complexes were done by taking Human cervical cancer (HeLa) cells and toxicity of the test compounds were analyzed by using normal human kidney cell (HEK). The complexes CuQ2, CuQ3 and CuQ4 showed better cytotoxic activity against HeLa cells as compared with the standard cisplatin. Among the complexes, CuQ3 exhibited higher activity with least IC 50 value (17 µM). [ABSTRACT FROM AUTHOR]

Two new cationic Cu(II) complexes of cyclam (1,4,8,11-tetraazacyclotetradecane) and aminocarboxylate coligands glycine or alanine have been synthesized. The complexes were characterized by elemental analysis (C, H and N), molar electrical conductivity, magnetic susceptibility measurement at room temperature, spectral methods (UV/Vis and Fourier transform infrared), as well as by thermogravimetric (TG) and differential thermal analysis (DTA). The analytical data of the complexes show the formation of mononuclear complexes with general formula [Cu(L)cyc](ClO4)2·nH2O, A) L = glycine, n = 1.5 and B) L = alanine, n = 2.5. The tetradentate ligand cyclam was coordinated to metals through four N donors. The spectroscopic data suggested that the amino carboxylate ligands coordinated via their carboxylate ion moieties. The six- -coordinate octahedral geometry around Cu(II) in both complexes was presumed. TG-DTA analysis indicated that complex B decomposed exothermally in a single step in the range of 310–400°C. The cytotoxic activity of Cu(II) complexes and the starting ligands were tested against human cervix adenocarcinoma cell line (HeLa), human melanoma (FemX) and human colon carcinoma (LS174). The IC50 values for the Cu(II) complexes were from 48.35–82.25 μM. Both complexes were tested for their antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and the yeast Candida albicans.

The in vitro biological properties of previously obtained copper(II) complexes of arylmethylene-bis(4-hydroxy-6-methyl-2H-pyran-2-ones) were studied. The cytotoxic properties of all complexes against human cervical cancer cell line HeLa were determined. The antibacterial properties of the copper(II) complexes against Gram-negative and Gram-positive bacteria were determined. Di[3,3′-(phenylmethylene)-bis(4-hydroxy-6-methyl-2H-pyran-2-one)]copper(II) and di{3,3′-[(3-nitrophenyl)methylene]-bis(4-hydroxy-6-methyl-2H-pyran-2-one)}copper(II) tetrahydrates were characterized by pronounced algaecidal activity in vitro against Dunaliella salina. The prospects of searching for pharmacologically active substances of interest as potential drugs in series of copper(II) complexes of arylmethylene-bis(4-hydroxy-6-methyl-2H-pyran-2-ones) are shown. [ABSTRACT FROM AUTHOR]

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa. [ABSTRACT FROM AUTHOR]

Reaction of copper(II) acetate with 5-nitro-2-furoic acid (NO2-Hfur) and N-donor ligands 2,2'‑bipyridine (bpy) and pyridine (py) has resulted in complexes [Cu(NO2-fur)2(H2O)2]·2H2O (I), [Cu(NO2-fur)2(py)2(H2O)] (II), and binuclear [Cu2(NO2-fur)4(bpy)2]·H2O (III) whose structure was determined by X‑ray diffraction study. Cation Cu2+ is in square-planar (I) or square-pyramidal (II, III) environment and has CN(Cu) = 4 (I) or 5 (II, III), respectively. Stability of complexes I–III in solid phase has been determined by synchronous thermal analysis, stability in solutions has been studied by electronic absorption spectroscopy. Compounds I and II are thermally stable (>100°С). The presence of nitro group in the complexes causes strong exothermal effects, whose intensity is leveled by donor ligand. The storage of solutions of the compounds in 5% glucose solution and 0.9% NaCl for 2 days according to UV spectroscopy causes no their degradation. Biological activity of complexes I–III was studied in vitro toward non-pathogenic strain M. smegmatis (behaves as a model for M. tuberculosis); antimicrobial activity of compound II toward a number of Gram-positive and Gram-negative bacteria has been investigated. [ABSTRACT FROM AUTHOR]

The two new complexes, namely [NiU2(H2O)2]SO4, (NiU) and [CuU2(H2O)2]SO4, (CuU) [U = 5,6-diamino-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione monohydrate] were synthesized and characterized by elemental analysis, physicochemical, spectroscopic, (UV-visible, IR, ESI-MS, and XRD), thermal analysis and cyclic voltametric techniques. As showed in the data obtained, an octahedral geometry has been assigned for the two complexes. The data proved that the new complexes NiU and CuU have anticancer activities against colon cancer (HCT-116), epithelioid carcinoma (HeLa), and prostate adenocarcinoma (PC3) human cancer cell lines. The apoptotic pathway for both NiU and CuU complexes was via p53 elevation, which can arrest the cell cycle and activate the release of cytochrome c. The HCT-116 cells were treated with either NiU or CuU complexes had increased the production of caspase-9, which can activate the production of caspase-3 that degrades all the proteins in the cell, leading to apoptotic cell death. Consequently, the two complexes have promising anticancer activities. [ABSTRACT FROM AUTHOR]

Two new families of Cu(II) and Co(II) mononuclear complexes with mixed ligands, [Cu(VanTrpt)(bipy)]·MeOH (CuVanTrpt), [Cu(VanSer)(bipy)]·4H2O (CuVanSer), [Cu(VanTyr)(bipy)]·H2O (CuVanTyr), [Cu(VanThr)(bipy)]·MeOH (CuVanThr), [Co(VanTrpt)(bipy)(OH2)]·H2O·MeOH (CoVanTrpt), [Co(VanSer)(bipy)(OH2)]·MeOH (CoVanSer), [Co(VanTyr)(bipy)(OH2)]·3H2O·MeOH (CoVanTyr), and [Co(VanThr)(bipy)(OH2)] (CoVanThr), (VanX are Schiff base proligands resulted from the condensation of o‐vanillin with D,L‐tryptophan (VanTrpt), L‐serine (VanSer), L‐tyrosine (VanTyr), and L‐threonine (VanThr), respectively, and bipy is 2,2′‐bipyridine), have been obtained and characterized on the basis of elemental analysis, magnetic measurements, and spectral data (FT‐IR and UV–Vis–Nir spectroscopy). Crystal structures of CuVanTrpt, CuVanSer, and CuVanTyr have been solved by single‐crystal X‐Ray diffraction. Biological evaluation revealed that they are cytotoxic in HeLa (human carcinoma of the uterine cervix) and LSR‐SF‐SR (rat sarcoma induced by Rous sarcoma virus strain Schmidt‐Ruppin) cells, showing an enhancement of cytotoxicity dependent of concentration and treatment time. The most pronounced cytotoxic effect is expressed by CuVanSer and CoVanSer. Various cytopathological changes of both types of cancer cells were observed after treatment with Cu(II) and Co(II) complexes for 72 h at concentrations of 100 and 200 μg ml−1. LSR‐SF‐SR cells were found to be relatively more sensitive to the cytotoxic effect of the complexes investigated as compared to HeLa cells. [ABSTRACT FROM AUTHOR]

