Fragmentation reactions of aromatic cation radicals: a tool for the detection of electron transfer mechanisms in biomimetic and enzymatic oxidations.

Coupled electron and proton transfer reactions play a key role in the mechanisms of biological energy transduction.1–3 Such reactions are also fundamental for artificial energy-related systems such as fuel cells, chemical sensors, and other electrochemical devices. Biological examples include, among others, cytochrome c oxidase,4,5 bc1 complex,6,7 and photosynthetic reaction centers.8,9 In such systems, electrons tunnel between redox cofactors of an enzyme, while the coupled protons are transferred either across a single hydrogen bond or between protonatable groups along special proton-conducting channels. In this paper general theories and models of coupled electron transfer/proton transfer (ET/PT) reactions are discussed. Pure electron transfer reactions in proteins have been thoroughly studied in the past, both experimentally10–17 and theoretically.18–25 The coupled reactions are relatively new and currently are gaining attention in the field.6,8,26–43 Two types of coupled reactions can be distinguished. In concerted electron and proton transfer reactions (denoted PCET in Refs. 29,30,43–45, although this term is also used more generally), both the ET and PT transitions occur in one step. Such concerted processes occur in reactions in which proton transfer is typically limited to one hydrogen bond; however, examples with multiple hydrogen bond rearrangements are also known.46 In sequential reactions, the transitions occur in two steps: ET/PT or PT/ET. Typically each individual step is uphill in energy, while the coupled reaction is downhill. A sequential reaction can proceed along two parallel channels: ET then PT (EP) or PT then ET (PE). In each channel the reaction involves two sequential steps: uphill activation, and then downhill reaction to the final product state. The lifetime of the activated complex is limited by the back reaction. The general formula for the rate of such reactions can be easily developed. In the context of bioenergetics issues, however, it is interesting to analyze all of the possible cases separately because each corresponds to a different mechanism: for example, an electron can go first and pull out a proton; alternatively, a proton can go first and pull out an electron; or an electron can jump back and forth between donor and acceptor and gradually pull out a proton. In enzymes involving coupled proton and electron transport, the exact mechanism of the reaction is of prime interest. First we will consider a simple four-state model of reactions where the proton moves across a single hydrogen bond; both concerted and sequential reactions will be treated. Then we will consider models for long-distance proton transfer, also denoted proton transport or proton translocation. Typically, electron transfer coupled to proton translocation in proteins involves an electron tunneling over a long distance between two redox cofactors, coupled to a proton moving along a proton conducting channel in a classical, diffusion-like random walk fashion. Again, separately the electron and proton transfer reactions are typically uphill, while the coupled reaction is downhill in energy. The schematics of this process is shown in Fig. 1. The kinetics of such reactions can be much different from those involving proton transfer across a single hydrogen bond. In this paper, we will discuss the specifics of such long-distance proton-coupled reactions. Fig. 1 Schematics of the electron transfer reaction coupled to proton translocation. In the reaction, an electron is tunneling over a long distance between two redox cofactors, O and R, and a coupled proton is transferred over a proton conducting channel. The ... Following the review of theoretical concepts, a few applications will be discussed. First the phenoxyl/phenol and benzyl/toluene self-exchange reactions will be examined. The phenoxyl/phenol reaction involves electronically nonadiabatic proton transfer and corresponds to a proton-coupled electron transfer (PCET) mechanism, whereas the benzyl/toluene reaction involves electronically adiabatic proton transfer and corresponds to a hydrogen atom transfer (HAT) mechanism. Comparison of these two systems provides insight into fundamental aspects of electron-proton interactions in these types of systems. Next a series of theoretical calculations on experimentally studied PCET reactions in solution and enzymes will be summarized, along with general predictions concerning the dependence of rates and kinetic isotope effects (the ratio of the rate constants for hydrogen and deuterium transfer) on system properties such as temperature and driving force. The final application that will be discussed is cytochrome c oxidase (CcO). CcO is the terminal component of the electron transport chain of the respiratory system in mitochondria and is one of the key enzymes responsible for energy generation in cells. The intricate correlation between the electron and proton transport via electrostatic interactions, as well as the kinetics of the coupled transitions, appear to be the basis of the pumping mechanism in this enzyme.

Review: 180 refs.

