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A dichlorophenyl substituted nitronyl nitroxide radical 2-(2,6-dichlorophenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (L) is prepared, its structure and magnetic properties are studied. It is shown that the interaction of bis(hexafluoroacetylacetonato)copper(II) [Cu(hfac)2] with L leads to the formation of the {[Cu(hfac)2][Cu(hfac)2L2]} heterospin complex whose crystal structure consists of pseudo-polymer chains formed by alternating single-spin [Cu(hfac)2] and three-spin [Cu(hfac)2L2] fragments. It is established that the temperature dependence of magnetic susceptibility of {[Cu(hfac)2][Cu(hfac)2L2]} is determined by ferromagnetic exchange interactions between unpaired electrons of Cu(II) ions and the axially coordinated L in three-spin fragments. [ABSTRACT FROM AUTHOR]

To increase the number of potential materials for application as MRI contrast agents, several Cu(II) complexes were synthesized. Cu(II) complexes were chosen because they are less expensive in comparison with the presently used Gd(III), Mn(II) and other agents. Pyridine-2-carboximidamide (1), pyrimidine-2-carboximidamide (2) and pyrazole-2-carboximidamide (3) in the form of different salts along with CuCl2 and NaCl or CuBr2 and NaBr were used to obtain four Cu(II) complexes: dichloro-pyrimidine-2-carboximidamide copper(II) (4), dibromo-pyrimidine-2-carboximidamide copper(II) (5), dichloro-pirazole-2-carboximidamide copper(II) (6), and dibromo-pirazole-2-carboximidamide copper(II) (7). X-ray diffraction analysis revealed that molecular complexes 4–7 contain square planar coordinated Cu(II) atoms and their structures are very similar, as well as their packing in crystals, which allows us to consider them isomorphs. The same synthetic approach to complex preparation where NaCl or NaBr was not used brought us to the formation of dimeric complexes μ-chloro{chloro(pyridine-2-carboximidamide)copper(II)} (8) and μ-chloro{chloro(pyrimidine-2-carboximidamide)copper(II)} (9). In the dimeric complexes, two fragments which were the same as in monomeric complexes 4–7 are held together by bridging Cu-Cl bonds making the coordination of Cu equal to 5 (square pyramid). In dimeric complexes, axial Cu-Cl bonds are 2.7360 and 2.854 Å. These values are Cu-Cl bonds on the edge of existence according to statistical data from CSD. Synthesized complexes were characterized by IR spectroscopy, TGA, PXRD, EPR, and quantum chemical calculations. The higher thermal stability of monomer pyrimidine-based complexes with Cl and Br substituents makes them more prospective for further studies. [ABSTRACT FROM AUTHOR]

Four copper (II) complexes [Cu(L1)2] (1), [Cu(L2)2] (2), [Cu(L3)2] (3) and [Cu(L4)2] (4) with azo linked O,O donar ligands viz 2-hydroxy-5 (phenyldiazenyl)benzaldehyde (HL1), 1-(2-hydroxy-5-(phenyldiazenyl)phenyl)ethanone (HL2), 2-Hydroxy-5-p-tolylazo-benzaldehyde (HL3), 1-(2-Hydroxy-5-p-tolylazo-phenyl)-ethanone (HL4) have been prepared and characterized by different spectroscopy methods and published earlier by our research group. We investigated the interaction of Human Serum Albumin (HSA) with complexes 1–4 under physiological condition in phosphate buffer solution at pH 7.4 using various spectroscopic techniques. The fluorescence titration spectrum disclosed that the complex 1–4 quench the intrinsic fluorescence of HSA robustly through a static quenching mechanism. Binding constants (Kb) and the number of binding sites (n ≈ 1) were evaluated using modified Stern–Volmer equations. Binding constants were found to be 1.9, 6.6, 0.99 and 1.2x 105 (M−1) for complex 1, 2, 3 and 4 respectively. The CD spectra of free HSA and HSA with complexes 1–4 showed that the complexes have negligibleimpact on the secondary structure of HSA as theyremain helical even after the addition of complexes. Molecular docking study was performed to analyse the binding mode of complexes 1-4with HSA. Docking study revealed that hydrophobic and Vander waals interactions were considered to be the main interaction forces involved in the binding of HSA with complexes 1–4.

A new mononuclear Cu(II) complex [Cu(L2)(H2O)2], where L is the Schiff base 2-[2-(3-bromopropoxy)benzylideneamino] benzoic acid, was synthesized and covalently anchored onto an amino-functionalized SBA-15 mesoporous silica in order to obtain an efficient heterogeneous catalyst. The elemental, structural, textural and morphological characterization confirmed the coordination of the central Cu(II) ion with two ligands and two H2O molecules in the synthesized complex and its successful immobilization into the inner pore surface of the NH2-functionalized support without the loss of the mesoporous structure. The catalytic activity of the free or immobilized Cu(II) complex was tested in the oxidation of cyclohexene with H2O2 under an air atmosphere and the dismutation reaction of the superoxide radical anions with very good results. In addition, catalyst reuse tests claim its suitability in alkene oxidation processes or as a biomimetic catalyst. [ABSTRACT FROM AUTHOR]

The present work describes the complexation of the anti-inflammatory sialorphin derivative Pal-Lys-Lys-Gln-His-Asn-Pro-Arg (palmitic acid-lysine-lysine-glutamine-histidine-asparagine-proline-arginine) with Cu(II) ions in an aqueous solution, at a temperature of 25.0 ± 0.1 °C, over the whole pH range. The complexing properties were characterized by potentiometric and UV-Vis spectrophotometric methods. The potentiometric method was used to calculate the logarithms of the overall stability constants (log β) and the values of the stepwise dissociation constants (pKa) of the studied complexes. The percentage of each species formed in an aqueous solution was estimated from the species distribution curve as a function of pH. The absorbance (A) and molar absorption coefficient (ε) values for the Cu(II)-sialorphin derivative system were determined with UV-Vis spectroscopy. Our studies indicate that the sialorphin derivative forms stable complexes with Cu(II) ions, which may lead to future biological and therapeutic applications. [ABSTRACT FROM AUTHOR]

A series of nine 2,3-disubstituted-quinazolin-4(3H)-one derived Schiff bases and their three Cu(II) complexes was prepared and tested for their antimicrobial activities against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the substances were tested in vitro against Mycobacterium tuberculosis H37Ra ATCC 25177, M. kansasii DSM 44162 and M. smegmatis ATCC 700084. While anti-enterococcal and antimycobacterial activities were insignificant, 3-[(E)-(2-hydroxy-5-nitrobenzylidene)amino]-2-(2-hydroxy-5-nitrophenyl)-2,3-dihydroquinazolin-4(1H)-one (SB3) and its Cu(II) complex (SB3–Cu) demonstrated bacteriostatic antistaphylococcal activity. In addition, both compounds, as well as the other two prepared complexes, showed antibiofilm activity, which resulted in a reduction of biofilm formation and eradication of mature S. aureus biofilm by 80% even at concentrations lower than the values of their minimum inhibitory concentrations. In addition, the compounds were tested for their cytotoxic effect on the human monocytic leukemia cell line THP-1. The antileukemic efficiency was improved by the preparation of Cu(II) complexes from the corresponding non-chelated Schiff base ligands.

