Electrochemical Illumination of Intramolecular Communication in Ferrocene-Containing tris-β-Diketonato Aluminum(III) Complexes; Cytotoxicity of Al(FcCOCHCOCF3)3

The series of ferrocene-containing tris-β-diketonato aluminum­(III) complexes [Al­(FcCOCHCOR)3] (R = CF3, 1; CH3, 2; C6H5, 3; and Fc = ferrocenyl = Fe­(η5-C5H5)­(η5-C5H4), 4) were synthesized and investigated structurally and electrochemically; complex 1 was subjected to cytotoxicity tests. 1H NMR-spectroscopy distinguished between the mer and fac isomers of 2 and 3. Complex 1 existed only as the mer isomer. A single crystal X-ray crystallographic determination of the structure of a mer-isomer of Al­(FcCOCHCOCF3)3, 1, (Z = 4, space group P212121) demonstrated extensive delocalization of all bonds which explained the pronounced electrochemically observed intramolecular communication between molecular fragments. In contrast to electrochemical studies in CH2Cl2/[N­(nBu)4]­[PF6], the use of the supporting electrolyte [N­(nBu)4]­[B­(C6F5)4] allowed identification of all Fc/Fc+ electrochemical couples by cyclic and square wave voltammetry for 1–4. For R = Fc, formal reduction potentials of the six ferrocenyl groups were found to be E°′ = 33, 123, 304, 432, 583, and 741 mV versus free ferrocene respectively. Complex 1 (IC50 = 10.6 μmol dm–3) was less cytotoxic than the free FcCOCH2COCF3 ligand having IC50 = 6.8 μmol dm–3 and approximately 2 orders of magnitude less toxic to human HeLa neoplastic cells than cisplatin (IC50 = 0.19 μmol dm–3).一系列含二茂铁的三-β-二酮合铝(III)配合物[Al(FcCOCHCOR)₃]（其中R分别为CF₃（记为1）、CH₃（记为2）、C₆H₅（记为3），Fc为二茂铁基（ferrocenyl，即Fe(η⁵-C₅H₅)(η⁵-C₅H₄)，记为4））已被合成，并对其结构与电化学性质进行了系统研究；其中配合物1还开展了细胞毒性测试。氢核磁共振（¹H NMR）光谱法可区分配合物2与3的经式（mer）与面式（fac）异构体，而配合物1仅以经式异构体形式存在。对配合物1（Al(FcCOCHCOCF₃)₃）的经式异构体进行单晶X射线衍射（single crystal X-ray crystallography）结构解析，结果显示其晶胞参数Z=4，空间群为P2₁2₁2₁，该配合物中所有化学键均存在广泛离域，这一结果解释了电化学实验中观测到的分子片段间显著的分子内电子通信现象。与在CH₂Cl₂/[N(nBu)₄][PF₆]体系中的电化学研究不同，当使用支持电解质（supporting electrolyte）[N(nBu)₄][B(C₆F₅)₄]时，可通过循环伏安法（cyclic voltammetry）与方波伏安法（square wave voltammetry）分别确定配合物1~4的全部二茂铁/二茂铁正离子（Fc/Fc⁺）电化学氧化还原对。当R为Fc时，六个二茂铁基的条件还原电位（formal reduction potential）相对于游离二茂铁分别为E°′=33、123、304、432、583和741 mV。配合物1的半抑制浓度（IC₅₀）为10.6 μmol·dm⁻³，其细胞毒性弱于游离配体FcCOCH₂COCF₃（IC₅₀=6.8 μmol·dm⁻³），且对人HeLa肿瘤细胞的毒性仅约为顺铂（cisplatin，IC₅₀=0.19 μmol·dm⁻³）的百分之一，即低两个数量级。