From anodic oxidation of aliphatic Î±-amino acids to polypeptides by

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From anodic oxidation of aliphatic #-amino acids to polypeptides by quantum electrochemistry approach. Beyond Miller-Urey experiments Guillaume Herlem, Taleb Alhedabi, and Fabien Picaud J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b05910 • Publication Date (Web): 20 Aug 2019 Downloaded from pubs.acs.org on August 20, 2019

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Journal of the American Chemical Society

From anodic oxidation of aliphatic -amino acids to polypeptides by quantum electrochemistry approach. Beyond Miller-Urey experiments Guillaume Herlem1,*, Taleb Alhedabi1,2, Fabien Picaud1 1Nanomedicine

Lab EA4662, Bat. E, University of Bourgogne Franche-Comté, UFR Sciences & Techniques, 16 route de Gray, 25030 Besançon Cedex, France. 2Department of Chemistry, College of Science, University of Sumer, Thi-qar, Iraq. *e-mail: [email protected] ABSTRACT: For years, polypeptide formation has fascinated the scientific world since its understanding would be one of the possible explanation for the origin of life. Anodic oxidation of aliphatic -amino acids in aqueous electrolytes can result either in their decomposition or polymerization into polypeptide. This behavior depends experimentally on both amino acid concentration and pH. The elucidation of the involved mechanisms remains a challenge due to the multitude of products which can be obtained. In this context, the electrochemical behavior of glycine and alanine on a biased platinum surface was examined at the nanoscale by quantum electrochemistry via the effective screening medium method. Several electrochemical systems with different concentration and pH have been explored. Simulations of the anodic oxidation of the amino acids have not only confirmed their electropolymerization and decomposition at high and low concentrations, respectively, but have also revealed unsuspected mechanisms at the origin of polypeptide formation. This sheds new light on electrochemistry of -amino acids, occurrence of polypeptides and more generally on organic electrochemistry.

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INTRODUCTION The first electrochemical investigations on amino acids were reported in the early 1930’s and have been the subject for intensive characterization of the resulting products. Depending on experimental conditions, results were fundamentally different. Diluted aliphatic amino acids in aqueous solution when oxidized anodically on an electrode surface are decomposed into aldehyde, ammonia (or light amine) and carbon dioxide with possible further oxidations (adsorbed cyanides mainly)1-6: RCH(NH2)COOH +H2O RCHO + H2O

anodic oxidation

RCHO + NH3 + CO2 + H2

(1)

anodic oxidation

RCOOH + H2

(2)

But at higher concentration, the anodic oxidation of aliphatic amino acids in alkaline pH condition yields an electropolymerization process resulting in peptide bond formation, and then polypeptides (Figs. 1 and 2).7-18 This could explain the conditions of the progressive life occurrence. Based on recent first-principles quantum mechanics calculations, the influence of an electric field was taken into account to simulate the Miller-Strecker reaction leading to glycine from a gas mixture of ammonia, carbon monoxide, nitrogen, methane and water.19 Anyway, the polymerization of amino acids in water solution is thermodynamically unfavorable and needs activators (such as carbodiimide), and catalytic assistance.20 When experimental conditions are gathered, the electropolymerization process of amino acids comes from their anodic oxidation under an electric field action. It is controlled either from an external source (potentiostat) or from an internal one which is induced by a charged surface (electrode) at the solid/liquid interface. Although the modified electrode surfaces by peptides are useful for analytical or medical applications, the electrochemical route leading from amino acids to polypeptoids has not been explored so far due to the unresolved underlying. Indeed, there is still insufficient knowledge to understand the sudden electrogeneration of species when amino acids are anodically oxidized on a biased or charged surface. In contrast, the adsorption and irreversible electrooxidation behaviors of diluted amino acids on electrode surfaces (mainly platinum and gold) are well documented.5 The above information can be related to the electrochemical experiments of Miller and Urey.21 23 amino acids were detected in the original flasks in the light of recent analysis, but no peptide trace.22 We demonstrate here, for the first time, at the molecular level, a global mechanism of the electrochemical behavior of aliphatic -amino acids (glycine and alanine) on a biased platinum surface at low and high concentration. The anodic 2 ACS Paragon Plus Environment