Data of tertiary: secondary: primary C–H bond relative reactivity (TSP selectivity) for a number of electron transfer (ET) and hydrogen atom transfer (HAT) reactions of alkylbenzenes have been critically reviewed and in a few cases supplemented by additional experiments. The resulting picture indicates that there are significant differences in TSP selectivity between ET and HAT reactions. When the HAT mechanism is operating the reactivity order tertiary > secondary > primary C–H bond is always observed. This order never holds in reactions occurring by an ET mechanism where, generally, the secondary C–H bond is the most reactive one and the tertiary centre can be either more or even less reactive than the primary one. Whatever the possible reasons for these differences, it turns out that TSP C–H bond selectivity determinations can afford useful information with respect to the distinction between ET and HAT mechanisms in the oxidations of alkylbenzenes. To check this conclusion a study of TSP selectivity in the oxidation of alkylbenzenes promoted by metalloporphyrins and by microsomal cytochrome P-450 has been carried out, which has allowed us to assign a HAT mechanism to these reactions, in full accord with previous attributions.

The mechanistic dichotomy (hydrogen atom transfer or electron-transfer mechanism) in the oxidative N-dealkylation of a series 4-X-N,N-dimethylanilines (X = MeO, Me, H, Br, CF3, CN, NO2) by PhIO, catalyzed by tetrakis(pentafluorophenyl)porphyrin iron(LII) chloride (FeTPFPPCl), was investigated in CH2Cl2 by determining both the intra- and the intermolecular kinetic deuterium isotope effects and the effect of substituents on reactivity. The results were as follows: (a) The values of k(H)/k(D)(intra), obtained by the study of 4-X-N-methyl-N-trideuteriomethylanilines [2.0 (X = NO2), 2.0 (X = CN), 2.6 (X = Br), 3.1 (X = H), 3.2 (X = Me), 3.3 (X MeO)], regularly decreased on going from electron donating to electron withdrawing substituents, a trend exactly contrary to that found for the hydrogen atom transfer reactions of some of the same substrates with tert-butoxyl radicals. (b) The intermolecular kinetic deuterium isotope effects, k(H)/k(D)(inter), determined by competitive experiments with 4-X-substituted N,N-dimethyl- and N,N-bis(trideuteriomethyl)anilines [k(H)/k(D)(inter) for X H, Br, and MeO, 1.6, 1.5 and 1.9, respectively], were significantly different from the corresponding k(H)/k(D)(intra) values. (c) The relative reactivities of 4-X-substituted N,N-dimethylanilines, determined by competitive kinetics, spanned a reactivity range of 25 (from X = NO2 to X = MeO) and were nicely correlated by the substituent constants sigma(+). A rho value of -0.88 was determined by this correlation. The relative reactivity can also be fitted to the Rehm-Welter equation for electron-transfer reactions. A value of 47 kcal/mol for the reorganization energy was calculated. Altogether, the above results, and particularly points (a) and (b), allow us to dismiss the operation of a hydrogen atom transfer mechanism. A one electron transfer mechanism is instead consistent with these results and appears therefore the most likely pathway for the oxidative N-demethylation of N,N-dimethylanilines catalyzed by iron porphyrins. The intramolecular kinetic deuterium isotope effect profile is a useful tool for distinguishing electron transfer from hydrogen atom transfer mechanisms.

