The electrochemical approach to concertedproton—electron transfers in the oxidationof phenols in waterCyrille Costentin, Cyril Louault, Marc Robert, and Jean-Michel Saveant1

Laboratoire d’Electrochimie Moleculaire, Unite Mixte de Recherche, Universite-Centre National de la Recherche Scientifique No. 7591, Universite ParisDiderot, Batiment Lavoisier, 15 Rue Jean de Baïf, 75205 Paris Cedex 13, France

Contributed by Jean-Michel Saveant, September 9, 2009 (sent for review August 5, 2009)

Establishing mechanisms and intrinsic reactivity in the oxidation ofphenol with water as the proton acceptor is a fundamental taskrelevant to many reactions occurring in natural systems. Thanks tothe easy measure of the reaction kinetics by the current and thesetting of the driving force by the electrode potential, the elec-trochemical approach is particularly suited to this endeavor. De-spite challenging difficulties related to self-inhibition blocking theelectrode surface, experimental conditions were established thatallowed a reliable analysis of the thermodynamics and mechanismsof the proton-coupled electron-transfer oxidation of phenol to becarried out by means of cyclic voltammetry. The thermodynamiccharacterization was conducted in buffer media whereas the mech-anisms were revealed in unbuffered water. Unambiguous evidenceof a concerted proton–electron transfer mechanism, with water asproton acceptor, was thus gathered by simulation of the experi-mental data with appropriately derived theoretical relationships,leading to the determination of a remarkably large intrinsic rateconstant. The same strategy also allowed the quantitative analysisof the competition between the concerted proton–electron trans-fer pathway and an OH�-triggered stepwise pathway (protontransfer followed by electron transfer) at high pHs. Investigation ofthe passage between unbuffered and buffered media with theexample of the PO4H2

�/PO4H2� couple revealed the prevalence ofa mechanism involving a proton transfer preceding an electrontransfer over a PO4H2�-triggered concerted process.

electrochemistry � phenol oxidation � proton-coupled electron transfer

In the active attention that is currently devoted to proton-coupled electron transfers (PCET), in which proton and

electron transfers involve different molecular centers, the oxi-dation of phenols has played a prominent role in view of itsrelevance to reactions occurring in natural systems, particularly,but not exclusively, to the oxidation of tyrosine in photosystemII (1–3). Photosystem II is the most prominent example (4–6),but evidence has been gathered that similar processes areinvolved in the functioning of several other biochemical systems(7). Another aspect of the oxidative PCET chemistry of phenolsis related to other biological roles, notably their antioxidantproperties (8–10). Oxidative dehydrodimerization of phenols isalso an important class of reactions, being involved in the firststages of natural processes such as lignin formation (11, 12). Lastbut not least, phenol oxidation has important synthetic applica-tions (13).

Unraveling the mechanisms of PCETs is an important taskfrom a fundamental viewpoint and is also in conjunction with therelevance of these reactions to natural and synthetic processes.

As sketched in Scheme 1, in the PCET process that precedesdimerization, the stepwise pathways form a square reactionscheme that may involve electron transfer first, followed byproton transfer (EPT pathway) or, conversely, proton transferfirst followed by electron transfer (PET pathway). In the con-certed proton and electron transfer (CPET) pathway, proton andelectron transfers are concerted. The particular interest of CPET

pathways is that they allow bypassing the high-energy interme-diates involved in the stepwise pathways.

The occurrence of concerted processes has been establishedin the oxidation of phenols bearing an attached amino groupin an effort to mimic the role of the histidine that captures theproton resulting from the oxidation of tyrosine in photosystemII (14–17).

Water is a ubiquitous proton donor and acceptor, the role ofwhich in PCET reactions is obviously of considerable interest.Among the nonelectrochemical quests for CPET processes in theoxidation of phenols (18) where water appears as the protonacceptor, two contrasting behaviors have been reported: In thestop-flow oxidation of phenols by hexachloroiridateIV (19),the rate constant was found independent of pH, whereas in theoxidation of tyrosine and phenol by a photogenerated rutheni-um(II) trisbipyridine complex (20) it exhibits a 1/2-slope varia-tion, the latter behavior being explained by means of the highlyproblematic (21) notion of a pH-dependent driving force. Infront of such an uncertain situation, we reasoned that theelectrochemistry of phenols in water may offer a way of not onlydiscriminating between stepwise and concerted pathways butalso of characterizing the CPET reaction in terms of drivingforce and intrinsic properties. The latter opportunity derivesfrom the setting of the driving force by means of the electrodepotential.

