Journal of Organometallic Chemistry ( IF 2.3 ) Pub Date : 2020-12-19 , DOI: 10.1016/j.jorganchem.2020.121659 Amal Benamrane , Brian Herry , Veacheslav Vieru , Suparna Chakraborty , Supratim Biswas , Sharon Prince , Christoph Marschner , Burgert Blom
A series of salt complexes of the type [RuCl(η6-arene)(κ2-dppm)]+[AgCl(hfac)(PMe3)]−(arene = benzene (1a) or p-cymene (1b), hfac = hexafluoroacetylacetato) have been prepared in a facile route by reaction of [RuCl2(η6-arene)Cl(κ1-dppm)] with [Ag(hfac)(PMe3)]. The iron complex: [CpFe(CO)(κ2-dppm)]+ [AgI(hfac)(PMe3)]− (4) (Cp = η5-C5H5) was also isolated in an analogous fashion by reacting the known complex [CpFeI(CO)(κ1-dppm)] with [Ag(hfac)(PMe3)]. The complexes were fully characterised by spectroscopic means including multinuclear NMR spectroscopy, IR, ESI-MS and UV-Vis. In all cases broad signals are observed in the 31P{1H} NMR spectra corresponding to the P atom in the anion [AgX(hfac)(PMe3)]− (X = Cl or I) which suggests fluxional behaviour. Confirming this picture, the single crystal X-ray diffraction analysis of [CpFe(CO)(κ2-dppm)]+ [hfac]− (4-D) is presented, obtained as a decomposition product of compound 4 corresponding with the loss of “AgI(PMe3)”. The nature of the elusive anion [AgX(hfac)(PMe3)]− was investigated by DFT methods (BP86 functional, the ma-def2-SVP basis set for all atoms) showing a weak interaction between the oxygen atoms of the hfac− moiety and the Ag centre. Calculated IR spectra were compared to those obtained experimentally and show an excellent agreement, confirming this picture. The in vitro cytotoxicity on two breast cancer cell-lines (MCF-7 and MDA-MB-231) of all compounds is reported and compared to cisplatin as positive control. The tetrafluoroborate complexes: type [RuCl(η6-arene)(κ2-dppm)]+BF4− (arene = benzene (2a) or p-cymene (2b)) were also prepared and tested in order to elucidate the effect of the silver anion on cytotoxicity and selectivity in 1a and 2a. Moreover, the complex [CpFe(CO)(κ2-dppm)]+BF4− (3) was also prepared for comparison to 4, bearing the silver anion. In general, all complexes exhibit remarkable cytotoxicity and selectivity profiles on both cell-lines, and out-perform cisplatin. The presence of silver in the anion (in compounds 1a, 1b and 4) on average enhance their cytotoxicity compared to their corresponding BF4 analogues. The most active and selective in the entire series is compound 4, which demonstrates that these compounds represent high potential in anticancer applications. Moreover, compounds 4 and 1a inhibited the long-term survival and migration of oestrogen receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines tested respectively. Additionally, compounds 4 and 1a induced morphological and molecular characteristics of apoptosis in MCF-7 and MDA-MB-231 breast cancer cells respectively.
中文翻译:
含银的阴离子的钌和铁基络合物,作为新型抗癌剂
一系列所述类型的盐络合物的合成将[RuCl(η 6 -arene)(κ 2 -dppm)] + [氯化银(HFAC)(PME 3)] - (芳烃=苯(1A)或p -cymene(1B), HFAC = hexafluoroacetylacetato)已经被以容易的路线由反应制备的合成将[RuCl 2(η 6 -arene)氯(κ 1 -dppm)]与[Ag(上HFAC)(PME 3)]。铁络合物:[CpFe的量(CO)(κ 2 -dppm)] + [碘化银(HFAC)(PME 3)] - (4)(CP =η 5 -C 5 H ^ 5)也以类似的方式由已知的络合物反应分离[CpFeI(CO)(κ 1 -dppm)]与[Ag(上HFAC)(PME 3)]。通过包括多核NMR光谱,IR,ESI-MS和UV-Vis在内的光谱学手段对复合物进行了充分表征。在所有情况下,在31 P { 1 H} NMR光谱中观察到与阴离子[AgX(hfac)(PMe 3)] -(X = Cl或I)中的P原子相对应的宽信号。确认这张照片,的单晶X射线衍射分析[CpFe的量(CO)(κ 2 -dppm)] + [HFAC] - (4- d给出),作为化合物4的分解产物获得,对应于损失“ AgI(PMe 3)”。难以捉摸的阴离子的性质[卤化银(HFAC)(PME 3)] - ,通过DFT法研究(BP86功能,对于所有的原子的MA-DEF2-SVP基组)表示HFAC的氧原子之间的弱相互作用-部分和银中心。将计算得出的红外光谱与通过实验获得的红外光谱进行比较,并显示出极好的一致性,从而证实了这张照片。在体外对所有化合物的两种乳腺癌细胞系(MCF-7和MDA-MB-231)的细胞毒性被报告并与顺铂作为阳性对照。四氟硼酸配合物:式将[RuCl(η 6-arene)(κ 2 -dppm)] + BF 4 - (芳烃=苯(2A)或对甲基异丙基苯(2b中还制备))和测试,以阐明银阴离子对细胞毒性和选择性的影响1A和2a。而且,络合物[CpFe的量(CO)(κ 2 -dppm)] + BF 4 - (3),还制备用于比较4,轴承银阴离子。通常,所有复合物在两种细胞系中均表现出显着的细胞毒性和选择性,并且表现优于顺铂。阴离子中存在银(在化合物1a,1b中和4)与它们相应的BF 4类似物相比平均增强它们的细胞毒性。在整个系列中最具活性和选择性的是化合物4,这表明这些化合物在抗癌应用中具有很高的潜力。此外,化合物4和1a分别抑制了雌激素受体阳性(MCF-7)和三阴性(MDA-MB-231)乳腺癌细胞系的长期存活和迁移。此外,化合物4和1a分别诱导MCF-7和MDA-MB-231乳腺癌细胞凋亡的形态和分子特征。