A controllable mechanistic transition of charge transfer in helical peptides: from hopping to superexchange

Yu, Jingxian; Horsley, John R.; Abell, Andrew D.

doi:10.1039/c7ra07753j

Cited by 5 publications

(9 citation statements)

References 62 publications

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“…The others are two-step sequential hopping pathways originating at Aib1, passing through either the peptide backbone (Aib4, red arrows) or the amide-containing side bridge/side chain (blue arrows), and terminating at Aib6. 26 The overall computed superexchange rate constant (k ET,super ) is 2.28 × 10 11 s −1 for constrained 9, while the overall hopping electron transfer rate constant via its backbone is smaller (k ET,hop1 = 2.36 × 10 9 s −1 ). In contrast, linear 10 has an overall k ET,super of 6.57 × 10 12 s −1 , while the overall k ET,hop1 via the backbone is greater (1.00 × 10 15 s −1 ).…”

Section: Accounts Of Chemical Researchmentioning

confidence: 94%

“…One involves one-step superexchange between the first and last residues (Aib1 and Aib6), as shown by the green arrows. The others are two-step sequential hopping pathways originating at Aib1, passing through either the peptide backbone (Aib4, red arrows) or the amide-containing side bridge/side chain (blue arrows), and terminating at Aib6 …”

Section: Backbone Rigidity and Controllable Mechanistic Transitionmentioning

confidence: 99%

“…The latest constrained density functional theory (cDFT) provides a natural way to define diabatic states by imposing the charge (or spin) constraints on arbitrary molecular fragments and calculating the properties of individual states . This is called the Marcus theory in conjunction with constrained density functional theory (cDFT-Marcus). , …”

Section: Introductionmentioning

confidence: 99%

“…24 This is called the Marcus theory in conjunction with constrained density functional theory (cDFT-Marcus). 25,26 This Account focuses mainly on our recent novel findings on the relationship between the electron transfer kinetics (i.e., k ET and the formal potential E 0 ) and the electron transfer dynamics, including the influence of secondary structure, backbone rigidity, and electron-rich side chains, from an electrochemical and first-principles perspective. We also discuss the correlation between electron transfer and electronic transport, as well as the role of quantum interference in peptides.…”

Section: Introductionmentioning

confidence: 99%

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Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Horsley

2018

Acc. Chem. Res.

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Molecular electronics is at the forefront of interdisciplinary research, offering a significant extension of the capabilities of conventional silicon-based technology as well as providing a possible stand-alone alternative. Bio-inspired molecular electronics is a particularly intriguing paradigm, as charge transfer in proteins/peptides, for example, plays a critical role in the energy storage and conversion processes for all living organisms. However, the structure and conformation of even the simplest protein is extremely complex, and therefore, synthetic model peptides comprising well-defined geometry and predetermined functionality are ideal platforms to mimic nature for the elucidation of fundamental biological processes while also enhancing the design and development of single-peptide electronic components. In this Account, we first present intramolecular electron transfer within two synthetic peptides, one with a well-defined helical conformation and the other with a random geometry, using electrochemical techniques and computational simulations. This study reveals two definitive electron transfer pathways (mechanisms), the natures of which are dependent on secondary structure. Following on from this, electron transfer within a series of well-defined helical peptides, constrained by either Huisgen cycloaddition, ring-closing metathesis, or a lactam bridge, was determined. The electrochemical results indicate that each constrained peptide, in contrast to a linear counterpart, exhibits a remarkable shift of the formal potential to the positive (>460 mV) and a significant reduction of the electron transfer rate constant (up to 15-fold), which represent two distinct electronic "on/off" states. High-level calculations demonstrate that the additional backbone rigidity provided by the side-bridge constraints leads to an increased reorganization energy barrier, which impedes the vibrational fluctuations necessary for efficient intramolecular electron transfer through the peptide backbone. Further calculations reveal a clear mechanistic transition from hopping to superexchange (tunneling) stemming from side-bridge gating. We then extended our research to fine-tuning of the electronic properties of peptides through both structural and chemical manipulation, to reveal an interplay between electron-rich side chains and backbone rigidity on electron transfer. Further to this, we explored the possibility that the side-bridge constraints present in our synthetic peptides provide an additional electronic transport pathway, which led to the discovery of two distinct forms of quantum interferometer. The effects of destructive quantum interference appear essentially through both the backbone and an alternative tunneling pathway provided by the side bridge in the constrained β-strand peptide, as evidenced by a correlation between electrochemical measurements and conductance simulations for both linear and constrained β-strand peptides. In contrast, an interplay between quantum interference effects and vibrational fluctuations ...