Among previous electrochemical studies of phenols, cyclicvoltammetry in aprotic solvents and in a methanol–water mix-ture of coniferyl alcohol, one of the precursor phenols of lignin,has been reported, leading—with the help of pulse radiolysis—tothe determination of the standard potential of the phenoxyl/

Author contributions: C.C., M.R., and J.-M.S. designed research; C.C., C.L., M.R., and J.-M.S.performed research; C.L. analyzed data; and J.-M.S. wrote the paper.

The authors declare no conflict of interest.

1To whom correspondence should be addressed. E-mail: saveant@laposte.net.

This article contains supporting information online at www.pnas.org/cgi/content/full/0910065106/DCSupplemental.

Scheme 1. Ar: phenyl or other aryl groups, ArOH��: cation radical of ArOH.HZ�/Z (charge not shown) is any electroinactive acid-base couple present,including notably the H3O�/H2O and H2O/OH� couples.

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phenoxide couple and of Pourbaix plots in the methanol–watermedium (22–25). The mechanism of the PCET processes pre-ceding dimerization was not addressed in these cases as well asin other contributions (26–29) simply because the notion of aconcerted proton–electron transfer pathway was not part of thetheoretical framework at the time. It should be noted, en passant,that characterization of electrochemical CPET processes arescarce even outside the domain of phenol oxidation (30). In arecent preliminary note, the phenoxyl radical produced by CPEToxidation of the phenol was protected against follow-up dimer-ization by ortho and para tert-butyl groups (31). This strategy hasthe advantage not only of simplifying the electrochemical reac-tion mechanism but also of minimizing the passivation of theelectrode resulting from the reaction of phenoxyl radicals withthe electrode material and/or from the formation of polymerdeposits on the electrode surface. The price to pay is insolubilityin water, necessitating large additions of an alcohol leading toproblems in the measure of H� concentration and in theidentification of the active proton-accepting and -donating spe-cies in the medium.

We therefore reasoned that, despite challenging difficulties, itwould be worth investigating the mechanism of such reactions byelectrochemical means with the main goal of answering thefollowing question in mind: Is a concerted mechanism involvingwater as a proton acceptor (H2O–CPET) involved in the PCETprocess that precedes dimerization as sketched in Scheme 1?Simple phenol was taken as example, one advantage being thatits solubility allows one to use pure water as the solvent with theappending benefit of a clear and simple measure of pH.

A mandatory task was then to define the conditions underwhich self-inhibition by phenoxyl radicals and follow-up productsof the electrochemical oxidative process is minimized in cyclicvoltammetry. This investigation was conducted in bufferedmedia, leading, after the kinetic effect of dimerization has dulybeen taken into account, to the establishment of a reliablePourbaix plot relating the apparent standard potential to the pH.Once the thermodynamic framework of the CPET process hasthus been established, one could think to tackle the mechanismanalysis in the same buffered media. However, a combination ofunfavorable factors hinders the achievement of this task, namelythe rapidity of electron and proton transfers associated withmechanism overlap over extended sections of the available pHrange. A more productive strategy consisted in analyzing thereaction kinetics in unbuffered water as a function of pH underthe same conditions that minimize self-inhibition. Under theseconditions, the stepwise PET pathway only involves OH� as aproton acceptor. The PET pathway therefore rapidly shuts downas the pH decreases. In the remaining competition between theEPT and CPET pathways, unambiguous evidence of a concertedproton–electron transfer mechanism, with water as the soleproton acceptor, could then be gathered. We also investigatedthe mechanism by which the overall reaction is accelerated by theaddition of a buffer to the system.

In all cases, the investigation was limited to the electrodepotential range where the one-electron oxidation leading to thephenoxyl radical that eventually dimerizes takes place. A furtheroxidation step leading to two-electron products appears at morepositive potentials under the form of a wave, often almostmerged with the discharge of the supporting electrolyte.

Results and Discussion1. Buffered Media. Establishing the Thermodynamic Framework.

1.1 Avoiding Self-Inhibition. Self-inhibition (32) produces dramaticeffects on the cyclic voltammetric responses that may completelyobscure mechanistic analyses based on the variations of peakcurrents and potentials with scan rate and concentrations (33).As detailed in the SI Appendix these effects can be neglected

provided that phenol concentration is held below 1 mM and scanrates are held above 0.1 V/s. Under these conditions, the peakpotential is expected to obey Eq. 1, which applies to a reactionin which fast and reversible electron and proton transfersprecede a rate-determining dimerization (34–36).