Cu(II) complexes of positively charged amino acids L–Lysine and L‐Arginine appended to an anthracene unit and phenanthroline bases, namely [Cu(Anth‐Lys)(L)(ClO4)] (1, 2) and [Cu(Anth‐Arg)(L)(ClO4)] (3, 4) where L is 1,10‐phenanthroline (phen, 1 and 3), dipyrido[3,2‐a : 2′,3′‐c]phenazine (dppz, 2 and 4) were synthesized and fully characterized by various spectral and analytical methods. Cu(II) centered broad and weak d‐d band in the visible region along with phenanthroline based π→π* and n→π* bands in the UV region were observed in the electronic spectra of the complexes recorded in DMF‐Tris‐HCl buffer (1 : 4 v/v) (pH 7.2). The complexes 1–4 show efficient DNA binding propensity. They also demonstrated strong binding affinity for human serum albumin (HSA). The complexes showed efficient visible light‐induced cytotoxicity against A549 (human lung carcinoma), HaCaT (human epidermal keratinocytes) and MDA‐MB‐231(human breast cancer cells) cells with low dark toxicity. They generate both singlet oxygen (1O2) and hydroxyl radical (⋅OH) as reactive oxygen species (ROS) upon excitation with visible light which is believed to be responsible for killing cancer cells. Significant changes in the nuclear morphology of the HaCaT cells were observed when treated with complexes 2 and 4 in visible light compared to the non‐irradiated cells. [ABSTRACT FROM AUTHOR]

From reaction mixture containing the same reagents, the two Cu(II) complexes, with dicyanamide (dca) bridges, [Cu(bpy)(dca)2]n (1) and [Cu(bpy)Cl(dca)]n·H2O (2) (bpy = 2,2′-bipyridine) were prepared. The complexes were characterized by elemental analysis, FTIR spectroscopy and X-ray single crystal techniques. In both complexes, the geometry of the Cu(II) atom is best described as a slightly distorted square pyramidal. A zigzag chain structure is formed in both structures by dca units serving as an end-to-end bridging ligand. In addition, studies on antibacterial activity of the compounds against Gram(+) (Staphylococcus aureus ATCC-6538) and Gram(–) (Escherichia coli ATTC-8739, Pseudomonas aeruginosa ATCC-27853 and Enterobacter aerogenes ATCC-13048) bacteria have been performed using disc-diffusion and microdilution broth techniques. Both complexes were found to be significantly more effective against Gram(–) bacteria E. Coli than against the other bacteria. [ABSTRACT FROM AUTHOR]

Background: Pyrazolyl borate derivatives are versatile ligands that can be coordinated with transition metals and formated a variety of different coordination modes. Copper complexes are highly active in biological applications and have high bioactivity. Because of the above description and applications, in the present work, synthesis and characterization of pyrazolyl borate derivative ligands and their Cu(II) complex were reported. The structure of the synthesized complex was determined by X-ray crystallography. In addition, the antimicrobial activity of the synthesized compounds along with the molecular docking of them was investigated. Methods: N-donor pyrazolyl borate derivative ligands abbreviated as K[HB(PzMe2)3] and K[H2B(PzMe2)2] and their Cu(II) complex were synthesized and characterized. The synthesized ligands and complex were evaluated for antibacterial activities against the gram-positive (B. subtilis) and the gram-negative (S. enterica) bacteria. Also, their molecular docking with B. subtilis SMC head domain (PDB ID: 5H67) as the possible targets was investigated. Results: The in vitro and in silico results showed, among the investigated compounds, complex [Cu(H2B(PzMe2)2)(HB(PzMe2)3)] indicated the highest antibacterial activity. Also, the Statistical analysis showed that the difference between the obtained data was significant. Conclusion: We have synthesized N-donor pyrazolyl borate derivatives and their copper (II) complex. Single X-ray results indicated the Cu(II) complex adopted an N5 environment around the metal center with a distorted square pyramidal geometry. The obtained binding energy of molecular docking studies is in direct correlation with the in vitro antibacterial studies. Briefly, the reported Cu(II) complex may be considered as a potential antibacterial candidate.

To increase the number of potential materials for application as MRI contrast agents, several Cu(II) complexes were synthesized. Cu(II) complexes were chosen because they are less expensive in comparison with the presently used Gd(III), Mn(II) and other agents. Pyridine-2-carboximidamide (1), pyrimidine-2-carboximidamide (2) and pyrazole-2-carboximidamide (3) in the form of different salts along with CuCl2 and NaCl or CuBr2 and NaBr were used to obtain four Cu(II) complexes: dichloro-pyrimidine-2-carboximidamide copper(II) (4), dibromo-pyrimidine-2-carboximidamide copper(II) (5), dichloro-pirazole-2-carboximidamide copper(II) (6), and dibromo-pirazole-2-carboximidamide copper(II) (7). X-ray diffraction analysis revealed that molecular complexes 4–7 contain square planar coordinated Cu(II) atoms and their structures are very similar, as well as their packing in crystals, which allows us to consider them isomorphs. The same synthetic approach to complex preparation where NaCl or NaBr was not used brought us to the formation of dimeric complexes μ-chloro{chloro(pyridine-2-carboximidamide)copper(II)} (8) and μ-chloro{chloro(pyrimidine-2-carboximidamide)copper(II)} (9). In the dimeric complexes, two fragments which were the same as in monomeric complexes 4–7 are held together by bridging Cu-Cl bonds making the coordination of Cu equal to 5 (square pyramid). In dimeric complexes, axial Cu-Cl bonds are 2.7360 and 2.854 Å. These values are Cu-Cl bonds on the edge of existence according to statistical data from CSD. Synthesized complexes were characterized by IR spectroscopy, TGA, PXRD, EPR, and quantum chemical calculations. The higher thermal stability of monomer pyrimidine-based complexes with Cl and Br substituents makes them more prospective for further studies.

Methods for the synthesis of new ditopic organic ligands containing coordinating fragments of two types, terpyridine and thiohydantoin, have been developed. The complex formation reactions of the synthesized ligands with copper(II) chloride were studied. As a result, two types of coordination compounds were isolated and characterized by electron spectroscopy, elemental analysis, and cyclic voltammetry: copper(I,II) bis-ligand tetranuclear mixed-valent complexes and a monoligand binuclear complex containing two copper(II) ions. The cytotoxic activity of the obtained coordination compounds with respect to the MCF7, A549, and HEK293 cell lines was studied. [ABSTRACT FROM AUTHOR]

Four novel proton transfer compounds (1-4) obtained between 2-aminopyridine (1), 2-amino-4- methylpyridine (2), 2-amino-5-methylpyridine (3), 2-amino-6-methylpyridine (4) and 2,4- dichloro-5-sulfamoylbenzoic acid (Hsba) and their Cu(II) complexes (6-10) have been synthesized. The structures of powdery salts (1-4) and complexes (6-10) have been suggested by spectral (1H-NMR, FT-IR and UV–Vis), elemental analysis, AAS, molar conductivity and magnetic susceptibility techniques of 6-10 have also been reported. The structures of metal complexes (6-10) were observed octahedral according to spectroscopic analysis results. Additionally, anti-microbial and anti-fungal activities of all compounds have been tested against Escherichia coli (ATCC 25922) (Gram negative), Enterococcus faecalis (ATCC 29212) (Gram positive), Staphylococcus aureus (ATCC 29213) (Gram positive), and Candida Albicans (ATCC 14053) (yeast), Candida parapisilosis (ATCC 22019) (yeast), and Candida krusei (ATCC 6258) (yeast). The results were comparisoned with the antibiotics, Fluconazole as anti-fungal agent and Cefepime, Levofloxacin, Vancomycin as anti-microbial agents. Activity against all compounds bacteria and yeasts was observed. Therefore, all compounds may be utilized for the synthesis of new anti-microbial and anti-fungal. Compounds with the best activity are 2 (15.60 µg/mL) for S. aureus, 2, 8 and 11 (31.25 µg/mL) for E. Faecalis, 2a5mp, 1, 2 and 9 (31.25 µg/mL) for E. Coli, Cu(OAc)2.2H2O, 1, 2 and 9 (31.25 µg/mL) for C. Parapsilosis, Hsba (15.60 µg/mL) for C. Albicans and Hsba and 8 (31.25 µg/mL) for C. Krusei. [ABSTRACT FROM AUTHOR]

Spirocyclopentyl derivatives of cyanophenyl-substituted nitroxyl radicals (2-(4′-cyanophenyl)-4,5-bis(spirocyclopentyl)-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NN) and the corresponding iminonitroxyl 2-(4′-cyanophenyl)-4,5-bis(spirocyclopentyl)-4,5-dihydro-1H-imidazole-1-oxyl (IN)) are synthesized; their structure and magnetic properties are studied. Interaction of IN and NN with bis(hexafluoroacetylacetonato) copper(II) [Cu(hfac)2] leads to the formation of heterospin chain polymeric {[Cu(hfac)2]2(IN)}, {[Cu(hfac)2]3(NN)2}, and layered {[Cu(hfac)2]3(NN)2}·C7H16 complexes. It is shown that the layered {[Cu(hfac)2]3(NN)2}·C7H16 is a soft ferromagnet that transforms into a magnetically ordered state at helium temperatures. [ABSTRACT FROM AUTHOR]

