Department of Chemical Sciences, University of Padova, Italy.
Dalton Trans. 2011 Nov 28;40(44):11885-95. doi: 10.1039/c1dt11504a. Epub 2011 Oct 5.
During the last decade, our research group has prepared a number of metal dithiocarbamato derivatives of Pt, Pd and Au that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Furthermore, we have already published the synthesis, characterization and in vitro cytotoxicity studies of novel ruthenium(III) dithiocarbamato complexes such as [RuL(3)] monomers (11) and α-[Ru(2)L(5)]Cl dimers (12) with five different dithiocarbamate ligands. As both the monomer and the dinuclear complexes have shown significant antitumor activity in different human tumor cell lines, we decided to widen the characterization studies and to analyse thoroughly their behavior in physiological-like medium by UV-visible and CD spectroscopy. In the present paper we report on the crystal structure of [Ru(DMDT)(3)], [Ru(PDT)(3)] and [Ru(ESDT)(3)] complexes and we determine the spin state of the paramagnetic Ru(III) by means of Evans' method. Then, we discuss in detail the UV-visible spectral data of the complexes in different medium. All the studied complexes are stable in dimethyl sulfoxide, and show low solubility in phosphate buffered saline solution, particularly the monomer species, even at low concentration, while increased solubility for both types of complexes have been found in the presence of bovine serum albumin (BSA). Moreover, no changes on the coordination sphere of the metal, as well as no direct interaction between the BSA protein and the complex have been identified by UV-visible spectroscopy. However, some conformational changes on the BSA structure, induced by the ruthenium(III) complexes have been confirmed by CD spectroscopy, indicating a probable secondary electrostatic interaction between the metal complex and the peptide. In addition, no significant interaction has been demonstrated with the components of Dulbecco's Modified Eagle's Medium, used for the in vitro assays.
在过去的十年中，我们的研究小组已经制备了一些金属二硫代氨基甲酸盐的铂、钯和金的衍生物，这些衍生物预计将具有顺铂的主要特征，同时具有更高的活性、更好的选择性和生物利用度，以及更低的副作用。此外，我们已经发表了新型钌(III)二硫代氨基甲酸盐配合物如[RuL(3)]单体(11)和α-[Ru(2)L(5)]Cl 二聚体(12)的合成、表征和体外细胞毒性研究，这些配合物具有五种不同的二硫代氨基甲酸盐配体。由于单体和双核配合物在不同的人肿瘤细胞系中都表现出显著的抗肿瘤活性，我们决定扩大其表征研究，并通过紫外-可见和 CD 光谱法在生理样介质中对其行为进行深入分析。在本文中，我们报道了[Ru(DMDT)(3)]、[Ru(PDT)(3)]和[Ru(ESDT)(3)]配合物的晶体结构，并通过 Evans 法确定了顺磁性 Ru(III)的自旋态。然后，我们详细讨论了配合物在不同介质中的紫外-可见光谱数据。所有研究的配合物在二甲亚砜中稳定，在磷酸盐缓冲盐水溶液中的溶解度较低，特别是单体物种，即使在低浓度下，而在牛血清白蛋白(BSA)存在下，两种类型的配合物的溶解度都有所增加。此外，通过紫外-可见光谱法未发现金属配合物的配位球发生变化，也未发现 BSA 蛋白与配合物之间存在直接相互作用。然而，CD 光谱证实了一些 BSA 结构的构象变化，这些变化是由钌(III)配合物引起的，表明金属配合物与肽之间可能存在二次静电相互作用。此外，与用于体外测定的 Dulbecco's Modified Eagle's Medium 的成分也没有证明存在显著的相互作用。
