Syntheses and crystal structures of tetracopper(II) complexes bridged by asymmetric N,N'-bis(substituted)oxamides: Molecular docking, DNA-binding and in vitro anticancer activity.
Two new tetranuclear copper(II) complexes of the formulae [Cu4(oxbm)2(phen)2](NO3)2⋅6H2O (1) and [Cu4(oxbpa)2(phen)2](ClO4)2·4H2O (2), where H3oxbm and H3oxbpa stand for N-(2-aminopropyl)-N'- (2-carboxylatophenyl)oxamide and N-hydroxypropyl-N'-(2-carboxylatophenyl)oxamide, respectively, and phen is 1,10-phenanthroline, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR and electronic spectrum studies, and X-ray single crystal diffraction. In the two tetracopper(II) complexes, the presence of the circular tetracopper(II) cations is assembled by a pair of cis-oxamido-bridged dicopper(II) units through carboxyl bridges, in which Cu1 is located in a distorted square-planar environment, while Cu2 is in a distorted square-pyramidal geometry. Numerous hydrogen bonds link complex 1 or 2 into a 2-D infinite network. The interactions of the two tetracopper(II) complexes with DNA are investigated both theoretically and experimentally, revealing that these tetracopper(II) complexes can interact with HS-DNA in the mode of intercalation, and complex 1 possesses stronger intercalating ability. The molecular docking of the two tetranuclear copper(II) complexes with the self-complementary DNA duplex of sequence d(ACCGACGTCGGT)2 facilitates the binding events. Cytotoxicity experiments indicate that the two tetracopper(II) complexes exhibit cytotoxic effects against human hepatocellular carcinoma cell SMMC-7721 and human lung adenocarcinoma cell A549. Interestingly, the cytotoxic activities of the two tetracopper(II) complexes are consistent with their DNA-binding abilities, following the order of 1>2. The main results suggest that different bridging ligands in tetracopper(II) complexes may play an important role in the DNA-binding properties and cytotoxic activities.
Marine Drug & Food Institute Ocean University of China, Qingdao, Shandong 266003, PR China.
Xue-Jie
XJ
Li
Kang
K
Zheng
Ling-Dong
LD
Wang
Yan-Tuan
YT
Li
Zhi-Yong
ZY
Wu
Cui-Wei
CW
Yan
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D010072:Oxamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010618:Phenanthrolines; D003300:Copper; D004247:DNA; D010072:Oxamic Acid; C008728:oxamide; C025205:1,10-phenanthroline
Crystal structures; DNA-binding properties; Dissymmetric N,N′-bis(substituted)-oxamides; In vitro anticancer activities; Molecular docking; Tetracopper(II) complexes