Ep � Eap0 � 0.903 RT/F � �RTln 10/3F� log�4RTkdimC0/3Fv�

[1]

(Eap0 is the pH-dependent apparent standard potential giving

rise to the Pourbaix diagram as discussed in more detail insection 1.2).

These observations led us to use a scan rate of 0.2 V/s and aphenol concentration of 0.2 mM to safely avoid the interferenceof self-inhibition in the characterization of the thermodynamicsin buffered media.

1.2. Thermodynamics of the Reaction. Because the oxidation waveshifts toward more positive potentials when going to smaller pHs,the background current had to be systematically subtracted fromthe phenol-oxidation response and the adherence to Eq. 1checked at each pH. The resulting voltammograms are displayedin Fig. 1A as a function of pH.

The resulting diagram of the peak potential vs. pH shown inFig. 1B has the aspect of a Pourbaix plot with a 59.2-mV slopewith linear variation below pH � 10 (the phenol pK) and ahorizontal asymptote above pH � 10. The peak potentialcontains, however, a contribution of the follow-up dimerizationas expressed by Eq. 1. Indeed, if all of the electron-transfer andproton-transfer steps in Scheme 1 are at equilibrium, the ther-modynamics of the conversion of ArOH into ArO• gives rise,whatever the pathways that are followed, to an apparent stan-dard potential Eap

0 , the variation of which with pH is precisely thesought Pourbaix diagram

A B

C

Fig. 1. Determining the thermodynamics of phenol oxidation. (A) Cyclicvoltammetry of 0.2 mM PhOH in 0.05-M Britton Robinson buffers at 0.2 V/s asa function of pH. pH values from right to left: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12. (B)Peak potential (in V vs. NHE) as a function of pH at 0.2 V/s. (C) Variation of theapparent standard potential with pH (Pourbaix diagram), showing the zonesof thermodynamic stability of the various species and the characteristic pKsand standard potentials. All potentials are referred to the NHE.

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Eap0 � EPET

0 � �RT ln 10/F� log� 1 � 10�pH/10�pKArOH

1 � 10�pH/10�pKArOH•�� .

Therefore, subtracting the contribution of dimerization, taking2kdim � 2.6 � 109 M�1 s�1 (37), (with v � 0.2 V/s and C0 � 0.2mM) leads to the effective Pourbaix diagram shown in Fig. 1C,where EPET

0 (V vs. NHE) � 0.803. This value is significantlysmaller, by 57 mV, than the value reported earlier by using asimilar method (38) and is approximately the same as the value0.79 V vs. NHE, previously determined by means of pulseradiolysis (39). The value reported in reference 38 results,presumably, because no precautions were taken to avoid self-inhibition.

The zones of thermodynamic stability of the various speciesmay be thus be defined [pKArOH � 10, pKArOH�� � �2 (40)] asshown in Fig. 1C. The four standard potentials to be used in theexpression of the driving forces for the PET, EPT, H2O-CPET,and PO4H�-CPET reactions ensue (Fig. 1C).

2. Unbuffered Media. The same scan rate and concentrationconditions as defined in buffered media were also applied in thepresent case. The voltammograms obtained at 0.2 V/s with0.2-mM phenol in unbuffered water at pHs ranging from 2 to 12(Fig. 2A) are strikingly different from those obtained in buffers(Fig. 1): Starting from basic media, the oxidation wave now splitsin two waves as the pH decreases. The first wave, which takesplace in the same potential region as in buffered media, rapidlydecreases with the pH at the expense of a more positive secondwave. The variations of the peak potential of the two waves withpH (Fig. 3A) also show a strong contrast with the behaviorobserved in buffers.

2.1. The OH�–PET Pathway. The only base in the unbufferedmedium able to deprotonate the phenol and thus launch the PETpathway is the OH� ion. Above the phenol pK, the phenoxideion predominates, and the reaction simply consists in its oxida-tion yielding the phenoxyl radical, which dimerizes eventually. Asthe pH decreases below the pK, fast deprotonation of phenol bythe OH� ions still present continues to produce the phenoxideion and hence the radical and the dimer in the framework of theCE mechanism (36) that we have named the PET pathway.Because on the one hand the medium is not buffered and, on theother, deprotonation is very fast, diffusion of OH� ions towardthe electrode becomes the most important rate-controllingfactor. Phenol concentration is another essential parameterbecause it determines the amount of proton equivalents that aregenerated upon oxidation, making the pH decrease during thecourse of the cyclic voltammogram. These various factors can beput together within a kinetic model that leads to an integralequation of the current-potential response (see SI Appendix),which is used to simulate satisfactorily the data reported in Fig.2B by using the parameter values listed in Table 1.

