title: 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(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.
authors.affiliation: Department of Chemistry, Jadavpur University, Kolkata, 700 032, India.
authors.forename: Sambuddha
authors.initials: S
authors.lastname: Banerjee
authors.forename: Susmita
authors.initials: S
authors.lastname: Mondal
authors.forename: Soma
authors.initials: S
authors.lastname: Sen
authors.forename: Saurabh
authors.initials: S
authors.lastname: Das
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes
authors.forename: Corrado
authors.initials: C
authors.lastname: Rizzoli
authors.forename: Cédric
authors.initials: C
authors.lastname: Desplanches
authors.forename: Chitra
authors.initials: C
authors.lastname: Mandal
authors.forename: Samiran
authors.initials: S
authors.lastname: Mitra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D053837:DNA Cleavage; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D007938:Leukemia / Q000188:drug therapy*; D008214:Lymphocytes / Q000187:drug effects*; D008968:Molecular Conformation; D011725:Pyridines / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D011725:Pyridines; C432864:pyridine-2-carbaldehyde; D003300:Copper; D004247:DNA; C034306:4,4'-bipyridyl