Flat, Ferrocenyl‐Conjugated Peptides: A Combined Electrochemical and Spectroscopic Study

Abstract

We synthesized two homo-peptide series, based on the C α,βdidehydroalanine residue. One series was functionalized with a ferrocene (Fc) moiety at the N-terminus, the other series with a Fc at the C-terminus. These conjugates adopt the flat, fully extended conformation, also known as 2.0 5 -helix. Cyclic voltammetry measurements revealed that the peptide length does not affect the redox behavior of Fc, independently on the peptide end at which it is appended. This outcome perfectly fits with the presence of fully-extended peptides, as in this 3D-structure the dipole moment is negligible. Thus, we confirm the results of our previous study with two Fc pendants: fully-extended, αpeptide stretches prevent or reduce the charge transfer along the peptide chain.

Helical versus Flat Bis-Ferrocenyl End-Capped Peptides: The Influence of the Molecular Skeleton on Redox Properties

“…The comparison among three bis-ferrocenyl, end-capped peptide series, namely Fc-CO-(Aib) n -NH-Fc (n = 1-5) [25,26], Fc-CO-(∆Ala) n -NH-Fc (n = 1-4) [28] and Fc-CO-[L−Dap(Boc)] n -NH-Fc (1-4) here reported, highlights the important role that peptide helices play in charge transmission, and the influence of the peptide skeleton on the redox properties of these ferrocenyl-conjugated foldamers. Indeed, when the Fc-peptide-Fc series are based on Aib or on side-chain-protected Dap residues, the conformational analysis in the solid state (X-ray crystal structures) and in solution (IR and 2D NMR) strongly indicates that these peptides adopt a 3 10 -helical structure.…”

“…The comparison of the potential variations with those of the unique bis-Fc homopeptide examples reported before, Fc-CO-(Aib)n-NH-Fc (n = 1-5) [25,26] and Fc-CO-(ΔAla)n-NH-Fc (n = 1-4) [28], allows us to shed some light on how the charge transfer across the peptide main chain is influenced by the nature of the peptide secondary structure, exploiting the effect of the positive charges produced by single and double oxidations (Figure 8). This behavior is due to the peptide macrodipole that is oriented in the same or opposite direction with respect to the position of the Fc involved in the redox event [65].…”

“…The comparison of the potential variations with those of the unique bis-Fc homopeptide examples reported before, Fc-CO-(Aib)n-NH-Fc (n = 1-5) [25,26] and Fc-CO-(ΔAla)n-NH-Fc (n = 1-4) [28], allows us to shed some light on how the charge transfer across the peptide main chain is influenced by the nature of the peptide secondary structure, exploiting the effect of the positive charges produced by single and double oxidations (Figure 8). Mainly, it appears that in the 310-helical homopeptides of L-Dap(Boc) and Aib amino acids, characterized by active dipole moments, an important and continuous variation of E1/2 occurs as the peptide length is increased, positive and negative depending on the orientation of the peptide dipole moment with respect to Fc.…”

“…The characteristics of Fc, such as excellent stability in solution and air, flexibility in organic chemistry and a reversible electrochemical behavior, make it advantageous in labeling biomolecules [64]. In addition, electrochemistry on Fc-terminal peptides provides information on the effect of folding and length of the peptide chain [23][24][25][26][27][28].…”

“…This class of peptides has allowed researchers to design systems with new redox triggered functions, such as chirality organization [1,11], chirality dependence charge transfer rate [2], photodynamic anticancer [3,7], antibacterial [4,10], antimicrobial [6] and antimalarial [7] activities, supramolecular gelation [8,18], potential bioinspired electronic materials [9], changes in the self-assembly [12], sensory applications [13,14,19], enzymatic fuel cells [15,16] and bioelectrocatalysts [22]. In particular, we have employed a single Fc group as a scaffold to support peptide secondary structural motifs, such as 3 10 -helices with α-amino isobutyric acid (Aib) [23] or L -2,3-diamino propionic ( L -Dap) acid [24], and the 2.0 5 -helix based on C α,β -didehydroalanine (∆Ala) [25].…”