2.2. The H2O–CPET Pathway. As the first wave vanishes upondecreasing the pH, a question arises concerning the nature of theoxidative dehydrodimerization mechanism at the henceforthpredominating second wave. Because the PET pathway is shutdown, the only remaining possibilities are the stepwise EPTpathway and the concerted CPET pathway. It is interesting tonote that once the first wave has completely disappeared, thelocation of the second wave remains the same down to pH � 4,with a peak potential (black stars in Fig. 3A) well above its valuein buffered media, until it catches up to the buffered medium(59-mV slope, straight line in Fig. 3A). This behavior is aconsequence of the absence of buffering, whatever the reactionmechanism, reversible electron and proton transfers within anEPT pathway or reversible concerted proton–electron transferin a CPET pathway. In both cases, the generation of protonsupon electron transfer decreases the local pH. The evacuation ofthe protons produced by diffusion from the electrode thusbecomes a crucial rate-controlling factor. In this context, phenolconcentration is an important parameter because it is a measureof the maximal amount of protons produced. Upon decreasingthe pH, the amount of protons generated by the oxidationbecomes small as compared with the concentration of protonsalready present, leading to the same behavior observed in thebuffered media of the same pH.

This effect is not mechanism-discriminating, but the EPTmechanism can be ruled out for the following kinetic reasons. Inthe successive steps of this reaction sequence recalled in Scheme1, the ratio of the deprotonation and protonation rate constants,K�p � k�p/k�p � 100 (see pKs in Fig. 1C). To give this pathwaythe best chance to compete, we selected for simulation of cyclicvoltammetric responses, a very rapid electron transfer so as toobtain a Nernstian behavior and the maximal conceivable value,1013 s�1, for the deprotonation rate constant by water. We see inFig. 3A that the simulated peak potentials are much too positiveas compared with the experimental peak potentials and, in Fig.3B, that the voltammogram shapes do not agree. The reason forthis behavior is that the deprotonation/protonation step is not atequilibrium because the reprotonation step is not much fasterthan the follow-up dimerization and diffusion of the phenoxylradical. The result is that the protonation step interferes in thekinetics of the overall process, making it occur at a potentialmore positive than if the deprotonation/protonation step were atequilibrium. These observations unambiguously establish theoccurrence of the CPET mechanism.

Repeating the cyclic voltammetric analysis in heavy water ledto the results reported in Fig. 3A (gray stars). In the CPETpotential domain, the peak potentials are more positive in D2O

A B

Fig. 2. Oxidation of phenol in unbuffered water. (A) Cyclic voltammetry of0.2 mM PhOH in unbuffered water at 0.2 V/s as a function of pH. pH valuesfrom right to left: 2, 3, 4, 5, 6, 7, 8, 8.5, 9, 9.5, 9.5, 10, 11, 12. (B) Basic unbufferedwater (first five voltammograms of Fig. 2A) showing the decrease of the peakcurrent with the pH (dots) as compared with the simulation (full line) (seeparameter values in Table 1) of an OH�–PET pathway according to Eq. 2. Thepeak currents ip are normalized versus the value at pH � 12.

A B

Fig. 3. Cyclic voltammetry of 0.2 mM PhOH. (A) Peak potential as a functionof pH, at 0.2 V/s. Open circles, in 0.05-M Britton Robinson buffer; black stars,unbuffered water; gray stars, unbuffered heavy water (for the definition ofpD, see SI Appendix); gray crosses, simulation according to a Nernstian EPTmechanism. (B) Cyclic voltammograms at pH � 7.2. Black, experimental; gray,simulated [using the DigiElch package (42) and the parameters in Table 1]according to a Nernstian EPT mechanism.

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than in H2O, indicating a significant H/D isotope effect. Thisobservation suggests the interference of the CPET kinetics inaddition to proton diffusion. To characterize the kinetics of theCPET reaction, additional experiments were carried out as afunction of the scan rate at pH 7.2, right in the middle of the pHrange of interest. The results are shown in Fig. 4A.