Electron transfer (ET) reactions are crucial for energy and substance metabolism in living organisms. Notably, ET reactions between proteins are believed to have protein-specific regulatory mechanisms distinct from those of small molecules, primarily due to the extended ET distance between redox centers within the fluctuating structures of proteins. The mitochondrial respiratory chain, comprising a series of interprotein ET reactions, functions to pump protons from the matrix to the intermembrane space by transferring electrons between proteins constituting the respiratory chain. This process creates a proton concentration gradient across the mitochondrial membrane, which ATP synthase utilizes to synthesize ATP, the energy currency for cells. The ET reactions in the mitochondrial respiratory chain culminate in cytochrome c oxidase (CcO), which accepts electrons from cytochrome c (Cyt c) and reduces molecular oxygen to water. Although the reduction of molecular oxygen to water by CcO requires four electrons, Cyt c acts as a one-electron carrier, necessitating tight regulation of its ET reaction to prevent the production of highly cytotoxic reactive oxygen species from incomplete oxygen reduction. Due to its biological significance, the ET reaction from Cyt c to CcO has been the subject of extensive research, most of which has examined the ET reaction from Cyt c to detergent-solubilized CcO in buffer solutions. However, CcO is embedded in the inner mitochondrial membrane and operates under molecular crowding conditions where a variety of molecules, ranging from small ions to large macromolecules, coexist in cells. Consequently, the surrounding environment differs significantly from that in previous ET reaction experiments involving Cyt c and detergent-solubilized CcO. Notably, previous studies have indicated that the dynamic properties of proteins, specifically “conformational fluctuations” or transient changes in protein structure, significantly impact the ET from Cyt c to CcO. Moreover, lipid bilayers, such as the inner mitochondrial membrane in which CcO is embedded, influence the dynamics of the embedded proteins. Different physical properties of cellular solutions, such as viscosity, osmotic pressure, and excluded volume effects, can also affect protein “structural fluctuations”. To address these differences, we employed CcO embedded in lipid bilayers instead of using detergent solubilization, to examine the ET reaction from Cyt c under conditions that closely resemble those within cells, specifically under molecular crowding conditions. This approach aims to elucidate how intracellular environmental factors, such as lipid bilayer embedding and the presence of molecular crowding agents, influence the ET reaction. By thoroughly examining their impact on the ET reaction, we aim to identify the intracellular environmental factors regulating the ET reaction from Cyt c to CcO within the cell. As an artificial lipid bilayer model, we used bicelles, which exhibit dynamic properties similar to those of cellular lipid bilayers. We monitored the ET reaction from Cyt c to CcO embedded in bicelles composed of the phospholipids DMPC and DHPC, and kinetically analyzed the reaction using Michaelis-Menten analysis. Although there was no significant change in the Michaelis-Menten constant (K m), which approximately corresponds to the dissociation constant for complex formation between Cyt c and CcO, indicating that the Cyt c interaction sites in bicelle-reconstituted CcO are similar to those in detergent-solubilized CcO, the k cat was accelerated by reconstituting CcO into bicelles. Given that the k cat corresponds to the rate constant for the transition of the Cyt c-CcO complex to an ET-active complex via “structural fluctuations”, it is hypothesized that the interaction between CcO and the lipid bilayer in bicelles accelerates the ET reaction from Cyt c to CcO by modulating the structural fluctuations of CcO. Conversely, the presence of sugars such as sucrose as molecular crowding agents decreased the k cat. The concentration dependence of the molecular crowding agents suggested that an increase in solution viscosity suppresses the ET reaction more effectively than osmotic pressure, as a physical property of the solution. Solution viscosity limits the magnitude of conformational fluctuations in proteins. Consequently, high-viscosity environments suppress the structural fluctuations necessary for the transition from the Cyt c - CcO complex to the ET-active complex. In summary, our results suggest that interactions between lipid bilayers and ET proteins, as well as the molecular crowding environment in cells, regulate ET reactions through the modulation of structural fluctuations in ET proteins.

This paper describes a mechanistic crossover driven by steric hindrance, from C-alkylation (SUB(C)) to dissociative electron transfer (ET), in the reactions between cyanoformaldehyde anion radical and alkyl chlorides of variable steric size (alkyl = Me, Et, i-Pr, t-Bu). The computations provide structural details on the transition state (TS) structures which undergo this mechanistic transformation, and thereby enable links to experimental investigations on the relationship between classical substitution mechanisms and their ET counterparts to be drawn. The TS's of the interchanging mechanisms possess the C- - -C- - -Cl structure, where the first C is the carbon atom of the formyl group. It is found that the TS's for the less hindered substrates (Me, Et), with R(CC) = 2.35 and 2.45 Å, collapse to C-alkylation product, hence a SUB(C) mechanism. As steric hindrance increases (i-Pr, t-Bu) and the C- - -C distance increases to 2.57 Å and then to 2.96 Å, the TS falls apart to dissociated ET products, hence an ET mechanism. This is therefore an isostructural mechanistic transformation within a narrow range of change in the C- - -C distance. A third mechanism of O-alkylation (SUB(O)) is also observed, but while its TS undergoes O- - -C loosening by the steric hindrance, no mechanistic transformation occurs. This dichotomy of the steric hindrance is analyzed with use of the valence bond configuration mixing (VBCM) method and shown to originate in the parity (odd vs even) of the number of electrons which participate in the bond reorganization. The VBCM method projects that ET and SUB(C) mechanisms are nascent from the VB mixing of the same set of configurations, and as such the two mechanisms are "entangled" and their corresponding TS's involve hybrid characters. Near the changeover zone (e.g., where the TS for the i-PrCl substrate is located in Figure 6), the degree of entanglement is strong, and may lead to surface bifurcation. The origins of the experimentally observed residual stereoselectivity of ET reactions are discussed in this respect and as a result of radical collapse. The ET-TS which emerges from the computations possesses significant and variable bonding which conforms to simple orbital selection rules (refs 1, 10, and 11). The importance of probing the bonding is discussed along with potential strategies thereof.