The interest in the use of copper as a metal scaffold for the development of novel chemotherapeutics has considerably grown in recent years. This is mainly due to the relatively lower toxicity of copper complexes with respect to platinum drugs (i.e., cisplatin), the different mechanisms of action, and the cheaper cost. In the last decades, hundreds of copper-based complexes were developed and screened as anticancer agents, with the antesignanus of all compounds being copper bis-phenanthroline [Cu(phen)2]2+ developed by D.S. Sigman in the late 1990s. In particular, copper(phen) derivatives have been shown high interest in their capacity to interact with DNA by nucleobase intercalation. Here, we report the synthesis and chemical characterization of four novel copper(II) complexes functionalised with phenanthroline derivatives containing biotin. Biotin, also known as Vitamin B7, is involved in a series of metabolic processes, and its receptors are often overexpressed in many tumour cells. A detailed biological analysis including cytotoxicity in 2D and 3D, cellular drug uptake, DNA interaction, and morphological studies are discussed.

Monomeric [Cu(DACH)(L)]2+ (DACH=1,2‐diaminocyclohexane) heteroleptic copper(II) complexes (1–4) on reaction with diphenyl phosphate yielded dinuclear phosphate bridged copper(II) complexes [Cu2L2(dpp)3]+ (5–7), [dpp=diphenyl phosphate; L=bpy (5), Phen (6), 5, 6 dimethyl phenanthroline, (7)] and a tetra‐nuclear [Cu4(2,9‐dmp)2(dpp)4(OH)2]2+ complex (8) (2, 9 dmp=2, 9 dimethyl phenanthroline). Interestingly, isomeric ligands 5,6‐dmp and 2,9‐dmp yielded dinuclear complex 7 and tetra‐nuclear complex 8 triggered by steric effects. Even though the initial combination contains mixed bidentate ligands, the resulting complexes have only one type of bidentate ligand around the copper(II) ions. These reactions involve ligand expulsion to form the phosphate bridged complexes. All the phosphate bridged complexes 5–8 were characterized by elemental analysis, absorption spectrum, FT‐IR, ESI‐MS, and single‐crystal XRD. The molecular structures show Cu(II) in square pyramidal/trigonal bipyramidal geometry with phosphate in μ‐1,3‐bridging mode. All complexes exhibit intra‐antiferromagnetic interactions with negative J values from variable temperature magnetic susceptibility study by SQUID measurements. [ABSTRACT FROM AUTHOR]

Three copper(II) complexes (I–III) bearing N,O‐bidentate ligands (L1–L3), derived from 2‐methylquinoline and cyclic secondary amines (including pyrrolidine, morpholine, and 4‐methylpiperidine), were successfully prepared and successively employed in construction of CN bonds via the Chan–Lam coupling of 1H‐imidazole derivatives with arylboronic acids. X‐ray diffraction analysis demonstrated that the central copper(II) atom of II adopted the distorted tetrahedral geometry, which was four coordinated by one nitrogen atom and one oxygen atom from L2 as well as two chloride atoms. Catalytic studies indicated that complex II displayed higher activity in Chan–Lam reaction than complex I or III. The present protocol for N,O‐coordinated‐copper complex‐catalyzed CN coupling reaction exhibited some advantages such as wide scope of substrates, good yields, and mild conditions. [ABSTRACT FROM AUTHOR]

The veterinary 16-membered macrolide antibiotics tylosin (HTyl, 1a) and tilmicosin (HTilm, 1b) react with copper(II) ions in acetone at metal-to-ligand molar ratio of 1:2 to form blue (2) or green (3) metal(II) coordination species, containing nitrate or chloride anions, respectively. The complexation processes and the properties of 2–3 were studied by an assortment of physicochemical techniques (UV-Vis, EPR, NMR, FTIR, elemental analysis). The experimental data revealed that the main portion of copper(II) ions are bound as neutral EPR-silent dinuclear complexes of composition [Cu2(µ-NO3)2L2] (2a–b) and [Cu2(µ-Cl)2Cl2(HL)2] (3a–b), containing impurities of EPR-active mono-species [Cu(NO3)L] (2a'–b') and [CuCl2(HL)] (3a'–b'). The possible structural variants of the dinuclear- and mono-complexes were modeled by the DFT method, and the computed spectroscopic parameters of the optimized constructs were compared to those measured experimentally. Using such a combined approach, the main coordination unit of the macrolides, involved in the complex formation, was defined to be their mycaminosyl substituent, which acts as a terminal ligand in a bidentate mode through the tertiary nitrogen atom and the oxygen from a deprotonated (2) or non-dissociated (3) hydroxyl group, respectively. [ABSTRACT FROM AUTHOR]

Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (1 – 3) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex 3). In addition, a control compound (complex 4) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes 1 – 3 was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order 3 > 2 > 1 , giving the IC 50 values ranging from 2.874 ± 0.155 μM to 31.47 ± 0.29 μM against five cancer cell lines. Complex 4 showed less activity in comparison with complex 1 – 3. Notably, complexes 1 – 3 displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex 4 (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound 3 induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes 3 and 4 was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex 3 interacted with DNA in an intercalating mode, but the interaction mode of compound 4 with DNA was electrostatic interaction. A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands displayed a potent and selective anticancer activity. [Display omitted] • A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands displayed a potent anticancer activity. • The introduction of 1,8-naphthalimide improved both the anticancer activity and selectivity of the series of copper (II) complexes. • The aliphatic chain length of ligands regulated the anticancer activity of this series of compounds. [ABSTRACT FROM AUTHOR]