A new series of ternary metal complexes, including Co(II), Ni(II), Cu(II), and Zn(II), were synthesized and characterized by elemental analysis and diverse spectroscopic methods. The complexes were synthesized from respective metal salts with Schiff's-base-containing amino acids, salicylaldehyde derivatives, and heterocyclic bases. The amino acids containing Schiff bases showed promising pharmacological properties upon complexation. Based on satisfactory elemental analyses and various spectroscopic techniques, these complexes revealed a distorted, square pyramidal geometry around metal ions. The molecular structures of the complexes were optimized by DFT calculations. Quantum calculations were performed with the density functional method for which the LACVP++ basis set was used to find the optimized molecular structure of the complexes. The metal complexes were subjected to an electrochemical investigation to determine the redox behavior and oxidation state of the metal ions. Furthermore, all complexes were utilized for catalytic assets of a multi-component Mannich reaction for the preparation of -amino carbonyl derivatives. The synthesized complexes were tested to determine their antibacterial activity against E. coli, K. pneumoniae, and S. aureus bacteria. To evaluate the cytotoxic effects of the Cu(II) complexes, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) cells compared to normal cells, cell lines such as human dermal fibroblasts (HDF) were used. Further, the docking study parameters were supported, for which it was observed that the metal complexes could be effective in anticancer applications. [ABSTRACT FROM AUTHOR]

The present work describes the complexation of the anti-inflammatory sialorphin derivative Pal-Lys-Lys-Gln-His-Asn-Pro-Arg (palmitic acid-lysine-lysine-glutamine-histidine-asparagine-proline-arginine) with Cu(II) ions in an aqueous solution, at a temperature of 25.0 ± 0.1 °C, over the whole pH range. The complexing properties were characterized by potentiometric and UV-Vis spectrophotometric methods. The potentiometric method was used to calculate the logarithms of the overall stability constants (log β) and the values of the stepwise dissociation constants (pKa) of the studied complexes. The percentage of each species formed in an aqueous solution was estimated from the species distribution curve as a function of pH. The absorbance (A) and molar absorption coefficient (ε) values for the Cu(II)-sialorphin derivative system were determined with UV-Vis spectroscopy. Our studies indicate that the sialorphin derivative forms stable complexes with Cu(II) ions, which may lead to future biological and therapeutic applications.

In this study, two new proton transfer salts of sulfonamide derivatives of maleic acid, namely (ClHabt)+(mabsmal)– (1) and (ClHabt)+(pabsmal)– (2), were obtained from 2-amino-6-chlorobenzo­thiazole (Clabt) and N-(3-sulfamoylphenyl)maleamide acid (Hmabsmal) and N-(4-sulfamoyl­phenyl)maleamide acid (Hpabsmal), respectively. Also, the Cu(II) complexes (3 and 4) of salts (1 and 2) and of Hmabsmal (5) were prepared. Compounds 1‒5 were characterized by elemental, NMR (1H and 13C), FTIR, and thermal analyses, as well as UV-Vis, magnetic moment, and molar conductivity measurements. Carbonic anhydrase isoenzymes (hCA I and II) were purified from human erythrocyte cells by affinity chromatography. The effects of the synthesized compounds on the hydratase and esterase activities of CA isoenzymes were studied in vitro. The results reveal that the synthesized compounds inhibit both esterase and hydratase activities of hCA I and hCA II. The inhibition constants of the compounds (Ki) were determined according to the esterase activity measurements. Ki values of 1‒5 are in the range of 0.06 ± 0.003 µM and 4.25 ± 0.100 µM for hCA I, and of 0.02 ± 0.001 µM and 3.21 ± 0.200 µM for hCA II.

The novel diazenyl pyridinone heterocyclic ligands and their Cu(II) complexes have been prepared and characterized utilizing miscellaneous analytical tools, thermogravimetric analysis (TGA), and nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), electron paramagnetic resonance (EPR), and ultraviolet–visible spectroscopies. The investigated ligands are coordinated in a bidentate fashion through the azo nitrogen atom and the hydroxyl oxygen atom to the Cu(II) center. The EPR spectra indicated that the obtained complexes were monomeric, and density functional theory (DFT) calculations confirmed that the Cu(II) atom adopted a six‐coordinated octahedral geometry. The ligands and their complexes were investigated for their in vitro antimicrobial activity against some types of bacteria and fungi. The antioxidant and anticancer activities of the complexes were also assessed. The results show that these complexes exhibit higher antitumor efficiency and selectivity index against the models of human breast adenocarcinoma cells MCF‐7 and human primary hepatocytes THLE‐2 than the reference standard material doxorubicin. The results were supported by DFT calculations, molecular docking, and Hirshfeld surface analysis. [ABSTRACT FROM AUTHOR]

The mononuclear Cu(II) complex, Zn(II) complex, and homodinuclear Zn(II)-Zn(II) complex of 2-mercaptoquinoline N-oxide, have been synthesized as possible antibacterial agents. Their crystal structures analyzed by X-ray diffraction methods have shown that the structures of the two mononuclear complexes and a homodinuclear complex are markedly different. The antibacterial activities of complexes were investigated using the Oxford Cup method, and the result indicated that complexes have good antibacterial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. [ABSTRACT FROM AUTHOR]

In this study, two new proton transfer salts of sulfonamide derivatives of maleic acid, namely (ClHabt)+(mabsmal)- (1) and (ClHabt)+(pabsmal)- (2), were obtained from 2-amino-6-chlorobenzothiazole (Clabt) and N-(3-sulfamoylphenyl)maleamide acid (Hmabsmal) and N-(4-sulfamoylphenyl) maleamide acid (Hpabsmal), respectively. Also, the Cu(II) complexes (3 and 4) of salts (1 and 2) and of Hmabsmal (5) were prepared. Compounds 1‒5 were characterized by elemental, NMR (¹H and 13C), FTIR, and thermal analyses, as well as UV-Vis, magnetic moment, and molar conductivity measurements. Carbonic anhydrase isoenzymes (hCA I and II) were purified from human erythrocyte cells by affinity chromatography. The effects of the synthesized compounds on the hydratase and esterase activities of CA isoenzymes were studied in vitro. The results reveal that the synthesized compounds inhibit both esterase and hydratase activities of hCA I and hCA II. The inhibition constants of the compounds (Ki) were determined according to the esterase activity measurements. Ki values of 1‒5 are in the range of 0.06 ± 0.003 μM and 4.25 ± 0.100 μM for hCA I, and of 0.02 ± 0.001 μM and 3.21 ± 0.200 μM for hCA II. [ABSTRACT FROM AUTHOR]

Thiosemicarbazones are class of compounds which are obtained by the condensation of thiosemicarbazide with carbonyl compounds. The transition metal complexes of thiosemicarbazones are widely considered due to their broad spectrum of biological activities such as antibacterial, antitumor and antifungal activities. In present research work a series of four novel Cu(II) aryl thiosemicarbazones complexes having the general composition [Cu(L1)2Cl2], [Cu(L2)2Cl2], [Cu(L3)2Cl2] and [Cu(L4)2Cl2]{where L1= 4-nitroacetophenone thiosemicarbazones (4NAT), L2 = 3-nitrobenzaldehyde thiosemicarbazone (3NBT), L3 = 4-hydroxybenzaldehyde thiosemicarbazone (4HBT) and L4 = 4-aminoacetophenone thiosemicarbazone (4AAT)} have been synthesized by the reaction of thiosemicarbazide with substituted aromatic aldehydes and ketones by conventional heating as well as microwave irradiations method followed by complexation with Cu(II) metal. The synthesized compounds have been characterised by elemental analysis, melting point determination, FTIR, UV-visible spectral analysis. Thiosemicarbazone ligands behave as bidentate ligand and forms octahedral complexes with Cu(II). The synthesized ligands and their new metal complexes have been screened in vitro for antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis bacteria. The result shows that all the Cu(II) complexes are potent antibacterial agents against these bacteria. [ABSTRACT FROM AUTHOR]

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells. [ABSTRACT FROM AUTHOR]

