Search

The crystal structures of bis[1-ethyl-6-fluoro-4-oxo-7-(piperazin-1-ium-4-yl)-1,4-dihydroquinoline-3-carboxylato]copper(II) sulfate heptahydrate, [Cu(C 16 H 18 FN 3 O 3 ) 2 ]SO 4 ·7H 2 O or [Cu(nor) 2 ]SO 4 ·7H 2 O (nor is norfloxacin), and bis{1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimide}dinitratocopper(II), [Cu(NO 3 ) 2 (C 8 H 13 N 3 O 4 S) 2 ] or [Cu(NO 3 ) 2 (tnz) 2 ] (tnz is tinidazole), were solved by X-ray diffraction. Both complexes crystallize in the space group P2 1 /c, with Z = 4 (for nor) and Z = 2 (for ntz) molecules per unit cell. In [Cu(nor) 2 ]SO 4 ·7H 2 O, the Cu II ion is at the centre of a square-planar environment, trans coordinated to two independent norfloxacin molecules in the zwitterionic form acting as bidentate ligands through one of the carboxyl (cbx) and the carbonyl (cb) O atoms. The solid is further stabilized by an extensive network of N-H...O(sulfate), N-H...O(cbx), N-H...OW, OW-H...O(sulfate) and OW-H...OW hydrogen bonds. The [Cu(NO 3 ) 2 (tnz) 2 ] complex is centrosymmetric, with the Cu II ion in a square planar environment, coordinated to a tinidazole molecule acting as a monodentate ligand through its imidazole N atom and to one nitrate O atom. The vibrational FT-IR absorption spectra and thermal behaviour of the complexes were also studied and are briefly discussed based on the crystal structures.

We report here the synthesis, crystal structure, characterization and anticancer activity of a copper(ii)-hydrazone complex, [Cu(MeBHoVa)(H2O)2](NO3) (for short, CuHL), against human breast cancer cells on monolayer (2D) and spheroids/mammospheres (3D). The solid-state molecular structure of the complex has been determined by X-ray diffraction methods. The conformational space was searched and geometries were optimized both in the gas phase and including solvent effects by computational methods based on DFT. The compound has been characterized in the solid state and in solution by spectroscopic (FTIR, Raman, UV-vis) methods. The results were compared with those obtained for the hydrazone ligand and complemented with DFT calculations. Cell viability assays on MCF7 (IC50(CuHL) = 1.7 ± 0.1 μM, IC50(CDDP) = 42.0 ± 3.2 μM) and MDA-MB-231 (IC50(CuHL) = 1.6 ± 0.1 μM, IC50(CDDP) = 131.0 ± 18 μM) demonstrated that the complex displays higher antitumor activity than cisplatin (CDDP) on 2D and 3D human breast cancer cell models. Molecular docking and molecular dynamics simulations showed that CuHL could interacts with DNA, inducing a significant genotoxic effect on both breast cancer cells from 0.5 to 1 μM. On the other hand, CuHL increases the ROS production and induces cell programmed death on breast cancer cells at very low micromolar concentrations (0.5-1.0 μM). Moreover, the compound decreased the amount of breast CSCs on MCF7 and MDA-MB-231 cells reducing the percentage of CD44+/CD24-/low cells from 0.5 to 1.5 μM. In addition, CuHL overcame CDDP with an IC50 value 65-fold lower against breast multicellular spheroids ((IC50(CuHL) = 2.2 ± 0.3 μM, IC50(CDDP) = 125 ± 4.5 μM)). Finally, CuHL reduced mammosphere formation capacity, hence affecting the size and number of mammospheres and showing that the complex exhibits antitumor properties on monolayer (2D) and spheroids (3D) derived from human breast cancer cells.

