Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560012, India.
Inorg Chem. 2010 Feb 1;49(3):849-59. doi: 10.1021/ic900701s.
Oxovanadium(IV) complexes [VO(L)(B)]Cl(2) (1-3), where L is bis(2-benzimidazolylmethyl)amine and B is 1,10-phenanthroline (phen), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) or dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been prepared, characterized, and their photo-induced DNA and protein cleavage activity studied. The photocytotoxicity of complex 3 has been studied using adenocarcinoma A549 cells. The phen complex 1, structurally characterized by single-crystal X-ray crystallography, shows the presence of a vanadyl group in six-coordinate VON(5) coordination geometry. The ligands L and phen display tridentate and bidentate N-donor chelating binding modes, respectively. The complexes exhibit a d-d band near 740 nm in 15% DMF-Tris-HCl buffer (pH 7.2). The phen and dpq complexes display an irreversible cathodic cyclic voltammetric response near -0.8 V in 20% DMF-Tris-HCl buffer having 0.1 M KCl as supporting electrolyte. The dppz complex 3 exhibits a quasi-reversible voltammogram near -0.6 V (vs SCE) that is assignable to the V(IV)-V(III) couple. The complexes bind to calf thymus DNA giving binding constant values in the range of 6.6 x 10(4)-2.9 x 10(5) M(-1). The binding site size, thermal melting and viscosity binding data suggest DNA surface and/or groove binding nature of the complexes. The complexes show poor "chemical nuclease" activity in dark in the presence of 3-mercaptopropionic acid or hydrogen peroxide. The dpq and dppz complexes are efficient photocleavers of plasmid DNA in UV-A light of 365 nm via a mechanistic pathway that involves formation of both singlet oxygen and hydroxyl radicals. The complexes show significant photocleavage of DNA in near-IR light (>750 nm) via hydroxyl radical pathway. Among the three complexes, the dppz complex 3 shows significant BSA and lysozyme protein cleavage activity in UV-A light of 365 nm via hydroxyl radical pathway. The dppz complex 3 also exhibits photocytotoxicity in non-small cell lung carcinoma/human lung adenocarcinoma A549 cells giving IC(50) value of 17 microM in visible light (IC(50) = 175 microM in dark).
[VO(L)(B)]Cl(2) (1-3)型氧钒(IV)配合物已被制备、表征，并研究了其对 DNA 和蛋白质的光诱导切割活性。使用腺癌细胞 A549 研究了配合物 3 的光细胞毒性。通过单晶 X 射线晶体学结构表征的 phen 配合物 1 显示出六配位 VON(5)配位几何结构中的钒氧基基团。配体 L 和 phen 分别呈现出三齿和双齿 N-供体螯合结合模式。在 15% DMF-Tris-HCl 缓冲液(pH 7.2)中，这些配合物在近 740nm 处显示出 d-d 带。在 20% DMF-Tris-HCl 缓冲液中，phen 和 dpq 配合物在 0.1 M KCl 作为支持电解质的情况下，在近-0.8V 处显示出不可逆的阴极循环伏安响应。dppz 配合物 3 在近-0.6V(相对于 SCE)处表现出准可逆的伏安图，可归因于 V(IV)-V(III)偶。配合物与小牛胸腺 DNA 结合，给出结合常数值在 6.6 x 10(4)-2.9 x 10(5) M(-1)范围内。结合位点大小、热融解和粘度结合数据表明，这些配合物具有 DNA 表面和/或沟结合性质。在 3-巯基丙酸或过氧化氢存在下，这些配合物在黑暗中表现出较差的“化学核酸酶”活性。dpq 和 dppz 配合物在 365nm 的 UV-A 光下通过涉及形成单线态氧和羟基自由基的机制途径有效切割质粒 DNA。这些配合物在近红外光(>750nm)下通过羟基自由基途径显著切割 DNA。在这三种配合物中，dppz 配合物 3 在 365nm 的 UV-A 光下通过羟基自由基途径显示出对 BSA 和溶菌酶蛋白的显著切割活性。dppz 配合物 3 在非小细胞肺癌/人肺腺癌细胞 A549 中也表现出光细胞毒性，在可见光下的 IC(50)值为 17μM(在黑暗下的 IC(50)值为 175μM)。