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Section: Accounts Of Chemical Researchmentioning

confidence: 94%

Section: Backbone Rigidity and Controllable Mechanistic Transitionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Horsley

2018

Acc. Chem. Res.

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“…Furthermore, the efficiency of ETp in peptides is enhanced by helical secondary structure, which is in turn defined by temperature . The inclusion of amino acids with electron-rich side chains facilitates ET across a peptide, while a side chain constraint or tether, which rigidifies the backbone dramatically, decreases ET in solution. ,− These two main experimental techniques, namely, solution-based electrochemistry (ET) and solid-state junction conductance (ETp), are widely employed to investigate charge transfer across self-assembled monolayers (SAMs) of peptides. , Specifically, the electrical current across solid-state molecular junctions can be investigated as a function of applied voltage, using SAM-based peptide ensembles sandwiched between two metallic electrodes . ET through such a peptide monolayer can be studied in solution by replacing one electrode of the molecular junction with a redox-active moiety to provide the electron transfer rate constant ( k et ). ,, …”

Section: Introductionmentioning

confidence: 99%

Backbone-Constrained Peptides: Temperature and Secondary Structure Affect Solid-State Electron Transport

Guo

Horsley

et al. 2019

J. Phys. Chem. B

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The primary sequence and secondary structure of a peptide are crucial to charge migration, not only in solution (electron transfer, ET), but also in the solid-state (electron transport, ETp). Hence, understanding the charge migration mechanisms is fundamental to the development of biomolecular devices and sensors. We report studies on four Aib-containing helical peptide analogues: two acyclic linear peptides with one and two electron-rich alkene-based side chains, respectively, and two peptides that are further rigidified into a macrocycle by a side bridge constraint, containing one or no alkene. ETp was investigated across Au/peptide/Au junctions, between 80 and 340 K in combination with the molecular dynamic (MD) simulations. The results reveal that the helical structure of the peptide and electron-rich side chain both facilitate the ETp. As temperature increases, the loss of helical structure, change of monolayer tilt angle, and increase of thermally activated fluctuations affect the conductance of peptides. Specifically, room temperature conductance across the peptide monolayers correlates well with previously observed ET rate constants, where an interplay between backbone rigidity and electron-rich side chains was revealed. Our findings provide new means to manipulate electronic transport across solid-state peptide junctions.

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A Bimane‐Based Peptide Staple for Combined Helical Induction and Fluorescent Imaging

et al. 2020

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The thiol-selective fluorescent imaging agent, dibromobimane, has been repurposed to crosslink cysteine-and homocysteinecontaining peptides, with the resulting bimane linker acting as both a structural constraint and a fluorescent tag. Macrocyclisation was conducted on nine short peptides containing two cysteines and/or homocysteines, both on-resin and in buffered aqueous solution, to give macrocycles ranging in size from 16 (i,i + 2) to 31 (i,i + 7) atoms. The structures were defined by CD, NMR structure calculations by using Xplor-NIH, NMR secondary shift and J HαNH analyses to reveal helical structure in the i,i + 4 (1, 2), and i,i + 3 (5) constrained peptides. Cellularuptake studies were conducted with three of the macrocycles. Subsequent confocal imaging revealed punctate fluorescence within the cytosol indicative of peptides trapped in endocytic vesicles. These studies demonstrate that dibromobimane is an effective tool for defining secondary structure within short peptides, whilst simultaneously introducing a fluorescent tag suitable for common cell-based experiments.

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A controllable mechanistic transition of charge transfer in helical peptides: from hopping to superexchange

Abstract: A controllable mechanistic transition of charge transfer in helical peptides is demonstrated as a direct result of side-bridge gating.

Cited by 5 publications

References 62 publications

Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Peptides as Bio-Inspired Electronic Materials: An Electrochemical and First-Principles Perspective

Backbone-Constrained Peptides: Temperature and Secondary Structure Affect Solid-State Electron Transport

A Bimane‐Based Peptide Staple for Combined Helical Induction and Fluorescent Imaging

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