The mode of anticancer activity of simple ferrocenes often relies on their intracellular oxidation with the formation of cytotoxic ferrocenium species. The former compounds should be considered as prodrugs and derived from them ferroceniums as drugs. The drugs are 17e^– organometallic species. Therefore, they are chemically unstable and decompose with formation of free cyclopentadienyl ligands (which are further transformed to more stable species) and iron ions. The short lifetime of ferrocenium drugs limits the anticancer effect of ferrocene prodrugs. In this paper we prepared a series of acylated aminoferrocene monomers, dimers, and higher oligonuclear complexes Fc_N (where N = 1–4). Drugs [Fc_N]⁺ derived from Fc_N (N > 1) are more stable than monomeric [Fc]⁺, provided that the ferrocene units are electronically coupled. Correspondingly, we expected that Fc_N species will be more potent anticancer agents in comparison to the related monomers. These assumptions were confirmed for dimer 10. We observed that this prodrug has sufficient solubility in aqueous solution (100 μM) and favorable lipophilicity (log P = 2.2 ± 0.2). Ferrocene units in 10 are efficiently electronically coupled via a −C(═O)NH– linker according to cyclic voltammetry, differential pulse voltammetry, and spectroelectrochemistry. We observed that 10 is the most efficient catalyst of the production of reactive oxygen species (ROS) and the most active anticancer agent in comparison to control monomers and their mixtures.

中文翻译：

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电子偶联的低聚二茂铁的抗癌作用

简单的二茂铁的抗癌活性模式通常取决于它们的细胞内氧化以及细胞毒性二茂铁物种的形成。前一种化合物应被视为前药，而从二茂铁中衍生而来则是药物。这些药物是17e ^–有机金属物种。因此，它们在化学上是不稳定的，并且会分解形成游离的环戊二烯基配体（进一步转变为更稳定的物种）和铁离子。二茂铁鎓药物的寿命短限制了二茂铁前药的抗癌作用。在本文中，我们制备了一系列酰化的氨基二茂铁单体，二聚体和高级寡核配合物Fc _N（其中N = 1-4）。药物[Fc _N ] ⁺如果二茂铁单元是电子偶联的，则衍生自Fc _N（N > 1）的化合物比单体[Fc] ⁺稳定。相应地，我们预期与相关单体相比，Fc _N物种将是更有效的抗癌剂。这些假设已被二聚体10证实。我们观察到该前药在水溶液（100μM）中具有足够的溶解度，并具有良好的亲脂性（log P = 2.2±0.2）。根据循环伏安法，微分脉冲伏安法和光谱电化学，通过-C（= O）NH-接头有效地偶联了10个二茂铁单元。我们观察到10 与对照单体及其混合物相比，它是生产活性氧（ROS）的最有效催化剂，也是活性最高的抗癌剂。