title: Synthesis and structure elucidation of new μ-oxamido-bridged dicopper(II) complexes showing in vitro anticancer activity: Evaluation of DNA/protein-binding properties by experiment and molecular docking.
abstract: Two new μ-oxamido-bridged dicopper(II) complexes formulated as [Cu2(hmdoxd)(H2O)(Me2bpy)]-(ClO4)·DMF (1) and [Cu2(hmdoxd)(bpy)](ClO4)·CH3OH (2), where H3hmdoxd is N-(2-hydroxy-5-methylphenyl)-N'-[2-(dimethylamino)ethyl]oxamide; Me2bpy and bpy stand for 4,4'-dimethyl-2,2'-bipyridine and 2,2'-bipyridine, respectively, were synthesized and structurally characterized. The single-crystal X-ray diffraction analysis reveals that the copper(II) ions in complexes 1 and 2 are bridged by the cis-hmdoxd(3-) with corresponding Cu⋯Cu separations of 5.1596(6) and 5.1562(6) Å, respectively, in which the endo- and exo-copper(II) ions are located in square-planar and square-pyramidal geometries, respectively, for 1, and square-planar environments for 2. In the crystals of the two complexes, there are abundant hydrogen bonds and π-π stacking interactions contributing to the supramolecular structure. The DNA/protein-binding property of the two complexes are studied both theoretically and experimentally, indicating that complexes 1 and 2 can interact with DNA in the mode of intercalation and partial intercalation, respectively, and effectively bind to protein BSA via the favored binding sites Trp213 for 1 and Trp134 for 2. In vitro anticancer activities showed that the two complexes are active against the selected tumor cell lines, and the anticancer activities are consistent with their DNA/protein-binding affinities following the order of 1>2. The effect of the hydrophobicity of both the bridging and terminal ligands in the dicopper(II) complexes on DNA/protein-binding events and in vitro anticancer activities is preliminarily discussed.
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China. Electronic address: yantuanli@ouc.edu.cn.
authors.forename: Yan-Tuan
authors.initials: YT
authors.lastname: Li
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wu
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China. Electronic address: cuiweiyan@ouc.edu.cn.
authors.forename: Cui-Wei
authors.initials: CW
authors.lastname: Yan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D062105:Molecular Docking Simulation
chemical_list: D000970:Antineoplastic Agents; D003300:Copper
keywords: Cytotoxicity; DNA/protein-binding property; Hydrophobicity; Molecular docking; μ-Oxamido-bridged dicopper(II) complexes