TRIS(PHENANTHROLINE)RUTHENIUM(II) - STEREOSELECTIVITY IN BINDING TO DNA
TRIS(PHENANTHROLINE)RUTHENIUM(II) - STEREOSELECTIVITY IN BINDING TO DNA
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DOI：
10.1021/ja00319a043
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发表时间：
1984-01-01
影响因子：
15
通讯作者：
GOLDBERG, JM
中科院分区：
文献类型：
--
作者：
BARTON, JK;DANISHEFSKY, AT;GOLDBERG, JM
手性配合物三邻菲咯啉钌（II）（phen）3 Ru 2+通过插层方式与DNA结合，并发现与右手双链体结合具有对映体选择性，光谱、流体力学和结合参数与插层结合模式一致。减色性表示金属与配体电荷转移带的强度降低17%，并且增强的发光伴随着与双链体的结合。对于给定的钌浓度，发现δ的发光更强。在DNA的存在下，与λ异构体相比，异构体。实验激发态寿命的（phen）3Ru 2+异构体的DNA的存在下增加相同。因此，较高的发射强度反映了Δ的较大亲和力。螺旋的异构体。对双链体的对映体偏好在封闭环状DNA的凝胶电泳实验中也是明显的。两种异构体都解旋和重绕超螺旋pColEl DNA，但对于给定的添加钌浓度，更多的双链体解旋是明显的，（phen）3Ru 2+。通过平衡透析获得的外消旋（phen）3Ru 2+与小牛胸腺DNA的结合等温线产生了固有的结合常数，K（0）= 6.2 × 10 - 6。103 M-1，并且显示金属络合物在饱和时占据4个碱基对位点。此外，透析液在光学上富含不太受欢迎的λ。对映体。Z-DNA对外消旋（phen）3Ru 2+的透析不导致类似的光学富集。结果都是一致的嵌入模型，其中的立体选择性是基于不同的空间相互作用之间的nonintercalated菲咯啉配体的手性复合物和右手的DNA磷酸骨架。观察到的对映体选择性说明了螺旋对称性对药物识别的重要性，并提供了一条路线，设计探针的右手和左手的DNA。
The chiral complexes tris(phenanthroline)ruthenium(II), (phen)3Ru2+, bind to DNA by intercalation, and enantiomeric selectivity in binding to a right-handed duplex is found. Spectroscopic, hydrodynamic and binding parameters are consistent with the intercalative mode of association. Hypochromicity represented a 17% decrease in intensity in the metal to ligand charge-transfer band and enhanced luminescence accompany binding to the duplex. For a given ruthenium concentration, greater luminescence is found for the .delta. isomer in the presence of DNA than for the .LAMBDA. isomer. The experimental excited-state lifetimes of (phen)3Ru2+ isomers increased identically in the presence of DNA. Therefore the higher emission intensity reflects the larger affinity of the .DELTA. isomer for the helix. An enantiomeric preference for the duplex is evident also in gel electrophoresis experiments with closed circular DNA. Both isomers unwind and rewind supercoiled pColEl DNA, but for a given added ruthenium concentration, more duplex unwinding is apparent with .DELTA.-(phen)3Ru2+. Binding isotherms for racemic (phen)3Ru2+ with calf thymus DNA, obtained by equilibrium dialysis, yield an intrinsic binding constant, K(0) = 6.2 .times. 103 M-1, and show the metal complex to occupy a 4 base-pair site at saturation. In addition, dialysates are optically enriched in the less favored .LAMBDA. enantiomer. Dialysis of Z-DNA against racemic (phen)3Ru2+ does not lead to similar optical enrichment. The results are all consistent with an intercalative model where the stereoselectivity is based upon the different steric interactions between the nonintercalated phenanthroline ligands of the chiral complex and the right-handed DNA phosphate backbone. The enantiomeric selectivity observed illustrates the importance of helix symmetry to drug recognition and provides a route to design probes for right- and left-handed DNA.