Modulation of Ferrocene-Ferrocene Interactions by Varying Their Reciprocal Positions in _L-Dap/Aib Helical Peptides

In this work, we developed two new polyfunctional hybrid systems in which the presence of Fc redox "antennas" on peptide scaffolds allows for a modulation of their electronic properties. Specifically, we synthesized two helical hexapeptides containing four Aib (alpha-amionoisobutyric acid) and two (L)-Dap (2,3-diamino propionic acid) residues. (L)-Dap side chains were then functionalized with Fc moieties. The structures of the two 3(10) helical peptides, namely Z-Aib-(L)-Dap(Fc)-Aib-Aib-(L)-Dap(Fc)-Aib-NH-iPr and Z-Aib-(L)-Dap(Fc)-Aib-(L)-Dap(Fc)-Aib-Aib-NH-iPr, were investigated by X-ray diffraction, 2D-NMR, CD and IR spectroscopies. Due to the helical conformation, in Z-Aib-(L)-Dap(Fc)-Aib-Aib-(L)-Dap(Fc)-Aib-NH-iPr, the Fc groups are located on the same face of the helix, but in Z-Aib-(L)-Dap(Fc)-Aib-(L)-Dap(Fc)-Aib-Aib-NH-iPr, they are located on opposite faces. Surprisingly, two bands were found through DPV for Z-Aib-(L)-Dap(Fc)-Aib-(L)-Dap(Fc)-Aib-Aib-NH-iPr, indicating an electrostatic interaction between the Fc groups despite their longer reciprocal distance with respect to that in Z-Aib-(L)-Dap(Fc)-Aib-Aib-(L)-Dap(Fc)-Aib-NH-iPr. CD experiments at different concentrations evidenced aggregation for Z-Aib-(L)-Dap(Fc)-Aib-(L)-Dap(Fc)-Aib-Aib-NH-iPr, even at high dilutions, thus suggesting that the Fc-Fc electrostatic interaction could be of an intermolecular nature.