• Two Cu(II)-complexes 1 and 2 were synthesized and characterized. • Complexes 1 and 2 can degrade 86.9 % and 97.0% MB in 24 min, respectively. • Both complexes could be used repeatedly for the degradation of MB. • The main reactive species for MB degradation were ·OH and h+. Two Cu(II)-complexes [Cu(Hcpota)(4,4′-bpy)(H 2 O)] n 1 and [Cu(Hcpota)(1,4-bib)(H 2 O)] n 2 based on a semirigid ligand 2-(4-carboxyphenoxy)terephthalic acid (H 3 cpota) were solvothermally prepared and characterized. Complexes 1 and 2 exhibit an unprecedented 2D 4-connected framework with a {44.62} topology, comprising the Cu(II) ion with square pyramidal coordination. The three-dimensional frameworks are constructed by O–H···O hydrogen bonds. Magnetization analyses were conducted and revealed that complexes 1 and 2 have ferromagnetic properties. The photodegradation of Methylene blue dye was studied based on 1 and 2 as photocatalysts. The results indicated that complexes 1 and 2 exhibited remarkable photodegradation efficiencies of 86.9 % and 97.0 % after 24 min, respectively. Furthermore, pseudo-first-order kinetics was assumed for the photocatalytic reaction with a rate constant of 0.052 and 0.109 min−1 for 1 and 2. The impact of factors, including the initial concentration of MB, catalyst dosage, pH value, H 2 O 2 concentration, and temperature on the degradation process of MB was thoroughly examined. The complexes exhibited excellent recyclability and stability as photocatalysts. Trapping experiments and LC-MS studies revealed that the primary active species responsible for the degradation reaction are hydroxyl radicals (·OH) and holes (h+). Two Cu(II)-based complexes synthesized via the solvothermal method have been utilized as catalysts for UV–vis light-induced dye degradation, the introduction of H 2 O 2 significantly enhances the efficiency. [Display omitted] [ABSTRACT FROM AUTHOR]

Three new oxygen bridged binuclear and mononuclear copper(II) complexes having general formulae [L2Cu(2,2′-bipyridine)2CuL2] (A), [L′2Cu(2,2′-bipyridine)H2O] (B), [L″2Cu(2,2′-bipyridine)2CuL″2] (C) where L = ortho-nitrophenyl acetate, L′ = para-methoxyphenyl acetate and L″ = para-bromophenyl acetate have been prepared and characterized spectroscopically as well as structurally. The geometry around each Cu(II) ion was found square pyramidal in all the complexes. FT-IR data of the complexes were in agreement with that of the single crystal XRD. Electronic absorption spectra indicated broad absorption bands with λmax = 671, 715 and 700 nm typical of Cu2+ with 2B1g as ground state in A-C, respectively. Crystalline nature of the complexes was ascertained from its powder XRD spectra which showed several peaks in 2θ range 5–30. Electrochemistry yielded two redox pairs conforming to irreversible Cu(III)/Cu(II) and Cu(II)/Cu(I) processes typical of complexes with Cu2+ redox centers. Complex-surfactant interactions were studied via conductometry and absorption spectrophotometry. DNA binding abilities of complexes A-C were studied via absorption spectrophotometry, cyclic voltammetry, spectrofluorometry and viscosity measurement. The former three techniques yielded excellent intrinsic binding constant values for complexes. The excellent DNA-binding potency heralds the biological importance of the synthesized complexes.

Continuing our search for metal drugs with markedly higher toxicity to cancer cells than to normal cells, we evaluated the effect of 2,2'-bipyridine (bpy) as a co-ligand in the compounds [Cu(μ-O,O'-NO 3 )(l-Arg)(bpy)]NO 3 } n (1), [CuCl(l-Arg)(bpy)]Cl·3H 2 O (2) (l-Arg= l-arginine), on DNA interaction, cytotoxic and antiproliferative activity, compared to the effects induced by other co-ligands i.e. 1,10-phenanthroline (phen) and SCN - ions, in similar Cu(II) compounds we have studied previously. Potentiometric, EPR and UV-Vis experiments were first used to structurally characterise the complexes formed in solutions 1 and 2 and in model Cu(II)/bpy/l-Arg systems. Gel electrophoresis in the presence of H 2 O 2 was used to identify DNA damage by 1 and 2. In addition, cyclic voltammetry of both compounds was performed to confirm the existence of Cu(II)/Cu(I) redox pairs involved in the free radical mechanism of this DNA damage. The DNA binding constants of 1 and 2 were determined spectrophotometrically. The selectivity of the cytotoxic and antiproliferative activity of compounds 1 and 2 was tested in vitro against human lung adenocarcinoma (A549), liver cancer (HepG2) and normal cells in comparison with those previously observed by us for compounds consisting of phen and SCN - ligands. Molecular docking calculations were performed for [Cu(l-Arg)(bpy)] 2+ (present in solutions of 1 and 2) interacting with B-DNA (aureolin), metalloproteinase (S. aureus) and penicillin-binding protein (E. coli) to determine the nature of the complex-receptor interaction, potential binding modes and energies., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or there view of, the manuscript entitled: Solution structure, oxidative DNA damage, biological activity and molecular docking of ternary copper(II) L−argininato complexes., (Copyright © 2024. Published by Elsevier B.V.)

In recent years, copper carboxylate complexes have garnered significant interest for biological applications. This study focuses on 20 Cu(II) carboxylate complexes selected from our previous research. Due to the hydrophobic nature of these complexes, the 2-hydroxypropyl-β-cyclodextrin (2HPβCD) was employed as a carrier to reduce toxicity and increase solubility for controlling drug delivery. Monte Carlo calculations were performed to confirm the interaction between the optimized structures of Cu(II) complexes and 2HPβCD, forming a host-guest system. All the structures were simulated and optimized using DFT-D calculations in Material Studio 2017. The results indicated that a neutral medium is more favorable for the adsorption of these complexes into 2HPβCD. More negative binding energy values suggested strong and energetically favorable adsorption on 2HPβCD. Complexes 4, 5, and 7 exhibited the highest interaction, making them excellent candidates for drug delivery systems. DFT-D calculations were also used to investigate the release of complexes, revealing that complexes 5, 14, and 19 were difficult to release due to their lowest energy. In contrast, complexes 8, 9, and 16 were found to be most efficient to release due to weak non-covalent interactions with 2HPβCD as we can predict from binding energy obtained by DFT-D. No specific trend was observed in the interaction of the complexes with 2HPβCD. Additionally, the effects of these complexes on c-kit tyrosine kinase and Mushroom tyrosinase were studied by molecular docking. The results demonstrated that all the complexes interacted with the active site of respective receptors through hydrophobic interactions. Complexes containing 1,10-phenanthroline and 2,2-bipyrdine were identified as having a strong, spontaneous binding ability with receptors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Herein, we report the synthesis of mixed-ligand Cu(II) complexes of metformin and ciprofloxacin drugs together with 1,10-phenanthroline as a co-ligand. The synthesized complexes were characterized using different spectroscopic and spectrometric techniques. In vitro cytotoxic activity against human breast adenocarcinoma cancer cell line (MCF-7) as well as antibacterial activity against two gram-negative and two gram-positive bacterial strains were also investigated. The analyses of the experimental results were supported using quantum chemical calculations and molecular docking studies against estrogen receptor alpha (ERα; PDB: 5GS4). The cytotoxicity of the [Cu(II) (metformin) (1,10-phenanthroline)] complex (1), with IC50 of 4.29 µM, and the [Cu(II) (ciprofloxacin) (1,10-phenanthroline)] complex (2), with IC50 of 7.58 µM, were found to be more effective than the referenced drug, cisplatin which has IC50 of 18.62 µM against MCF-7 cell line. The molecular docking analysis is also in good agreement with the experimental results, with binding affinities of –7.35, –8.76 and –6.32 kcal/mol, respectively, for complexes 1, 2 and cisplatin against ERα. Moreover, complex 2 showed significant antibacterial activity against E. coli (inhibition diameter zone, IDZ, = 17.3 mm), P. aeruginosa (IDZ = 17.08 mm), and S. pyogen (IDZ = 17.33 mm), at 25 μg/ml compared to ciprofloxacin (IDZ = 20.0, 20.3, and 21.3 mm), respectively. Our BOILED-egg model indicated that the synthesized metal complexes have potentially minimal neurotoxicity than that of cisplatin.