We report the synthesis and biological evaluation of a ternary copper complex, [Cu(5HTP)(phen)(H 2 O)](NO 3 ).2H 2 O, with the antioxidant agent 5-hydroxytryptophan (5-HTP) and phenanthroline (phen, added to improve its lipophilicity and membrane transport). The crystal structure of the complex was determined by X-ray diffraction methods. The complex showed antioxidant, antimicrobial, antitumor and antimetastatic properties with an adequate safety profile. The interaction of the metal with phen promotes cellular copper accumulation and cytotoxicity on human lung A549 cell line (IC 50  = 3.6 μM). Furthermore, the viability of the normal human fetal lung fibroblast cell line (MRC-5) is not altered by the complex. An oxidative stress mechanism for the anticancer effect has been determined: cellular increase of reactive oxygen species (ROS), decrease of the glutathione (GSH) and oxidized GSH (GSSG) ratio and alteration of the mitochondrial potential. The complex also displays antimetastatic activities with inhibition of cell adhesion, invasion and migration. It has not mutagenic behavior and no toxicity on Artemia salina indicating its potential to act as an effective and safety antimicrobial and antitumor drug., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In the current study the ability of copper complex to exert multiple biological activities is combined with the pharmacological action of sertraline (SerH 2 Cl, antidepressant drug). The hydrated and anhydrous forms of the tetrachlorocuprate(II) salts, namely (SerH 2 ) 2 [CuCl 4 ]·½H 2 O and (SerH 2 ) 2 [CuCl 4 ], were synthesized and characterized by physicochemical methods. The crystal structures were determined by X-ray diffraction methods. The hydrate complex crystallizes in the monoclinic P2 1 space group with a=8.0807(2) Å, b=36.2781(8) Å, c=12.6576(3) Å, β=95.665(2)°, and Z=4 molecules per unit cell and the un-hydrate in P2 1 with a=13.8727(6) Å, b=7.5090(3) Å, c=18.618(1) Å, β=104.563(6)°, and Z=2. It has been suggested that Cu(II) ions might be critical in the development of mood disorders, showed potent biocidal activity, and also acted as analgesic adjuvant. To improve sertraline efficiency, the antidepressant and analgesic activities of the complex have been assessed in rats denoting a marked synergistic effect. Antithyroid and antimicrobial activities were also evaluated. Because depressive disorders and hyperthyroidism diseases led to an oxidative stress state, antioxidant capability has also been tested. The complex behaved as a good superoxide radical scavenger (IC 50 =6.3×10 -6 M). The ability of the complex to act as bromoperoxidase mimic was assessed. A pseudo-first order constant of k=0.157±0.007min -1 has been determined. The complex evidences promising biological-pharmacological activities and the albumin binding studies showed a K b of 2.90×10 3 M -1 showing an improvement in the uptake of sertraline by albumin at 8h incubation (time required for effective interaction of sertraline with the protein)., (Copyright © 2017 Elsevier Inc. All rights reserved.)

A new Cu(II) complex with the antihypertensive drug telmisartan, [Cu8Tlm16]·24H2O (CuTlm), was synthesized and characterized by elemental analysis and electronic, FTIR, Raman and electron paramagnetic resonance spectroscopy. The crystal structure (at 120 K) was solved by X-ray diffraction methods. The octanuclear complex is a hydrate of but otherwise isostructural to the previously reported [Cu8Tlm16] complex. [Cu8Tlm16]·24H2O crystallizes in the tetragonal P4/ncc space group with a = b = 47.335(1), c = 30.894(3) Å, Z = 4 molecules per unit cell giving a macrocyclic ring with a double helical structure. The Cu(II) ions are in a distorted bipyramidal environment with a somewhat twisted square basis, cis-coordinated at their core N2O2 basis to two carboxylate oxygen and two terminal benzimidazole nitrogen atoms. Cu8Tlm16 has a toroidal-like shape with a hydrophobic nanometer hole, and their crystal packing defines nanochannels that extend along the crystal c-axis. Several biological activities of the complex and the parent ligand were examined in vitro. The antioxidant measurements indicate that the complex behaves as a superoxide dismutase mimic with improved superoxide scavenger power as compared with native sartan. The capacity of telmisartan and its copper complex to expand human mesangial cells (previously contracted by angiotensin II treatment) is similar to each other. The antihypertensive effect of the compounds is attributed to the strongest binding affinity to angiotensin II type 1 receptor and not to the antioxidant effects. The cytotoxic activity of the complex and that of its components was determined against lung cancer cell line A549 and three prostate cancer cell lines (LNCaP, PC-3, and DU 145). The complex displays some inhibitory effect on the A549 line and a high viability decrease on the LNCaP (androgen-sensitive) line. From flow cytometric analysis, an apoptotic mechanism was established for the latter cell line. Telmisartan and CuTlm show antibacterial and antifungal activities in various strains, and CuTlm displays improved activity against the Staphylococcus aureus strain as compared with unbounded copper(II).

