Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43214, USA.
Philos Trans A Math Phys Eng Sci. 2013 Jun 17;371(1995):20120135. doi: 10.1098/rsta.2012.0135. Print 2013 Jul 28.
The cyclometallated Ru(II) complexes cis-Ru(phpy)(phen)(CH3CN)2 (1; phpy(-)=deprotonated 2-phenylpyridine, phen=1,10-phenanthroline) and cis-Ru(phpy)(bpy)(CH3CN)2 (2; bpy=2,2'-bipyridine) were investigated as potential agents for photodynamic therapy. The presence of phpy(-) in the coordination sphere results in a red-shift of the Ru→phen and Ru→bpy metal-to-ligand charge transfer of 1 and 2, respectively, thus improving the tissue penetration of light while maintaining the efficient photo-induced ligand exchange required for DNA binding. The 14-fold enhancement of OVCAR-5 cell death that occurs upon irradiation with 690 nm light can be attributed to photo-aquation. The role of glutathione (GSH) on the toxicity of the complex was also explored. Complexes 1 and 2 undergo ligand substitution in the presence of GSH in the dark, such that the metal may covalently bind to biomolecules. The combination of photo-induced ligand exchange and GSH-facilitated ligand exchange may explain the observed cytotoxicity.
顺式-Ru(phpy)(phen)(CH3CN)2（1；phpy(-)=去质子化的 2-苯基吡啶，phen=1,10-菲咯啉）和顺式-Ru(phpy)(bpy)(CH3CN)2（2；bpy=2,2'-联吡啶）是两种被研究用作光动力疗法的潜在药物的环金属化 Ru(II) 配合物。在配位球中存在 phpy(-) 会导致 1 和 2 的 Ru→phen 和 Ru→bpy 金属到配体电荷转移分别红移，从而提高光的组织穿透力，同时保持与 DNA 结合所需的高效光诱导配体交换。在 690nm 光照射下，OVCAR-5 细胞死亡增加了 14 倍，这可以归因于光致水合作用。还探索了谷胱甘肽 (GSH) 对配合物毒性的作用。在黑暗中，配合物 1 和 2 会在 GSH 的存在下发生配体取代，使得金属可能与生物分子发生共价结合。光诱导配体交换和 GSH 促进的配体交换的结合可能解释了观察到的细胞毒性。