• Two novel Cu(II) complexes based on adenine show potent anticancer activity. • Cytotoxicity surpasses cisplatin, especially with a methyl group at C-5. • Cu(II) complex C2 emerges as a powerful chemotherapeutic agent. • C2′s efficacy involves ROS elevation, DNA damage, mitochondrial disruption, and apoptosis. • Adenine-based Cu(II) complexes, particularly C2, demonstrate superior cytotoxicity, marking a significant advance in anticancer drug discovery. Platinum-based chemotherapeutics have played a critical role in oncology for decades. However, their broader utility is hindered by the advent of severe side effects and the emergence of drug resistance. The pursuit of alternative agents, particularly non-platinum (non-Pt) metal complexes, has gained momentum in current research. Designing efficacious non-Pt metal agents that target DNA poses a complex challenge. In this study, we present the strategic design, synthesis, and thorough characterization of two innovative copper(II) complexes leveraging adenine as a ligand, a potential avenue to overcome these challenges. Our investigation demonstrates the superior cytotoxicity of these copper(II) complexes compared to the benchmark cisplatin, with complex C2 exhibiting the most promising anticancer activity, showcasing an impressive IC 50 value of 4.51 μM in MGC-803 cells. Mechanistic insights underscore that complex C2 executes its cytotoxic effects by instigating DNA damage, orchestrating cell cycle arrest at the G2 phase, perturbing mitochondrial membrane potential, inducing ROS production, and ultimately triggering apoptotic pathways. These findings significantly emphasize the potential of designing novel adenine-based anticancer metal complexes targeting DNA, portraying a compelling trajectory for advancing anticancer drug development. Mechanisms of C2 Compound-induced Cytotoxicity in Cancer Cells Synopsis: This study highlights the pursuit of non-platinum metal complexes as alternative anticancer agents to overcome drug resistance and severe side effects associated with platinum-based chemotherapeutics. Copper(II) complex C2 emerges as a promising candidate, demonstrating superior cytotoxicity by targeting DNA and triggering multiple pathways for apoptosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Complexes [Cu(PI) 2 (H 2 O)](NO 3) 2 (1), [Cu(PBI) 2 (NO 3)]NO 3 (2), [Cu(TBI) 2 (NO 3)]NO 3 (3), [Cu(BBIP) 2 ](ClO 4) 2 (4) and [Cu(BBIP)(CH 3 OH)(ClO 4) 2 ] (5) were synthesized from the reactions of Cu(II) salts with 2-(2′-pyridyl)imidazole (PI), (2-(2′-pyridyl)benzimidazole (PBI), 2-(4′-thiazolyl)-benzimidazole (TBI), 2,6-bis(benzimidazol-2-yl)-pyridine (BBIP), respectively. Their compositions and crystal structures were determined. Their in-vitro antitumor activities were screened on four cancer cell lines and one normal cell line (HL-7702) using cisplatin as the positive control. Complexes 2 and 4 show higher cytotoxicity than the other three complexes. The cytotoxicity of complex 2 are comparable to those for cisplatin, and the cytotoxicity for 4 are much higher than those for cisplatin. From a viewpoint of antitumor, 2 might be a nice choice on the tumor cell line of T24 because its IC50 values on T24 and HL-7702 are 15.03 ± 1.10 and 21.34 ± 0.35, respectively. Thus, a mechanistic study for complexes 2 and 4 on T24 cells was conducted. It revealed that they can reduce mitochondrial membrane potential and increase mitochondrial membrane permeability, resulting in increased intracellular ROS levels, Ca2+ inward flow, dysfunctional mitochondria and the eventual cell apoptosis. In conclusion, they can induce cell apoptosis through mitochondrial dysfunction. These findings could be useful in the development of new antitumor agents. We report here five Cu(II) complexes bearing imidazole derivative ligands with different ligand skeletons, some of which present cytotoxicity comparable to cisplatin or even higher than cisplatin. [Display omitted] • Complexes with different ligand skeletons and structures show different cytotoxicity; • Some complexes present cytotoxicity comparable to or even higher than cisplatin; • Cell apoptosis through mitochondrial pathway. [ABSTRACT FROM AUTHOR]

The biomolecule chelidonic acid (H2chel, 4-oxo-4H-pyran-2,6-dicarboxylic acid) has been used to build new coordination polymers with the bridging N,N′-ligands 4,4′-bipyridine (4,4-bipy) and 1,2-bis(4-pyridyl)ethane (bpe). Four compounds have been obtained as single crystals: 1D cationic coordination polymers [M(4,4-bipy)(OH2)4]2+ with chelidonate anions and water molecules in the second coordination sphere in 1∞[Zn(4,4-bipy)(H2O)4]chel·3H2O (2) and in the two pseudopolymorphic 1∞[Cu(4,4-bipy)(H2O)4]chel·nH2O (n = 3, 4a; n = 6, 4b), and the 2D neutral coordination polymers 2∞[Zn(chel)(4,4-bipy)(H2O)]·2H2O (1) and 2∞[Zn(chel)(bpe)(H2O)]·H2O (3) where the chelidonate anion acts as a bridging ligand. The effects of the hydrogen bonds on the crystal packing were analyzed. The role of the water molecules hosted within the crystals lattices was also studied.

Two copper(II) complexes [Cu(H pmoh)(NO 3)(NCS)] (1) and [Cu(peoh)(N 3)] 2 (2) were designed and synthesized by reaction of Cu(NO 3) 2 · 3H 2 O with hydrazone Schiff base ligands,abbreviated with H pmoh and H peoh. H pmoh and H peoh were prepared by condensation reaction of octanoic hydrazide with pyridine-2-carboxyaldehyde and 2-acetylpyridine, respectively. Complexes 1 and 2 were characterized using different analytical techniques such as FT-IR, UV–Vis, IR, EPR and single X-ray diffraction (XRD) analyses as well as computational methods (DFT). The XRD of 1 and 2 shows a mononuclear or a dinuclear structure with the copper(II) centre adopting a slightly distorted square pyramidal geometry. In water-containing solution and in DMSO, 1 and 2 undergo a partial transformation with formation of [Cu(H pmoh)(NO 3)(NCS)] (1) and [Cu(H pmoh)(NO 3)(H 2 O/DMSO)] (1a) in one system and [Cu(peoh)(N 3)] (2a) in the other one, as supported by DFT calculations. Docking simulations confirmed that the intercalation is the preferred binding mode with DNA for 1 , 1a and 2a , but suggested that the minor groove binding is also possible. A significant fluorescence quenching of the DNA–ethidium bromide conjugate was observed upon the addition of complexes 1 and 2 with a quenching constant around 104 M−1 s−1. Finally, both 1 and 2 were examined for anti-cancer activity using MDA-MB-231 (human breast adenocarcinoma) and A375 (malignant melanoma) cell lines through in vitro MTT assay which suggest comparable cancer cell killing efficacy, with the higher effectiveness of 2 due to the dissociation into two [Cu(peoh)(N 3)] units. The synthesis and characterization of two new mononuclear and dinuclear copper(II) complexes with hydrazone Schiff base ligands were reported. Both of them bind to calf thymus-DNA with an intercalative binding and show high cytotoxicity against MDA-MB-231 (human breast adenocarcinoma) and A375 (malignant melanoma) cell lines. [Display omitted] • Two copper(II) complexes with hydrazone Schiff base ligands were studied. • One mononuclear and one dinuclear Cu(II) species were characterized. • Dinuclear complex dissociate into two monomeric Cu(II) moieties in solution. • Both the complexes show interaction with CT-DNA. • Both the complexes are active against MDA-MB-231 and A375 cell lines. [ABSTRACT FROM AUTHOR]

