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Two vanadium(V) Schiff base complexes, [VO2L1] (1) and [VO2L2] (2) [where HL1 = 2-((2-morpholinoethylimino)methyl)-6-ethoxyphenol and HL2 = 2-((2-(dimethylamino)ethylimino)methyl)-4-bromophenol], were synthesized and characterized by elemental and spectral analysis. The structures of both complexes were confirmed by single-crystal X-ray diffraction studies. To investigate the redox properties of the complexes, electrochemical measurements were performed in solution. Density functional theory (DFT) calculations have been performed using hybrid functional PBE0. The DFT optimized results were found to agree well with the experimental results. Topological features derived from the Bader's theory of atoms in molecules (AIM) approach have also been applied. Phenoxazinone synthase like activities (conversion of o-aminophenol to 2-aminophenoxazine-3-one) of both complexes were investigated spectrophotometrically. [ABSTRACT FROM AUTHOR]

A dimeric complex of Cu(ii) with tinidazole characterized earlier was used to study radiosensitizing attributes. Studies reveal that the complex is better than tinidazole in sensitizing radiation-induced damage of nucleic acid bases uracil and thymine, radiation-induced double strand modification of calf thymus DNA and modification of DNA within MCF-7 breast cancer cells. The unique aspect of this study is that in spite of a substantial decrease in the generation of the nitro-radical anion (NO2Ṗ−) following complex formation of tinidazole with Cu(ii), no decrease was observed in the radiosensitizing attribute of nitroimidazoles. Rather the complex was clearly ahead of tinidazole with regard to radiosensitization. Hence, complex formation of important drug molecules are an advantage since it helps to target DNA better. This study serves as a good example where a common intermediate (NO2Ṗ−) responsible for efficacy as well as toxic side effects can be suitably tuned in its generation using a modified form of 5-nitroimidazole (here tinidazole) to be able to strike the correct balance between efficacy and toxic side effects. [ABSTRACT FROM AUTHOR]

A monomeric complex of Cu(ii) with tinidazole [Cu(tnz)2Cl2] was synthesized. The complex decreases the formation of the nitro-radical anion (NO2Ṗ−), which was followed by an enzyme assay involving xanthine oxidase, a model nitro-reductase. It has a binding constant value with DNA comparable to that of tinidazole. In addition to the drug efficacy of the nitro radical anion, it also has neurotoxic side effects; so it is essential to control its formation to an optimum, sufficient for bringing about cytotoxic activity on disease causing microbes but avoiding excess that could make it neurotoxic. If this is achieved through modification of the 5-nitroimidazole moiety then too much NO2Ṗ− would not be generated, implying that the chances of the drug causing any harm to the host due to toxic side effects could be reduced. However, with decreased NO2Ṗ− formation, in an effort to decrease complications, a certain amount of therapeutic efficacy would be compromised. Therefore, the biological activity of tinidazole and its modified form, a monomeric complex, was investigated to see how the latter compares with tinidazole under comparable conditions. Studies revealed that, in spite of decreased NO2Ṗ− formation, the complex showed similar activity to that of tinidazole on two bacterial strains and an amoeba strain, implying that it has other attributes, not known for 5-nitroimidazoles, that enable it to match the efficacy of tinidazole. The study suggests that there is a substantial decrease in NO2Ṗ− due to the formation of the tinidazole complex, meaning that the toxic side effects are likely to be reduced which is an advantage as it would improve the therapeutic index. [ABSTRACT FROM AUTHOR]

Variation of pyridyl based receptors around a Cu(ii) center results in structural diversity allowing redox triggered Cu(ii)/Cu(i) fluorescence switch for intracellular Cu(i) imaging. Single crystal X-ray structures of 2-hydroxy-6-methylnicotinic acid (L1), its mono nuclear Cu(ii) complex, viz. [Cu(L1)2(H2O)(SO4)]·2H2O (C1a), polymeric Cu(ii) complex (C1b) and a dinuclear Cu(ii) complex of 2-(naphthalen-2-ylmethylsulfanyl)-nicotinic acid (L4), viz. [Cu2(L4)4(H2O)2]·1.12H2O (C4) with a Cu–Cu distance of 2.6028(7) Å are reported. Moreover, C1a interacts with calf thymus DNA, which is useful for disruption of normal DNA activity with plausible applications in biology (binding constant, K′ = 1.56 × 104). Chemical or electrochemical reduction of C1a generates a fluorescent Cu(i) complex. The lowest detection limit of L1 for Cu(i) is 50 μM. The association constant of L1 for Cu+ is 7.09 × 102. Quenching constants of Cu(ii) for L1, L2, L3 and L4 are 4 × 105, 4.2 × 106, 8.9 × 105 and 4.4 × 106, respectively. The magnetic behavior of C1b indicates a ferromagnetic one-dimensional solid. [ABSTRACT FROM AUTHOR]

