Tomoyuki Morita

Electron Hopping over 100 Å Along an α Helix

Electron transfer through biomolecules has been of great interest for the understanding of energy conversion and mass transduction in nature and for the development of molecularbased electronics. In particular, the electron transfer in electron-transport proteins has been widely studied by spectroscopies with engineered proteins 14–16] and by electrochemistry with proteins immobilized on a metal surface. More specifically, the electron transfer through a helices has attracted much attention because their parallel assemblies are a universal motif found in biological electron-transfer systems, and the helices are considered to play important roles in long-range electron transfer in proteins. Therefore, the electron transfer through model helical peptides has been extensively studied by various techniques in solution 17] and on metal surfaces. These studies have revealed interesting features: 1) a helical peptide is a good mediator of electron tunneling compared to hydrocarbon chains; 2) the helix macrodipole accelerates the electron transfer, as demonstrated in solution and on a metal surface; and 3) at longer distances beyond a critical molecular length, the electron-transfer mechanism switches from simple electron tunneling to another mechanism characterized by a very shallow distance dependence. 27] For the last feature, two mechanisms have been proposed: a hopping mechanism with the amide groups as hopping sites, 28] and molecular dynamics-associated electron tunneling. Efficient hole hopping along bases in DNAs has been generally recognized. 5] Electron transfer through peptide nucleic acids (PNAs) has also been investigated and the contribution of a hopping mechanism has been proposed. On the other hand, despite of a lot of studies, the hopping contribution in peptide electron transfer still remains a matter of debate. In this study, we prepared well-defined self-assembled monolayers (SAMs) on gold from helical peptides of different lengths from 8 mer to 64 mer, and studied the electron transfer through the helices electrochemically. We observed nonexponential distance dependence and high activation energies of the electron transfer, which suggest a hopping mechanism with the amide groups as hopping sites. This suggestion has been successfully validated by in-depth calculations taking tunneling and hopping into consideration. Importantly, the 64-mer helical peptide provides an electron path of over 100 along the helix and a regular monolayer of approximately 80 in thickness, in which electrons are exchanged at a significant rate constant of 0.5 s 1 for electron transfer through dielectric organic materials. SAMs of redox-terminated helical peptides have been employed as ideal model systems to study the electron transfer through helical peptides. 19,22, 27, 34–36] We synthesized 8-, 16-, 32-, 48-, and 64-mer helical peptides carrying a lipoic acid for the linker to gold at the N terminus and a redoxactive ferrocene unit at the C terminus (A8, A16, A32, A48, A64, respectively; Figure 1). The helix segment has an

Effects of Monolayer Structures on Long-Range Electron Transfer in Helical Peptide Monolayer

Self-assembled monolayers of alpha-helical peptides were prepared on gold, and the effects of the monolayer structures (kind of constituent amino acid, molecular orientation, and molecular packing) on long-range electron transfer through the helical peptides were studied. The helical peptides were 16mer peptides having a thiophenyl linker at the N-terminal for immobilization on gold and a redox active ferrocene moiety at the C-terminal as an electron-transfer probe. The peptides were immobilized on gold by a gold-sulfur linkage and the electron transfer from the ferrocene moiety to gold was studied by electrochemical methods. When two types of the peptides, one with the repeating unit of Leu-Aib (Aib represents 2-aminoisobutyric acid) and the other with that of Ala-Aib, were compared, the electron transfer was found one order slower in the Leu-Aib peptide monolayer than that in the Ala-Aib peptide monolayer. The self-assembled monolayers of the Ala-Aib peptide with mixing of three different lengths of the peptides, 8mer, 12mer, and 16mer without a ferrocene moiety, were also prepared. The monolayer regularity in terms of molecular orientation and packing was higher roughly in the order of the monolayers mixed with 16mer > 12mer > no additive > 8mer, but the electron transfer became faster in the opposite order. The logarithms of the standard rate constants showed a nearly linear relationship with the direct distances between the ferrocene moiety and gold (beta = 0.32 A (-1)). Some data deviated from this linear relationship, but the deviations could be explained from the difference in the molecular packing, which was evaluated from the monolayer capacitance. It is thus concluded that an electron is transferred along a few molecules along the surface normal so that the vertical orientation or the increase of the interchain backbone separation slows down the electron transfer. Further, it is demonstrated that a tightly packed monolayer, where vibrational mode is restricted, suppresses the electron transfer. Three models are proposed to account for the observed molecular dynamics effects on the basis of either electron-transfer mechanism of electron tunneling or sequential hopping.