Copper can be opportunely complexed to modulate oncogenic pathways, being a promising strategy for cancer treatment. Herein, three new copper(II) complexes containing long-chain aliphatic hydrazides and 1,10-phenanthroline (1,10-phen), namely, [Cu(octh)(1,10-phen)(H 2 O)](NO 3) 2 1 , [Cu(dech)(1,10-phen)(H 2 O)](NO 3) 2 2 and [Cu(dodh)(1,10-phen)(H 2 O)](NO 3) 2.H 2 O 3 (where octh = octanoic hydrazide, dech = decanoic hydrazide, dodh = dodecanoic hydrazide) were successfully prepared and characterized by several physical-chemical methods. Furthermore, X-ray structural analysis of complex 2 indicated that the geometry around the copper(II) ion is distorted square-pyramidal, in which hydrazide and 1,10-phenanthroline act as bidentate ligands. A water molecule in the apical position completes the coordination sphere of the metal ion. All new copper(II) complexes were cytotoxic to breast cancer cell lines (MCF7, MDA-MB-453, MDA-MB-231, and MDA-MB-157) and selective when compared to the non tumor lineage MCF-10A. In particular, complex 2 showed half-maximal inhibitory concentration (IC 50) values ranging between 2.7 and 13.4 μM in MDA-MB231 cells after 24 and 48 h of treatment, respectively. Furthermore, this complex proved to be more selective for tumor cell lines when compared to doxorubicin and docetaxel. Complex 2 inhibited the clonogenicity of MDA-MB231 cells, increasing adenosine diphosphate (ADP) hydrolysis and upregulating ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1) transcriptional levels. In this sense, we suggest that the inhibitory effect on cell proliferation may be related to the modulation of adenosine monophosphate (AMP) levels. Thus, a novel copper(II) complex with increased cytotoxic effects and selectivity against breast cancer cells was obtained, contributing to medicinal chemistry efforts toward the development of new chemotherapeutic agents. Three new copper(II) complexes containing long-chain aliphatic hydrazides and 1,10-phenanthroline were synthesized and characterized. Complex 2 was the most promising, exhibiting cytotoxicity and selectivity against triple-negative breast cancer cells. This compound also impaired the clonogenicity, increasing adenosine diphosphate (ADP) hydrolysis and upregulating ecto-nucleoside triphosphate diphosphohydrolase 1 (ENTPD1) transcriptional level. [Display omitted] • New Cu(II) complexes were prepared and characterized by physical-chemical methods. • New Cu(II) complexes are selectively cytotoxic to mammary tumor cells. • Complex 2 impairs proliferation of breast cancer cells. • Complex 2 alters purinergic signaling increasing adenosine tri-phosphate hydrolisis. [ABSTRACT FROM AUTHOR]

• Norcraugsodine-Cu(II) complexes were synthesized and characterized. • In vitro ct -DNA/ t RNA/BSA binding studies were performed by biophysical techniques. • Cu(II)-norcraugsodine complexes 1 and 2 displayed strong binding with ct -DNA. • 2 cleaved plasmid pBR322 DNA efficiently by discernible hydrolytic cleavage pathway. • 2 showed good cytotoxic response against all the tested cancer cells with GI 50 < 10. Amaryllidaceae alkaloid are well known for their myriad pharmacological properties such as Alzheimer's dementia, antimicrobial, and antitumor. The therapeutic potency of this bio-pharmacophore was attributed to the presence of its versatile ring structure and carbon skeleton of alkaloid group. Herein, we have reported the synthesis of Cu(II) norcraugsodine Schiff base complexes 1 and 2 and their characterization by analytical, and spectroscopic methods. The comprehensive biological evaluation was done by carrying out interaction studies with therapeutic intracellular targets, ct -DNA, t RNA and BSA protein using complementary biophysical techniques. The corroborative results of binding experiments revealed that both complexes exhibit high propensity against ct -DNA (4.98 × 104 M−1 and 6.19 × 104 M−1) as compared to t RNA (2.00 × 104 M−1 and 3.21 × 104 M−1), attenuating the effect of ligand scaffold on therapeutic potency of drug candidates, and the order of binding was found to be 2 > 1 > SBL. To gain mechanistic insight of inhibition, DNA cleaving ability of complexes was evaluated by gel electrophoretic assay, the complexes were treated in presence of various activator and scavengers. The cleavage was found to be concentration-dependent exhibiting inhibition in presence of pre‑hydroxyl radical scavenger (EtOH), implicating that the cleavage was mediated by discernible hydrolytic pathway. The complexes and the ligand SBL were evaluated for the cytotoxicity response against four resistant cancer cell lines, both the complexes showed much enhanced potency as compared to ligand SBL against most of the cell lines, while complex 2 was more active than 1 towards resistant breast cancer cell line MDA-MB-231. All these studies reconfirmed that on complexation with copper, the therapeutic potency was enhanced multifold as compared to free organic Schiff base. [Display omitted] [ABSTRACT FROM AUTHOR]

The effects of two anticancer active copper(II) mixed-ligand complexes of the type [Cu(qui)(mphen)]Y·H2O, where Hqui = 2-phenyl-3-hydroxy- 1H-quinolin-4-one, mphen = bathophenanthroline, and Y = NO3 (complex 1) or BF4 (complex 2) on the activities of different isoenzymes of cytochrome P450 (CYP) have been evaluated. The screening revealed significant inhibitory effects of the complexes on CYP3A4/5 (IC50 values were 2.46 and 4.88 μM), CYP2C9 (IC50 values were 16.34 and 37.25 μM), and CYP2C19 (IC50 values were 61.21 and 77.07 μM). Further, the analysis of mechanisms of action uncovered a non-competitive type of inhibition for both the studied compounds. Consequent studies of pharmacokinetic properties proved good stability of both the complexes in phosphate buffer saline (>96% stability) and human plasma (>91% stability) after 2 h of incubation. Both compounds are moderately metabolised by human liver microsomes (1 and 2 to interact with major metabolic pathways of drugs and, as a consequence of this finding, their apparent incompatibility in combination therapy with most chemotherapeutic agents.