This work describes the design of novel Cu(II) complexes and their application in the photocatalytic degradation of methylene blue (MB). The same photocatalyst exhibits antibacterial activity against Escherichia coli (gram-negative) and Bacillus circulans (gram-positive). The characterisation of the photocatalysts has been done by several up-to-date physical methods. The rationale behind the photocatalysts' beneficial intervention is discussed in this study. Statistical analysis of the degradation of MB is done using a one-way ANOVA, and the significance of means is determined by a multiple comparison test using Turkey HSD. Also, the degradation of MB follows pseudo first-order kinetics with high correlation coefficient values (R2 > 0.95), making them useful as simple and low-cost organic dye degradation agents. [ABSTRACT FROM AUTHOR]

Schiff bases, which are formed by the reaction of primary amines and carbonyl compounds, are commonly used as ligands. Schiff bases can be formed by the addition of aminothiols, o-aminophenols, α-amino acids and aminoalcohols with acetyl acetone or salicylaldehyde. Many scientists have been interested with Schiff bases, which have a wide range of use in the synthesis of coordination compounds as ligands and have obtained different compounds. Schiff bases are compounds that can find application in many areas of chemistry such as industry, medicine, pharmacy, paint industry, textile industry. Especially biochemistry and analytical chemistry applications are quite remarkable. It is very important to examine the physical and chemical behavior of Cu(II) complexes formed with Schiff base ligands due to the role of the trace element copper in health and many biological activities of copper complexes. Therefore, in this study; the new sterically hindered three salicylaldimine ligands were synthesized from reaction of 2,4,6-tri-tert-butylaniline with 3,5-di-tert-butyl-2-hydroxybenzaldehyde, 3-tert-butyl 2-hydroxybenzaldehyde and 5-tert-butyl-2-hydroxybenzaldehyde. Then, 2 Cu(II) complexes from the Cu(II) salt of these ligands were synthesized. The Structures of new sterically hindered salicylaldimin ligand and metal complexes based on tri-tert-butylaniline synthesized were characterized by melting point, UV-Vis, FT-Ir, elemental analysis, magnetic susceptibility, featured of ¹H NMR and 13C NMR. [ABSTRACT FROM AUTHOR]

The crystal structures and biological properties of [N′-(2-oxidobenzylidene)-N-(prop-2-en-1-yl)-carbamohydrazonothioato(2-)](1,10-phenanthroline)copper hemihydrate [Cu(1,10-Phen)(L)]·0.5H2O (I) and [N′-(2-oxidobenzylidene)-N-(prop-2-en-1-yl)-carbamohydrazonothioato(2-)](2,2′-bipyridine)copper hemihydrate [Cu(2,2′-BPy)(L)]·0.5H2O (II), where Н2L is 2-(2-hydroxybenzylidene)-N-(prop-2-en-1-yl)hydrazinecarbothioamide, are determined. The asymmetric unit of the unit cell in the crystal structures of I and II contains a copper complex with bidentate amine and a ligand coordinated by the azomethine nitrogen atom, the deprotonated phenolic oxygen atom, and the sulfur atom in the thiol form. The coordination polyhedron of the copper atom in compounds I and II is a distorted tetragonal pyramid. Obtained coordination compounds I and II exhibit antimicrobial and antifungal activities and have minimum inhibitory concentration and bactericidal concentration values in a range of 1.5-500 µg/mL. The study of the antioxidant activity shows that compounds I and II are less active than uncoordinated thiosemicarbazone H2L, but more active than trolox used in medical practice. [ABSTRACT FROM AUTHOR]

In this paper, the reactions of anhydrous copper(II) chloride in methanolic solution with alanine, glycine, histidine, L-tryptophan, and melatonin were investigated and the resulting products were characterized by FTIR spectroscopy. Based on FTIR characterization, it was shown that these reaction conditions result in the formation of Cu(II) complexes with glycine and alanine, which are more complex structures than bis(glycinato) - and bis(alaninato) copper(II) complexes. Analysis of the FTIR spectrum of the histidine complex shows the participation of several groups in coordination at the Cu(II) center. The complex prepared with melatonin shows unusual changes in the spectral region of the amidic nitrogen bonds. The latter observation is very significant for very few known metal complexes of melatonin, while the synthesis of most of them is an experimentally demanding process with simultaneous control of several parameters. The antioxidant capacity of the synthesized complexes was examined, with the CEAC range from 121.6 to 734.4 µM. The lowest values of antioxidant capacity were recorded for the copper complex with tryptophan, while the highest values were recorded for the copper complex with alanine. A high antioxidant capacity of the copper complex with melatonin (673.8 µM) was also observed. [ABSTRACT FROM AUTHOR]

• Synthesis and characterization : three novel copper(II) complexes were synthesized and structurally characterized using X-ray single-crystal diffraction. • Molecular interactions : key intermolecular interactions, including hydrogen bonding and π interactions, were identified through Hirshfeld surface analysis and molecular docking. • Biological activity : the complexes exhibited strong DNA binding affinity and demonstrated superior cytotoxicity against HepG2 cancer cells compared to standard chemotherapeutic agents. • Antimicrobial efficacy : complexes 2 and 3 showed moderate antibacterial activity against Staphylococcus aureus. • Potential applications : the study provides a foundation for developing new metal-based therapeutics and environmental remediation agents. Three distinct copper(II) complexes were synthesized using 3,3,3-Triphenylpropionic acid (TPPA) and varying N,N'-chelators, resulting in unique structural and biological properties. The complexes [Cu(TPPA) 2 (Bipy)(H 2 O) 2 ·(H 2 O)] (1), [Cu(TPPA) 2 (Phen)(H 2 O) 2 ·0.5(H 2 O)] (2), and [Cu(TPPA) 2 (MeBipy)·2(C 2 H 3 N)] (3) were thoroughly characterized using single-crystal X-ray diffraction, PXRD, FT-IR, and NMR techniques to confirm their distinct geometries and coordination environments (TPPA=3,3,3-Triphenylpropionic acid, Bipy=2,2′-Bipyridine, Phen=1,10-Phenanthroline, and MeBipy=5,5′-Dimethyl-2,2′-Dipyridyl). Hirshfeld surface analysis provided quantitative insights into the molecular interactions within the complexes, while molecular docking studies revealed a strong binding affinity to PI3K kinase, with calculated binding energies of −10.4, −10.5, and −11.7 kcal/mol for complexes 1, 2, and 3, respectively. DNA fluorescence spectroscopy demonstrated significant ct-DNA binding, with the quencher rate coefficients of 0.1278 for complex 1, 0.2664 for complex 2, and 0.2434 for complex 3. When compared to sodium penicillin, which exhibited an OD600 value of 0.06, complex 2 and complex 3 demonstrated moderate antibacterial activity against Staphylococcus aureus with OD600 values of 0.176 and 0.219, respectively. The IC50 values of complexes 1, 2, and 3 in HepG2 cancer cell inhibition assays were determined to be 0.588, 0.357, and 0.397 μM, respectively. These results demonstrate their superior cytotoxicity compared to Cisplatin and Carboplatin. The findings suggest that these complexes may offer promising avenues for further research and development in antimicrobial and anticancer therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of acenaphthene quinone thiosemicarbazone and its Cu(II) complexes. • Absorption and emission spectroscopy-based DNA/BSA binding investigations. • The capacity of the complexes to bind BSA was examined using molecular docking. • Used DFT to account for the electronic structural properties of Cu(II) complexes and a good score for drug-likeness property was gained in the Swiss-ADME study. • MCF-7, A459, HeLa cancer and normal Vero cells cytotoxicity investigations. Three Cu(II) complexes (CTS1 - CTS3) of acenaphthene quinone thiosemicarbazone with various N -terminal substitutions were synthesized. The prepared compounds were characterized via different spectroscopic analyses. The square planar structure formed by the ligands with Cu(II) (tridentate manner, ONS donor) is confirmed through EPR spectral analysis. The DNA binding studies performed using UV–visible and fluorescence spectroscopy point out that, all complexes showing significant interaction with DNA and CTS2 were the strongest (K b = 6.46 × 106 M−1 & K app = 2.5 × 106 M−1). A similar binding trend is observed towards the BSA protein (CTS2 with high K b value, 1.76 × 105 M−1). The docking studies with EGFR protein (PDB ID: 5EDQ) reveal that CTS2 has the highest affinity towards them with a docking energy of − 7.41 Kcal/mol. The DFT investigations account for the stability (CTS3 has better structural stability with a high band gap, 0.10634 eV) and biological activity of complexes (CTS2 has a stronger biological activity due to its low ω value, 0.5864 eV). The lipophilicity (LogP ˃ 5) values obtained via Swiss-ADME studies are satisfactory and indicate that all 3 complexes have the potential to function as good oral drug candidates. The MTT assay results showed that CTS2 was the most effective against human breast (MCF-7), lung (A549), and cervical (HeLa) cancer cell lines, with IC 50 values of 11.5, 43.9, and 19.6 μM, respectively. Conversely, CTS2 showed the least cytotoxicity (IC 50 = 79.7 μM) when it came to normal (Vero) kidney epithelial cells. [ABSTRACT FROM AUTHOR]

