Metal coordination of ferrocene-histidine conjugates

This study presents a few bis(histidine) ligands working to build a small peptidic model system of zinc structural sites. Ferrocene-peptide conjugates Fc[CO-His(Trt)-His(Trt)-OMe]₂ (3), Fc[CO-His(Trt)-Asp(OMe)-OMe]₂ (4), and Fc[CO-His(Trt)-Glu(OMe)-OMe]₂ (5) were synthesized and characterized spectroscopically. ¹H-NMR and IR spectroscopic studies reveal hydrogen bonding interactions and while more detailed circular dichroism studies show a 1,2'-P helical "Herrick conformation" for Fc-conjugates 4 and 5, we discovered M-helical chirality in Fc-peptide 3. The half-wave potentials (E_1/2) of ferrocene-peptides follow the sequence 3 < 5 < 4 which is rationalized by the capability of the peptide side chains to stabilize the oxidized ferrocene-peptide form. The diffusion coefficient (D) and electron transfer rate constant (k_sh) values for all Fc-conjugates were determined by their resultant cyclic voltammetry data. The interactions for all Fc-conjugates were probed with metal ions Zn²⁺, Cd²⁺, Ni²⁺, Cu²⁺, Mn²⁺, and Mg²⁺ which were detected to interact at 1 : 1 ratio between the ligand and metal ion verified by ¹H-NMR and UV titration studies, electrochemical investigations, and ESI-MS experiments. Electrochemical studies for all Fc-conjugates exhibit anodic potential shifts upon the addition of metal ions, which follow the order Cu²⁺ > Zn²⁺ > Ni²⁺ > Cd²⁺ > Mn²⁺ > Mg²⁺. NMR spectroscopic experiments show that the two nitrogen atoms present on each imidazole ring of His residues are the site of metal coordination. There is a strong indication that peptide conjugates 4 and 5 in the presence of Zn²⁺ enforce a coordination number of four as the CD spectra of Fc-conjugates 4 and 5 exhibited a red shift which corresponds to the third and fourth coordination sites occupied by neutral carbonyl oxygen donor atoms, in addition, carbonyl amide appears downward shifted in wavenumber upon metal addition.