目前，双二钌桨轮配合物被用作基于金属的药物。有人提出，它们的电荷和空间位阻性质决定了其对蛋白质的选择性。本研究使用第一个具有两个甲酰胺配体的可溶于水的双二钌配合物[Ru2Cl(DPhF)2(O2CCH3)2]以及两个衍生物[Ru2Cl(DPhF)(O2CCH3)3]和K2[Ru2(DPhF)(CO3)3]（DPhF- = N，N'-二苯甲酰胺配体），其中一个含有一个甲酰胺配体。通过鸡蛋白中的卵白溶酶（HEWL）评估了它们的蛋白质结合性质。结果证实了双二钌配合物的相互作用类型（配位键/非配位键）与其电荷之间的关系。结晶介质也是一个关键因素。在所有情况下，双二钌物种均保持M-M键并产生稳定的加合物。我们还评估了这些双二钌配合物在一个真核细胞模型上的抗增殖性能。我们的数据显示，甲酰胺配体的数量与双二钌衍生物对人类上皮癌细胞的抗癌活性之间存在相关性。增加的细胞毒性可能与空间位阻增加和Ru25+离子核电子密度增加有关。然而，还必须考虑将双二钌物种的亲脂性通过引入第二个N，N'-二苯甲酰胺配体来增加的影响。本研究阐明了一种系统方法，从而揭示了双二钌化合物的相关性质，以设计基于金属的金属药物和双二钌金属酶。版权所有 © 2023. Elsevier B.V. 发表。

Paddlewheel diruthenium complexes are being used as metal-based drugs. It has been proposed that their charge and steric properties determine their selectivity towards proteins. Here, we explore these parameters using the first water-soluble diruthenium complex bearing two formamidinate ligands, [Ru2Cl(DPhF)2(O2CCH3)2], and two derivatives, [Ru2Cl(DPhF)(O2CCH3)3] and K2[Ru2(DPhF)(CO3)3] (DPhF- = N,N'-diphenylformamidinate), with one formamidinate. Their protein binding properties have been assessed employing hen egg white lysozyme (HEWL). The results confirm the relationship between the type of interaction (coordinate/non-coordinate bonds) and the charge of diruthenium complexes. The crystallization medium is also a key factor. In all cases, diruthenium species maintain the M-M bond and produce stable adducts. The antiproliferative properties of these diruthenium complexes have been evaluated on an eukaryotic cell-based model. Our data show a correlation between the number of the formamidinate ligands and the anticancer activity of the diruthenium derivatives against human epithelial carcinoma cells. Increased cytotoxicity may be related to increased steric hindrance and Ru25+ core electronic density. However, the effect of increasing the lipophilicity of diruthenium species by introducing a second N,N'-diphenylformamidinate must be also considered. This work illustrates a systematic approach to shed light on the relevant properties of diruthenium compounds to design metal-based metallodrugs and diruthenium metalloenzymes.Copyright © 2023. Published by Elsevier B.V.