• A distorted octahedral copper(II) and nickel(II) complexes containing 2,2′:6′,2″-terpyridine was synthesized and characterized. • Synthesized complexes show good CT-DNA and BSA binding activity. • Antiproliferative activity on human breast cancer (MCF-7) and lung cancer (A549 and H1299) cell lines of the synthesized complexes are comparable with cisplatin. • Molecular docking analysis was carried out against ALK (anaplastic lymphoma kinase), Hsp90 (Heat shock protein 90), EGFR (epidermal growth factor receptor), BHb (bovine hemoglobin), HER2 (human epidermal growth factor receptor 2), and B-DNA. Cu(II) and Ni(II) complexes, [Cu(NNN) 2 ](NO 3) 2 (1) and [Ni(NNN) 2 ](NO 3) 2 (2) (NNN-donor ligand: 2,2′:6′,2″-terpyridine), have been synthesized and characterized by electronic absorption spectroscopy, CHN analysis, FTIR, ESI-MS and X-ray crystallography techniques. Interaction of the complexes 1 and 2 with biomolecules (calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)) has been investigated by electronic absorption and fluorescence spectroscopy. The results show that the complexes 1 and 2 can bind to CT-DNA via a moderate intercalation mode. Moreover, the fluorescence quenching mechanism between the complexes 1 and 2 and BSA is a static quenching process. The antiproliferative activities of the complexes 1 and 2 against human breast cancer (MCF-7) and lung cancer (A549 and H1299) cell lines were investigated. The complex 1 was found to have promising antiproliferative activity in selected cell line, with lower IC 50 values than cisplatin. Molecular docking studies conducted across the complexes 1 and 2 have provided their potential as prospective chemotherapeutic agents against tumors. The complexes 1 and 2 demonstrated spontaneous binding with targets including anaplastic lymphoma kinase (ALK), heat shock protein 90 (Hsp90), epidermal growth factor receptor (EGFR), bovine hemoglobin (BHb), human epidermal growth factor receptor 2 (HER2), and B-DNA. These interactions are primarily driven by van der Waals forces and π-π interactions. Determining binding constants and the multiplicity of binding sites enhances understanding of these molecular interactions. [Display omitted] [ABSTRACT FROM AUTHOR]

Cisplatin remains the most widely used chemotherapeutic agent in cancer treatment; however, its inherent drawbacks have fueled the development of novel metalloanticancer drugs. In this study, two novel Cu(II) complexes (Cu1 and Cu2) were designed and synthesized. Notably, these Cu(II) complexes showed higher cytotoxicity against HL-7402 cells than cisplatin. Moreover, Cu(II) complexes significantly inhibited liver cancer growth in a xenograft model. A mechanism study revealed that the Cu(II) complexes reduced the mitochondrial membrane potential of cancer cells, produced excessive reactive oxygen species (ROS), induced mitochondrial DNA (mtDNA) damage, and ultimately facilitated cancer cell apoptosis. The Cu(II) complex induced cancer cells apoptosis by facilitating mitochondrial dysfunction, excessive ROS generation, and mtDNA damage. [Display omitted] • Two Cu(II) complexes were synthesized and showed obvious growth inhibition on HL7402 cells in vitro. • The Cu(II) complexes inhibit tumor growth through inducing mitochondrial DNA damage and mitochondria-mediated apoptosis. • The Cu(II) complexes exhibited excellent anti-tumor effects in vivo. [ABSTRACT FROM AUTHOR]

A new series of ternary metal complexes, including Co(II), Ni(II), Cu(II), and Zn(II), were synthesized and characterized by elemental analysis and diverse spectroscopic methods. The complexes were synthesized from respective metal salts with Schiff’s-base-containing amino acids, salicylaldehyde derivatives, and heterocyclic bases. The amino acids containing Schiff bases showed promising pharmacological properties upon complexation. Based on satisfactory elemental analyses and various spectroscopic techniques, these complexes revealed a distorted, square pyramidal geometry around metal ions. The molecular structures of the complexes were optimized by DFT calculations. Quantum calculations were performed with the density functional method for which the LACVP++ basis set was used to find the optimized molecular structure of the complexes. The metal complexes were subjected to an electrochemical investigation to determine the redox behavior and oxidation state of the metal ions. Furthermore, all complexes were utilized for catalytic assets of a multi-component Mannich reaction for the preparation of -amino carbonyl derivatives. The synthesized complexes were tested to determine their antibacterial activity against E. coli, K. pneumoniae, and S. aureus bacteria. To evaluate the cytotoxic effects of the Cu(II) complexes, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) cells compared to normal cells, cell lines such as human dermal fibroblasts (HDF) were used. Further, the docking study parameters were supported, for which it was observed that the metal complexes could be effective in anticancer applications.

The two ligands 2-(1-(2-(4,6-dimorpholino-1,3,5-triazin-2-yl)hydrazono)ethyl)aniline (DMAT) and 2-(1-(2-(4,6-dimorpholino-1,3,5-triazin-2-yl)hydrazono)ethyl)phenol (DMOHT) were used to synthesize three heteroleptic Cu(II) complexes via a self-assembly technique. The structure of the newly synthesized complexes was characterized using elemental analysis, FTIR and X-ray photoelectron spectroscopy (XPS) to be [Cu(DMAT)(H2O)(NO3)]NO3.C2H5OH (1), [Cu(DMOT)(CH3COO)] (2) and [Cu(DMOT)(NO3)] (3). X-ray single-crystal structure of complex 1 revealed a hexa-coordinated Cu(II) ion with one DMAT as a neutral tridentate NNN-chelate, one bidentate nitrate group and one water molecule. In the case of complex 2, the Cu(II) is tetra-coordinated with one DMOT as an anionic tridentate NNO-chelate and one monodentate acetate group. The antimicrobial, antioxidant and anticancer activities of the studied compounds were examined. Complex 1 had the best anticancer activity against the lung carcinoma A-549 cell line (IC50 = 5.94 ± 0.58 µM) when compared to cis-platin (25.01 ±2.29 µM). The selectivity index (SI) of complex 1 was the highest (6.34) when compared with the free ligands (1.3–1.8), and complexes 2 (0.72) and 3 (2.97). The results suggested that, among those compounds studied, complex 1 is the most promising anticancer agent against the lung carcinoma A-549 cell line. In addition, complex 1 had the highest antioxidant activity (IC50 = 13.34 ± 0.58 µg/mL) which was found to be comparable to the standard ascorbic acid (IC50 = 10.62 ± 0.84 µg/mL). Additionally, complex 2 showedbroad-spectrum antimicrobial action against the microbes studied. The results revealed it to possess the strongest action of all the three complexes against B. subtilis. The MIC values found are 39.06, 39.06 and 78.125 μg/mL for complexes 1–3, respectively. [ABSTRACT FROM AUTHOR]