The following kinetic model may be used to simulate the cyclicvoltammograms and derive the standard rate constant of theCPET reaction. In the writing of the CPET pathway (Scheme 1),the CPET reaction itself appears as involving ternary kinetics(the electrode plus two molecules) in both directions. Becausewater is the solvent, its activity and concentration are consideredas constant and may be removed from the expression of theequilibrium and kinetic laws. As discussed previously (43, 44),the rate law for an electrochemical CPET reaction may beapproximated by a Butler–Volmer relationship with a transfercoefficient equal to 0.5:

i/FS � kSCPET exp��F /2RT��E � ECPET

0 ���ArOH�0

� ��ArO•�0�H��0/CS�exp���F /RT��E � ECPET0 �� ,

where the []0 are the concentrations at the electrode surface inmol/L. Cs is the standard concentration that we take equal to 1mol/L. ECPET

0 , the standard potential governing the CPETpathway, has the value indicated in Fig. 1C. Determination ofkS

CPET, the corresponding standard rate constant, is the mainobjective of the kinetic analysis of the system. This value leadsto the integral equation of the CPET wave (see SI Appendix),which depends on the parameter

p �kS

CPET�C0/CS�1/2

�DArOH�1/4�DH��1/4�Fv /RT�1/3�4kdimC0/3�1/6 , [2]

which measures the competition between the CPET reaction andthe follow-up dimerization for the kinetic control of the wholeprocess (p30 and p3�, respectively). Simulation of the exper-imental voltammograms shown in Fig. 4B led to a quite satis-factory fit for kS

CPET � 25 � 5 cm s�1.A similar approach was also used to derive the value of kS

CPET

in heavy water. Simulation (Table 1) of the peak potential in thezone where it is constant and equal to 1.140 V vs. NHE—

between pH 6 and 8—leads to the following value of thestandard rate constant: kS

CPET(D) � 10 � 2 cm s�1. The H/Dkinetic isotopic effect is therefore equal to 2.5, a value expectedfor an adiabatic or quasiadiabatic CPET electrochemical reac-tion (26).

One may wonder why such high values of an electrochemicalstandard rate constant could be reached at very moderate scanrates. The reason for this is that the follow-up dimerization tendsto make the preceding electron transfer the rate-determiningstep in unbuffered as well as in buffered media. This tendencyis stronger in unbuffered media because reprotonation of ArO•

is more difficult, as attested by the terms C0/CS and DH� in Eq.2, which are absent in the expression the competition parameterwould have in buffered media (45):

p �kS

CPET

�DArOH�1/2�Fv /RT�1/3�4kdimC0/3�1/6 .

With the values listed in Table 1, p � 0.5 at 0.2 V/s in unbufferedwater, indicating a mixed kinetic control by electron transfer anddimerization, allowing the determination of the standard rateconstant. In the corresponding buffer medium p � 200, leavingno chance for electron transfer to participate in the kineticcontrol.

3. Passage from Unbuffered to Buffered Media. Additional Concertedor PET Pathways? Once the mechanisms taking place in completeabsence of buffer have been established, it is interesting to

A B

Fig. 4. Cyclic voltammetry of 0.2 mM PhOH in unbuffered water at pH � 7.2as a function of scan rate. From bottom to top: 0.1, 0.2, 0.5, 0.7 V/s. (A)Experimental. (B) Simulated (see SI Appendix) by using the values in Table 1.

A B

C D

Fig. 5. Passage from unbuffered to buffered media. Cyclic voltammetry of0.2 mM PhOH at pH 7.2 in phosphate buffer at 0.2 V/s as a function of bufferconcentration. (A) From right to left: to Z0 � 0.0078, 0.2, 0.4, 0.6, 0.78, 7.8 mM.(B) H/D isotope effect: cyclic voltammograms of 0.2-mM PhOH at pH (or pD) 7in 0.5-mM phosphate buffer in H2O (full line) and D2O (dashed line). (C)Variation of the peak current with Z0. Dots, experimental data; line, predictionfor the PO4H2�–PET mechanism (see section 3). (D) Variation of the peakpotential with Z0. Dots, experimental data; line, prediction for the PO4H2�–PET mechanism (see section 3).

Table 1. Simulation parameters

Parameters Values

Potentials (V vs. NHE) EPETdim � 0.714, EPET

0 � 0.803, EEPT0 � 1.519,

ECPET0 (H2O) � 1.400, ECPET

0 (D2O) � 1.421Diffusion coefficients �105 (cm2 s�1) DPhOH � 3.7, DOH� � 5.4, DH� � 9.3, DD� � 6.6 (41), DPO4H2� � 1Standard rate constants (cm s�1) kS

CPET(H) � 25 � 5, kSCPET(D) � 10 � 2

Rate constants (M�1 s�1 or s�1) 2kdim � 2.6 � 109, kp � 1011, k�p � 1013

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investigate what happens upon progressive addition of a bufferto the solution. Selecting the PO4H2

�/PO4H2� couple as arepresentative example, successive additions of the two membersin equal amounts—so as to maintain the pH � 7.2—resulted inthe appearance of a new wave in front of the H2O-CPET wave,which grows at the expense of the latter (Fig. 5A) until it reachesa steady value, the wave being then identical to that observed ina buffered medium at the same pH.