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oxidation of glycine or alanine occurs in the vacuum|slab|metal configuration in the effective screening medium (ESM) method. It simulates an electrochemical cell at the nanometer scale in the density functional theory (DFT) framework when the atoms are subject to first principle molecular dynamics (FPMD). Our calculations used planewave ultrasoft pseudopotentials for elements at the PBE functional level of theory. The ESM method allowing the connection between quantum chemistry and electrochemistry was implemented in the Quantum Espresso code.23-24 Details of the calculations are given in the SI part. The precursors needed in the peptidomimetic synthesis are electrogenerated as soon as the specified charge is applied during the simulation. Upon the electric field generated from a positively charged platinum surface, we are going to examine which species (placed in the layer between the two semi-infinite metallic electrodes) are involved and how they react. RESULTS AND DISCUSSION Experimental electrochemical behavior of glycine. At diluted glycine concentration, the experimental anodic oxidation leads to a monoelectronic oxidative decarboxylation in agreement with literature, as depicted in reaction (3):5, 25-27 H3N CH2 COOH

-6 e-

CO2 + NC- + 3H2

(3)

Experimentally, potential control of the reaction by cyclic voltammetry may prevent any decomposition into cyanide, hydrogen and carbon dioxide according to the mechanism depicted in Figure 2. The formation of methylenimmonium cation was proposed as a step in a mechanism describing the anodic oxidation of glycine. It was asserted rather than really deduced from FTIR spectroelectrochemical studies.28 Further oxidation of methylenimmonium cation leads to its dehydrogenation which has been widely investigated.29-30 In situ spectroelectrochemical experiments demonstrated that cyanide anions are the main product from oxidative decomposition of glycine either in acidic or alkaline medium.31-32 However, these cyanides electrogenerated during the glycine oxidation may adsorb on the electrode in acidic medium but rather dissolves into alkaline solution. Only the electropolymerization of concentrated -amino acids is observed experimentally in alkaline conditions as shown by surface characterizations (Figure 1a and Figure SI1).9 These latter show an irreversible deposition of different polypeptides even after multiple rinsing. 3 ACS Paragon Plus Environment


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Figure 1 | Surface characterizations of electrodeposited L-alanine on smooth platinum surface electrode. a, scanning electron microscopy image observed from anodic oxidation of L-alanine 0.50 M in aqueous solution charged with NaBF4 0.01 M in alkaline medium at pH=13 (adjusted with NaOH). The electropolymerization is carried out by cyclic voltammetry between 0 and 1.9 V versus AgCl reference electrode during five cycles. Scan rate: 50 mV/s. A detail of the electrochemical behavior of L-alaninate in anodic oxidation on smooth platinum is given. b, Cyclic voltammetry of L-alanine (0.50 M) at pH=13. c, Quartz crystal microbalance experiment coupled to cyclic voltammetry at pH=13. The mass increase on platinum is linked to the potential versus reference electrode AgCl. The electrochemical deposition is monitored during five cycles between 0.0 and 1.9 V at a scan rate of 50 mV/s. This resulted in a thin film layer on the metal electrode, observed in Figure 2. d, Cyclic voltammogram of L-alanine at pH=1 as a comparison. There is no faradaic peak and no electrodeposition in acidic medium. Simulated electrochemical behavior of glycine At low concentration the model used to simulate the anodic oxidation of glycine in acidic condition consisted of one glycinium cation surrounded by eight water 4 ACS Paragon Plus Environment

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molecules and one chloride ion (for neutrality reason). This simulation in acidic form causes the gradual departure of six protons. When the ESM charge is set to +3, reaction (3) is achieved in less than 200 fs. After a first proton departure at 15 fs, an iminium ion is produced as an intermediate species at 41 fs, yielding decarboxylation at 71 fs. Our calculations agree well with experimental data, unless cyanide behavior. Two deprotonations occur at 90 and 112 fs and lead to hydrogen cyanide. After the deprotonation of the carboxylic group at 138 fs there is dissociation of hydrogen cyanide at 194 fs. Moreover, water oxidation is considerably inhibited by the presence of glycine at high charge during the simulation. This is in accord with experimental observation performed at high potential.28 In our calculations (ESM charge of +3 or +4), there is no decomposition of water nor glycine into aldehyde and then ammonia as in reaction (1), and even less over electrooxidation of aldehyde into carboxylic acid as summarized in reaction (2). Indeed, our calculations are limited by constant charge of +4, avoiding over oxidation. Furthermore, our calculations take place at an early stage of the anodic oxidation of glycine during about 1 ps. Reaction (1) is rather observed for prolonged electrolysis of a complex system where organic acids, ammonia, alcohols and carbon dioxide are electrogenerated.28

