Diiron bis-cyclopentadienyl bis-carbonyl cationic complexes with a bridging vinyliminium ligand, [Fe₂Cp₂(CO)(μ-CO){μ-η¹:η³-C³(R′)C²HC¹NMe(R″)}]CF₃SO₃ (R = Xyl = 2,6-C₆H₃Me₂, R′ = Ph, R″ = H, 2a; R = Xyl, R′ = R″ = Me, 2b; R = R′ = Me, R″ = H, 2c; R = Me, R′ = 2-naphthyl, R″ = H, 2d; R = Me, R′ = R″ = Ph, 2e), are easily available from commercial chemicals, robust in aqueous media and exert a variable in vitro cytotoxicity against cancer cell lines depending on the nature of the substituents on the vinyliminium ligand. The anticancer activity is, at least in part, associated to fragmentation reactions, leading to iron oxidation and active neutral and well-defined monoiron species. We report an innovative synthetic procedure for the preparation of 2a,c,d, and a facile method to access the monoiron derivative of 2a, i.e., [FeCp(CO){C¹(NMeXyl)C²HC³(Ph)C(O)}] (3a). According to IC₅₀ analyses at different times of incubation of the complexes, 3a is significantly faster in inhibiting cell viability compared to its diiron precursor 2a. The neutral complexes [Fe₂Cp₂(CO)(μ-CO){μ-k¹N:k¹C:k¹C-C³(R′)C²(Se)C¹(NMe₂)C⁴(CO₂Y)C⁵(CO₂Y)}] (R′ = Y = Me, 4a; R′ = Pr, Y = ^tBu, 4b; R′ = Y = Et, 4c) are obtained via the two-step modification of the vinyliminium moiety and comprise a bridging selenophene-decorated alkylidene ligand. The antiproliferative activity exhibited by 4a-c is moderate but comparable on the ovarian cancer cell line A2780 and the corresponding cisplatin resistant cell line, A2780cisR. Complexes 4a-c in aqueous solutions undergo progressive release of the alkylidene ligand as a functionalized selenophene, this process being slower in cell culture medium. Since the released selenophenes SeC¹{C(O)R′}C²(NMe₂)C³(CO₂Y)C⁴(CO₂Y) (R′ = Y = Me, 5a; R′ = Pr, Y = ^tBu, 5b) are substantially not cytotoxic, it is presumable that the activity of 4a-c is largely ascribable to the {Fe₂Cp₂(CO)₂} scaffold.

中文翻译：

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桥联C3-配体的二铁双环戊二烯基配合物的细胞毒活性

二铁双环戊二烯基二羰基阳离子络合物用桥连配位体vinyliminium，的[Fe ₂的Cp ₂（CO）（μ-CO）{μ-η ¹：η ³ -C ³（R'）C ² HC ¹ NME（R ”）}] CF ₃ SO ₃（R = Xyl = 2,6-C ₆ H ₃ Me ₂，R'= Ph，R''= H，2a ; R = Xyl，R'= R''= Me，2b ; R ＝ R′＝ Me，R″ ＝ H，2c； R ＝ Me，R′＝ 2-萘基，R″ ＝ H，2d； R ＝ Me，R′＝ R″ ＝ Ph，2e）可以很容易地从商业化学品中获得，在水性介质中具有稳健性，并且可以根据乙烯基亚胺配体上取代基的性质在体外对癌细胞系产生不同的细胞毒性。抗癌活性至少部分与片段化反应有关，从而导致铁氧化以及活性中性和定义明确的单铁物种。我们报告了一种创新的合成程序，用于制备2a，c，d和一种简便的方法来访问2a的单铁衍生物，即[FeCp（CO）{C ¹（NMeXyl）C ² HC ³（Ph）C（ O）}]（3a）。根据IC ₅₀在复合物孵育的不同时间进行分析，3a与其二铁前驱体2a相比，在抑制细胞活力方面明显更快。中性配合物的[Fe ₂的Cp ₂（CO）（μ-CO）{μ-K ¹ N：ķ ^1个C：ķ ¹的C-C ³（R'）C ²（SE）C ¹（NME ₂）C ⁴（CO ₂ Y）C ⁵（CO ₂ Y）}]]（R'= Y = Me，4a ; R'= Pr，Y = ^t Bu，4b ; R'= Y = Et，4c）是通过乙烯基亚胺部分的两步修饰获得的，并且包含桥联硒烯修饰的亚烷基配体。4a-c表现出的抗增殖活性中等，但在卵巢癌细胞系A2780和相应的顺铂耐药细胞系A2780cisR上具有可比性。水溶液中的配合物4a-c经历亚烷基配体的逐步释放，作为官能化的亚硒酚，该过程在细胞培养基中较慢。由于释放的硒代硒化合物SeC ¹ {C（O）R'} C ²（NMe ₂）C ³（CO ₂ Y）C ⁴（CO ₂ Y）（R'= Y = Me，5a ; R'= Pr，Y =^t Bu，5b）基本上没有细胞毒性，推测4a-c的活性很大程度上归因于{Fe ₂ Cp ₂（CO）₂ }支架。