title: Synthesis and crystal structure of new dicopper(II) complexes having asymmetric N,N'-bis(substituted)oxamides with DNA/protein binding ability: In vitro anticancer activity and molecular docking studies.
abstract: Two new dicopper(II) complexes bridged by asymmetric N,N'-bis(substituted)oxamide ligands: N-(5-chloro-2-hydroxyphenyl)-N'-[2-(dimethylamino)ethyl]oxamide (H3chdoxd) and N-hydroxypropyl-N'-(2-carboxylatophenyl)oxamide (H3oxbpa), and end-capped with 2,2'-bipyridine (bpy), namely [Cu2(ClO4)(chdoxd)(CH3OH)(bpy)]·H2O (1) and [Cu2(pic)(oxbpa)(CH3OH)(bpy)]·0.5CH3OH (2) (pic denotes picrate anion), have been synthesized and characterized by elemental analysis, molar conductivity measurement, IR and electronic spectral studies, and single-crystal X-ray diffraction. The X-ray diffraction analysis revealed that both the copper(II) ions bridged by the cis-oxamido ligands in dicopper(II) complexes 1 and 2 are all in square-pyramidal environments with the corresponding Cu⋯Cu separations of 5.194(3) and 5.1714(8)Å, respectively. In the crystals of the two complexes, there are abundant hydrogen bonds and π-π stacking interactions contributing to the supramolecular structure. The reactivities toward herring sperm DNA (HS-DNA) and bovine serum albumin (BSA) of the two complexes are studied both theoretically and experimentally, indicating that both the two complexes can interact with the DNA in the mode of intercalation, and effectively bind to BSA via the favored binding sites Trp134 for the complex 1 and Trp213 for the complex 2. Interestingly, the in vitro anticancer activities of the two complexes against the selected tumor cell lines are consistent with their DNA/BSA-binding affinities following the order of 1>2. The effects of coordinated counterions in the two complexes on DNA/BSA-binding ability and in vitro anticancer activity are 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: Ling
authors.initials: L
authors.lastname: Zhu
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: Key Laboratory of Marine Drug, Chinese Ministry of Education, Ocean University of China, 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: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism*; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012710:Serum Albumin, Bovine; D003300:Copper; D004247:DNA; D010072:Oxamic Acid; C008728:oxamide
keywords: Asymmetric N,N′-bis(substituted)oxamides; Crystal structure; DNA-binding; Dicopper(II) complexes; In vitro cytotoxicity; Molecular docking; Protein BSA interaction