Figure 2 | Anodic oxidation of diluted glycinium salt in acidic medium. After a first deprotonation at 15 fs, an iminium ion is produced as intermediate species at 41 fs, yielding decarboxylation at 71 fs. Deprotonation of the methylenimmonium 5 ACS Paragon Plus Environment


cation occurs at 90 and 112 fs and leads to hydrogen cyanide. After the deprotonation of the carboxylic group at 138 fs there is a dissociation of the hydrogen cyanide at 194 fs. The decomposition of glycine into cyanide, dihydrogen and carbon dioxide in acidic condition can be seen in video S1 as well as the XYZ coordinates of the initial system in supporting information. This is shown in Figure SI2 for ease of reading. At higher concentration of glycine in water, the simulation consisted in three glycinate ions surrounded by water molecules and neutralized with lithium ions (Figure 3a). As soon as the simulation is switched on, the situation is completely different from the diluted case. Foremost, the Kolbe electrolysis does not occur on any of the glycinate molecules during the whole simulation although the carboxyl group is an electron-withdrawing group. Regarding glycinate 3, the bond between the carboxyl and the methylene bridge stretches to a maximum of 1.617 Å but never breaks. There is a partial anodic oxidation of methylene bridge from glycinate 1 and glycinate 2 forming iminium ions at 6 and 31 fs. As the system is always biased, the iminium from glycinate 1 is transformed into nitriloacetate ion with loss of four protons: two from methylene bridge and two from amine at 53 and 56 fs. Their fast diffusion occurs immediately at the counter-electrode (ESM). Their reduction is effective at t=64 fs at the limit between the slab and the counter-electrode via the ESM offset simulating the potential barrier that delimits the ESM region. The intramolecular rearrangement of glycinate 1 into nitriloacetate occurs in less than 100 fs. Statistically, nitrile can be protonated into nitrilium ion from a vicinal water molecule, as encountered in some calculations from the same starting configuration. It is believed to be an intermediate in many reactions and MCR such as Passerini and Ugi reactions.33 Whatever the case, it does not prevent the reaction from continuing. An additional simulation carried out with nitrilium ion as precursor instead of nitriloacetate one, also resulted in electropolymerization of all the electroactive molecules. Another video available online as Video S3 illustrates this alternative. The dihydrogen formed at the ESM counter-electrode has been removed from the simulation as it occurs experimentally through gas bubbling. Indeed simulations performed with it, did not show any change in the final obtained products, unless increasing time. Their presence hinders only the ESM counter-electrode in time simulation. In these circumstances, a new modelization is relaunched with the freshly made precursor. It starts from the configuration where the newly electrogenerated nitriloacetate ion has just appeared in solution in presence of the two glycinate 6 ACS Paragon Plus Environment

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molecules, while keeping the same conditions as for the previous simulation (pH and box size) and illustrated Figure 3b.

Figure 3 | Nanoelectrochemical cell view and snapshots of electropolymerization versus time. Prior to any simulation, the three glycinate ions were placed at positions 1, 2 and 3. Position 1 is the closest molecule from the Pt electrode while position 3 is in front of the counter electrode, at the limit of the ESM potential barrier. Glycinate 2 occupies an intermediate position. Under anodic oxidation, glycinate ions 1 and 2 are transformed into new species, but not decomposed. The same positions were kept for alaninate ions. Due to ESM boundary conditions chosen (vacuum-slab-metal), 7 ACS Paragon Plus Environment