A new copper(II) complex of santonic acid [Cu(2)(sant)(4)(H(2)O)(2)].2(1/2)H(2)O has been prepared and characterized by electronic, vibrational, EPR spectral studies, and stability determinations in solution. The presence of two antiferrromagnetically coupled copper centers in the solid state was detected by EPR. The dinuclear Cu(II) complex crystallizes in the tetragonal P4(3)2(1)2 space group, with a=b=14.498(3), c=64.07(1)A. Biological studies indicate that the complex displays interesting potential antitumoral actions.

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.

Two new complexes [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl] (2)(2-OH-Hip)(2) (1) and [Co(2-OH-Hip)(Imz)(3)].H(2)O (2) (with Imz=Imidazol and 2-OH-Hip=2-hydroxyhippuric acid) were prepared and characterized. The molecular structures and the solution and solid state behavior of the complexes were investigated. Complex 1 crystallizes in the monoclinic space group P2(1)/c with a=16.880(1), b=8.046(1), c=24.683(1) A, beta=107.88(1) degrees, and Z=2, while complex 2 crystallizes in the orthorhombic space group Pbca with a=11.712(2), b=15.741(4), c=22.254(4) A, and Z=8. The [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl](2)(2-OH-Hip)(2) solid consists in two distinct monomeric Cu(II) complexes: one of them is neutral octahedral [Cu(Imz)(4)Cl(2)] and the other, charged square basis pyramida [Cu(Imz)(4)Cl](+). The 2-hydroxyhippuric acid, which here acts as a counter ion, is deprotonated at its carboxylic group. Cobalt(III) ion in [Co(2-OH-Hip)(Imz)(3)].H(2)O is at the center of an octahedral environment, coordinated to three Imidazol ligands and to a triply deprotonated 2-hydroxyhippuric acid molecule acting as a tridentate ligand. Aqueous solution equilibrium of the quaternary system Cu(2+)/2-OH-Hip/Imz/H(+) was studied by potentiometric titrations.

The molecular structure of [Cu(sulfadimet)(2)].SO(CH(3))(2) (sulfadimet=sulfadimethoxine=4-p-aminobenzenesulfonamido-2,6-dimethoxypyrimidine) was determined by single crystal X-ray diffractometry. It crystallizes in the monoclinic space group P2(1)/c with Z=4. The Cu(II) cation is in a distorted CuN(5) square pyramidal coordination, involving four sulfadimethoxine molecules, one of them acting as a bidentate ligand. The infrared spectrum is briefly discussed on the basis of the structural peculiarities of the complex.

Three new copper(II) complexes of stoichiometry [Cu(L-dipeptide)].nH(2)O, containing as ligands the dipeptides L-alanine-L-isoleucine, L-alanine-L-threonine and L-alanine-L-tyrosine were prepared. They were characterized by single crystal X-ray diffractometry, and electronic and infrared spectroscopy. In all cases, the Cu(II) cation has essentially the same elongated square pyramidal coordination, being equatorially cis coordinated by a N(2)O(2) arrangement of ligand atoms and axially by a carbonyl oxygen atom. The compounds show rather similar polymeric structures which resemble those recently reported for the [Cu(ala-val)] and [Cu(ala-phe)] complexes. The electronic and infrared spectra are briefly discussed on the basis of the structural peculiarities of the complexes. Superoxide dismutase (SOD)-like activity was also tested for the compounds.

