Unraveling the Interplay of Backbone Rigidity and Electron Rich Side-Chains on Electron Transfer in Peptides: The Realization of Tunable Molecular Wires

Abstract

Electrochemical studies are reported on a series of peptides constrained into either a 310-helix (1–6) or β-strand (7–9) conformation, with variable numbers of electron rich alkene containing side chains. Peptides (1 and 2) and (7 and 8) are further constrained into these geometries with a suitable side chain tether introduced by ring closing metathesis (RCM). Peptides 1, 4 and 5, each containing a single alkene side chain reveal a direct link between backbone rigidity and electron transfer, in isolation from any effects due to the electronic properties of the electron rich side-chains. Further studies on the linear peptides 3–6 confirm the ability of the alkene to facilitate electron transfer through the peptide. A comparison of the electrochemical data for the unsaturated tethered peptides (1 and 7) and saturated tethered peptides (2 and 8) reveals an interplay between backbone rigidity and effects arising from the electron rich alkene side-chains on electron transfer. Theoretical calculations on β-strand models analogous to 7, 8 and 9 provide further insights into the relative roles of backbone rigidity and electron rich side-chains on intramolecular electron transfer. Furthermore, electron population analysis confirms the role of the alkene as a “stepping stone” for electron transfer. These findings provide a new approach for fine-tuning the electronic properties of peptides by controlling backbone rigidity, and through the inclusion of electron rich side-chains. This allows for manipulation of energy barriers and hence conductance in peptides, a crucial step in the design and fabrication of molecular-based electronic devices.

Exploiting the interplay of quantum interference and backbone rigidity on electronic transport in peptides: a step towards bio-inspired quantum interferometers

“…17 Furthermore, 1 H NMR J NHCαH coupling constants consistent with a β-strand structure 18 were observed for these peptides. The conformations of 3 and 4 were confirmed as 3 10 -helical, based on observed CαH(i) to NH(i+1) and medium range CαH(i) to NH(i+2) ROESY correlations 5 ( Fig. S3 and S4).…”

“…These values are comparable to other carbon nanotube electrode studies. 5,6,24 The formal potentials (E o ) and apparent electron transfer rate constants (k et ) were estimated using Laviron's formalism ( Fig. 3b and 3d, Table 1).…”

“…Our earlier studies 4,5 suggest that this may be the result of the additional backbone rigidity imparted by the sidebridge constraint, which restricts the precise backbone torsional motion required by a hopping mechanism to facilitate intramolecular electron transfer through the peptide. 16,27 However, it is also possible that the side-chain tether can provide an additional electron transport pathway.…”

“…Peptides can also be specifically constrained into well-defined secondary structures such as helices and β-strands that are known to play a role in electron transfer. 3 With this in mind, we recently demonstrated that linking the side-chains of amino acids within a peptide with a covalent constraint, introduced by either Husigen cycloaddition 4 or ring closing metathesis, 5 impedes charge transfer. A peptide can be constrained in this way into a well-defined helical or β-strand conformation with the appropriate choice of linker.…”

Conjugated Cofactor Enables Efficient Temperature-Independent Electronic Transport Across ∼6 nm Long Halorhodopsin

“…11 Studies with α-aminoisobutyric acid-rich hexapeptides, constrained into a 3 10 -helix and β-sheets, demonstrated that the presence of CC bonds influences backbone rigidity and promotes electron transfer across the peptide. 12,13 Solid-state electron transport measurements via different protein monolayers have shown that at room temperature (RT) ETp across bR is comparatively more efficient than across the globular proteins that we have measured so far, taking in account the differences in transport length across the protein. 6 In view of this, we examined whether Halorhodopsin (phR) as a homologue of bacteriorhodopsin (bR) might be even more efficient conductor, when immobilized with bacterioruberin oriented perpendicular to the electrodes ( Figure 1, right, device scheme).…”