The reactions of four cymene-capped ruthenium(II) compounds with pro-apoptotic protein, cytochrome c (Cyt), and anti-proliferative protein lysozyme (Ly) in carbonate buffer were investigated by ESI–MS, UV–vis absorption, and CD spectroscopy. The complexes with two chloride ligands (C2 and C3) were more reactive toward proteins than those with only one (C1 and C4), and the complex with S,N-chelating ligand (C4) was less reactive than one with O,N-chelating ligand (C1). Dehalogenated complexes are most likely species, initially coordinating proteins for all tested complexes. During the time, protein adducts vividly exchanged non-arene organic ligand L with CO₃²⁻ and OH⁻, while cymene moiety was retained. In water, only dehalogenated adducts were identified suggesting that in vivo, in the presence of various anions, dynamic ligand exchange could generate different intermediate protein species. Although all complexes reduced Cyt, the reduction was not dependent on their reactivity to protein, implying that initially noncovalent binding to Cyt occurs, causing its reduction, followed by coordination to protein. Cyt reduction was accompanied with rupture of ferro-Met 80 and occupation of this hem coordination site by a histidine His-33/26. Therefore, in Cyt with C2 and C3, less intensive reduction of hem iron leaves more unoccupied target residues for Ru coordination, leading to more efficient formation of covalent adducts, in comparison to C1 and C4. This study contributes to development of new protein-targeted Ru(II) cymene complexes, and to the design of new cancer therapies based on targeted delivery of Ru(II) arene complexes bound on pro-apoptotic/anti-proliferative proteins as vehicles.

中文翻译：

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钌 (II)-伞花烃复合物与溶菌酶和细胞色素 c 的相互作用。

通过 ESI-MS、UV-vis 吸收和 CD 研究了四种伞花烃封端的钌 (II) 化合物与促凋亡蛋白、细胞色素 c (Cyt) 和抗增殖蛋白溶菌酶 (Ly) 在碳酸盐缓冲液中的反应光谱学。具有两个氯配体（C2和C3）的复合物比只有一个（C1和C4）的复合物对蛋白质的反应性更强，而具有S , N -螯合配体（C4）的复合物则比与O , N -的复合物反应性小。螯合配体 ( C1）。脱卤复合物是最有可能的物种，最初协调所有测试复合物的蛋白质。在此期间，蛋白质加合物生动地交换了非芳烃有机配体 L 与 CO ₃ ^2-和 OH ^-，而伞花烃部分被保留。在水中，仅鉴定出脱卤加合物，这表明在体内，在存在各种阴离子的情况下，动态配体交换可以产生不同的中间蛋白质种类。尽管所有复合物都减少了 Cyt，但这种减少并不取决于它们与蛋白质的反应性，这意味着最初与 Cyt 发生非共价结合，导致其减少，然后与蛋白质配位。Cyt 减少伴随着 ferro-Met 80 的破裂和组氨酸 His-33/26 占据这个下摆协调位点。因此，与C2和C3相比，在 Cyt 中，与C2和C3 相比，较低强度的 hem 铁还原会留下更多未占据的 Ru 配位目标残基，从而更有效地形成共价加合物。C1和C4。该研究有助于开发新的靶向蛋白质的 Ru(II) 伞花烃复合物，并有助于设计基于靶向传递结合在促凋亡/抗增殖蛋白上的 Ru(II) 芳烃复合物作为载体的新癌症疗法。