Rajendiran Venugopal, Murali Mariappan, Suresh Eringathodi, Sinha Sarika, Somasundaram Kumaravel, Palaniandavar Mallayan
School of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
Dalton Trans. 2008 Jan 7(1):148-63. doi: 10.1039/b710578a.
A series of mixed ligand ruthenium(II) complexes Ru(pdto)(diimine)2/(PF6)2 1-3 and Ru(bbdo)(diimine), 4-6, where pdto is 1,8-bis(pyrid-2-yl)-3,6-dithiooctane, bbdo is 1,8-bis(benzimidazol-2-yl)-3,6-dithiooctane and diimine is 1,10-phenanthroline (phen), dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been isolated and characterised by analytical and spectral methods. The complexes Ru(pdto)(phen)2 la, Ru(pdto)(dpq)(Cl 2a, Ru(bbdo)(phen)2 4a and Ru(bbdo)(dpq)2 5 have been structurally characterized and their coordination geometries around ruthenium(II) are described as distorted octahedral. In la, 4a and 5 the two thioether sulfur and two py/bzim nitrogen atoms of the tetradentate pdto/bbdo ligand are folded around Ru(II) to give predominantly a "cis-alpha" configuration. (I)H NMR spectral data of the complexes support this configuration in solution. In Ru(pdto)(dpq)Cl 2a with a distorted octahedral coordination geometry, one of the two py nitrogens of pdto is not coordinated. The DNA binding constants (Kb: 2, 2.00 +/- 0.02 x 10(4) M(-1), s = 1.0; 3, 3.00 +/- 0.01 x 10(6) M(-1), s = 1.3) determined by absorption spectral titrations of the complexes with CT DNA reveal that 3 interacts with DNA more tightly than 2 through partial intercalation of the extended planar ring of coordinated dppz with the DNA base stack. The DNA binding affinities of the complexes increase with increase in the number of planar aromatic rings in the co-ligand, and on replacing both the py moieties in pdto complexes (1-3) by bzim moieties to give bbdo complexes (4-6). Upon interaction with CT DNA the complexes 1, 2, 5 and 6 show a decrease in anodic current in the cyclic voltammograms. On the other hand, interestingly, 3 and 4 show an increase in anodic current suggesting their involvement in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 6 alters the superhelicity of DNA upon binding with supercoiled pBR322 DNA. The cytotoxicities of the dppz complexes 3 and 6, which avidly bind to DNA, have been examined by screening them against cell lines of different cancer origins. It is noteworthy that 6 exhibits selectivity with higher cytotoxicity against the melanoma cancer cell line (A375) than other cell lines, potency approximately twice that of cisplatin and toxicity to normal cells 3 and 90 times less than cisplatin and adriamycin respectively.
一系列混合配体钌（II）配合物Ru(pdto)(二亚胺)2/(PF6)2 1 - 3和Ru(bbdo)(二亚胺) 4 - 6已被分离出来，其中pdto是1,8 - 双（吡啶 - 2 - 基）- 3,6 - 二硫代辛烷，bbdo是1,8 - 双（苯并咪唑 - 2 - 基）- 3,6 - 二硫代辛烷，二亚胺是1,10 - 菲咯啉（phen）、二吡啶并[3,2 - d:2',3' - f] - 喹喔啉（dpq）和二吡啶并[3,2 - a:2',3' - c]菲嗪（dppz），并通过分析和光谱方法进行了表征。配合物Ru(pdto)(phen)2 1a、Ru(pdto)(dpq)Cl 2a、Ru(bbdo)(phen)2 4a和Ru(bbdo)(dpq)2 5已进行了结构表征，其围绕钌（II）的配位几何形状被描述为扭曲八面体。在1a、4a和5中，四齿pdto/bbdo配体的两个硫醚硫原子和两个吡啶/苯并咪唑氮原子围绕Ru(II)折叠，主要形成“顺式 - α”构型。配合物的（1）H NMR光谱数据支持溶液中的这种构型。在具有扭曲八面体配位几何形状的Ru(pdto)(dpq)Cl 2a中，pdto的两个吡啶氮原子之一未配位。通过配合物与CT DNA的吸收光谱滴定法测定的DNA结合常数（Kb：2，2.00±0.02×10(4) M(-（1）)，s = 1.0；（（3）），3.00±0.01×10(6) M(-（1）)，s = 1.3）表明，（3）通过配位的dppz的扩展平面环与DNA碱基堆积的部分插入，比（2）与DNA的相互作用更紧密。配合物的DNA结合亲和力随着共配体中平面芳香环数量的增加而增加，并且在将pdto配合物（1 - 3）中的两个吡啶部分都替换为苯并咪唑部分以得到bbdo配合物（4 - 6）时也增加。与CT DNA相互作用时，配合物1、2、5和6在循环伏安图中阳极电流降低。另一方面，有趣的是，（3）和（4）显示阳极电流增加，表明它们参与电催化鸟嘌呤氧化。有趣的是，在所有配合物中，只有（6）与超螺旋pBR322 DNA结合时会改变DNA的超螺旋度。通过针对不同癌症起源的细胞系进行筛选，研究了与DNA紧密结合的dppz配合物（3）和（6）的细胞毒性。值得注意的是，（6）表现出选择性，对黑色素瘤癌细胞系（A375）的细胞毒性高于其他细胞系，效力约为顺铂的两倍，对正常细胞的毒性分别比顺铂和阿霉素低3和90倍。