Concerns on increasing trends of multidrug resistance (MDR) around the world have triggered the need to investigate and develop new therapeutic strategies and potent antibacterial drugs. Polymyxins, a class of polycationic antimicrobial peptides, have been regarded as the last-line therapy against Gram-negative bacteria due to limited new antibiotics and phenylalanine-arginine β-naphthylamide (PAβN), a peptidomimetic compound has been characterised as an efflux pump inhibitor (EPI) that have been investigated to overcome efflux-mediated multidrug resistance. In this work, the antibacterial activity of two Schiff base ligands derived from the condensation of S-benzyl dithiocarbazate with 4-carboxybenzaldehye (SB4CB) and 4-formyl-3-hydroxybenzoic acid (SBFH) their copper(II) complexes (Cu(SB4CB)2 and Cu(SBFH)2) were tested individually, and the most promising compound was tested in combination with polymyxin B (POLY) and PAβN against different bacteria, such as antibiotic-susceptible strains: Acinetobacter baumannii ATCC 19606, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC 35923; multidrug-resistant strains: A. baumannii ATCC BAA-1797, E. coli BAA-196, P. aeruginosa ATCC BAA-2108 and S. aureus ATCC 43300. Initial minimum inhibition concentration (MIC) results showed the Cu(II) complexes Cu(SB4CB)2 and Cu(SBFH)2, demonstrated obvious antibacterial activity as compared to the ligand alone. Fractional inhibitory concentration (FIC) index showed improved MIC values with additivity and synergistic effect for Cu(SBFH)2 in combination with POLY and PAβN. From the in silico molecular docking investigation, Cu(SBFH)2 was shown to engage in hydrophobic interactions via its phenyl rings with surrounding hydrophobic residues in the binding pocket of S. aureus NorA, E. coli AcrB, P. aeruginosa MexB and A. baumannii AdeB efflux pumps. The phenyl rings of the ligand could also form π-π stacking with adjacent residues in the binding site of A. baumannii AdeB. Besides, hydrogen bonding and π-cation interactions were also observed via the carboxyl group, hydroxyl group and phenyl ring of SBFH moiety, respectively with nearby residues in the E. coli AcrB binding pocket. This study indicates that the combination strategy of Cu(SBFH)2 with POLY and PAβN enhances therapeutic potential and sheds light on the binding pockets inside bacteria efflux pumps and the binding interactions of ligand in the binding site. [ABSTRACT FROM AUTHOR]

Cooper(ii) complexes represent a promising group of compounds with antimicrobial and antifungal properties. In the present work, a series of Cu(ii) complexes containing the non-steroidal anti-inflammatory drugs, tolfenamic acid, mefenamic acid and flufenamic acid as their redox-cycling functionalities, and 1,10-phenanthroline as an intercalating component, has been studied. The antibacterial activities of all three complexes, [Cu(tolf-O,O′)2(phen)] (1), [Cu(mef-O,O′)2(phen)] (2) and [Cu(fluf-O,O′)2(phen)] (3), were tested against the prokaryotic model organisms Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and their antifungal activities were evaluated towards the yeast, Saccharomyces cerevisiae (S. cerevisiae). The antibacterial activity of both strains has been compared with the antibiotic Neomycin. The calculated IC50 values revealed slight differences in the antibacterial activities of the complexes in the order 1 ∼ 3 > 2. The most profound growth inhibition of E. coli was observed, at its highest concentration, for the complex 1, which contains chlorine atoms in the ligand environment. The trend obtained from IC50 values is generally in agreement with the determined MIC values. Similarly, the complex 1 showed the greatest growth inhibition of the yeast S. cerevisiae and the overall antifungal activities of the Cu(ii) complexes were found to follow the order 1 > 3 ≫ 2. However, for complex 2, even at the highest concentration tested (150 μM), a 50% decrease in yeast growth was not achieved. It appears that the most potent antimicrobial and antifungal Cu(ii) complexes are those containing halogenated NSAIDs. The mechanisms by which Cu(ii) complexes cause antibacterial and antifungal activities can be understood on the basis of redox-cycling reactions between cupric and cuprous species which lead to the formation of free radicals. The higher efficacy of the Cu(ii) complexes against bacterial cells may be due to an absence of membrane-protected nuclear DNA, meaning that on entering a cell, they can interact directly with its DNA. Contrastingly, for the complexes to interact with the DNA in yeast cells, they must first penetrate through the nuclear membrane.

The activity and interacting ability of a polyamidoamine (PAMAM) dendrimer modified with 4-N-methylpiperazine-1,8-naphthalimide units (termed D) and complexed by Cu(ii) ions, towards healthy and cancer cells were studied. Comparative electron paramagnetic resonance (EPR) studies of the Cu(ii)-D complex are presented: coordination mode, chemical structure, flexibility and stability of these complexes, in the absence and presence of myeloid cancer cells and peripheral blood mononuclear cells (PBMC). The interactions of Cu(ii) ions in the biological media at different equilibrium times were studied, highlighting different stability and interacting conditions with the cells. Furthermore, flow cytometry and confocal analysis, trace the peculiar properties of the dendrimers in PBMC and U937 cells. Indeed, a new probe (Fly) was used as a potential fluorescent tool for biological imaging of Cu(ii). The study highlights that dendrimer and, mainly, the Cu(ii) metallodendrimer are cytotoxic agents for the cells, specifically for U937 tumor cells, inducing mitochondrial dysfunction, ROS increase and lysosome involvement. The metallodendrimer shows antitumor selectivity, fewer affecting healthy PBMC, inducing a massive apoptotic cell death on U937 cells, in line with the high stability of this complex, as verified by EPR studies. The results underline the potentiality of this metallodendrimer to be used as anticancer drug. [ABSTRACT FROM AUTHOR]

New pyrazole derivatives were prepared and used to synthesize new bioactive agents from Cu(II) complexes that have OSN donors. Analytical and spectral (IR, UV-Vis, MS, 1H NMR, ESR & XRD) instruments characterized these complexes as well as their corresponding ligands. The bonding mode has been modified from ligand to ligand and the molar ratio for isolated complexes has also varied (1:1/1:2, M:L). The geometry of isolated complexes was commonly proposed, based on electronic transitions and ESR spectral-parameters. Via computational approaches, these structures were optimized using standard programs (Gaussian 09 & HyperChem 8.1) under the required basis set. Consequently, important physical characteristics have been obtained after finishing the optimization process. Inhibition behavior of all new synthesizes was studied by MOE module as in-silico approach which conducted versus the crystal structure of NUDT5 protein (6gru) of breast cancer cells. The interaction features summarized from docking processes, reveal effective inhibition validity for new Cu(II) complexes versus breast cancer cells. This according to scoring energy values and the stability of docking complexes in true interaction path (bond length ≤3.5 Å) particularly with Cu(II)-L3 and Cu(II)-L4 complexes. This reflects the possibility of successful behavior during practical application through in-vitro assay that intended in this study. Finally, the degree of toxicity of such new compounds to the breast cancer cell line was determined by in-vitro screening. To judge perfectly on their toxicity, in-vitro screening must compared to positive control as Doxorubicin (reference drug). IC50 values were calculated and represent Cu(II) complexes as outstanding cytotoxic agents which revealed superiority on the reference drug itself.

Two novel benzoylthioureas derived from gallic acid, (tri‐O‐acetyl)galloyl‐N,N‐diethylthiourea HL1, and cinnamic acid, cinnamoyl‐N,N‐diethylthiourea HL2 have been successfully prepared and characterized by means of elemental analysis, IR, NMR, high‐resolution MS, and X‐ray crystallography. The organic ligands react with Ni(AcO)2 and Cu(AcO)2 in MeOH under formation of bis‐complexes with the compositions of [M(L)2] (M=Ni2+, Cu2+; L=L1, L2). Similar reactions with Co(AcO)2, however, result in Co(III) tris‐complexes [Co(L)3] (L=L1, L2) with the metal ions oxidized presumably by atmospheric dioxygen. X‐ray crystallography and spectroscopic characterization reveal a cis square‐planar coordination in the bis‐complexes and facial octahedral geometry in the tris‐complexes. In all of metal complexes, the deprotonated organic compounds ({L1}− and {L2}−) serve as (S,O)‐bidentate ligands. The ligand HL1 and its Ni(II) and Cu(II) complexes exhibit weak antiproliferative effects on the human MCF7 breast and HepG2 liver cancer cells with IC50 values in the range of 60–115 μM. Surprisingly, the tris‐complex [Co(L1)3] exhibits high cytotoxicity with IC50 values of 22.23±1.58 μM for MCF7 and 28.30±3.09 μM for HepG2 cancer cells. The activity against MCF7 cells is even more than that of cisplatin under the same conditions. [ABSTRACT FROM AUTHOR]