A 1 : 2 copperII complex of 1-amino-4-hydroxy-9,10-anthraquinone (QH) having the molecular formula CuQ2 was prepared and characterized by elemental analysis, NMR, FTIR, UV-vis and mass spectroscopy. The powder diffraction of the solid complex, magnetic susceptibility and ESR spectra were also recorded. The presence of the planar anthraquinone moiety in the complex makes it extremely difficult to obtain a single crystal suitable for X-ray diffraction studies. To overcome this problem, density functional theory (DFT) was used to evaluate an optimized structure of CuQ2. In the optimized structure, it was found that there is a tilt of the two planar aromatic anthraquinone rings of the complex with respect to each other in the two planes containing the O–Cu(ii)–O plane. The present study is an important addition to the understanding of the structural aspects of metal-anthracyclines because there are only a few reports on the actual structures of metal-anthracyclines. The theoretical vibrational spectrum of the complex was assigned with the help of vibrational energy distribution analysis (VEDA) using potential energy distribution (PED) and compared with experimental results. Being important in producing the biochemical action of this class of molecules, the electrochemical behavior of the complex was studied in aqueous and non-aqueous solvents to find certain electrochemical parameters. In aqueous media, reduction involves a kinetic effect during electron transfer at an electrode surface, which was characterized very carefully using cyclic voltammetry. Electrochemical studies showed a significant modification in the electrochemical properties of 1-amino-4-hydroxy-9,10-anthraquinone (QH) when bound to CuII in the complex compared to those observed for free QH. This suggests that the copper complex might be a good choice as a biologically active molecule, which was reflected in the lack of stimulated superoxide generation by the complex. [ABSTRACT FROM AUTHOR]

An acetate-bridged binuclear Cu(II) complex of the antiparasitic drug ornidazole was synthesized and characterized by different techniques. Single crystal X-ray diffraction revealed that the complex had a paddle wheel structure. Enzymatic assay experiments performed under anaerobic conditions on ornidazole and its Cu(II)-complex using xanthine oxidase as a model nitro-reductase showed that complex formation is able to cause a significant decrease in the reduction of the nitro group on the imidazole ring. Reduction products of 5-nitroimidazoles interact with DNA, causing destruction of the double helical structure and strands, leading to the inhibition of protein synthesis. Although not directly coordinated to the metal center, such a decrease in the generation of nitro radical anion through complex formation would result in decreased cytotoxicity of the complex, which could be a disadvantage from the standpoint of drug efficacy. For this reason, other aspects associated with the drug action of 5-nitroimidazoles, such as DNA binding, were studied. Experiments using cyclic voltammetry revealed that the binding of the complex was almost comparable to ornidazole. Bactericidal activity of ornidazole and the complex was studied on two separate bacterial strains, showing that the complex was comparable to ornidazole. Nitro radical anions are known to adversely affect the central nervous system, and this study showed that the Cu(II) complex has the ability to decrease the generation of NO2Ṗ− to an extent that struck the correct balance for beneficial activity, as cytotoxicity due to ornidazole was not affected. [ABSTRACT FROM AUTHOR]

A monomeric complex of Zn II with ornidazole [Zn(Onz) 2 Cl 2 ] decreases formation of the nitro-radical anion (R-NO 2 ˙ - ), and this is realized by recording it in an enzyme assay using xanthine oxidase, which is a model nitro-reductase. Although the formation of R-NO 2 ˙ - is essential for drug action, as it is also associated with neurotoxic side effects, it is imperative to control its generation in order to avoid excess presence. With a decrease in R-NO 2 ˙ - , while the neurotoxic side effects should decrease, it can be expected that a compromise with regard to therapeutic efficacy will be seen since the complex will be less active in the free radical pathway. Since R-NO 2 ˙ - is crucial for the functioning of 5-nitroimidazoles, we attempted to find out if its biological activity is affected in any way in our effort to control its formation. For this purpose, Entamoeba histolytica (HM1:IMS Strain) was chosen as a biological target to realize the performance of the complex with respect to ornidazole (R-NO 2 ). The experiments revealed that the complex not only compares well with ornidazole, but in fact, under longer exposure times, it also performs better than it. This efficacy of the complex was seen despite a decrease in R-NO 2 ˙ - , as identified by an enzyme assay, and this was probably due to certain attributes of the complex formation that are not known for ornidazole. These attributes outweigh any loss in efficacy in the free radical pathway following complex formation. This is certainly an advantage of complex formation and helps to improve the therapeutic index. This study has attempted to look at some of the possible reasons why the complex performs better than ornidazole. One reason is its ability to bind to DNA better than ornidazole does, and this can be understood by following the interaction of ornidazole and its Zn(ii) complex with calf-thymus DNA using cyclic voltammetry. Therefore, this study showed that despite a decrease in R-NO 2 ˙ - , the complex does not compromise its efficacy, and this was examined using a biological target. In addition, the complex is likely to have less toxic side effects on the host of the disease-causing microbes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A 1 : 2 copper(II) complex of 1-amino-4-hydroxy-9,10-anthraquinone (QH) having the molecular formula CuQ2 was prepared and characterized by elemental analysis, NMR, FTIR, UV-vis and mass spectroscopy. The powder diffraction of the solid complex, magnetic susceptibility and ESR spectra were also recorded. The presence of the planar anthraquinone moiety in the complex makes it extremely difficult to obtain a single crystal suitable for X-ray diffraction studies. To overcome this problem, density functional theory (DFT) was used to evaluate an optimized structure of CuQ2. In the optimized structure, it was found that there is a tilt of the two planar aromatic anthraquinone rings of the complex with respect to each other in the two planes containing the O-Cu(II)-O plane. The present study is an important addition to the understanding of the structural aspects of metal-anthracyclines because there are only a few reports on the actual structures of metal-anthracyclines. The theoretical vibrational spectrum of the complex was assigned with the help of vibrational energy distribution analysis (VEDA) using potential energy distribution (PED) and compared with experimental results. Being important in producing the biochemical action of this class of molecules, the electrochemical behavior of the complex was studied in aqueous and non-aqueous solvents to find certain electrochemical parameters. In aqueous media, reduction involves a kinetic effect during electron transfer at an electrode surface, which was characterized very carefully using cyclic voltammetry. Electrochemical studies showed a significant modification in the electrochemical properties of 1-amino-4-hydroxy-9,10-anthraquinone (QH) when bound to Cu(II) in the complex compared to those observed for free QH. This suggests that the copper complex might be a good choice as a biologically active molecule, which was reflected in the lack of stimulated superoxide generation by the complex.

