The electrochemical approach to concerted proton— electron transfers in the oxidation of phenols in water Cyrille Costentin, Cyril Louault, Marc Robert, and Jean-Michel Save´ant1 Laboratoire d’Electrochimie Mole´culaire, Unite´ Mixte de Recherche, Universite´-Centre National de la Recherche Scientifique No. 7591, Universite´ Paris Diderot, Baˆtiment Lavoisier, 15 Rue Jean de Baïf, 75205 Paris Cedex 13, France Contributed by Jean-Michel Save´ant, September 9, 2009 (sent for review August 5, 2009)
electrochemistry 兩 phenol oxidation 兩 proton-coupled electron transfer
I
n the active attention that is currently devoted to protoncoupled electron transfers (PCET), in which proton and electron transfers involve different molecular centers, the oxidation of phenols has played a prominent role in view of its relevance to reactions occurring in natural systems, particularly, but not exclusively, to the oxidation of tyrosine in photosystem II (1–3). Photosystem II is the most prominent example (4–6), but evidence has been gathered that similar processes are involved in the functioning of several other biochemical systems (7). Another aspect of the oxidative PCET chemistry of phenols is related to other biological roles, notably their antioxidant properties (8–10). Oxidative dehydrodimerization of phenols is also an important class of reactions, being involved in the first stages of natural processes such as lignin formation (11, 12). Last but not least, phenol oxidation has important synthetic applications (13). Unraveling the mechanisms of PCETs is an important task from a fundamental viewpoint and is also in conjunction with the relevance of these reactions to natural and synthetic processes. As sketched in Scheme 1, in the PCET process that precedes dimerization, the stepwise pathways form a square reaction scheme that may involve electron transfer first, followed by proton transfer (EPT pathway) or, conversely, proton transfer first followed by electron transfer (PET pathway). In the concerted proton and electron transfer (CPET) pathway, proton and electron transfers are concerted. The particular interest of CPET www.pnas.org兾cgi兾doi兾10.1073兾pnas.0910065106
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.
pathways is that they allow bypassing the high-energy intermediates involved in the stepwise pathways. The occurrence of concerted processes has been established in the oxidation of phenols bearing an attached amino group in an effort to mimic the role of the histidine that captures the proton resulting from the oxidation of tyrosine in photosystem II (14 –17). Water is a ubiquitous proton donor and acceptor, the role of which in PCET reactions is obviously of considerable interest. Among the nonelectrochemical quests for CPET processes in the oxidation of phenols (18) where water appears as the proton acceptor, two contrasting behaviors have been reported: In the stop-flow oxidation of phenols by hexachloroiridateIV (19), the rate constant was found independent of pH, whereas in the oxidation of tyrosine and phenol by a photogenerated ruthenium(II) trisbipyridine complex (20) it exhibits a 1/2-slope variation, the latter behavior being explained by means of the highly problematic (21) notion of a pH-dependent driving force. In front of such an uncertain situation, we reasoned that the electrochemistry of phenols in water may offer a way of not only discriminating between stepwise and concerted pathways but also of characterizing the CPET reaction in terms of driving force and intrinsic properties. The latter opportunity derives from the setting of the driving force by means of the electrode potential. Among previous electrochemical studies of phenols, cyclic voltammetry in aprotic solvents and in a methanol–water mixture of coniferyl alcohol, one of the precursor phenols of lignin, has been reported, leading—with the help of pulse radiolysis—to the 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:
[email protected].
This article contains supporting information online at www.pnas.org/cgi/content/full/ 0910065106/DCSupplemental.