Copper(II) complexes of sulfonamides have found importance in biological and pharmaceutical systems. This study focuses on copper(II) complexes that were synthesized by precipitation method. The spectroscopic characterization was done by different techniques like FT-IR, UV–Vis, and ESI-MS. Compound 6 [Cu(L2)]2·2DMSO [HL = 4-((naphthalene-1-sulfonamido)methyl)cyclohexanecarboxylic acid] was recrystallized from DMSO, and its structure was determined by single-crystal X-ray diffraction to confirm the results of the synthesis of series of compounds. The geometry around each Cu(II) is tetrahedral bipyramidal with monodentate DMSO at the apical and bidentate carboxylates in the equatorial positions and a Cu–Cu bond. The synthetic compounds were screened for their biological applications involving antibacterial (Escherichia coli [E.C], Staphylococcus aureus [S.A], Sheigella sonnei [S.S], Bacillus subtilis [B.S], Nesseria gonorrhoeae [N.G], and Chromohalobacter israelensis [C.I]), antifungal (Aspergillus niger [A.N] and Neurospora crassa [N.C]), enzyme inhibition (acetylcholinesterase [AChE] and butyrylcholinesterase [BChE]), and antioxidant study. Furthermore, molecular docking study of all compounds was performed against enzymes and DNA using AutoDock Tools version 1.5.6. After confirmation of DNA-interaction through docking studies, nuclease activity was performed using agarose gel electrophoresis method and all compounds have been found to cleave DNA. These results concluded that copper complexes of sulfonamide may be good induction in the future for medical purposes. [ABSTRACT FROM AUTHOR]

A series of 2-(hydroxyphenyl)-1H-benzo[d]imidazols bearing readily oxidizable 2,6-di-tert-butyl-phenol substituents and bischelate Cu(II) complexes based on these ligands were synthesized. The structure of the compounds was characterized by NMR, IR, mass spectroscopy and X-ray crystallographic analysis and redox behavior explored using ESR spectra and cyclic voltammetry. Under oxidation with PbO2 in toluene solution both the ligands and Cu(II) complexes form stable phenoxyltype radicals. As shown by ESR measurements and DFT calculations, no exchange interaction exists between unpaired electrons located on metal and oxygen centers in the biradical Cu (II) complexes. The ligands and complexes reveal antioxidant radical scavenging activity measured spectrophotometrically and using ESR and DPPH-tests. [ABSTRACT FROM AUTHOR]

• A new a five-coordinate square pyramidal copper(II) complex containing Schiff base based on 5-chlorosalicylaldehyde and L-tryptophan was synthesized and characterized. • Synthesized complexes show good CT-DNA and BSA binding activity. • The radical scavenging activities of the synthesized complexes by DPPH and H 2 O 2 methods are comparable to standard antioxidants. • Antiproliferative activity on breast cancer cells (MCF-7 and MDA-MB-231) and healthy breast epithelial cells (MCF-10A) of the synthesized complexes are comparable with cisplatin and paclitaxel. • The copper(II) mixed ligand complex containing 3,5-dichlorosalicylaldehyde and L-tryptophan based Schiff base with 1,10-phenanthroline induced apoptosis through caspase independent pathways. Three new copper(II) complexes, [Cu(5-ClSal-Trp)(H 2 O) 2 ] (1), [Cu(5-ClSal-Trp)(phen)] ·C 2 H 5 OH (2) and [Cu(3,5-ClSal-Trp)(phen)] (3) (5-ClSal-Trp: Schiff base derived from 5-chlorosalicylaldehyde and L-tryptophan, 3,5-ClSal-Trp: Schiff base derived from 3,5-dichlorosalicylaldehyde and L-tryptophan, phen: 1,10-phenanthroline), have been synthesized and characterized by electronic absorption spectroscopy, CHN analysis, FTIR, ESI-MS and XRD techniques. Interaction of the complexes 1-3 with biomolecules {calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)} has been investigated by electronic absorption and fluorescence spectroscopy. The results show that the complexes 1-3 can bind to CT-DNA via a moderate intercalation mode. Moreover, the fluorescence quenching mechanism between the complexes 1-3 and BSA is a static quenching process. Radical scavenging activity studies reveal that the complexes 1 - 3 show a moderate activity. Antiproliferative effects of the complexes 1 - 3 on both breast cancer cells (MCF-7 and MDA-MB-231) and healthy breast epithelial cells (MCF-10A) were also investigated using the Sulforhodamine B (SRB) viability assay. The results demonstrated that the complexes 1 - 3 exhibited a more pronounced cytotoxic effect on cancer cells compared to normal breast epithelial cells. Among the complexes, the best cytotoxic activity was obtained for the complex 3 against both human breast cancer cell lines. Further analysis indicated that the complex 3 induced apoptosis, as evidenced by fluorescent staining, positive Annexin-V-FITC staining, and the involvement of caspase. Subsequent to the administration of the complex 3 , an evaluation of intracellular reactive oxygen species (ROS) generation was conducted through the utilization of dihydroethidium (DHE) fluorescent staining. A potent drug candidature of three new copper(II) complexes have been synthesized and characterized by CHN analysis, FTIR, ESI-MS and XRD techniques. The complexes have been analyzed biomolecular interactions by spectroscopic methods. Furthermore, radical scavenging and antiproliferative activities of the complexes were also investigated. [Display omitted] [ABSTRACT FROM AUTHOR]

In order to improve the previously observed antichagasic activity of Cu(II) complexes containing 2-chlorobenzhydrazide (2-CH), we report herein the synthesis and anti-Trypanosoma cruzi activity of novel copper complexes containing 2-methoxybenzhydrazide (2-MH), 4-methoxybenzhydrazide (4-MH) and three α-diimine ligands, namely, 1,10-phenanthroline (phen), 2,2-bipyridine (bipy) and 4-4′-dimethoxy-2-2′-bipyridine (dmb). Two of these complexes showed higher in vitro anti-Trypanosoma cruzi activity when compared to benznidazole, the main drug used in Chagas disease treatment. One of them, the copper complex with 4-MH and dmb, [Cu(4-MH)(dmb)(ClO4)2], exhibited a higher selectivity index than that recommended for preclinical studies. Considering this observation, complex [Cu(4-MH)(dmb)(ClO4)2] was selected for preliminary in vivo assays, which verified that this compound was able to reduce parasitemia by 64% at the peak of infection. Further investigations were performed on all compounds. The Cu(II) complexes bind to ct-DNA with Kb values in the range of 103–104 M–1, with [Cu(4-MH)(dmb)(ClO4)2] showing the highest Kb value (1.45 × 104 M–1). Molecular docking simulations predicted that [Cu(4-MH)(dmb)(ClO4)2] binds in the minor groove of the double helix of ct-DNA and forms one hydrogen bond.

The present study aims to synthesize new copper(II) complexes in the presence of maltol, sodium saccharin and 3-hydroxyflavone. Characterization of the structure of Cu(II) complexes was carried out by FT-IR, CHN analysis and X-ray crystallography. Methods including fluorescence spectroscopy and molecular docking methods were applied to investigate the interaction of copper(II) complexes with human serum albumin. The cytotoxicity of complexes was screened for antiproliferative activity against human breast cancer cells (MCF-7), and cis-platin used as a comparative standard by MTT assay. The experimental results indicated that the fluorescence quenching of HSA by complexes 1–5 was a static quenching. Also, the results showed that complex 3, [Cu(saccharin)(bpca)(H2O)], has higher cytotoxicity compared to other compounds and cis-platin. [ABSTRACT FROM AUTHOR]

A new crystal structure for complex [Cu2Cl2(bipy)2(μ-Cl)(μ-CH3O)] was obtained. X-ray diffraction data showed dinuclear complexes with metal-ions seated on two symmetrically related pentacoordinated environment, in which, a trigonal bipyramidal (TBPY-5) coordination polyhedra was observed. While chloride was detected as monodentate and as a bridging-ligand, the diimine unit and a bridging oxygen from methoxide occupied the remaining positions. The crystal structure accounted for dinuclear complexes interacting to each other via H-bonds involving C–H groups of bipy and monodentate chloride anions of an adjacent molecule. Theoretical studies were conducted by DFT methods employing B3LYP in combination with 6-31G(d). Larger basis sets (6-311G(d) and cc-pVDZ) were taken into account to assess the performance of B3LYP/6-31G(d) in dealing with equilibrium geometry and population analysis. This standard methodology showed to be a reasonable performer to reproduce geometric parameters keeping the computational cost very low. A new crystal structure for complex [Cu2Cl2(bipy)2(μ-Cl)(μ-CH3O)] was obtained, for which, DFT calculations were conducted for the further understanding of geometric and electronic properties. [ABSTRACT FROM AUTHOR]

Unusual coordination of Cu(II) with the pyrrolidine N atom of nicotine in aqueous solution that could promote the formation of carcinogenic N-nitrosonornicotine in raw medical tobacco was shown using circular dichroism. [ABSTRACT FROM AUTHOR]