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A monomeric complex of Cu(II) with tinidazole [Cu(tnz)2Cl2] was synthesized. The complex decreases the formation of the nitro-radical anion (NO2˙−), 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 NO2˙− 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 NO2˙− 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 NO2˙− 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 NO2˙− 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.

The antibacterial efficacy of a Cu(II) complex of $$\hbox {2-hydroxyphenyl-azo-2}^{\prime }\hbox {-naphthol}$$ (HPAN) was studied on gram-positive Bacillus subtilis and gram-negative Escherichia coli. In vitro antimicrobial activity was determined by an agar-well diffusion assay and minimum inhibitory concentration. $$\hbox {Cu}^{\mathrm{II}}(\hbox {HPAN})_{2}$$ was found to be better than HPAN in antibacterial activity. Although both bacterial strains succumbed to high concentrations of each compound, at low concentrations only $$\hbox {Cu}^{\mathrm{II}}(\hbox {HPAN})_{2}$$ was active on B. subtilis. To explain the observations, reductive cleavage of the azo-bond to aromatic amines was followed by an in vitro enzyme assay using cell extracts of E. coli containing azo-reductase. Interaction of $$\hbox {Cu}^{\mathrm{II}}(\hbox {HPAN})_{2}$$ with calf thymus DNA was compared with HPAN for correlation with antibacterial activity. Enzyme-assay on the reductive degradation of azo bond and DNA interaction do not individually explain trends observed in antibacterial activity. Comparable binding of $$\hbox {Cu}^{\mathrm{II}}(\hbox {HPAN})_{2}$$ and HPAN with calf thymus DNA was attributed to the presence of anionic species of the complex in solution. Significant activity of the complex was probably due to effective cellular uptake of it by bacterial cells as shown by a fluorescence study. The activity of the complex resembled some established antimicrobial agents. Since the complex has a moiety, not common to most antibacterial agents, resistance towards it should be significantly less, hence an advantage. Synopsis: $$\hbox {2-Hydroxyphenyl-azo-2}^{\prime }\hbox {-naphthol}$$ (HPAN) and its $$\hbox {Cu}^{\mathrm{II}}$$ complex were screened for antibacterial activity by agar-well diffusion assay and minimum inhibitory concentration. Studies on azo bond cleavage by enzyme assay and DNA binding of the compounds were done to explain the antibacterial activity. The pronounced activity of $$\hbox {Cu}^{\mathrm{(II)}}$$ -HPAN is attributed to an effective cellular uptake by bacterial cells.

Reductive cleavage of azo bond in a CoIIcomplex of HPIA decreased significantly implying less toxicity. On human colon carcinoma HCT116, ALL MOLT-4 & MCF-7 breast cancer cells complex was more effective than HPIA but less toxic towards normal cells.

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)]center dot 2H(2)O (C1a), polymeric Cu(II) complex (C1b) and a dinuclear Cu(II) complex of 2-(naphthalen-2-ylmethylsulfanyl)nicotinic acid (L4), viz. [Cu-2(L4)(4)(H2O)(2)]center dot 1.12H(2)O (C4) with a Cu-Cu distance of 2.6028(7) angstrom 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 x 10(4)). Chemical or electrochemical reduction of C1a generates a fluorescent Cu(I) complex. The lowest detection limit of L1 for Cu(I) is 50 mu M. The association constant of L1 for Cu+ is 7.09 x 10(2). Quenching constants of Cu(II) for L1, L2, L3 and L4 are 4 x 10(5), 4.2 x 10(6), 8.9 x 10(5) and 4.4 x 10(6), respectively. The magnetic behavior of C1b indicates a ferromagnetic one-dimensional solid.