Herein, we discuss the synthesis, structural and spectroscopic characterization, and biological activity of five heteroligand copper(II) complexes with diethylnicotinamide and various fenamates, as follows: flufenamate (fluf), niflumate (nifl), tolfenamate (tolf), clonixinate (clon), mefenamate (mef) and N, N-diethylnicotinamide (dena). The complexes of composition: [Cu(fluf)2(dena)2(H2O)2] (1), [Cu(nifl)2(dena)2] (2), [Cu(tolf)2(dena)2(H2O)2] (3), [Cu(clon)2(dena)2] (4) and [Cu(mef)2(dena)2(H2O)2] (5), were synthesized, structurally (single-crystal X-ray diffraction) and spectroscopically characterized (IR, EA, UV-Vis and EPR). The studied complexes are monomeric, forming a distorted tetragonal bipyramidal stereochemistry around the central copper ion. The crystal structures of all five complexes were determined and refined with an aspheric model using the Hirshfeld atom refinement method. Hirshfeld surface analysis and fingerprint plots were used to investigate the intermolecular interactions in the crystalline state. The redox properties of the complexes were studied and evaluated via cyclic voltammetry. The complexes exhibited good superoxide scavenging activity as determined by an NBT assay along with a copper-based redox-cycling mechanism, resulting in the formation of ROS, which, in turn, predisposed the studied complexes for their anticancer activity. The ability of complexes 1–4 to interact with calf thymus DNA was investigated using absorption titrations, viscosity measurements and an ethidium-bromide-displacement-fluorescence-based method, suggesting mainly the intercalative binding of the complexes to DNA. The affinity of complexes 1–4 for bovine serum albumin was determined via fluorescence emission spectroscopy and was quantitatively characterized with the corresponding binding constants. The cytotoxic properties of complexes 1–4 were studied using the cancer cell lines A549, MCF-7 and U-118MG, as well as healthy MRC-5 cells. Complex 4 exhibited moderate anticancer activity on the MCF-7 cancer cells with IC50 = 57 μM.

Three new tripod tetradentate phenolate-amines (H2L1, H2L4 and H2L9), together with seven more already related published ligands, were synthesized, and characterized. With these ligands, two new dinuclear doubly-bridged-phenoxido copper(II) complexes (3, 4), and six more complexes (1, 2, 5–8), a new trinuclear complex (9) with an alternative doubly-bridged-phenoxido and –methoxido, as well as the 1D polymer (10) were synthesized, and their molecular structures were characterized by spectroscopic methods and X-ray single crystal crystallography. The Cu(II) centers in these complexes exhibit distorted square-pyramidal arrangement in 1–4, mixed square pyramidal and square planar in 5, 6, and 9, and distorted octahedral (5+1) arrangements in 7 and 8. The temperature dependence magnetic susceptibility study over the temperature range 2–300 K revealed moderate–relatively strong antiferromagnetic coupling (AF) (|J| = 289–145 cm−1) in complexes 1–6, weak-moderate AF (|J| = 59 cm−1) in the trinuclear complex 9, but weak AF interactions (|J| = 3.6 & 4.6 cm−1) were obtained in 7 and 8. No correlation was found between the exchange coupling J and the geometrical structural parameters of the four-membered Cu2O2 rings.

As depicted in the inset of Figure S4, the redox currents of B 1 b -CPE (or B 2 b -CPE) are proportional to the scan rates, suggesting that the redox process occurring on B 1 b -CPE (or B 2 b -CPE) is surface-controlled. Keywords: copper(II) complexes; crystal structures; electrochemical sensors; oxygen evolution reaction (OER) EN copper(II) complexes crystal structures electrochemical sensors oxygen evolution reaction (OER) 157 164 8 03/11/22 20220201 NES 220201 1 Introduction Metal-organic compounds (MOCs) are a kind of crystalline materials formed by the combination of organic ligands and metal ions or metal clusters [[1]], [[2]], [[3]]. The Cu-O bond lengths are 1.9676(14)-1.9728(14) Å, and the Cu-N distance is 2.1433(15) Å. The bond angles are in the range 90.70(6)-101.77(6)° for O-Cu-N and 87.72(7)-167.55(6)° for O-Cu-O. The bond length and angle information is listed in Table S1. Cyclovoltammograms of the carbon paste electrodes modified with complexes B 1 b and B 2 b ( B 1 b -CPE and B 2 b -CPE) in 0.1 M H SB 2 sb SO SB 4 sb + 0.5 M Na SB 2 sb SO SB 4 sb electrolyte solution (scan rates: 20-500 mV s SP -1 sp ) are shown in Figure S4. [Extracted from the article]

A method for the preparation of new organic ligands combining in their structure a 2-(pyridin-2-yl)benzothiazole moiety capable of coordinating metal iones and a thioacetate group, which makes it possible to adsorb the obtained compounds on a gold surface, has been developed. Using cyclic voltammetry, the possibility of chemisorption of the obtained compounds on the surface of gold electrodes and obtaining complexes of adsorbed ligands with CuCl2 has been shown. [ABSTRACT FROM AUTHOR]

This study aimed to encapsulate and characterise a potential anti-tuberculosis copper complex (CuCl2(INH)2.H2O:I1) into polymeric nanoparticles (PNs) of polymethacrylate copolymers (Eudragit®, Eu) developed by nanoprecipitation method. NE30D, S100 and, E100 polymers were tested. The physicochemical characterisations were performed by DLS, TEM, FTIR, encapsulation efficiency and, in vitro release studies. Encapsulation of I1 in PN-NE30D, PN-E100, and PN-S100 was 26.3%, 94.5%, 22.6%, respectively. The particle size and zeta potentials were 82.3 nm and -24.5 mV for PNs-NE30D, 304.4 nm and þ18.7 mV for PNs-E100, and 517.9 nm and -6.9 mV for PNs-S100, respectively. All PDIs were under 0.5. The formulations showed an I1 controlled release at alkaline pH with 29.7% from PNs-NE30D, 7.9% from PNs-E100 and, 28.1% from PNsS100 at 1 h incubation. PNs were stable for at least 3 months. Particularly, PNs-NE30D demonstrated moderate inhibition of M. tuberculosis and low cytotoxic activity. None of the PNs induced mutagenicity. [ABSTRACT FROM AUTHOR]

