title: Five water-soluble zwitterionic copper(II)-carboxylate polymers: role of dipyridyl coligands in enhancing the DNA-binding, cleaving and anticancer activities.
abstract: Five water-soluble zwitterionic copper-carboxylate polymers were prepared from the reaction of N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide (H3CmdcpBr) with Cu(NO3)2 in the presence of NaOH by modulating the temperature, solvent and ancillary dipyridyl ligands. These complexes include a 1D ladder-shaped polymer {[Cu3(Cmdcp)2(OH)2(H2O)2]·H2O}n () formed in H2O at room temperature, and a 2D network polymer {[Cu(Cmdcp) (H2O)2]·2H2O}n () isolated in H2O at 135 °C. At 100 °C in H2O/DMF, the same reaction in the presence of an additional 2,2'-bipyridine (bipy) gave a 2D zwitterionic complex {[Cu(Cmdcp)(bipy)]·3H2O}n () together with a 1D double-stranded polymer {[Cu(Cmdcp)(H2O)2]·H2O}n () as a minor product. The replacement of bipy with phenanthroline (phen) afforded a 1D zigzag polymer chain {[Cu(Cmdcp)(phen)(H2O)]2·9H2O}5 (). All these complexes were characterized by IR, elemental analyses and single crystal X-ray crystallography. Agarose gel electrophoresis (GE) and ethidium bromide (EB) displacement experiments indicated that complex exhibited the highest pBR322 DNA cleaving ability with the catalytic efficiency (kmax/KM) of 14.80 h(-1) mM(-1) and the highest binding affinity toward calf-thymus DNA. The MTT assay indicated that complex showed significant inhibitory activity toward the proliferation of several tumor cells. Its IC50 value was at micromolar level and lower than those of cisplatin and complexes , especially toward resistant lung adenocarcinoma cell A549.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, P. R. China. jxchen@smu.edu.cn whchen@smu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Tang
authors.forename: Shui-Ping
authors.initials: SP
authors.lastname: Yang
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Li
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Zhao
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Chen
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry* / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008958:Models, Molecular; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D011108:Polymers; D014867:Water; D015082:2,2'-Dipyridyl; D003300:Copper; D004247:DNA; C427203:calf thymus DNA