Two different mechanisms may be acting in the passage froman unbuffered to a buffered medium. One is the PET mechanismshown in Scheme 1, in which again Z � PO4H2� (Z0 is then thebulk concentration of PO4H2�); Fig. 5 C and D illustrate thegood adherence to experimental data of predictions based onthe PO4H2�–PET mechanism (see SI Appendix), both in termsof peak current and potential with the parameter values.

A PO4H2�–CPET pathway should also be envisaged becauseit benefits from a better driving force than the H2O–CPETpathway. Indeed, although the driving force of the CPETreactions do not depend on pH (21), the standard potentialdefining the driving force of the reaction is obtained from theapparent standard potential at a pH equal to the pK of theproton acceptor under consideration. It thus appears from Fig.1C that the PO4H2�–CPET pathway has a driving force advan-tage of 0.425 eV over the H2O–CPET pathway. Although thecharacteristic equations are not exactly the same, the predictionsfor the PO4H2�–CPET pathway would involve, as for thePO4H2�–PET pathway, a variation with buffer concentrationsimilar to Fig. 5C. Discrimination from the PO4H2�–PET mech-anism, rather, derives from the absence of the H/D isotope effectas shown in Fig. 5B.

Indeed, in the CPET case, because the buffer is involved in a‘‘termolecular’’ process in both directions (electrode � phenol �PO4H2� in oxidation; electrode � phenoxyl radical � PO4H2

�

in reduction), at the buffer concentration (0.5 mM) where theexperiment in Fig. 5B was carried out, the rate-determining stepshould be the CPET reaction. In fact, at this buffer concentra-tion, kS,PO4

CPETH2� should be as large as 140–240 cm s�1 for the

kinetic control to pass from electron transfer to dimerization(see SI Appendix). Because kS,PO4

CPETH2� is obviously much smaller

(compare with kS,H2OCPET � 25 cm s�1, i.e., 0.5 cm s�1 per water

molecule), we may conclude that the reaction is kineticallycontrolled by the CPET electron transfer step and shouldtherefore exhibit a significant H/D isotope effect. Its absence, atthe level of the PO4H2�-triggered oxidation wave (first wave inFig. 5B), consequently rules out this mechanism at the benefit ofthe PO4H2�–PET pathway, which is not expected to show anysignificant H/D isotope effect (see SI Appendix).

Concluding Remarks. The most important finding of this work isthe demonstration that a concerted proton–electron transfermechanism is operating in the electrochemical oxidation ofphenol. To our knowledge, the identification of such a reactionpathway in the electrochemical dehydrodimerizations of phenolsin which water acts as the proton acceptor is a previouslyundescribed finding. The use of unbuffered media was essentialin this venture. It indeed allows for the rapid shutting-down ofthe PET (proton transfer first followed by electron transfer)pathway at pHs close to the phenol pK. A large pH domain isthus open for investigating the other pathways, making it possibleto identify unambiguously the concerted pathway, to determinethe corresponding standard rate constant, and to measure theH/D kinetic isotope effect. Reaching these unambiguous con-clusions required a careful estimation of the scan rate andconcentration conditions under which self-inhibition can betrimmed down to negligible. These efforts also led to an accuratedetermination of the thermodynamics of the reaction, providingan essential framework for mechanism analysis.

It is also worth noting that, thanks to the use of unbufferedmedia at intermediate pHs, cyclic voltammetry allowed a straightvisualization of the competition between the PET and CPETpathway.

Another point worth emphasizing is the inability of the EPTpathway to compete efficiently with the CPET pathway, illus-trating the avoidance of high-energy intermediates on the reac-tion pathway.

The electrochemical H2O-CPET reaction is characterized byan exceptionally large standard rate constant. It would beinteresting to see whether the ensuing expectation of a similarlylarge intrinsic rate constant in homogeneous phenol oxidation isindeed observed, opening the appending question of activationcontrol vs. the forward and reverse diffusion.

Another finding that will be interesting to compare withhomogeneous processes is the fact that the addition of a bufferbase-like PO4H2�, drives the system toward a PET pathwayrather than toward a CPET pathway.

Materials and MethodsThe electrochemical kinetics were obtained from cyclic voltammetric experi-ments on a glassy carbon electrode carefully polished before each run. Detailson the methods and materials used are given in the SI Appendix.

