Bugarcic Tijana, Habtemariam Abraha, Stepankova Jana, Heringova Pavla, Kasparkova Jana, Deeth Robert J, Johnstone Russell D L, Prescimone Alessandro, Parkin Andrew, Parsons Simon, Brabec Viktor, Sadler Peter J
School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, UK.
Inorg Chem. 2008 Dec 15;47(24):11470-86. doi: 10.1021/ic801361m.
The synthesis and characterization of ruthenium(II) arene complexes (eta(6)-arene)Ru(N,N)Cl, where N,N = 2,2'-bipyridine (bipy), 2,2'-bipyridine-3,3'-diol (bipy(OH)(2)) or deprotonated 2,2'-bipyridine-3,3'-diol (bipy(OH)O) as N,N-chelating ligand, arene = benzene (bz), indan (ind), biphenyl (bip), p-terphenyl (p-terp), tetrahydronaphthalene (thn), tetrahydroanthracene (tha) or dihydroanthracene (dha), are reported, including the X-ray crystal structures of [(eta(6)-tha)Ru(bipy)Cl][PF(6)] (1), [(eta(6)-tha)Ru(bipy(OH)O)Cl] (2) and [(eta(6)-ind)Ru(bipy(OH)(2))Cl][PF(6)] (8). Complexes 1 and 2 exibit CH (arene)/pi (bipy or bipy(OH)O) interactions. In the X-ray structure of protonated complex 8, the pyridine rings are twisted (by 17.31 degrees). In aqueous solution (pH = 2-10), only deprotonated (bipy(OH)O) forms are present. Hydrolysis of the complexes was relatively fast in aqueous solution (t(1/2) = 4-15 min, 310 K). When the arene is biphenyl, initial aquation of the complexes is followed by partial arene loss. Complexes with arene = tha, thn, dha, ind and p-terp, and deprotonated bipyridinediol (bipy(OH)O) as chelating ligands, exhibited significant cytotoxicity toward A2780 human ovarian and A549 human lung cancer cells. Complexes [(eta(6)-bip)Ru(bipy(OH)O)Cl] (7) and [(eta(6)-bz)Ru(bipy(OH)O)Cl] (5) exhibited moderate cytotoxicity toward A2780 cells, but were inactive toward A549 cells. These activity data can be contrasted with those of the parent bipyridine complex [(eta(6)-tha)Ru(bipy)Cl][PF(6)] (1) which is inactive toward both A2780 ovarian and A549 lung cell lines. DFT calculations suggested that hydroxylation and methylation of the bipy ligand have little effect on the charge on Ru. The active complex [(eta(6)-tha)Ru(bipy(OH)O)Cl] (2) binds strongly to 9-ethyl-guanine (9-EtG). The X-ray crystal structure of the adduct [(eta(6)-tha)Ru(bipy(OH)O)(9-EtG-N7)][PF(6)] shows intramolecular CH (arene)/pi (bipy(OH)O) interactions and DFT calculations suggested that these are more stable than arene/9-EtG pi-pi interactions. However [(eta(6)-ind)Ru(bipy(OH)(2))Cl][PF(6)] (8) and [(eta(6)-ind)Ru(bipy)Cl][PF(6)] (16) bind only weakly to DNA. DNA may therefore not be the major target for complexes studied here.
报道了钌（II）芳烃配合物(η⁶ - 芳烃)Ru(N,N)Cl的合成与表征，其中N,N = 2,2'-联吡啶（bipy）、2,2'-联吡啶 - 3,3'-二醇（bipy(OH)₂）或去质子化的2,2'-联吡啶 - 3,3'-二醇（bipy(OH)O）作为N,N - 螯合配体，芳烃 = 苯（bz）、茚满（ind）、联苯（bip）、对三联苯（p - terp）、四氢萘（thn）、四氢蒽（tha）或二氢蒽（dha），包括[(η⁶ - tha)Ru(bipy)Cl][PF₆]（1）、[(η⁶ - tha)Ru(bipy(OH)O)Cl]（2）和[(η⁶ - ind)Ru(bipy(OH)₂)Cl][PF₆]（8）的X射线晶体结构。配合物1和2表现出CH（芳烃）/π（bipy或bipy(OH)O）相互作用。在质子化配合物8的X射线结构中，吡啶环发生扭曲（扭曲角度为17.31°）。在水溶液（pH = 2 - 10）中，仅存在去质子化的（bipy(OH)O）形式。配合物在水溶液中的水解相对较快（半衰期t₁/₂ = 4 - 15分钟，310K）。当芳烃为联苯时，配合物的初始水合作用之后是部分芳烃损失。以tha、thn、dha、ind和p - terp为芳烃，去质子化的联吡啶二醇（bipy(OH)O）作为螯合配体的配合物，对A2780人卵巢癌细胞和A549人肺癌细胞表现出显著的细胞毒性。配合物[(η⁶ - bip)Ru(bipy(OH)O)Cl]（7）和[(η⁶ - bz)Ru(bipy(OH)O)Cl]（5）对A2780细胞表现出中等细胞毒性，但对A549细胞无活性。这些活性数据可与母体联吡啶配合物[(η⁶ - tha)Ru(bipy)Cl][PF₆]（1）的数据形成对比，后者对A2780卵巢癌细胞系和A549肺癌细胞系均无活性。密度泛函理论（DFT）计算表明，bipy配体的羟基化和甲基化对Ru上电荷的影响很小。活性配合物[(η⁶ - tha)Ru(bipy(OH)O)Cl]（2）与9 - 乙基鸟嘌呤（9 - EtG）强烈结合。加合物[(η⁶ - tha)Ru(bipy(OH)O)(9 - EtG - N7)][PF₆]的X射线晶体结构显示分子内CH（芳烃）/π（bipy(OH)O）相互作用，DFT计算表明这些相互作用比芳烃/9 - EtG π - π相互作用更稳定。然而，[(η⁶ - ind)Ru(bipy(OH)₂)Cl][PF₆]（8）和[(η⁶ - ind)Ru(bipy)Cl][PF₆]（16）与DNA的结合较弱。因此，DNA可能不是此处所研究配合物的主要作用靶点。
