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

Abstract

Syntheses and crystal structures of four new hydrazone-based Cu(II) complexes, [{Cu(L¹)(H₂O)}2(µ-pyraz)](ClO₄)₂ (1), [{Cu(L¹)(OClO₃)}₂(µ-4,4'-bipy)] (2), [{Cu(L²H)}(µ-pyraz){Cu(L²H)(OClO₃)}].(ClO₄) (3) and [{Cu(L²)}₂(µ-bpe)] (4) [L¹H = condensation product of benzhydrazide and pyridine-2-carbaldehyde and L²H₂ = 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 π-π 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 10⁵ 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 (80 µM) even for 24 h as determined by different cell cytotoxicity assays. Preliminary results also showed that, at 20 µM, 1 could selectively induce apoptosis in leukemic cells without affecting normal lymphocytes.