The mechanisms of electron transfer of association of chemoorganotrophic bacteria to the anode in microbial fuel cells are summarized in the survey. These mechanisms are not mutually exclusive and are divided into the mechanisms of mediator electron transfer, mechanisms of electron transfer with intermediate products of bacterial metabolism and mechanism of direct transfer of electrons from the cell surface. Thus, electron transfer mediators are artificial or synthesized by bacteria riboflavins and phenazine derivatives, which also determine the ability of bacteria to antagonism. The microorganisms with hydrolytic and exoelectrogenic activity are involved in electron transfer mechanisms that are mediated by intermediate metabolic products, which are low molecular carboxylic acids, alcohols, hydrogen etc. The direct transfer of electrons to insoluble anode is possible due to membrane structures (cytochromes, pili, etc.). Association of microorganisms, and thus the biochemical mechanisms of electron transfer depend on the origin of the inoculum, substrate composition, mass transfer, conditions of aeration, potentials and location of electrodes and others, that are defined by technological and design parameters.

Photooxygenations of PhSMe and Bu2S sensitized by N-methylquinolinium (NMQ+) and 9,10-dicyanoanthracene (DCA) in O2-saturated MeCN have been investigated by laser and steady-state photolysis. Laser photolysis experiments showed that excited NMQ+ promotes the efficient formation of sulfide radical cations with both substrates either in the presence or in absence of a cosensitizer (toluene). In contrast, excited DCA promotes the formation of radical ions with PhSMe, but not with Bu2S. To observe radical ions with the latter substrate, the presence of a cosensitizer (biphenyl) was necessary. With Bu2S, only the dimeric form of the radical cation, (Bu2S)2+*, was observed, while the absorptions of both PhSMe+* and (PhSMe)2+* were present in the PhSMe time-resolved spectra. The decay of the radical cations followed second-order kinetics, which in the presence of O2, was attributed to the reaction of the radical cation (presumably in the monomeric form) with O2-* generated in the reaction between NMQ* or DCA-* and O2. The fluorescence quenching of both NMQ+ and DCA was also investigated, and it was found that the fluorescence of the two sensitizers is efficiently quenched by both sulfides (rates controlled by diffusion) as well by O2 (kq = 5.9 x 10(9) M(-1) s(-1) with NMQ+ and 6.8 x 10(9) M(-1) s(-1) with DCA). It was also found that quenching of 1NMQ* by O2 led to the production of 1O2 in significant yield (PhiDelta = 0.86 in O2-saturated solutions) as already observed for 1DCA*. The steady-state photolysis experiments showed that the NMQ+- and DCA-sensitized photooxygenation of PhSMe afford exclusively the corresponding sulfoxide. A different situation holds for Bu2S: with NMQ+, the formation of Bu2SO was accompanied by that of small amounts of Bu2S2; with DCA, the formation of Bu2SO2 was also observed. It was conclusively shown that with both sensitizers, the photooxygenations of PhSMe occur by an electron transfer (ET) mechanism, as no sulfoxidation was observed in the presence of benzoquinone (BQ), which is a trap for O2-*, NMQ*, and DCA-*. BQ also suppressed the NMQ+-sensitized photooxygenation of Bu2S, but not that sensitized by DCA, indicating that the former is an ET process, whereas the second proceeds via singlet oxygen. In agreement with the latter conclusion, it was also found that the relative rate of the DCA-induced photooxygenation of Bu2S decreases by increasing the initial concentration of the substrate and is slowed by DABCO (an efficient singlet oxygen quencher). To shed light on the actual role of a persulfoxide intermediate also in ET photooxygenations, experiments in the presence of Ph2SO (a trap for the persulfoxide) were carried out. Cooxidation of Ph2SO to form Ph2SO2 was, however, observed only in the DCA-induced photooxygenation of Bu2S, in line with the singlet oxygen mechanism suggested for this reaction. No detectable amounts of Ph2SO2 were formed in the ET photooxygenations of PhSMe with both DCA and NMQ+ and of Bu2S with NMQ+. This finding, coupled with the observation that 1O2 and ET photooxygenations lead to different product distributions, makes it unlikely that, as currently believed, the two processes involve the same intermediate, i.e., a nucleophilic persulfoxide. Furthermore, the cooxidation of Ph2SO observed in the DCA-induced photooxygenation of Bu2S was drastically reduced when the reaction was performed in the presence of 0.5 M biphenyl as a cosensitizer, that is, under conditions where an (indirect) ET mechanism should operate. This observation confirms that a persulfoxide is formed in singlet oxygen but not in ET photosulfoxidations. The latter conclusion was further supported by the observation that also the intermediate formed in the reaction of thianthrene radical cation with KO2, a reaction which mimics step d (Scheme 2) in the ET mechanism of photooxygenation, is an electrophilic species, being able to oxidize Ph2S but not Ph2SO. It is thus proposed that the intermediate involved in ET sulfoxidations is a thiadioxirane, whose properties (it is an electrophilic species) seem more in line with the observed chemistry. Theoretical calculations concerning the reaction of a sulfide radical cation with O2-* provide a rationale for this proposal.