The main goal of this work was to report the synthesis, characterization, and cytotoxicity study of a novel copper(II)-sunitinib complex, CuSun. It has been synthesized and characterized in solid state and in solution by different methods (such as DFT, FTIR, Raman, UV-vis, EPR, NMR, etc.). The solid-state molecular structure of trichlorosunitinibcopper(II), where sunitinib: N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide, for short Cu(Sun)Cl3, was determined by X-ray diffraction. It crystallizes in the triclinic space group P-1 with a = 7.9061(5) Å, b = 12.412(1) Å, c = 13.7005(8) Å, α = 105.021(6)°, β = 106.744(5)°, γ = 91.749(5)°, and Z = 2 molecules per unit cell. Also, we have found π-π interactions and classic and non-classic H-bonds in the crystal structure by using Hirshfeld surface analysis. In the speciation studies, the complex has dissociated in protonated sunitinib and chlorocomplex of copper(II), according to 1HNMR, EPR, UV-vis and conductimetric analysis. Molecular docking of the complex in both, ATP binding site and allosteric site of VEGFR2 have shown no improvement in comparison to the free ligand. Besides, cytotoxicity assay on HepG2 cell line shows similar activity for complex and ligand in the range between 1–25 μM supporting the data obtained from studies in solution. [ABSTRACT FROM AUTHOR]

Two new copper(II)-hydrazone complexes with 2,2́ bipyridine or 1,10 phenanthroline as coligands were synthesized and characterized by spectroscopic methods. Their molecular structures were confirmed by single crystal X-ray diffraction. Both complexes were evaluated as antitumour agents. They showed higher cytotoxic activity against lung, bone and breast cancer cells lines than cisplatin. [Display omitted] • Two ternary Cu(II) hydrazone complexes were synthesized and characterized. • The complexes crystallize in a CuO 2 N 3 distorted square pyramidal environment. • The hydrazone adopts different tautomeric forms in the environment of each compound. • EPR data are consistent with the dx2-y2 ground state determined by XRD. • They are more cytotoxic than cisplatin on lung, bone and breast cancer cells lines. Two new penta-coordinated copper(II) hydrazone coordination compounds with 2,2́ bipyridine (I) or 1,10 phenanthroline (II) as coligands are synthesized and characterized in the solid state and in solution by spectroscopic methods (FTIR, Raman, UV–vis, EPR). Single crystal X-ray studies show that they have closely related molecular structures with the copper center in a distorted square pyramidal O 2 N 3 environment. The N -acylhydrazone, 4-hydroxy-NŃ-(E)2-hydroxy-3-methoxybenzylidene]benzohydrazide, H 2 L, coordinates tridentate through its ONO donor atoms as monoanion (HL-) in the cationic complex (I) , [Cu(HL)(bipy)](NO 3). During the period that takes the synthesis reaction of compound (II) , [Cu(L)(o -phen)] to complete, keto-amine to enol-imine tautomerization of H 2 L occurs and the hydrazone coordinates tridentate as dianionic ligand (L2-). The fivefold coordination sphere of the complexes is completed with the nitrogen atoms of the respective coligands. Cytotoxicity studies against bone (MG-63, IC 50 (I) = 5.6 ± 1.0 , IC 50 (II) = 3.5 ± 0.3), breast (MCF7, IC 50 (I) = 10.8 ± 1.9, IC 50 (II) = 4.0 ± 1.3), (MDA-MB-231, IC 50 (I) = 11.4 ± 0.6, IC 50 (II) = 5.3 ± 0.2) and lung cancer cells (A549, IC 50 (I) = 7.7 ± 0.7, IC 50 (II) = 7.0 ± 0.4) reveals increased effectiveness of both complexes compared with the free ligand, the copper nitrate salt and the reference metallodrug cisplatin (CDDP). [ABSTRACT FROM AUTHOR]

