The Influence of Secondary Structure on Electron Transfer in Peptides

Abstract

A series of synthetic peptides containing 0–5 α-aminoisobutyric acid (Aib) residues and a C-terminal redox-active ferrocene was synthesised and their conformations defined by NMR and circular dichroism. Each peptide was separately attached to an electrode for subsequent electrochemical analysis in order to investigate the effect of peptide chain length (distance dependence) and secondary structure on the mechanism of intramolecular electron transfer. While the shorter peptides (0–2 residues) do not adopt a well defined secondary structure, the longer peptides (3–5 residues) adopt a helical conformation, with associated intramolecular hydrogen bonding. The electrochemical results on these peptides clearly revealed a transition in the mechanism of intramolecular electron transfer on transitioning from the ill-defined shorter peptides to the longer helical peptides. The helical structures undergo electron transfer via a hopping mechanism, while the shorter ill-defined structures proceeded via an electron superexchange mechanism. Computational studies on two β-peptides PCB-(β3Val-β3Ala-β3Leu)n–NHC(CH3)2OOtBu (n = 1 and 2; PCB = p-cyanobenzamide) were consistent with these observations, where the n = 2 peptide adopts a helical conformation and the n = 1 peptide an ill-defined structure. These combined studies suggest that the mechanism of electron transfer is defined by the extent of secondary structure, rather than merely chain length as is commonly accepted.