Five-Coordinated Geometries from Molecular Structures to Solutions in Copper(II) Complexes Generated from Polydentate-N-Donor Ligands and Pseudohalides.

A novel series of mononuclear five-coordinated pseudohalido-Cu(II) complexes displaying distorted square bipyramidal: [Cu(L1)(NCS)2] (1), [Cu(L2)(NCS)2] (2) and [Cu(L3)(NCS)]ClO4 (5) as well as distorted trigonal bipyramidal: [Cu(isp3tren)(N3)]ClO4 (3), [Cu(isp3tren)(dca)]ClO4 (4) and [Cu(tedmpza)(dca)]ClO4·0.67H2O (6) geometries had been synthesized and structurally characterized using X-ray single crystal crystallography, elemental microanalysis, IR and UV-vis spectroscopy, and molar conductivity measurements. Different N-donor amine skeletons including tridentate: L1 = [(2-pyridyl)-2-ethyl)-(3,4-dimethoxy)-2-methylpyridyl]methylamine and L2 = [(2-pyridyl)-2-ethyl)-(3,5-dimethyl-4-methoxy)-2-methyl-pyridyl]methylamine, and tetradentate: L3 = bis(2-ethyl-di(3,5-dimethyl-1H-pyrazol-1-yl)-[2-(3,4-dimethoxy-pyridylmethyl)]amine, tedmpza = tris[(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]amine and isp3tren = tris[(2-isopropylamino)ethyl)]amine ligands were employed. Molecular structural parameters such as nature of coligand, its chelate ring size and steric environment incorporated into its skeleton, which lead to adopting one of the two limiting geometries in these complexes and other reported compounds are analyzed and correlated to their assigned geometries in solutions. Similar analysis were extended to other five-coordinated halido-Cu(II) complexes.

Structurally diverse zinc(II) complexes containing tripodal tetradentate phenoxido-amines with promising antiproliferative effects.

Structurally diverse zinc(II) complexes with tripodal tetradentate phenolic-amines of variable substituents in the phenol and amine moieties were synthesized and thoroughly characterized. The two dinuclear [Zn2(L1)2](ClO4)2·MeOH (1), [Zn2(L2)2](ClO4)2 (2), and four mononuclear [Zn(L3)(H2O)]·MeOH (3), [Zn(L4)] (4), [Zn(L5)] (5) and [Zn(L6)] (6) complexes revealed distorted octahedral, trigonal-bipyramidal or tetrahedral geometries. The free HL1 and H2L3-6 ligands, and complexes 1-6 were evaluated for in vitro cytotoxicity against human cancer cell lines (A2780, A2780R, PC-3 and 22Rv1) and normal healthy MRC-5 cells. Overall results revealed high-to-moderate cytotoxicity (with the best IC50 values for complex 6 ranging from 2.4 to 4.5 µM), which is however, significantly higher than that of the reference drug cisplatin. The moderately active complexes 1-4 showed considerable selectivity on A2780 cells (IC50 ≈ 16.3-19.5 µM) over MRC-5 ones (with IC50 >50 µM for 1, 2 and 4, and with IC50 >25 µM for 3). The complexes 1, 2, and 6 and the ligand H2L6 were chosen for subsequent deeper biological evaluations. Their time-resolved cellular uptake and other cellular effects in A2780 cells were studied, such as cell cycle profile, intracellular ROS production, induction of apoptosis and activation of caspases 3/7. Complexes 1 and 2 caused significant G0/G1 cell cycle arrest in A2780 cells and antioxidant effects at normal conditions. They showed only limited effects on cellular processes connected with cytotoxicity, i.e. induction of apoptosis, depletion of mitochondrial membrane potential, and autophagy. These findings can be at least partly attributed to the low ability of the complexes to enter the A2780 cells and the depression of metabolic activity of the target cancer cells.

Dinuclear doubly bridged phenoxido copper(II) complexes as efficient anticancer agents.

Two cationic [Cu2(L1-2)2](ClO4)2 (1, 2), and four neutral doubly bridged-phenoxido-copper(II) complexes [Cu2(L3-4)2] (3, 4) and [Cu2(L5-6)2(H2O)]‧2H2O (5, 6) as well as 1D polymeric catena-[Cu(L7)] (7), where HL1-2 and H2L3-7 represent tripodal tetradentate pyridyl or aliphatic-amino groups based 2,4-disubstituted phenolates, were synthesized and thoroughly characterized by various spectroscopic methods and single crystal X-ray analysis. The molecular structures of the complexes exhibited diverse geometrical environments around the central Cu(II) atoms. The in vitro antiproliferative activity of the isolated complexes and selected parent free ligands were screened against some human cancer cell lines (A2780, A2780R, PC-3, 22Rv1, MCF-7). The most promising cytotoxicity against cancer cells were obtained for 1-6, while complex 6 was found as the best performing as compared to the reference drug cisplatin. The cytotoxicity study of complex 6 was therefore extended to wider variety of cancer cell lines (HOS, A549, PANC-1, CaCo2, HeLa) and results revealed its significant cytotoxicity on all investigated human cancer cells. The cell uptake study showed that cytotoxicity of 6 (3 µM concentration and 24 h of incubation) against A2780 cells was almost independent from the intracellular levels of copper. The effect of complexes 4, 6 and 7 on cell cycle of A2780 cells indicates that the mechanism of action in these complexes is not only different from that of cisplatin but also different among them. Complex 7 was able to induce apoptosis in A2780 cells, while complexes 4 and 6 did not and on the other hand, they showed considerable effect on autophagy induction and there are some clues that these complexes were able to induce cuproptosis in A2780 cells.

Metal complexes derived from hydrazoneoxime ligands: V. Spectral and structural studies on diacetylmonoxime n-alkanoylhydrazones and their nickel(II) and copper(II) complexes.

A series of diacetylmonoxime n-alkanoylhydrazones (H2L(n), n=4, 5, 6, 12 and 16) were prepared by the condensation of diacetylmonoxime with the corresponding n-alkanoylhydrazine in ethanol. The X-ray crystal structure of diacetylmonoxime octadecanoyl hydrazone has been solved and its molecular and supramolecular structures have been discussed. Both neutral dinuclear Cu(II) and Ni(II) complexes, [{M(L(n))}2] (M=Cu, Ni and n=4, 5, 6, 12 and 16) as well as cationic dinuclear Cu(II) complexes, [Cu2(L(n))(HL(n))]NO3 (n=12 and 16) have been also prepared and characterized by elemental analyses, FD- and ESI-mass spectra as well as IR, UV-Vis, (1)H NMR, (13)C NMR spectra. Variable temperature magnetic susceptibility measurements for dinuclear Cu(II) complexes have been also discussed.