Through a redox process, an in situ transformation of propylthiouracil led to the formation of a trisulfur ligand forming with Cu(II) a lantern-like binuclear complex [Cu 2 (ptu-S-ptu) 2 ]. The complex behaves as a promiscuous promising catalyst. It possesses peroxidase-like activity catalyzing phenol red bromination, the oxidation of pyrogallol, and behaves as a superoxide dismutase (SOD) mimic compound. Insights into their reactivity are analyzed by comparison with a family of other sulfur-containing copper(II) metal complexes. [Display omitted] Through a redox process, an in situ transformation of propylthiouracil led to the formation of a trisulfur ligand that coordinates Cu(II) ion forming a lantern-like binuclear copper(II) complex [Cu 2 (ptu-S-ptu) 2 ]. The complex was characterized by elemental analysis, spectroscopic techniques (FTIR, UV–Vis, EPR, and Hirshfeld surfaces analyses.), single-crystal X-Ray analysis, and its optimized molecular structure was obtained by DFT calculations. It crystallizes as a twin in the space group P -1, with two different, though closely related, centrosymmetric binuclear complexes per unit cell. The (ptu-S-ptu)2− thiouracil rings are nearly perpendicular to each other and their N and O atoms equatorially cis -coordinate the two copper ions in a two-fold Cu-OCN-Cu bridging mode. The four-fold bridging configuration is completed by another (ptu-S-ptu)2− ligand, inversion-related through the middle of the Cu...Cu contact. The elongated octahedral coordination around each copper is completed by the linking S-atom of the ligand at the axial position. The crystallographic results point to a copper d(x2-y2) d -orbital for the electron (or hole) ground state and optimal overlap of this orbital with molecular electronic path bridging the two metal atoms, hence indicating a relatively large antiferromagnetic coupling between them. The designed complex behaves as a promiscuous promising catalyst. It possesses intrinsic peroxidase-like activity catalyzing phenol red bromination in the presence of H 2 O 2 at room temperature, and the oxidation of pyrogallol, and behaves as a superoxide dismutase (SOD) mimic compound acting on superoxide anion. Additionally, insights into their reactivity are analyzed by comparison with a family of other sulfur-containing copper(II) metal complexes in an attempt to explain the differences in catalytic properties and to determine the structural properties that affect the reactivity with substrates. Albumin interactions studies are also incorporated. [ABSTRACT FROM AUTHOR]

Abstract: The formation and characterisation of a polymeric copper complex produced by chemical reaction between copper (II) ions and 3-mercapto-1-propanesulphonate sodium salt (MPSA) were studied. The formation of this complex, followed by sequential UV–visible spectroscopic measurements, involves the reduction of Cu(II) ions to Cu(I) by MPSA, the latter being oxidised to bis-(3-sulphopropyl)-disulphide (SPS), a dimer of MPSA. In the presence of oxygen, the re-oxidation of Cu(I) to Cu(II) results in the formation of polymeric complex species consisting of [Cu(SO3(CH2)3S–S(CH2)3SO3)(H2O)4] units. Single crystal X-ray diffraction shows that this polymeric copper complex crystallizes in the monoclinic C2/c space group. The Cu(II) ion in the complex structure lies on an inversion centre in an elongated octahedral environment, equatorially coordinated to four water molecules and axially to two MPSA ligands through one of their sulphonic oxygen atoms. The complex units are arranged in the lattice as polymeric [Cu(SPS)(H2O)4] n molecules extending along the crystal [101] direction. The IR and Raman spectra as well as TGA and DTA data are reported. The stepwise thermal decomposition from room temperature up to 1000°C begins with the loss of water molecules and ends with the formation of copper sulphide species. [Copyright &y& Elsevier]