Bis-amino Acid Derivatives of 1,1′-Ferrocenedicarboxylic Acid: Structural, Electrochemical, and Metal Ion Binding Studies

We report on the structural and electrochemical investigation of 1,1′-ferrocenedicarboxylic acid derivatives of tryptophan (Fc­[CO-Trp-OMe]2 - Fc-conjugate 1), threonine (Fc­[CO-Thr-OMe]2 – Fc-conjugate 2), aspartic acid (Fc­[CO-Asp-OMe]2 - Fc-conjugate 3) and glutamic acid (Fc­[CO-GluOMe]2 - Fc-conjugate 4) and their hydrolyzed analogues 1a–4a respectively (Scheme ). CD and NMR spectroscopy established 1,2′-“Herrick conformation” in solution, having intramolecular interstrand hydrogen bonds for all Fc-conjugates. However, in solid state, Fc­[CO-Trp-OMe]2 exists in “Herrick conformation” whereas Fc­[CO-Thr-OMe]2 is present in anti conformation. In solution, the involvement of indole NH of Trp and alcoholic proton of Thr in intermolecular hydrogen bonding has been explored by temperature- and concentration-dependent NMR studies. The half-wave potentials (E1/2) of ferrocene-conjugates follow the sequence 1 which is explained by the contribution of amino acid side chain functionalities toward the stability of ferrocenium ion. The CV of the Fc-conjugate 1/1a (having Trp moiety) displays two redox processes, one of which is assigned to the Fc group, and the other being related to the indole group. The oxidation peak potential of indole was found to depend strongly on the pH of the medium. The values of diffusion coefficient (D) and electron transfer rate constant (ksh) for all Fc-conjugates were determined from their corresponding cyclic voltammograms. In addition, metal ion interactions were studied with hydrolyzed Fc-conjugates 2a–4a using CV and DPV. Upon binding to metal ions, the electrochemical changes associated with the hydrolyzed Fc-conjugates correlated to the charge density of the binding metal ion.

本研究报道了色氨酸（tryptophan）、苏氨酸（threonine）、天冬氨酸（aspartic acid）与谷氨酸（glutamic acid）的1,1'-二茂铁二甲酸衍生物（分别为Fc[CO-Trp-OMe]₂——二茂铁缀合物1、Fc[CO-Thr-OMe]₂——二茂铁缀合物2、Fc[CO-Asp-OMe]₂——二茂铁缀合物3及Fc[CO-GluOMe]₂——二茂铁缀合物4）及其各自的水解类似物1a~4a（如Scheme所示）的结构与电化学表征。通过圆二色谱（Circular Dichroism, CD）与核磁共振波谱（Nuclear Magnetic Resonance, NMR）表征证实，所有二茂铁缀合物在溶液中均呈现1,2′-Herrick构象，并存在分子内链间氢键。但在固态状态下，Fc[CO-Trp-OMe]₂仍以Herrick构象存在，而Fc[CO-Thr-OMe]₂则呈现反式构象。在溶液体系中，通过温度依赖与浓度依赖的核磁共振波谱研究，证实了色氨酸残基的吲哚NH与苏氨酸残基的醇羟基质子参与了分子间氢键的形成。各二茂铁缀合物的半波电位（E₁/₂）遵循特定顺序，该规律可通过氨基酸侧链官能团对二茂铁阳离子稳定性的贡献予以阐释。针对含色氨酸残基的二茂铁缀合物1/1a的循环伏安法（Cyclic Voltammetry, CV）测试显示其存在两个氧化还原过程：其一归属于二茂铁基团，另一则与吲哚基团相关。研究发现吲哚基团的氧化峰电位强烈依赖于介质的pH值。通过各缀合物对应的循环伏安图，可计算得到其扩散系数（D）与电子转移速率常数（k_sh）。此外，本研究还采用循环伏安法（CV）与差分脉冲伏安法（Differential Pulse Voltammetry, DPV），针对水解型二茂铁缀合物2a~4a开展了金属离子相互作用研究。当与金属离子结合后，水解型二茂铁缀合物所产生的电化学变化与结合金属离子的电荷密度呈现显著相关性。