Conformational Analysis and Through‐Chain Charge Propagation in Ferrocenyl‐Conjugated Homopeptides of 2,3‐Diaminopropionic acid (Dap)

Abstract

This work reports a detailed conformational and electrochemical study of two series of ferrocene (Fc)-peptide conjugates, based on the side-chain protected, 2,3-diaminopropionic acid (LÀ Dap). In one series Fc is linked to the N-terminus, in the other to the C-terminus of the Dap homo-peptides. The conformational analysis carried out in solution (IR absorption and NMR) and in the crystal state (X-ray diffraction) suggests that these peptides adopt a 3 10 -helical structure. Cyclic voltammetry showed that the peptide length positively or negatively affects the oxidation potential of Fc. The two opposite trends are correlated to the different orientation of the macrodipole moment of the 3 10 -helix in the two series with respect to the position of the Fc group in the chain. Finally, the variation of the IR absorptions upon chemical oxidation indicates that our 3 10 -helical conjugates are very efficient in transferring the positive charge along the peptides through the H-bond network.

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

“…However, for the first time, we performed an in-depth analysis of the conformational preferences of Dap. Surprisingly, we found that the side-chain-protected Dap can fold into a β-turn or an incipient 3 10 -helix, as evidenced by our 2D NMR and X-ray crystal analyses, further supported by the electrochemical data [24].…”

“…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]. In Figure 7, the potential variations of mono-Fc peptides L -Dap(Boc) [24] are also reported. Similar slopes are calculated for the oxidation of Fc-NH in the 1-4 (−21 ± 4 mV) and Bz-[ L -Dap (Boc)] n -NH-Fc series (−23 ± 2 mV), and of Fc-CO in 1-4 (27 ± 5 mV) and Fc-CO-[ L -Dap(Boc)] n -NH-iPr (28 ± 3 mV).…”

“…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].…”

“…In the visible region, an absorption band appears around 758 nm after the addition of 1 equivalent of ferrocenium[BF 4 ], characteristic of the Fc + -NH group. After the successive addition of 1 equivalent of acetylferrocenium[BF 4 ], the typical absorption band around 620 nm of the Fc + -CO group is observed [24], while the intensity of the low-energy band decreases. For example, the visible spectra obtained by the stepwise oxidation of 4 (Figure 9, bold black line) clearly show the initial formation of the 4 + monocation (bold green line), which subsequently evolves into the 4 2+ dication (bold red line).…”

“…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].…”