School of Biomolecular and Physical Sciences, Griffith University, Brisbane, 4111, Queensland, Australia.
Dalton Trans. 2009 Dec 28(48):10861-70. doi: 10.1039/b912281h. Epub 2009 Oct 26.
The 1 : 2 adducts of copper(I) halides with 1,2-bis(2-pyridylphosphino)ethane (d2pype) have been synthesized and solution properties characterized by variable temperature (1)H, (31)P and (65)Cu NMR spectroscopy. Single-crystal structure determinations for the chloride, bromide and iodide complexes show these to crystallize from acetonitrile in the triclinic space group P1 as isostructural centrosymmetric dimers [(d2pype)Cu(mu-d2pype)(2)Cu(d2pype)]X(2).(solvent) with a approximately 12.6, b approximately 12.7, c approximately 15.3 A, alpha approximately 84, beta approximately 67, gamma approximately 84 degrees. In contrast to the analogous AuCl:2(d2pype) and AgNO(3):2(d2pype) adducts, in solution these CuX:2(d2pype) adducts (where X = Cl, Br and I) exist almost exclusively as bis-chelated monomeric [Cu(d2pype)(2)]X; evidence for an equilibrium between monomeric and dimeric forms is detected only for the CuCl adduct in methanol. Cytotoxicity studies in two human breast cancer lines and two matched liver progenitor cell lines indicate that [Cu(d2pype)(2)]Cl is non selectively toxic to both non-tumourigenic and tumourigenic cells. However, the analogous Au(I) compound [Au(d2pype)(2)]Cl, is toxic to highly tumourigenic cells and more selective in its toxicity to tumourigenic cells compared to non-tumourigenic cells. The significance of these results to the further development of selective, mitochondria-targeted, Au(I) antitumour complexes is discussed.
铜（I）卤化物与 1,2-双（2-吡啶基膦）乙烷（d2pype）的 1:2 加合物已被合成，并通过变温（1）H、（31）P 和（65）Cu NMR 光谱法对其溶液性质进行了表征。对于氯化物、溴化物和碘化物配合物的单晶结构测定表明，这些配合物从乙腈中以三斜晶系空间群 P1 结晶为等结构的中心对称二聚体[(d2pype)Cu(mu-d2pype)(2)Cu(d2pype)]X(2).(溶剂)，a 约为 12.6，b 约为 12.7，c 约为 15.3 A，alpha 约为 84，beta 约为 67，gamma 约为 84 度。与类似的 AuCl:2(d2pype)和 AgNO(3):2(d2pype)加合物相反，在溶液中，这些 CuX:2(d2pype)加合物（其中 X = Cl、Br 和 I）几乎仅以双螯合单体[Cu(d2pype)(2)]X 的形式存在；仅在甲醇中检测到 CuCl 加合物单体和二聚体形式之间的平衡。在两种人乳腺癌系和两种匹配的肝祖细胞系中的细胞毒性研究表明，[Cu(d2pype)(2)]Cl 对非肿瘤细胞和肿瘤细胞均具有非选择性毒性。然而，类似的 Au(I)化合物[Au(d2pype)(2)]Cl 对高度肿瘤细胞具有毒性，并且与非肿瘤细胞相比，对肿瘤细胞的毒性更具选择性。讨论了这些结果对进一步开发选择性、靶向线粒体的 Au(I)抗肿瘤配合物的意义。