the positive charge is applied on platinum and the electric field is generated between the working electrode (WE) and the ESM counter electrode (C-E), versus reference electrode (RE). This is given in Figure SI3 for ease of reading. An animation of the reaction between glycinate ions in the diffusion layer is available online as Video S2 where only glycinate ions are shown for clarity. In Figure 3b at 52 fs after biasing the system, the nitrogen from nitriloacetate ion attacks the carbon from the carboxylate of the adjacent glycinate 2, yielding imine bond formation. This latter is quite stable during 390 fs until nitrogen is protonated by a water molecule chelating a lithium ion while 1,2-addition of another water molecule occurred before (227 fs). This leads to the complete formation of a first peptide bond at 502 fs. There is no hydrolysis of the imine to give ketone or aldehyde. In the meantime at t=60 fs and during 20 fs, a labile hydrogen atom from methylene bridge (glycinate 2) migrates toward carboxylate (nitriloacetate), generating an iminium ion on glycinate 2. Quite immediately after the first peptide bond formation, at t=499 fs a coupling begins between nitrogen iminium and carbon carboxyl from protonated glycinate 3 at 502 fs via vicinal water. Following the HSAB principle, nitrogen iminium is a soft nucleophile center reacting on electrophile carbon carboxylate. Then, a four-membered heterocyclic ring is formed at t=607 fs where oxygen from carboxyl reacts with carbon from iminium. The ring opens at t=703 fs when the bond between oxygen and carbon from carboxyl breaks, revealing a second peptide bond. Polyglycine electropolymerization mechanism. The two peptide bonds electrogenerated during the trimerization process were investigated by metadynamics to estimate the Helmholtz free energy surface (FES) of the oligomerization reaction as a function of selected collective variables (CVs) which represent the minimal distance between the atoms of the different groups involved in the peptide bond formation. CV1 is related to the minimal distance between nitriloacetate and glycinate 2 ions while CV2 concerns the minimal distance between glycinate 2 and glycinate 3 ions. The resulting FES explored in the CV space is depicted in Figure 4 for two situations: in presence of LiOH used as electrolyte (Figure 4a) and in pure water (Figure 4b). The results evidenced one global minimum of about - 3.35±0.90 eV (Figure 4a) and about -1.20±0.40 eV (Figure 4b) for the trimerization process via peptide bond formation where the C-N bond length reached about 1.35 Å. Note that CVs can be nicely replaced by path CV able to track the creation of chemical bond dissociation in order to provide a handy 2D space to describe complex transformations in gas to liquid phases.34-35 8 ACS Paragon Plus Environment

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b

Figure 4 | Free energy landscape (in eV) of the trimerization process. a, Anodic oxidation of glycinate ions in an aqueous electrolyte charged with LiOH. b, Anodic oxidation of glycinate ions in pure water. The presence of an electrolyte stabilized the reaction compared to the situation observed in pure water. More, we found in pure water oscillations of intramolecular N-H and C=O vibration soliton. As already observed by FPMD calculations in literature,36 it corresponds to the amide I excitation giving rise to distortions in its own hydrogen bond which, in turn, localize the amide I excitation, and created a self-trapped state (of the amide I or of the electron). This quasiparticle is able to propagate along the α-helix self-trapped amide I excitation, even under applied electric field.37 The free energy map shows two very close localized peaks with intensities of -1.00±0.30 and -1.10±0.30 eV, related to this self-trapped state. The polypeptide chain created during the simulation is too short to have a pronounced α-helical structure, although it is initiated. This is in agreement with short α-helix in solution. In fact, there is not enough intramolecular interactions along a short polypeptide chain to generate its folding. But, large nonlinear excitations may occur,36 termed intrinsic localized modes (ILMs).38 However, our system is charged with salt ions chelating the polypeptide, which contributes to its stabilization. Nevertheless, it is statistically possible to meet situations where a backbone N-H group forms a hydrogen bond to a backbone C=O group of a nearby amino acid sequence. As such, an electropolymerization simulation carried out with two glycinate ions and one nitriloacetate ion in water and no supporting electrolyte gave rise to pronounced intramolecular hydrogen bonding.



Nanometer scale electrochemistry without supporting electrolyte leads to significant electromigration contribution to the mass transport of electroactive ions.39 Effectively in the new simulation, amino acids electropolymerize in a similar manner than that in presence of an electrolyte as shown Figure 5. In broad outline, a nucleophilic attack of the nitrogen nitriloacetate occurs on the electrophile carbon carboxyl from adjacent glycine 2 (t=46 fs). It is followed by one hydrogen methylene bridge departure toward one oxygen carboxylate from nitriloacetate (t=138 fs), and then iminium formation. At t=196 fs, one hydrogen iminium jumps to one oxygen carboxyl from glycinate 3 while that on imine takes its place (t=433 fs). The iminium from glycine 2 reacts with carbon carboxylate from glycinate 3 at t=500 fs, generating immediately a four-membered heterocyclic ring 10 fs after. It breaks at t=530 fs to generate the second peptide bond. From that moment, mainly polypeptide backbone relaxation occurred during the simulation, excepted that one hydrogen iminium goes on dehydrogenated imine at t=670 fs. a