Experimental Details. The effects of self-inhibition, a quantitative analysis ofthe OH�–PET, H2O–CPET, H2O–EPT, PO4H2�–PET and PO4H2�–CPET mecha-nisms, and procedures for numerical simulations can be found in the SIAppendix.

ACKNOWLEDGMENTS. Partial financial support from the Agence Nationalede la Recherche (Program blanc PROTOCOLE) is gratefully acknowledged.

1. Stubbe J, van der Donk WA (1998) Protein radicals in enzyme catalysis. Chem Rev98:705–762.

2. M, Sartor V, et al. (2004) Intraprotein electron transfer and proton dynamics duringphotoactivation of DNA photolyase from e. coli: Review and new insights from an‘‘inverse’’ deuterium isotope effect. Biochim Biophys Acta 1655:64–70.

3. Shih C, et al. (2008) Tryptophan-accelerated electron flow through proteins. Science320:1760–1762.

4. Tommos C, Babcock GT (2000) Proton and hydrogen currents in photosynthetic wateroxidation. Biochim Biophys Acta 1458:199–219.

5. Renger G (2004) Coupling of electron and proton transfer in oxidative water cleavagein photosynthesis. Biochim Biophys Acta 1655:195–204.

6. Meyer TJ, Huynh MHV, Thorp HH (2007) The possible role of proton-coupled electrontransfer (PCET) in water oxidation by photosystem II. Angew Chem Int Ed 46:5284–5304.

7. Miller AF (2008) Redox tuning over almost 1 V in a structurally conservedactive site: Lessons from Fe-containing superoxide dismutase. Acc Chem Res 41:501–510.

8. Williams LL, Webster RD (2004) Electrochemically controlled chemically reversibletransformation of �-tocopherol (vitamin E) into its phenoxonium cation. J Am ChemSoc 126:12441–12450.

9. Cotelle N, Hapiot P, Pinson J, Rolando C, Vezin H (2005) Polyphenols deriving fromchalcones: Investigations of redox activities. J Phys Chem B 109:23720–23729.

10. Webster RD (2007) New insights into the oxidative electrochemistry of vitamin E. AccChem Res 40:251–257.

11. Ralph J, et al. (2004) Lignins: Natural polymers from oxidative coupling of 4-hydroxy-phenyl-propanoids. Phytochem Rev 3:29–60.

12. Vanholme R, Morreel K, Ralph J, Boerjan W (2008) Lignin engineering. Curr Opin PlantBiol 11:278–285.

13. Morrow GW (2001) Anodic oxidation of oxygen-containing compounds. OrganicElectrochemistry, eds Lund H, Hammerich O (Marcel Dekker, New York) 4th Ed, pp589–620.

14. Rhile IJ, et al. (2006) Concerted proton-electron transfer in the oxidation of hydrogen-bonded phenols. J Am Chem Soc 128:6075–6088.

15. Costentin C, Robert M, Saveant JM (2006) Electrochemical and homogeneous proton-coupled electron transfers: Concerted pathways in the one-electron oxidation of aphenol coupled with an intramolecular amine-driven proton transfer. J Am Chem Soc128:4552–4553.

16. Markle TF, Rhile IJ, DiPasquale AG, Mayer JM (2008) Probing concerted proton-electron transfer in phenol-imidazoles. Proc Natl Acad Sci USA 105:8185–8190.

17. Costentin C, Robert M, Saveant JM (2007) Adiabatic and non-adiabatic concertedproton-electron transfers. Temperature effects in the oxidation of intramolecularlyhydrogen-bonded phenols. J Am Chem Soc 129:9953–9963.

18. Huynh MHV, Meyer TJ (2007) Proton-coupled electron transfer. Chem Rev 107:5004–5064.

Costentin et al. PNAS � October 27, 2009 � vol. 106 � no. 43 � 18147

CHEM

ISTR

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19. Song N, Stanbury DM (2008) Proton-coupled electron-transfer oxidation of phenols byhexachloroiridate (IV). Inorg Chem 47:11458–11460.

20. Irebo T, Reece SY, Sjodin M, Nocera DG, Hammarstrom L (2007) Proton-coupledelectron transfer of tyrosine oxidation: Buffer dependence and parallel mechanisms.J Am Chem Soc 129:15462–15464.

21. Costentin C, Robert M, Saveant JM (2007) Concerted proton-electron transfer reactionsin water. Are the driving force and rate constant depending on pH when water acts asproton donor or acceptor? J Am Chem Soc 129:5870–5879.

22. Hapiot P, et al. (1992) One-electron redox potentials for the oxidation of coniferylalcohol and analogues. J Electroanal Chem 328:327–331.