Four new mixed ligand copper(II) complexes with the general formula [Cu(L)(B)]n (1)–(4) (H2L = dehydroacetic acid benzoyl hydrazone Schiff base, B = H2O (1), DMSO (2), imidazole (imz) (3), n = 1) or pyridine (py) (4), n = 2) were synthesized. Characterization was performed by elemental analyses, FTIR, 1H NMR, electron paramagnetic resonance (EPR), ESI‐mass, and UV–visible) spectroscopy, together with magnetic susceptibility and molar conductivity measurements. The molecular structure of (2) and (4) complexes was investigated by X‐ray crystallography. The ligand behaves as a di‐basic tridentate ONO donor, coordinating to copper(II) center via deprotonated hydroxyl group, azomethine nitrogen, and deprotonated amide oxygen in a square planar (1)–(3) /square pyramidal geometry (4). The intercalation binding mode of the compounds with calf thymus DNA (ct DNA) and yeast (tRNA) and strong static interaction with bovine serum albumin (BSA) protein have been evaluated by absorption and emission spectroscopy. Further, in vitro cytotoxic activity of the compounds was examined on three human cancer cell lines; breast cancer (MCF7), colon cancer (HCT116), liver cancer (HepG2), and a normal lung fibroblast cell line (WI38) using cisplatin as a standard. Based on IC50 and therapeutic indices (TI), complexes (3) and (4) showed better activity than that of cisplatin. So both complexes were subjected for further studies viz, DNA fragmentation, cell apoptosis (annexin), and cell cycle analysis. They induced DNA fragmentation, and the HCT116 and HePG2 cell death were induced using (3) and (4) complexes, respectively, by apoptosis and cell cycle arrest at the G2/M phase. [ABSTRACT FROM AUTHOR]

The analysis of publications in 2020, devoted to the synthesis of copper(II) complexes and the study of their antimicrobial properties, indicates that this area of medicinal chemistry is promising. Organic compounds of various classes were studied as starting ligands. First of all, these are N-donor imines, amines, heterocyclic compounds, as well as N,O-donor ligands and sulfur-containing ligands. In most works, the fact of a higher biological activity of the metal complex in comparison with the corresponding ligand was established. Evaluating the influence of the nature of the metal on the antimicrobial activity of the metal complex, the authors most often come to the conclusion that it is copper(II) complexes that are the most effective inhibitors of the growth of pathogenic bacteria. The scale of the studies presented indicates a high interest in this group of metal complexes, and the results indicate good prospects for using copper complexes as antimicrobial drugs. [ABSTRACT FROM AUTHOR]

Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. FT1 crystallizes in the triclinic system while FT2 in the orthorhombic. The DNA cleavage activity of Cu(II) complexes was studied using plasmid pBR322 DNA by gel electrophoresis. All compounds cleave DNA on photoirradiation by oxidative mechanism. Two Schiff base ligands FT1 and FT2 and their Cu(II) complexes were synthesized and characterized by 1H NMR, ESI-MS, IR, UV-Visible, Fluorescence spectroscopy, EPR and single-crystal X-ray diffraction studies. Both the Cu(II) complexes of indole thiocarbohydrazones are shown to cleave plasmid pBR322 DNA by oxidative mechanism. [ABSTRACT FROM AUTHOR]

2-Hydroxy-5-methoxyphenylphosphonic acid (H3L1) and the complex [Cu(H2L1)2(H2O)2] were synthesized and characterized by IR spectroscopy, thermogravimetry, and X-ray diffraction analysis. The polyhedron of the copper atom is an axially elongated square bipyramid with oxygen atoms of phenolic and of monodeprotonated phosphonic groups at the base and oxygen atoms of water molecules at the vertices. The protonation constants of the H3L1 acid and the stability constants of its Cu2+ complexes in water were determined by potentiometric titration. The protonation constants of the acid in water are significantly influenced by the intramolecular hydrogen bond and the methoxy group. The H3L1 acid forms complexes CuL‒ and CuL24‒ with Cu2+ in water. [ABSTRACT FROM AUTHOR]

The formation of the binary Cu(II)-1,10ʹ-Phenanthroline (Phen, L) in aqueous solution was studied by means of electromotive force measurements (EMF). In addition, the Cu(II)-2,2ʹ-Bipyridine (Bipy, L) and Cu(II)-1,10ʹ-Phenanthroline ternary complexes were studied using the low molecular weight blood serum ligands: lactate (Lac−), Oxalate (Ox2-), citrate (Cit3-) and Phosphate (PO43-), in aqueous medium, at 25°C and using 1.0 mol.dm−3 KNO3 as ionic medium. The data obtained by potentiometric measurements were analysed using the LETAGROP least squares software. For the binary Cu(II)-1,10ʹ-Phenanthroline system the complexes [Cu(Phen)]2+, Cu(OH)2(Phen) and [Cu2(OH)2(Phen)2]2+ were detected. In the case of the ternary Cu(II)-L-Lac – system the species [Cu(L)(Lac)]+, Cu(Bipy)(Lac)(OH) and [Cu(Bipy)(Lac)(OH)2]− were observed, for the Cu(II)-L-Ox2 – system the complexes Cu(L)(Ox) and [Cu(L)(Ox)(OH)]− were obtained whereas for Cu(II)-L-Cit3 – system the species [Cu(L)(H2Cit)]+, Cu(L)(HCit) and [Cu(L)(Cit)]− were observed, and finally, in the Cu(II)-L-PO43 – system the complexes[Cu(L)(H2PO4)]+, Cu(L)(HPO4), [Cu(L)(PO4)]− and [Cu(Bipy)(PO4)(OH)]2− were detected. [ABSTRACT FROM AUTHOR]

New coordination compounds of copper(II) halides with 2-(3,5-dimethylpyrazol-1-yl)benzimidazole (L) are synthesized: CuLCl2 (I), [CuL2Cl]Cl⋅H2O⋅C2H5OH (II), and CuLBr2 (III). The compounds are characterized by IR spectroscopy, X-ray diffraction analysis, and static magnetic susceptibility. The crystal structure of compound II is determined by X-ray structure analysis (CIF file CCDC no. 2043452). The cytotoxic properties of ligands L and complexes I and II are studied. [ABSTRACT FROM AUTHOR]

This present work deals with the synthesizes of nine novel thiosemicarbazone copper(II) complexes {[Cu(L)2]Cl C3, [Cu(L)(bpy)]Cl C4–C6, [Cu(L) (phen)]Cl C7–C9 (where, L = H(L1)–H(L3), H(L1) = (E)-N-methyl-2- -(1-phenyl-2-((5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)thio)ethylidene)hydrazinecarbothioamide, H(L2) = (E)-N-ethyl-2-(1-phenyl-2-((5-(pyridin-3-yl)-4H- -1,2,4-triazol-3-yl)thio)ethylidene) hydrazinecarbothioamide, H(L3) = (E)-N- -phenyl-2-(1-phenyl-2-((5-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)thio)ethylidene) hydrazinecarbothioamide, bpy = 2,2′-bipyridyl and phen = 1,10-phenanthroline) with improved pharmacological results. The synthesized complexes were characterized by various spectral-analytical techniques. The structure of the copper(II) complexes C1–C9 was proposed by EPR spectroscopy. It confirmed the square planar coordination around Cu(II) complexes. The antibacterial screening of the complexes revealed that complexes C7 and C8 demonstrated significant activity against Gram-positive (B. thuringiensis) and Gram-negative (E. coli) bacteria. The concentration-dependent DNA cleavage activity of supercoiled (SC) pUC18 DNA exhibited complete DNA degradation effect on complex C6 at a minimum concentration of 40 μM. In vitro cytotoxic results showed that the mixed ligand copper(II) complexes C4, C5 and C7 exhibited higher effects on human cervical cancer cell lines, HeLa, when compared to cisplatin. Hence, the results obtained from each biological screening indicated the superior biological efficacy of the mixed ligand copper(II) complexes bearing diimine moieties. It could be considered as a promising alternative to an existing anticancer drug.