An acetate-bridged binuclear Cu((II)) complex of the antiparasitic drug ornidazole was synthesized and characterized by different techniques. Single crystal X-ray diffraction revealed that the complex had a paddle wheel structure. Enzymatic assay experiments performed under anaerobic conditions on ornidazole and its Cu((II))-complex using xanthine oxidase as a model nitro-reductase showed that complex formation is able to cause a significant decrease in the reduction of the nitro group on the imidazole ring. Reduction products of 5-nitroimidazoles interact with DNA, causing destruction of the double helical structure and strands, leading to the inhibition of protein synthesis. Although not directly coordinated to the metal center, such a decrease in the generation of nitro radical anion through complex formation would result in decreased cytotoxicity of the complex, which could be a disadvantage from the standpoint of drug efficacy. For this reason, other aspects associated with the drug action of 5-nitroimidazoles, such as DNA binding, were studied. Experiments using cyclic voltammetry revealed that the binding of the complex was almost comparable to ornidazole. Bactericidal activity of ornidazole and the complex was studied on two separate bacterial strains, showing that the complex was comparable to ornidazole. Nitro radical anions are known to adversely affect the central nervous system, and this study showed that the Cu((II)) complex has the ability to decrease the generation of NO2˙(-) to an extent that struck the correct balance for beneficial activity, as cytotoxicity due to ornidazole was not affected.

Syntheses and crystal structures of four new hydrazone-based Cu(ii) complexes, [{Cu(L(1))(H(2)O)}(2)(mu-pyraz)](ClO(4))(2) (), [{Cu(L(1))(OClO(3))}(2)(mu-4,4'-bipy)] (), [{Cu(L(2)H)}(mu-pyraz){Cu(L(2)H)(OClO(3))}].(ClO(4)) () and [{Cu(L(2))}(2)(mu-bpe)] () [L(1)H = condensation product of benzhydrazide and pyridine-2-carbaldehyde and L(2)H(2) = condensation product of benzoyl acetone and benzhydrazide], bridged by various organic spacers [pyrazine (pyraz), 4,4'-bipyridine (4,4'-bipy) and 1,2-di(4-pyridyl)ethane (bpe)] are reported in this paper. The single-crystal X-ray crystallographic studies reveal that all are dinuclear units where and form strong intermolecular H-bonding to form sheets of interconnected ions, whereas forms sheets of dinuclear chains through pi-pi interactions; in , molecules are linked only through van der Waals interactions. The variable-temperature magnetic moment studies reveal that and show antiferromagnetic coupling between the Cu(ii) centers at lower temperatures. The binding ability of with calf thymus DNA [CT-DNA] is reported using various spectroscopic studies (UV-Vis titration, circular dichroism and fluorescence). The binding constants of with CT-DNA, as calculated by different methodologies, are of the order of 10(5) M(-1). The mode of interaction between and CT-DNA has been predicted using circular dichroic (CD) spectroscopy, where it has been shown that most probably interacts with DNA via intercalation between the base pairs leading to a change in B-DNA conformation. is also able to cleave supercoiled (SC) plasmid DNA pUC19 in a time and dose dependent manner as demonstrated by agarose gel electrophoresis, and also demonstrates its potential to cleave the SC plasmid DNA via both oxidative and hydrolytic mechanisms. Approximately 50% of leukemic cells are found to be dead when two representative leukemic cell lines are exposed to ( approximately 80 muM) even for 24 h as determined by different cell cytotoxicity assays. Preliminary results also showed that, at 20 muM, could selectively induce apoptosis in leukemic cells without affecting normal lymphocytes.