铁(II)和钌(II)半夹心化合物囊括了一些有前景的临床前抗癌药物，其有效性可以通过配体的结构修饰进行调节。在此，我们将两个这样的生物活性金属中心结合在阳离子双(二苯基膦基)烷桥联的异二核[Fe2+,Ru2+]配合物中，以阐明配体结构变化如何调节化合物的细胞毒性。具体而言，合成并表征了类型为[(η5-C5H5)Fe(CO)2(κ1-PPh2(CH2)nPPh2)]{PF6}(n=1-5)，化合物1-5和异二核[Fe2+,Ru2+]配合物[(η5-C5H5)Fe(CO)2(μ-PPh2(CH2)nPPh2))(η6-p-cymene)RuCl2]{PF6}(n=2-5)(化合物7-10)。单核配合物对两种卵巢癌细胞株(A2780和顺铂耐药A2780cis)有中等毒性，IC50值范围从2.3±0.5 μM到9.0±1.4 μM。对于化合物7-10，随着Fe⋅⋅⋅Ru距离的增加，其细胞毒性增加，与其DNA亲和力一致。紫外可见光谱表明，异二核8-10中的氯配体在DNA相互作用实验的时间尺度上逐步被水取代，可能生成物种[RuCl(OH2)(η6-p-cymene)(PRPh2)]2+和[Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (其中PRPh2具有R = [-(CH2)5PPh2-Fe(C5H5)(CO)2]+)。结合DNA-相互作用和动力学数据的其中一种解释是，单(水)配合物可以通过核碱基配位与双链DNA相互作用。异二核10与谷胱甘肽(GSH)反应形成稳定的单和双硫酸盐加合物，10-SG和10-SG2，没有金属离子还原的证据(k1=1.07±0.17×10-1 min-1，k2=6.04±0.59×10-3 min-1，在37°C下)。这项工作凸显了Fe2+/Ru2+中心在这些异二核复合物的细胞毒性和生物分子相互作用方面的协同作用。Copyright © 2023 Elsevier Inc. All rights reserved.

Iron(II) and Ru(II) half-sandwich compounds encompass some promising pre-clinical anticancer agents whose efficacy may be tuned by structural modification of the coordinated ligands. Here, we combine two such bioactive metal centres in cationic bis(diphenylphosphino)alkane-bridged heterodinuclear [Fe2+, Ru2+] complexes to delineate how ligand structural variations modulate compound cytotoxicity. Specifically, Fe(II) complexes of the type [(η5-C5H5)Fe(CO)2(κ1-PPh2(CH2)nPPh2)]{PF6} (n = 1-5), compounds 1-5, and heterodinuclear [Fe2+, Ru2+] complexes, [(η5-C5H5)Fe(CO)2(μ-PPh2(CH2)nPPh2))(η6-p-cymene)RuCl2]{PF6} (n = 2-5) (compounds 7-10), were synthesized and characterised. The mononuclear complexes were moderately cytotoxic against two ovarian cancer cell lines (A2780 and cisplatin resistant A2780cis) with IC50 values ranging from 2.3 ± 0.5 μM to 9.0 ± 1.4 μM. For 7-10, the cytotoxicity increased with increasing Fe⋅⋅⋅Ru distance, consistent with their DNA affinity. UV-visible spectroscopy suggested the chloride ligands in heterodinuclear 8-10 undergo stepwise substitution by water on the timescale of the DNA interaction experiments, probably affording the species [RuCl(OH2)(η6-p-cymene)(PRPh2)]2+ and [Ru(OH)(OH2)(η6-p-cymene)(PRPh2)]2+ (where PRPh2 has R = [-(CH2)5PPh2-Fe(C5H5)(CO)2]+). One interpretation of the combined DNA-interaction and kinetic data is that the mono(aqua) complex may interact with dsDNA through nucleobase coordination. Heterodinuclear 10 reacts with glutathione (GSH) to form stable mono- and bis(thiolate) adducts, 10-SG and 10-SG2, with no evidence of metal ion reduction (k1 = 1.07 ± 0.17 × 10-1 min-1 and k2 = 6.04 ± 0.59 × 10-3 min-1 at 37 °C). This work highlights the synergistic effect of the Fe2+/Ru2+ centres on both the cytotoxicity and biomolecular interactions of the present heterodinuclear complexes.Copyright © 2023 Elsevier Inc. All rights reserved.