Metal Coordination to Unsymmetric 1, n′ ‐Disubstituted Ferrocene Histidine Peptides

Abstract

In this study, the coordination chemistry of unsymmetrical 1,n′-substituted ferrocene (Fc) peptide conjugates is explored, where the peptide substituents are two different histidine-containing peptides. The resulting Fc-conjugates serve as ligands for the formation of metal complexes, with the intention to generate complexes that possess a labile coordination site. The following Fc[CO-His(Trt)-OMe][COOMe] (1), Fc[CO-His(Trt)-Gly-OMe][CO-Gly-OMe] (2), Fc[CO-His(Trt)-His(Trt)-OMe][CO-His(Trt)-OMe] (3), and Fc[CO-His(Trt)-Gly-His(Trt)-OMe][CO-Gly-His(Trt)-OMe] (4) were synthesized and characterized. Each compound forms discrete complexes with metal divalent metal ions Zn2+, Co2+ and Cd2+, where a single metal ion is complexed by the metallo-ligand, as was confirmed spectroscopically. The redox properties of the Fc group are influenced by metal coordination to the peptide substituents and anodic shifts occur upon the addition of metal ions. These follow the order Zn2+ > Cd2+ > Co2+. NMR experiments indicated imidazole rings are the site of metal coordination. Fc-peptide conjugates display a switchable axial chirality that is dependent on metal complexation.