School of Physical, Environmental and Mathematical Sciences, University College, University of New South Wales, Australian Defence Force Academy, Campbell, ACT 2600, Australia.
Dalton Trans. 2010 Feb 28;39(8):2078-86. doi: 10.1039/b921172a. Epub 2010 Jan 7.
A simpler method for the purification of cucurbit[10]uril (Q[10]) from the Q[10].Q[5] inclusion complex is reported. 1,12-Diaminododecane was used to displace Q[5], as opposed to the synthetic melamine derivative currently used. The binding of trans-{PtCl(NH(3))(2)}(2)(micro-NH(2)(CH(2))(8)NH(2)) (CT008) and {Ru(phen)(2)}(2)(micro-bb(5)) {phen = 1,10-phenanthroline; bb(5) = 1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane} (Rubb(5)) to Q[10] was studied by (1)H NMR and luminescence spectroscopy, cyclic voltammetry and molecular modelling. The (1)H NMR resonances of the methylene protons in the bridging ligands of CT008 and Rubb(5) exhibited large upfield chemical shift changes upon addition of Q[10]. These shifts are indicative of encapsulation of the bridging ligand within the Q[10] cavity, with the metal centres positioned outside the portals. (1)H NMR-based kinetics experiments with Rubb(5) show the presence of a portal-bound intermediate which progresses to a completely encapsulated inclusion complex only after many hours. The large metal centres of Rubb(5) provide a restriction to the movement of the complex in and out of the cavity and result in binding kinetics that are slow on both the (1)H NMR and biological timescales. This result was consistent with molecular modelling simulations. Cyclic voltammetry showed that the Ru(III/II) couple of free Rubb(5) appeared at +1.058 V (vs Ag/AgCl), with the first ligand reduction observed as a shoulder ( approximately -1.38 V) on the edge of the solvent (water) front. The Q[10]-bound complex exhibited an anodic shift of 48 mV compared to the free metal complex. Luminescence spectroscopy of the binding of Rubb(5) to Q[10] yielded an approximate binding constant of 1.9 x 10(9) M(-1). Although CT008 was encapsulated within Q[10], the inclusion complex was not soluble in several buffers at pH 7.0. These results indicate that Q[10] is not an effective delivery vehicle for dinuclear platinum(II) anti-cancer drugs; however, due to the strong binding affinity and slow exchange rates, Q[10] does show considerable promise as a delivery mechanism for controlled slow release of large dinuclear ruthenium(II) complexes.
从 Q[10].Q[5]包合物中纯化瓜环（Q[10]）的一种更简单的方法被报道。使用 1,12-二氨基十二烷取代 Q[5]，而不是目前使用的合成三聚氰胺衍生物。反式 -{PtCl(NH(3))(2)}(2)(micro-NH(2)(CH(2))(8)NH(2))（CT008）和{Ru(phen)(2)}(2)(micro-bb(5))（phen = 1,10-菲咯啉；bb(5) = 1,5-双[4(4'-甲基-2,2'-联吡啶)]戊烷）与 Q[10]的结合通过（1）H NMR 和发光光谱、循环伏安法和分子建模进行了研究。CT008 和 Rubb(5)中的桥联配体的亚甲基质子的（1）H NMR 共振在加入 Q[10]后表现出很大的向上场化学位移变化。这些位移表明桥联配体被包封在 Q[10]腔体内，金属中心位于入口之外。Rubb(5)的基于（1）H NMR 的动力学实验表明存在一个入口结合的中间物，只有在数小时后才能完全转化为完全包封的包合物。Rubb(5)的大金属中心限制了复合物在腔体内外的运动，导致结合动力学在（1）H NMR 和生物时间尺度上都很慢。这一结果与分子建模模拟一致。循环伏安法表明，游离 Rubb(5)的 Ru(III/II) 对出现在 +1.058 V（相对于 Ag/AgCl），第一个配体还原在溶剂（水）前沿的边缘观察到一个肩（约 -1.38 V）。与游离金属配合物相比，与 Q[10]结合的复合物表现出 48 mV 的阳极位移。Rubb(5)与 Q[10]结合的荧光光谱得到了一个近似的结合常数为 1.9 x 10(9) M(-1)。尽管 CT008 被包封在 Q[10]中，但包含物在 pH 7.0 的几种缓冲液中都不溶解。这些结果表明，Q[10]不是二核铂(II)抗癌药物的有效递药载体；然而，由于强结合亲和力和缓慢交换速率，Q[10]作为控制大双核钌(II)配合物缓慢释放的递药机制具有相当大的前景。