Electron Transfer through a Self-Assembled Monolayer of a Double-Helix Peptide with Linking the Terminals by Ferrocene

A unique molecular structure, a double-helix peptide, was self-assembled on gold, and the electron transfer through the monolayer was studied. The double-helix peptide consists of two 9mer 3(10)-helical peptide chains having a disulfide group at each N terminal and being linked by a ferrocene dicarboxylic acid between the C terminals. Each helical peptide chain has three naphthyl groups in a linear arrangement along the helix. The monolayer properties and the electron transfer from the ferrocene unit to gold were studied with reference peptides with a similar double helix but without naphthyl groups, a single helix with a dicarboxylic ferrocene unit, and a single helix with a monocarboxylic ferrocene unit. It was demonstrated that the naphthyl groups on the side chains had no effect on electron transfer, and the electron-transfer rate in the double-helix monolayer was not promoted, despite the two electron pathways in the molecule. We propose that in the double-helix monolayer, molecular motions are suppressed, possibly by its rigid structure tethered by the two linkers on gold to cancel out acceleration effects of the 2-fold electron pathways and the ferrocene substitution number. The factors that affect the electron-transfer reaction across the helical peptide SAMs are discussed in depth.

Ultra-long-range electron transfer through a self-assembled monolayer on gold composed of 120-Å-long α-helices.

Electron transfer through α-helices has attracted much attention from the viewpoints of their contributions to efficient long-range electron transfer occurring in biological systems and their utility as molecular-electronics elements. In this study, we synthesized a long 80mer helical peptide carrying a redox-active ferrocene unit at the terminal and immobilized the helical peptide on a gold surface. The molecular length is calculated to be 134 Å, in which the helix accounts for 120 Å. The preparation conditions of the self-assembled monolayers were intentionally changed to obtain monolayers with different physical states to study the correlation between molecular motions and electron transfer. Ellipsometry and infrared spectroscopy showed that the helical peptide forms a self-assembled monolayer with vertical orientation. Electrochemical measurements revealed that an electron is transferred from the ferrocene unit to gold through the monolayer composed of this long helical peptide, and the experimental data are well explained by theoretical results calculated under the assumption that electron transfer occurs by a unique hopping mechanism with the amide groups as hopping sites. Furthermore, we have observed a unique dependence of electron transfer on the monolayer packing, suggesting the importance of structural fluctuations of peptides on the electron transfer controlled by the hopping mechanism.

Linker Effects on Monolayer Formation and Long-Range Electron Transfer in Helical Peptide Monolayers

Helical peptides carrying a ferrocene unit at the C-terminus were immobilized on gold at the N-terminus via three different linkers to form self-assembled monolayers, and the long-range electron transfer from the ferrocene unit to gold was electrochemically studied. The linkers are 4-thiobenzoic acid, 3-fluoro-4-thiobenzoic acid, and 2-methoxy-4-thiobenzoic acid. All the peptides formed a monolayer with vertical orientation but some differences in monolayer packing and ferrocene surface density as they formed. However, the treatment with dodecanethiol in a gas phase uniformed to show similar monolayer physical parameters, and the electron-transfer rate constants were reproducibly obtained as well. These three peptide monolayers exhibited the same electron-transfer rate constants despite three linkers with different oxidation potentials. On the other hand, the electron transfer was decelerated seemingly by reducing the ferrocene surface density. Theoretical calculations with simple models demonstrated that the experimental result supports a hopping mechanism rather than electron tunneling though it cannot be fully excluded.

Parallel assembly of dipolar columns composed of a stacked cyclic tri-β-peptide

A novel cyclic trimer of a β-amino acid, trans-2-aminocyclohexylcarboxylic acid, was synthesized and its conformation and ability to form assemblies investigated. FT-IR and NMR measurements and computational calculations showed that this cyclic tri-β-peptide has a C3-symmetric conformation with trans amide groups. A notable feature of the conformation is a vertical and parallel orientation of the three amide groups to the cyclic skeleton. The cyclic tri-β-peptide was crystallized from a solution in trifluoroacetic acid–methanol (or trifluoroacetic acid–water) to yield a rod-shaped molecular assembly, as observed by TEM. The electron crystallography of the rod-shaped assembly both in suspension and in ultrathin cross-section revealed that the cyclic tri-β-peptides were stacked up to form molecular columns, and that a two-fold screw symmetry operation along the column direction was present in the unit cell, which contained two cyclic tri-β-peptides. This indicates that all the amide groups are oriented in the same direction. Since any two molecular columns are staggered by a quarter of a c-axis length and aligned parallel to each other, the dipole moments of the columns are aligned to enhance the strength additively in the whole assembly.

Photoinduced Electron Transfer in Thin Layers Composed of Fullerene-Cyclic Peptide Conjugate and Pyrene Derivative

A bilayer structure was constructed on gold by Langmuir-Blodgett deposition of a fullerene (C 60)-cyclic peptide-poly(ethylene glycol) (PEG) conjugate and thereafter a pyrene derivative from the air/water interface. The cyclic peptide moiety acts as a scaffold to prevent the fullerenes from self-aggregation and accordingly makes the monolayer homogeneous and stable. In addition to this gold/C 60-cyclic peptide-PEG/pyrene bilayer, a pyrene monolayer, a gold/C 60-PEG conjugate/pyrene bilayer (lacking the peptide scaffold), and a gold/pyrene/C 60-cyclic peptide-PEG bilayer (with the opposite order of layers) were also prepared, and their anodic photocurrent generation were studied in an aqueous solution containing a sacrifice electron donor. The most efficient photocurrent generation was observed in the gold/C 60-cyclic peptide-PEG/pyrene bilayer. It is considered that the C 60 unit acts not only as sensitizer but also as an electron acceptor facilitating the electron transfer from the excited pyrene unit to gold, and that the fullerene layer suppresses quenching of the excited pyrene unit by energy transfer to gold. Furthermore, the cyclic peptide scaffold helps the fullerenes disperse without aggregation in the membrane and seems to protect their redox properties or inhibit self-quenching of their excited state. It is thus concluded that a bilayer structure with desired orientation of functional units is important for efficient photoinduced electron transfer and that a cyclic peptide scaffold is useful to locate hydrophobic functional groups properly in a thin layer.