We report stable and heterogeneous graphene oxide (GO)–intercalated copper as an efficient catalyst for the organic transformations in green solvents. The GO-intercalated copper(II) complex of bis(1,4,7,10-tetraazacyclododecane) [Cu(II)-bis-cyclen] was prepared by a facile synthetic approach with a high dilution technique. The as-prepared GO-Cu(II)-bis-cyclen nanocomposite was used as a click catalyst for the 1,3 dipolar Huisgen cycloaddition reaction of terminal alkyne and azide substrates. On directing a great deal of attention toward the feasibility of the rapid electron transfer rate of the catalyst in proliferating the yield of 1,2,3-triazole products, the click catalyst GO-Cu(II)-bis-cyclen nanocomposite was designed and synthesized via non-covalent functionalization. The presence of a higher coordination site in an efficient 2D nanocomposite promotes the stabilization of Cu(I) L-acetylide intermediate during the catalytic cycle initiated by the addition of reductants. From the XRD analysis, the enhancement in the d-interlayer spacing of 1.04 nm was observed due to the intercalation of the Cu(II)-bis-cyclen complex in between the GO basal planes. It was also characterized by XPS, FT-IR, RAMAN, UV, SEM, AFM, and TGA techniques. The recyclability of the heterogeneous catalyst [GO-Cu(II)-cyclen] with the solvent effect has also been studied. This class of GO-Cu(II)-bis-cyclen nanocomposite paves the way for bioconjugation of macromolecules through the click chemistry approach.

A series of benzoxazole based 5-(alkoxy)-2-(((4-(5-methylbenzoxazol-2-yl-)- phenyl)imino)methyl)phenol, HLn (n = 10, 12, 14) and their copper(II) complexes had been synthesized; molecular structures of all the organic compounds and the metal complexes were elucidated by various spectroscopic techniques along with elemental analyses. Thermotropic properties were investigated by a combination of POM observation, DSC analysis and X-ray diffraction experiments. All members of the series exhibit enantiotropic smectic-A (SmA) mesophase. DFT calculations imply stable electronic structure of the ligand; HLn (n = 12) as well as of its copper(II) complex.

A series of six heteroleptic copper(II) complexes with 2′-hydroxy-4-(dimethylamino)chalcone (HL) with the composition [Cu(N-N)(L)]NO3 (1–6), where N-N stands for dmbpy = 5,5′-dimethyl-2,2′-bipyridine (1), bphen = 4,7-diphenyl-1,10-phenanthroline (2), dbbpy = 4,4′-di-tert-butyl-2,2′-bipyridine (3), nphen = 5-nitro-1,10-phenanthroline (4), bpy = 2,2′-bipyridine, (5), and dpa = 2,2′-dipyridylamine (6), was prepared and thoroughly characterized. The in vitro cytotoxicity screening on eight human cancer cell lines identified complex 2, containing the bulkiest N-donor ligands (bphen) as highly cytotoxic against cancer cells, with IC50 values ranking from 1.0 to 2.3 μM, with good selectivity and low toxicity against healthy human fetal lung fibroblasts MRC-5. The cell-based assays, involving the most effective complex 2 in A2780 cancer cells, revealed its strong pro-apoptotic effects based on the effective activation of caspases 3/7, ROS overproduction, and autophagy in the A2780 cells while not impeding the cell cycle and mitochondrial membrane functions. The cellular uptake studies in A2780 and 22Rv1 cells uncovered no intracellular transport of the cationic complex 2, supporting the hypothesis that the in vitro anticancer effects of complex 2 are based on the combined extrinsic activation of apoptosis and autophagy induction.

The synthesis, characterization and biological profile (antioxidant capacity, interaction with calf-thymus DNA and serum albumins) of five neutral copper(II) complexes of 5–fluoro–salicylaldehyde in the absence or presence of the N,N’–donor co–ligands 2,2′–bipyridylamine, 2,9–dimethyl–1,10–phenanthroline, 1,10–phenanthroline and 2,2′–bipyridine are presented herein. The compounds were characterized by physicochemical and spectroscopic techniques. The crystal structures of four complexes were determined by single-crystal X-ray crystallography. The ability of the complexes to scavenge 1,1–diphenyl–picrylhydrazyl and 2,2′–azinobis(3–ethylbenzothiazoline–6–sulfonic acid) radicals and to reduce H2O2 was investigated in order to evaluate their antioxidant activity. The interaction of the compounds with calf-thymus DNA possibly takes place via intercalation as suggested by UV–vis spectroscopy and DNA–viscosity titration studies and via competitive studies with ethidium bromide. The affinity of the complexes with bovine and human serum albumins was examined by fluorescence emission spectroscopy revealing the tight and reversible binding of the complexes with the albumins.

The fundamental importance of copper as a redox-active metal essential to the functioning of several metabolic enzymes provides a wide range of its biological activity pathways. Copper(II) coordination compounds are known to exhibit potent antiproliferative, antibacterial, nuclease, anti-inflammatory and antimycobacterial activities. Hydrazones are organic ligands commonly used for complexation with copper(II) that possess antibacterial, antiviral and antifungal properties. Copper–ligand interaction might facilitate charge delocalization and increase net hydrophobicity of the system, resulting in its enhanced pharmacological activity. Coordination compounds of Cu(II) with 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde derived hydrazone, nitrofurantoin and ftivazide have been synthesized, characterized by means of elemental and XRD analysis, FT-IR, UV-Vis and NMR spectroscopy and tested for antibacterial activity in vitro on Gram-positive and Gram-negative bacteria.

As a continuation of our previous investigations aimed at the synthesis of novel nitrogen-containing heterocycles and their metal complexes, we have now prepared two series of compounds incorporating a phthalazine ring at the position C2 of 4,5-dihydro-1H-imidazole. The starting phthalazine (I) in the reaction with 2-chloroimidazoline (II) gives rise to the formation of pseudobase III. Then, compound III upon treatment with HOSA yields betaine which under basic conditions gives 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV). In turn, the reactions of compound IV with a variety of acyl and sulfonyl chlorides lead to the formation of benzamides (V) and benzenesulfonamides (VI). Moreover, compounds V and VI can be transformed into corresponding 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one derivatives VII and VIII. Such ligands are susceptible to the reaction with CuCl2 giving rise to the formation of corresponding copper(II) complexes: dichloro[2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine]copper(II) (1), dichloro[2-(1-benzoyl-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]copper(II) (2) and dichloro{bis-[2-(1-(phenylsulfonyl)-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]}copper(II) (3). The most promising results of biological studies were obtained for complex 1 towards the HeLa cell line (IC50 = 2.13 μM) without a toxic effect against fibroblasts BALB/3T3 (IC50 = 135.30 μM), which pointed towards its selectivity as a potential antitumor agent. It should be pointed out, that corresponding free ligand 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV) was less active than its metal complex (IC50 = 87.74 μM).