PNAS 兩 October 27, 2009 兩 vol. 106 兩 no. 43 兩 18143–18148
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Establishing mechanisms and intrinsic reactivity in the oxidation of phenol with water as the proton acceptor is a fundamental task relevant to many reactions occurring in natural systems. Thanks to the easy measure of the reaction kinetics by the current and the setting of the driving force by the electrode potential, the electrochemical approach is particularly suited to this endeavor. Despite challenging difficulties related to self-inhibition blocking the electrode surface, experimental conditions were established that allowed a reliable analysis of the thermodynamics and mechanisms of the proton-coupled electron-transfer oxidation of phenol to be carried out by means of cyclic voltammetry. The thermodynamic characterization was conducted in buffer media whereas the mechanisms were revealed in unbuffered water. Unambiguous evidence of a concerted proton– electron transfer mechanism, with water as proton acceptor, was thus gathered by simulation of the experimental data with appropriately derived theoretical relationships, leading to the determination of a remarkably large intrinsic rate constant. The same strategy also allowed the quantitative analysis of the competition between the concerted proton– electron transfer pathway and an OHⴚ-triggered stepwise pathway (proton transfer followed by electron transfer) at high pHs. Investigation of the passage between unbuffered and buffered media with the example of the PO4H2ⴚ/PO4H2ⴚ couple revealed the prevalence of a mechanism involving a proton transfer preceding an electron transfer over a PO4H2ⴚ-triggered concerted process.
phenoxide couple and of Pourbaix plots in the methanol–water medium (22–25). The mechanism of the PCET processes preceding dimerization was not addressed in these cases as well as in other contributions (26–29) simply because the notion of a concerted proton–electron transfer pathway was not part of the theoretical framework at the time. It should be noted, en passant, that characterization of electrochemical CPET processes are scarce even outside the domain of phenol oxidation (30). In a recent preliminary note, the phenoxyl radical produced by CPET oxidation of the phenol was protected against follow-up dimerization by ortho and para tert-butyl groups (31). This strategy has the advantage not only of simplifying the electrochemical reaction mechanism but also of minimizing the passivation of the electrode resulting from the reaction of phenoxyl radicals with the electrode material and/or from the formation of polymer deposits on the electrode surface. The price to pay is insolubility in water, necessitating large additions of an alcohol leading to problems in the measure of H⫹ concentration and in the identification of the active proton-accepting and -donating species in the medium. We therefore reasoned that, despite challenging difficulties, it would be worth investigating the mechanism of such reactions by electrochemical means with the main goal of answering the following question in mind: Is a concerted mechanism involving water as a proton acceptor (H2O–CPET) involved in the PCET process that precedes dimerization as sketched in Scheme 1? Simple phenol was taken as example, one advantage being that its solubility allows one to use pure water as the solvent with the appending benefit of a clear and simple measure of pH. A mandatory task was then to define the conditions under which self-inhibition by phenoxyl radicals and follow-up products of the electrochemical oxidative process is minimized in cyclic voltammetry. This investigation was conducted in buffered media, leading, after the kinetic effect of dimerization has duly been taken into account, to the establishment of a reliable Pourbaix plot relating the apparent standard potential to the pH. Once the thermodynamic framework of the CPET process has thus been established, one could think to tackle the mechanism analysis in the same buffered media. However, a combination of unfavorable factors hinders the achievement of this task, namely the rapidity of electron and proton transfers associated with mechanism overlap over extended sections of the available pH range. A more productive strategy consisted in analyzing the reaction kinetics in unbuffered water as a function of pH under the same conditions that minimize self-inhibition. Under these conditions, the stepwise PET pathway only involves OH⫺ as a proton acceptor. The PET pathway therefore rapidly shuts down as the pH decreases. In the remaining competition between the EPT and CPET pathways, unambiguous evidence of a concerted proton–electron transfer mechanism, with water as the sole proton acceptor, could then be gathered. We also investigated the mechanism by which the overall reaction is accelerated by the addition of a buffer to the system. In all cases, the investigation was limited to the electrode potential range where the one-electron oxidation leading to the phenoxyl radical that eventually dimerizes takes place. A further oxidation step leading to two-electron products appears at more positive potentials under the form of a wave, often almost merged with the discharge of the supporting electrolyte. Results and Discussion 1. Buffered Media. Establishing the Thermodynamic Framework. 1.1 Avoiding Self-Inhibition. Self-inhibition (32) produces dramatic effects on the cyclic voltammetric responses that may completely obscure mechanistic analyses based on the variations of peak currents and potentials with scan rate and concentrations (33). As detailed in the SI Appendix these effects can be neglected 18144 兩 www.pnas.org兾cgi兾doi兾10.1073兾pnas.0910065106
B
A
C
Fig. 1. Determining the thermodynamics of phenol oxidation. (A) Cyclic voltammetry of 0.2 mM PhOH in 0.05-M Britton Robinson buffers at 0.2 V/s as a 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 the apparent standard potential with pH (Pourbaix diagram), showing the zones of thermodynamic stability of the various species and the characteristic pKs and standard potentials. All potentials are referred to the NHE.