There is a growing appreciation of the important role that H-bond complexes can play in the mechanism of proton-coupled electron transfer (PCET) reactions. Until relatively recently it had been thought that PCET reactions always proceeded step-wise with sequential electron and proton transfer. Much of the recent fundamental interest in PCET stems from the realization that a third option is available, concerted electron and proton transfer or CPET in which the electron and proton both move in a single kinetic step. This interest in the concerted process has increased awareness of H-bonding states in PCET, since the concerted reaction occurs within a H-bonded intermediate. However, even if the proton and electron transfer is not concerted, the H-bonded complex formed in the process of proton transfer can play an important role in the PCET mechanism if it is sufficiently long-lived.Recently we have introduced a generally useful mechanistic framework with which to include H-bonding steps within an overall PCET pathway. This scheme, which for obvious reasons we call a “wedge”, is shown in Scheme 1 for the generic 1e−, 1H+ oxidation, AH + B = A + HB+ + e−. The front face in the wedge (in bold) is the standard electron transfer/proton transfer square scheme, with the two possible electron transfer reactions on the top and bottom edges, and the two possible proton transfers on the left and right edges. However, proton transfer reactions actually go through a H-bond intermediate, so a more accurate description of the proton transfer follows the dashed lines on the triangular sides of the wedge to and from the H-bond intermediates, A-H-B or A-H-B+, which are meant to represent the thermodynamically most stable H-bond complex in each oxidation state. If the H-bonded intermediate has sufficient lifetime, then electron transfer to/from the H-bond complex is also possible, represented by the rear edge of the wedge (thin solid line). If the proton moves from being more attached to A in A-H-B to being more attached to B in A-H-B+, then E° of this reaction is that of the CPET step, if the proton doesn’t move then the E° is simply that of oxidation of the H-bond complex. Either way, it is straightforward to show that E°(A-H-B0/+) has to have a value in between E°(AH0/+) and E°(A−/0). Thus the possibility of electron transfer through the H-bond complex opens up a pathway of intermediate potential for the overall reaction AH + B = A + HB+ + e−.The usefulness of the wedge scheme is demonstrated by its ability to explain the unusual electrochemistry of the phenylenediamine-based urea, U(H)H, which we have shown undergoes a self proton transfer upon oxidation to give half equivalent of the doubly oxidized quinoidal cation and half-equivalent of the electroinactive, protonated reduced urea, Scheme 2. The reaction gives chemically irreversible voltammetry in acetonitrile as would be expected given that the quinoidal cation is harder to reduce than the initially formed radical cation. However, it gives reversible voltammetry in methylene chloride, which can be explained by the greater stability of the H-bonded intermediate in this solvent. In addition, in methylene chloride, we are able to clearly observe a concentration and scan rate dependent conversion between two different reduction pathways on the return scan. This behavior cannot be explained by a simple square scheme, but is readily explained by the wedge scheme.In this presentation, we will report recent results on the voltammetry of U(H)H in the presence of guest molecules that H-bond to the starting, reduced state. We will show that their effect on the voltammetry can be explained in terms of two interlinked wedge schemes, one representing the electron transfer / H-bonding / proton transfer reactions of U(H)H with itself and the other representing the reactions with the added guest.