New methods for the electrochemical synthesis of copper(II) and zinc(II) coordination compounds with pyridinecarboxylic acids (nicotinic and picolinic) have been developed. The resulting compounds were characterized by quantitative analysis and IR spectroscopy. The vibrational frequencies of the synthesized compounds were calculated by a DFT quantum-chemical method, and the experimental IR spectra were interpreted on this basis. It was found that pyridinecarboxylate ions in all cases are coordinated both at the nitrogen atom and at the carboxylate group, however, in the case of nicotinic acid, this leads to the formation of coordination polymers, whereas for picolinic acid, the formation of mononuclear complexes is typical. [ABSTRACT FROM AUTHOR]

Within the framework of the present study, a polydentate ligand with S and N donor sites along with its CuII‐based chelates were prepared and characterized. Elemental and thermal analyses, μeff and ΛM measurements as well as spectroscopy techniques including FT‐IR, electronic spectra, and EPR are the characterization tools. Computational chemistry calculations were applied to confirm the geometrical assignments of the penta and hexa coordinated perchlorato and chloro derivatives, respectively. Octahedral and trigonal bipyramidal stereochemistries were assigned for these copper(II) chelates. Powder X‐ray spectroscopy data were processed by Expo 2014 computer program for the structural illustration of one of the existing octahedral metal complexes. Biomimicking of copper(II) containing proteins phenoxazinone synthase and catechol oxidase was studied and the obtained results demonstrated promising oxidase‐like activity of the present CuII‐base complexes. Kinetic measurements were also performed to identify the potential catalytic pathways of the studied oxidation processes. The type of the counter‐anion included in the complexes significantly controls the structural features and the catalytic properties. [ABSTRACT FROM AUTHOR]

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa.

N(4) modified copper thiosemicarbazones have been extensively studied for their anticancer potency toward various cancer cells as they exhibit less toxicity, wide spectrum of activity, non-resistance behavior and a novel mechanism of action as compared to that of platinum complexes. 5-Nitroisatin -4-thiomorpholinyl-3-thiosemicarbazone(L1), 5- nitroisatin -4, 4-dimethyl-3-thiosemicarbazone(L2), and their copper (II) complexes; CuL1 and CuL2 were prepared and characterized by elemental analysis, FTIR, NMR, ESI-HRMS, UV-Vis, TGA, PXRD (Le Bail fitting) and EPR techniques. PXRD analysis suggested that the copper (II) complexes possess a monoclinic crystal system with P1211 symmetry. The coordination of Cu(II) ion with thiosemicarbazones and one chloride ion suggests a distorted square planar geometry of complexes. All the compounds were screened against breast cancer (MCF-7 and MDA-MB231), skin cancer (A431) and normal prostate cell line (PNT2) in terms of cell viability and found that all the synthesized compounds exhibited in vitro antiproliferation toward the tested cancer cells. These complexes were found to be more effective on MDA-MB-231 than on A431 and MCF-7 cells. The molecule, CuL1 was found to show a better anticancer potency compared to CuL2 as CuL1 was found to be less toxic to normal PNT2 cell line. [ABSTRACT FROM AUTHOR]

To assess the donor-acceptor properties of the basic and acidic sites in pyrrolyl and diazolyl derivatives of cycloalkanones, the energies and the shapes of the frontier molecular orbitals of their tautomers and conformers were calculated and the maps of the charge density distribution were constructed. The competition of these sites in the formation of hydrogen and coordination bonds and the possibility of participation of the studied products as ligands in metal complexes were shown. Complexes of diazolyl derivatives with CuCl2 were obtained. The synthesis of 7-amino-2-(pyrrolidin-2-ylmethylene)indan-1-one was performed and its structure and propensity to UV-initiated E→Z isomerization were studied by NMR and IR spectroscopy. [ABSTRACT FROM AUTHOR]

The geometric structures of compounds CuL2 (L = R1N(O)–(O)CR2; R1 = tert-Bu, R2 = Ph (I) and R1 = Ph, R2 = tert-Bu (II)) are studied by X-ray diffraction analysis (XRD) in the crystalline state and by stationary EPR spectroscopy in a dichloromethane solution. According to the XRD data (CIF files CCDC nos. 1875367 and 2022310, respectively), in the crystalline state the copper atoms of both complexes exist in the planar-square environment of the oxygen atoms with the trans-coordination of the hydroxamate ligands. According to the EPR data for frozen solutions of the complexes in dichloromethane, the compounds coexist as two mononuclear forms A and B differed in magnetic resonance parameters. It is shown that compound IB forms aggregates when freezing the solution. The form B of compound II is an associate of the copper complex with the solvent molecules. The EPR data indicate that both forms of compounds I and IIA form no associates with the solvent molecules. [ABSTRACT FROM AUTHOR]

A new hydrazone ligand (FCSH; HL) was successfully synthesized by the reaction of salicylaldehyde hydrazone with 3‐formylchromone. Seven copper(II) hydrazone complexes have been synthesized by using several copper(II) salts (acetate, nitrate, sulfate, perchlorate, chloride, and bromide). Elemental analysis, electronic, infrared, mass, nuclear magnetic resonance, electron spin resonance spectra, thermal analysis, molar conductivity, and magnetic susceptibility measurements were used to characterize structures of the hydrazone ligand and its complexes. The ligand behaves as monobasic tridentate for all complexes except complex 2 (monobasic tetradentate) and complex 4 (neutral tridentate). All metal complexes exhibited octahedral geometries. With the aid of Coats–Redfern equations, the kinetic parameters (Ea, A, ∆H, ∆S, and ∆G) of the thermal decomposition stages were calculated and discussed. At the B3LYP/6‐311G(d,p) level engaged in the Gaussian 09 program, density functional theory (DFT) calculations were carried out to inspect the optimized structures of the chelating agent and its complexes. The hydrazone ligand and its copper(II) complexes showed antitumor activity towards HepG2 cell line. The docking study of the hydrazone ligand and its copper(II) complexes was investigated with the active site of the CDK2 kinase. [ABSTRACT FROM AUTHOR]