23. Hapiot P, Pinson J, Neta P, Rolando C, Schneider S (1993) Electrochemical and radiolyticmechanistic studies on the primary step of phenol coupling involved in lignification.New J Chem 17:211–224.

24. Hapiot P, et al. (1994) Mechanism of oxidative coupling of coniferyl alcohol. Phytochem36:1013–1020.

25. Fulcrand H, Hapiot P, Neta P, Pinson J, Rolando C (1997) Electrochemical and radiolyticoxidation of naturally occurring phenols. Analusis 25:M38–M43.

26. Costentin C (2008) Electrochemical approach to the mechanistic study of proton-coupled electron transfer. Chem Rev 108:2145–2179.

27. Richards JA, Whitson PE, Evans DH (1975) Electrochemical oxidation of 2,4,6-tri-tert-butylphenol. J Electroanal Chem 63:311–327.

28. Richards JA, Evans DH (1977) Electrochemical oxidation of 2,6-di-tert-butyl-4-isopropylphenol. J Electroanal Chem 81:171–187.

29. Speiser B, Rieker A (1979) Electrochemical oxidations: Part IV. Electrochemical inves-tigations into the behavior of 2,6-di-tert-butyl-4-(4-dimethylaminophenyl)-phenolpart 1. Phenol and the species derived from it: Phenoxy radical, phenolate anion andphenoxenium cation. J Electroanal Chem 102:373–395.

30. Costentin C, Robert M, Saveant JM, Teillout AL (2009) Concerted proton-coupledelectron transfers in aquo/hydroxo/oxo metal complexes: Electrochemistry of[OsII(bpy)2py(OH2)]2� in water. Proc Natl Acad Sci USA 106:11829–11836.

31. Costentin C, Louault C, Robert M, Saveant JM (2008) Evidence for concerted proton-electron transfer in the electrochemical oxidation of phenols with water as protonacceptor. Tri-tert-butylphenol. J Am Chem Soc 130:15817–15819.

32. Bhugun I, Saveant JM (1995) Derivatization of surfaces and self-inhibition in irrevers-ible electrochemical reactions: Cyclic voltammetry and preparative-scale electrolysis. JElectroanal Chem 395:127–131.

33. Saveant JM (2006) Elements of Molecular and Biomolecular Electrochemistry (Wiley,New York), Ch 1.

34. Saveant JM, Vianello E (1963) Etude de la polarisation chimique en regime de variationlineaire du potentiel. Cas d’une desactivation spontanee, rapide et irreversible duproduit de da reduction. C R Acad Sci 256:2597–2600.

35. Saveant JM, Vianello E (1967) Potential sweep voltammetry. Theoretical analysis ofmonomerization and dimerization mechanisms. Electrochim Acta 12:1545–1561.

36. Saveant, JM (2006) in Elements of Molecular and Biomolecular Electrochemistry(Wiley, New York), Chap 2 and 6.

37. Ye M, Schuler RH (1989) Second-order combination reactions of phenoxyl radicals. JPhys Chem 93:1898–1902.

38. Li C, Hoffman MZ (1999) One-electron redox potentials of phenols in aqueous solution.J Phys Chem B 103:6653–6656.

39. Lind J, Shen X, Eriksen TE, Merenyi G (1990) The one-electron reduction potential of4-substituted phenoxyl radicals in water. J Am Chem Soc 112:479–482.

40. Dixon WT, Murphy D (1976) Determination of the acidity constants of some phenol radicalcations by means of electron spin resonance. J Chem Soc Faraday Trans 72:1221–1230.

41. Lide RD (2007) Handbook of Chemistry and Physics, (CRC Press, Boca Raton, FL), 88thEd, pp 5-76–5-78.

42. Rudolph M (2003) Digital simulations on unequally spaced grids: Part 2. Using the boxmethod by discretisation on a transformed equally spaced grid. J Electroanal Chem543:23–39.

43. Costentin C, Robert M, Saveant JM (2006) Electrochemical concerted proton andelectron transfers. Potential-dependent rate constant, reorganization factors, protontunneling and isotope effects. J Electroanal Chem 588:197–206.

44. Costentin C, Robert M, Saveant JM (2007) Adiabatic and non-adiabatic concertedproton-electron transfers. Temperature effects in the oxidation of intramolecularlyhydrogen-bonded phenols. J Am Chem Soc 129:9953–9963.

45. Nadjo L, Saveant JM (1973) Linear sweep voltammetry. Kinetic control by charge transferand/or secondary chemical reactions. I. Formal kinetics. J Electroanal Chem 48:113.

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