b


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Figure 5 | Evolution of the reaction according to two quantities versus time under applied voltage. a, Contribution of wavefunctions to the charge density at the Fermi level of the system. A cation radical is electrogenerated (46 fs) on Nnitrile from nitriloacetate ion and reacts with nucleophilic site of Ccarboxyl from adjacent glycinate. Then, a new cation radical is formed on the terminal N iminium ion of the resulting dimer, and so on. b, Positive (yellow) and negative (blue) isosurfaces of charge density complete the contribution of wavefunctions to the charge density. As expected, the anodic oxidation of the system lowered the Fermi level of the electrode which tends to rise slightly as electropolymerization progresses during the electron transfer at the interface. The platinum atoms were removed for clarity. This brings us to the vibration soliton (Davydov-like soliton), i.e., the stabilization of the C=O stretching mode (amide I) by the hydrogen bond from a nearby N-H. The vibration solitons in action are available online as Video S4 where the H bond distortions are observed several times between 480 and 1000 fs. The free energy map of the vibration soliton in our system reveals two very close localized peaks with intensities of -1.00 and -1.10 eV and related to self-trapped state (Fig. 4b). The small energy difference between the two peak intensities (50±15 meV) corresponds to the strength of the hydrogen bond which is experimentally known to vary between 21.7 and 65.0 meV for proteins in solution.40 In addition, these states are stable at biological temperatures and have a lifetime of several tens of ps. As a consequence, we can describe four occurrences of solitons during the whole simulation. The first one lasted 70 fs and is formed between 480 and 550 fs, while a second one appeared between 610 and 650 fs. The third one is formed between 790 and 820 fs, and the last one started at 945 fs and never disappeared until the end of the simulation. Of course, each one is accompanied locally by an alternation of single and double bonds for both carbonyl and amine becoming alcohol and imine, 11 ACS Paragon Plus Environment


respectively. The electric field not only generates but accelerates the propagation of the soliton along the chain. From our electrochemical considerations, the oscillation motion of solitons promotes the charge transport processes across the amino acids in the system, and hence their electropolymerization.41 This virtuous circle is only possible if glycinate molecules are close enough to allow the drift of solitons in the diffusion layer. That is to say, the electropolymerization of amino acids occurs only when they are concentrated enough in solution. From glycine to side-chain -amino acids. Case of alanine electropolymerization. Experimentally in alkaline conditions, there is an optimized electropolymerization process occurring at high concentration which is not observed at acidic pH or at low concentration, as shown by EQCM measurements coupled to cyclic voltammetry (Figure 1b).11 There are two faradaic peaks (at 1.25 and 1.75 V) and the mass deposition is rather more important after the first peak beyond 1.25 V. During the simulation, the inductive donor effect of the methyl group on the side chain influences the electrochemical behavior of alanine, but does not prevent the whole electropolymerization process (Figure 6a). Whether at low or high alanine concentration, a fast decarboxylation of the alaninate appears when the system is biased. It occurs for concentrated alaninate close to the limit of the diffusion layer and the ESM region, or when diluted in the layer. In any case, the Kolbe electrolysis is followed by a departure of a hydrogen atom from the methyl group, yielding the formation of ethenamine. The simulation of alaninate electropolymerization is available online as Video S5. Always upon the action of the electric field, a nucleophilic attack of amine nitrogen atom from ethenamine is directed on the carboxylic group of the nearest alaninate (t=84 fs). During this time, the labile hydrogen atom on the -carbon of the alaninate protonates the less-substituted carbon of the vinyl group (t=36 fs), following Markovnikov orientation. The electropolymerization process then continues and is achieved at about t=565 fs, while remaining similar to that described for glycine.


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Figure 6 | Electropolymerization of three alaninate ions. a, Main steps of the electropolymerization process. b, the presence of a methyl group on the C position yields a much more stable oligomer than the one achieved via electropolymerization of glycinate ions, as shown by the FES plot given in eV. The situation is similar to that encountered with amino acid mutations and the consequence for polypeptide stability. Note also oscillations of amide I vibration mode due to vibration soliton during the simulation (see Video S5). The oligomerization process of alaninate was characterized by the same advanced sampling technique as for the electropolymerization of glycinate ions (Figure 6b). The free energy was plotted as a function of the selected CVs (minimal distances between ethenamine and alaninate 1 and between alaninate1 and alaninate2 involved in peptide bond formations, respectively CV1 and CV2) reaches a global minimum at -7.60±2.30 eV. This is twice the value found for glycine with a similar trimerization process. Although aliphatic glycine and alanine are nonpolar, the methyl group separating them makes the difference. The steric hindrance of the methyl group during the electropolymerization reaction affects drastically the free energy, but not the folding of the oligomer. This former has a comparable conformation whatever the kind of polypeptides folding, sketching a helix. In addition, the applied electric field during the simulations does not break the peptide bond once formed, nor prevents the folding of the oligomer. In this context, the transition from glycine to alanine can be reduced to well-known amino acid mutations. An amino acid exchanged into another one in the protein sequence changes the folding free energy and then protein stability or function. The FPMD 13 ACS Paragon Plus Environment