A first principles investigation of electron transfer between Fe(II) and U(VI) on insulating Al- vs. semiconducting Fe-oxide surfaces via the proximity effect

The dynamics and mechanism of the photoinduced electron transfer (PET) reaction between coumarin 307 (C307) and aromatic amines in micelles have been studied by using steady-state (S-S) and time-resolved (T-R) absorption and fluorescence spectroscopy. Based on the fluorescence quenching time scale, PET in micelles is grouped into two types: (i) ultrafast electron transfer (ET) due to the close contact of the donor and acceptor in micelles and (ii) diffusion averaged dynamic electron transfer (DADET) which is controlled by the diffusion of the reactants in micellar Stern layer and diffusion of the micelles. The DADET does not affect the photoionization and solvation processes whereas ultrafast ET competes with the photoionization and faster than the solvation process. Both ultrafast and DADET shows Marcus inversion in the ET rates at the similar exergonicity and indicates that the role of diffusion and solvent reorganization is negligible toward the activation barrier for the ET reaction in micelles. The activation barrier for the ET reactions in micelles is mainly due to intramolecular reorganization energy. The intramolecular reorganization energy must be higher in CTAB due to the photoionization and subsequent recombination and also involvement of triplet state in the PET. The ET reaction between coumarin radical cation and amine is reported for the first time in the C307-amine systems in micelles which are confirmed by the effect on amine concentration of the decay of coumarin radical cation and the dynamics of the ground-state recovery of C307. A mechanism for the PET reaction between C307-amine systems is proposed in micelles including photoionization, ultrafast and dynamic ET, and solvation dynamics.

Electron transfer (ET) through and between proteins is a fundamental biological process. The rates of ET depend upon the thermodynamic driving force, the reorganization energy, and the degree of electronic coupling between the reactant and product states. The analysis of protein ET reactions is complicated by the fact that non-ET processes might influence the observed ET rate in kinetically complex biological systems. This Account describes studies of the methylamine dehydrogenase-amicyanin-cytochrome c-551i protein ET complex that have revealed the influence of several features of the protein structure on the magnitudes of the physical parameters for true ET reactions and how they dictate the kinetic mechanisms of non-ET processes that sometimes influence protein ET reactions. Kinetic and thermodynamic studies, coupled with structural information and biochemical data, are necessary to fully describe the ET reactions of proteins. Site-directed mutagenesis can be used to elucidate specific structure-function relationships. When mutations selectively alter the electronic coupling, reorganization energy, or driving force for the ET reaction, it becomes possible to use the parameters of the ET process to determine how specific amino acid residues and other features of the protein structure influence the ET rates. When mutations alter the kinetic mechanism for ET, one can determine the mechanisms by which non-ET processes, such as protein conformational changes or proton transfers, control the rates of ET reactions and how specific amino acid residues and certain features of the protein structure influence these non-ET reactions. A complete description of the mechanism of regulation of biological ET reactions enhances our understanding of metabolism, respiration, and photosynthesis at the molecular level. Such information has important medical relevance. Defective protein ET leads to production of the reactive oxygen species and free radicals that are associated with aging and many disease states. Defective ET within the respiratory chain also causes certain mitochondrial myopathies. An understanding of the mechanisms of regulation of protein ET is also of practical value because it provides a logical basis for the design of applications utilizing redox enzymes, such as enzyme-based electrode sensors and fuel cells.

Mechanisms for control of biological electron transfer reactions

A series of synthetic peptides containing 0–5 a-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 ß-peptides PCB-(ß3Val-ß3Ala-ß3Leu)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.

Review: 22 refs.