Ferrocenoyl amino acids and peptides: probing peptide structure

Recent studies clearly show the utility of the carbodiimide protocol to attach the redox-active Fc moiety to the N-terminal side of amino acids and peptides under mild conditions, resulting in stable and often crystalline products that afford themselves to structural analysis by X-ray crystallography. Electrochemical studies of Fc-peptides show that there is a significant influence of the redox potential depending on the amino acid sequence. The Fc moiety is sensitive to structural changes that occur in the peptide to which it is attached. For helical Fc-oligoprolines, the redox potential of the Fc group makes it easier to oxidize as the oligoproline chain increases in length. Nonhelical peptides, having a similar primary but different secondary structure, give rise to very different redox potentials. The ramifications of these findings to biological systems are significant in that they provide further evidence that the redox properties of a metal center are influenced by factors that go beyond the primary ligand sphere and thus for the involvement of long-range interactions. The Fc group is clearly sensitive to the shape of the peptide. These effects are currently under more detailed investigation [45] in order to gain further insight into the electronic structure of these ferrocenoyl peptides. Although we are not yet in a position to distinguish between "sensing" coordination or "sensing" conformation changes, this effect is of interest because it may allow the development of peptidic sensors.