method combined to metadynamics provides insight into the initiation of polyalanine folding as well as of polyglycine one during the oligomerization process and shows a greater stability in the case of polyalanine. Another advantage of these calculations is that the folding evolution (from 310 to -helix, for instance) is automatically taken into account during the sampling. The limitation of the ESM method resides in the diffusion and convection of species which are not included in the Poisson equation. CONCLUSION The electropolymerization of -amino acids is a new way to synthesize polypeptides and could be considered as another brick in the origin of life. Electropolymerization occurs under an electric field that can be either external (potentiostat) or internal (charged surface). In a sense, this technique can be regarded as an extension of the Miller-Urey’s work to achieve peptides. One-pot electropolymerization process of aliphatic -amino acids can be regarded as multicomponent reaction cascades. While cascade reactions are often composed solely of intramolecular transformations, they can also occur intermolecularly.42 In this context, the electropolymerization of -amino acids falls under the category of multicomponent reactions, at least for alanine and glycine in alkaline condition. The intersection of mechanical methods rooted in the density functional theory framework and electrochemistry is an effective new tool to elucidate organic electrochemical reactions at the early stages. It is proposed here for the first time the study of the electrochemical behaviors of alanine and glycine while sweeping wide from low to high concentration. There is a rich electrochemistry during the anodic oxidation of alaninate or glycinate ions, as revealed at both molecular level and femtosecond timescale during the simulations. If these amino acids undergo decarboxylation and then form cyanide at low concentration during anodic oxidation, their electrochemical behavior differs strongly at higher concentration. Their oligomerization shows similar mechanism while precursors are different. Unexpectedly, one of the glycinate ions is transformed into nitriloacetate ion, and reacts with the carboxylate group of an adjacent glycinate ion. Meanwhile, an iminium is formed on the second glycinate and attacks a carboxylate of a third glycinate ion once the first peptide bond is achieved, resulting in a cascade reaction. The precursor of alanine electropolymerization is ethenamine after Kolbe electrolysis and dehydrogenation. This rich electrochemistry is followed by 14 ACS Paragon Plus Environment

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important in situ structural information such as the beginning of peptide folding assisted by vibration solitons (Davydov-like soliton) and propagation. It is possible to study systems large enough and take into account any kind of interactions under an applied electric field via the ESM method. Placing organic molecules in a slab between a working electrode and a counter-electrode (ESM) open up several interesting avenues for future electrochemical works. Understanding and/or predicting electrochemical reactions become a reality.



ASSOCIATED CONTENT Electrochemical measurements Cyclic voltammetry (CV) and electrochemical quartz microbalance (EQCM) were performed on a µAutolab potentiostat (Eco Chemie, The Netherlands) coupled to a PM710 microbalance (Maxtek, USA) on a smooth platinum-coated 6 MHz quartz (AT cut) as working electrode (1.37 cm²). All potential were quoted versus silver chloride reference electrode. Scan rate: 50 mV/s. Characterizations Thin film coatings electrogenerated from anodic oxidation of concentrated -amino acids on platinum were characterized by scanning electron microscope (SEM). Images were performed using a FEI Helios Nanolab 600i apparatus (FEI Winning Dual Beam Company, USA). Supporting information Full computational simulation details are provided in the supporting information, as well as the XYZ coordinates of all molecular systems discussed. AUTHOR INFORMATION Corresponding Author *[email protected] ORCID Guillaume Herlem: 0000-0002-9168-7850 Notes The authors declare no competing financial interest. ACKNOWLEDGEMENTS The authors would like to thank computational resources without which this work could not have been realized. First of all, this work was granted access to the HPC resources of IDRIS n°100837 under the allocation 2018-A0040810430 made by GENCI (Grand Equipement National de Calcul Intensif). Then, our thanks are addressed to the team of the Mésocentre of Franche-Comté, France.


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From anodic oxidation of aliphatic Î±-amino acids to polypeptides by

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