New bis-ferrocenyl end-capped peptides: synthesis and charge-transfer properties

In this article, the successful preparation of a new series of 3(10)-helical peptides of different length containing two terminal ferrocenyl (Fc) units and based on the strongly foldameric alpha-aminoisobutyric (Aib) acid is reported. The synthesis of the FcCO-(Aib)n-NHFc (n = 1-5) homo-peptides was performed by solution methods. Moderate to good yields (26-85%) were obtained in each of the difficult coupling steps of FcCOOH and the corresponding H-(Aib)n-NHFc compounds by C-activation with the 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide/7-aza-1-hydroxy-1,2,3-benzotriazole method. Information on the CO···HN intramolecularly hydrogen-bonded networks was initially obtained from FT-IR absorption measurements. The NH stretching (amide A) region allowed us to distinguish which amide protons are involved in intramolecular hydrogen bonds and indicates the formation of an incipient 3(10)-helix structure for peptides containing at least two Aib residues. This conclusion was confirmed by 1H NMR titrations of the NH groups of the peptides in CDCl3 with dimethylsulfoxide and by crystallographic analysis of the N-alpha-acylated FcCO-(Aib)5-NHFc pentapeptide amide. The two redox-active Fc groups covalently bound to the termini of the foldameric peptide architectures were used as electrochemical probes. The end-to-end effects of electron holes generated by single and double oxidations were analyzed by means of electrochemical and spectroelectrochemical techniques. The results of these studies indicate that charge transfer across the peptide main chain does occur in the five peptides. In particular, in the pentapeptide 5, charge is transferred through an intramolecular Fe···Fe separation of 14 Å.