Foldamer for novel peptide derivatives with pyrene units incorporated into the main chain

Abstract A novel foldamer with pyrene units incorporated into a peptide main chain was synthesized and its conformation in solution was investigated by spectroscopic measurements and computational calculations. The foldamer designed here contains 1-aminopyrene-8-carboxylic acid in the sequence, which residue is expected to change the peptide chain direction by 1201. A decapeptide, Boc–Ala–Pyr–Aib–Ala–Aib–Ala–Pyr–Aib–Ala–Aib–OMe, where Boc, Ala, Aib, Pyr, and OMe stand for t-butyloxycarbonyl group, L-alanine, a-aminoisobutyric acid, 1-aminopyrene-8-carboxylic acid, and methyl ester, respectively, was synthesized. Absorption spectroscopy in acetonitrile showed that the two pyrene units in the decapeptide do not interact with each other in the ground state. On the other hand, the fluorescence spectroscopy suggested that the two pyrene units are fixed at a certain distance that allows interaction in the excited state. The circular dichroism spectra showed distinct exciton coupling peaks around the pyrene absorption, further supporting that the two pyrene units have a specific spatial relationship. According to 1H NMR measurements, it was found that the decapeptide has two intramolecular hydrogen bondings and the amide protons of the two 1-aminopyrene-8-carboxylic acid residues are close to each other. The dihedral angles of C–N–Cα–C in the alanine residues were also determined. Taking all these findings into account, molecular mechanics and semiempirical computational calculations were carried out to give two conformations, left-handed and right-handed helices, in which the two pyrene units partially overlap with each other. Theoretical circular dichroism spectra werecalculated from these two conformations and compared to the experimental spectrum. It was shown that the left-handed helixconformation is the plausible conformation. The pyrene units incorporated into the main chain are considered to stack witheach other by an aromatic interaction, resulting in the formation of a helical structure as a whole.

Photocurrent generation by helical peptide monolayers integrating light harvesting and charge-transport functions.

In this study, we construct photoenergy-conversion systems with chromophores located with molecular precision to facilitate efficient light harvesting and charge transport. 3(10) -Helical peptides carrying a disulfide group at the N-terminal, linearly arranged six naphthyl groups at the side chains, and an energy acceptor (anthryl, pyrenyl, or N-ethylcarbazolyl group) at the C-terminal were immobilized on a gold surface via a gold-sulfur linkage to form a well-defined self-assembled monolayer with vertical orientation. The monolayer composed of helical peptides terminated with a naphthyl group instead of an energy acceptor was used as control. Upon photoexcitation of the naphthyl groups of the monolayers in solutions containing an electron donor, all the monolayers generated an anodic photocurrent. The photocurrent generation by the monolayers with an acceptor is composed of the following three steps: (1) photon capture by the side-chain naphthyl groups and energy transfer to the terminal acceptor (light harvesting), (2) electron donation from the aqueous donor to the excited acceptor (electron generation), and (3) electron transport from the terminal to gold via the side-chain naphthyl groups (electron hopping). Unfortunately, it was found that introduction of an energy acceptor facilitates the light-harvesting step but suppresses the electron-generation and electron-hopping steps, resulting in slight reduction of the efficiency of photocurrent generation compared to the control system. Further detailed discussion on photoenergy and electron transport processes shows a prospect to realize efficient photocurrent generation systems taking advantages of both light harvesting and charge-transport functions in future.

Second-harmonic generation from Langmuir-Blodgett film of cyclic peptide carrying two disperse red 1 on fused quartz surface.

Cyclic octapeptide carrying one or two nonlinear optical chromophores, disperse red 1 (DR‐1), was synthesized and immobilized on a substrate to attain an active surface for second‐harmonic generation (SHG). Each cyclic octapeptide was transferred on a fused quartz substrate by the Langmuir–Blodgett (LB) method to afford a uniform monolayer. Infrared reflection–absorption spectroscopy of the LB monolayer revealed that the cyclic skeleton lay roughly flat on the surface. The SHG intensity from the monolayer of the cyclic peptide with two DR‐1 units was stronger than that from that with one DR‐1 unit. The difference is discussed in terms of molecular orientation and surface density of the active chromophores. The cyclic peptide is shown here to be an effective scaffold to modify a substrate surface with functional groups of a monolayer with taking stability of the monolayer and orientation of the functional group into consideration. Copyright