Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
Dalton Trans. 2009 Dec 28(48):10806-12. doi: 10.1039/b915357h. Epub 2009 Oct 30.
The series of complexes cis-Rh(2)(mu-O(2)CCH(3))(2)(dppn)(L), where dppn = benzo[i]dipyrido[3,2-a:2',3'-c] phenazine, and L = bpy (2,2'-bipyridine) (1), phen (1,10-phenanthroline) (2), dpq (dipyrido[3,2-f:2',3'-h]quinoxaline) (3), dppz (dipyrido[3,2-a:2',3'-c]phenazine) (4), and dppn (5) were synthesized and their effect on the human cancer cells HeLa and COLO-316 was monitored. Complexes 1 and 2 interact with DNA through intercalation, whereas compounds 3-5 bind only electrostatically. It was found that the dirhodium complex 4 is the most effective compound at inhibiting cell viability of the human cancer cells HeLa and COLO-316. A general conclusion is that the hydrophobicity of the compounds correlates with their in cellulo activity in both cell lines. The ability of the compounds to reach nuclear DNA and form adducts was explored using the comet assay. The results indicate that compounds 1-5 either do not form adducts with DNA that are detrimental to the cell or that they are successfully repaired by the cellular machinery. The results of an annexin V assay indicate that compounds 1-4 trigger apoptosis, whereas compound 5 clearly does not. These findings are significant because they support the contention that dirhodium complexes can be tuned to direct their effect to cellular targets other than nuclear DNA.
该系列配合物顺式-[Rh(2)(mu-O(2)CCH(3))(2)(dppn)(L)] (2+)，其中 dppn = 苯并[i]二吡啶并[3,2-a:2',3'-c]吩嗪，和 L = bpy(2,2'-联吡啶)(1)，phen(1,10-菲咯啉)(2)，dpq(二吡啶并[3,2-f:2',3'-h]喹喔啉)(3)，dppz(二吡啶并[3,2-a:2',3'-c]吩嗪)(4)，和 dppn(5)被合成，其对人癌细胞 HeLa 和 COLO-316 的影响被监测。配合物 1 和 2 通过嵌入与 DNA 相互作用，而化合物 3-5 仅通过静电结合。发现二钌配合物 4 是抑制人癌细胞 HeLa 和 COLO-316 细胞活力的最有效化合物。一个总的结论是，化合物的疏水性与其在两种细胞系中的细胞内活性相关。使用彗星试验探索了化合物到达核 DNA 并形成加合物的能力。结果表明，化合物 1-5 要么不与 DNA 形成加合物，对细胞没有损害，要么被细胞机制成功修复。Annexin V 试验的结果表明，化合物 1-4 触发细胞凋亡，而化合物 5 则显然不会。这些发现意义重大，因为它们支持了这样一种观点，即二钌配合物可以被调谐以将其作用指向除核 DNA 以外的细胞靶标。
