Four new dinuclear Cu(II) hydrazone complexes using various organic spacers: syntheses, crystal structures, DNA binding and cleavage studies and selective cell inhibitory effect towards leukemic and normal lymphocytes

Syntheses and crystal structures of four new hydrazone-based Cu(II) complexes, [{Cu(L-1)(H2O)}(2)(mu-pyraz)](ClO4)(2) (1), [{Cu(L-1)(OClO3)}(2)(mu-4,4'-bipy)] (2), [{Cu((LH)-H-2)}(mu-pyraz){Cu((LH)-H-2)(OClO3)}]center dot(ClO4) (3) and [{Cu(L-2)}(2)(mu-bpe)] (4) [(LH)-H-1 = condensation product of benzhydrazide and pyridine-2-carbaldehyde and (LH2)-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 1 and 3 form strong intermolecular H-bonding to form sheets of interconnected ions, whereas 2 forms sheets of dinuclear chains through pi-pi interactions; in 4, molecules are linked only through van der Waals interactions. The variable-temperature magnetic moment studies reveal that 1 and 3 show antiferromagnetic coupling between the Cu(II) centers at lower temperatures. The binding ability of 1 with calf thymus DNA [CT-DNA] is reported using various spectroscopic studies (UV-Vis titration, circular dichroism and fluorescence). The binding constants of 1 with CT-DNA, as calculated by different methodologies, are of the order of 10(5) M-1. The mode of interaction between 1 and CT-DNA has been predicted using circular dichroic (CD) spectroscopy, where it has been shown that 1 most probably interacts with DNA via intercalation between the base pairs leading to a change in B-DNA conformation. 1 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 1 (similar to 80 mu M) even for 24 h as determined by different cell cytotoxicity assays. Preliminary results also showed that, at 20 mu M, 1 could selectively induce apoptosis in leukemic cells without affecting normal lymphocytes.