provided that phenol concentration is held below 1 mM and scan rates are held above 0.1 V/s. Under these conditions, the peak potential is expected to obey Eq. 1, which applies to a reaction in which fast and reversible electron and proton transfers precede a rate-determining dimerization (34–36). 0 ⫹ 0.903 RT/F ⫺ 共RTln 10/3F兲log共4RTk dimC 0/3Fv兲 Ep ⫽ Eap
[1] 0 (Eap
is the pH-dependent apparent standard potential giving rise to the Pourbaix diagram as discussed in more detail in section 1.2). These observations led us to use a scan rate of 0.2 V/s and a phenol concentration of 0.2 mM to safely avoid the interference of self-inhibition in the characterization of the thermodynamics in buffered media.
1.2. Thermodynamics of the Reaction. Because the oxidation wave
shifts toward more positive potentials when going to smaller pHs, the background current had to be systematically subtracted from the phenol-oxidation response and the adherence to Eq. 1 checked at each pH. The resulting voltammograms are displayed in Fig. 1A as a function of pH. The resulting diagram of the peak potential vs. pH shown in Fig. 1B has the aspect of a Pourbaix plot with a 59.2-mV slope with linear variation below pH ⫽ 10 (the phenol pK) and a horizontal asymptote above pH ⫽ 10. The peak potential contains, however, a contribution of the follow-up dimerization as expressed by Eq. 1. Indeed, if all of the electron-transfer and proton-transfer steps in Scheme 1 are at equilibrium, the thermodynamics of the conversion of ArOH into ArO• gives rise, whatever the pathways that are followed, to an apparent stan0 , the variation of which with pH is precisely the dard potential Eap sought Pourbaix diagram Costentin et al.
B
Fig. 2. Oxidation of phenol in unbuffered water. (A) Cyclic voltammetry of 0.2 mM PhOH in unbuffered water at 0.2 V/s as a function of pH. pH values from right to left: 2, 3, 4, 5, 6, 7, 8, 8.5, 9, 9.5, 9.5, 10, 11, 12. (B) Basic unbuffered water (first five voltammograms of Fig. 2 A) showing the decrease of the peak current with the pH (dots) as compared with the simulation (full line) (see parameter values in Table 1) of an OH⫺–PET pathway according to Eq. 2. The peak currents ip are normalized versus the value at pH ⫽ 12.
0 0 Eap ⫽ EPET ⫹ 共RTln 10/F兲log
冉
冊
1 ⫹ 10 ⫺pH/10 ⫺pKArOH . 1 ⫹ 10 ⫺pH/10 ⫺pKArOH•⫹
Therefore, subtracting the contribution of dimerization, taking 2kdim ⫽ 2.6 ⫻ 109 M⫺1 s⫺1 (37), (with v ⫽ 0.2 V/s and C0 ⫽ 0.2 mM) leads to the effective Pourbaix diagram shown in Fig. 1C, 0 where EPET (V vs. NHE) ⫽ 0.803. This value is significantly smaller, by 57 mV, than the value reported earlier by using a similar method (38) and is approximately the same as the value 0.79 V vs. NHE, previously determined by means of pulse radiolysis (39). The value reported in reference 38 results, presumably, because no precautions were taken to avoid selfinhibition. The zones of thermodynamic stability of the various species may be thus be defined [pKArOH ⫽ 10, pKArOH⫹ ⫽ ⫺2 (40)] as shown in Fig. 1C. The four standard potentials to be used in the expression 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 concentration
conditions as defined in buffered media were also applied in the present case. The voltammograms obtained at 0.2 V/s with 0.2-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 splits in two waves as the pH decreases. The first wave, which takes place in the same potential region as in buffered media, rapidly decreases with the pH at the expense of a more positive second wave. The variations of the peak potential of the two waves with pH (Fig. 3A) also show a strong contrast with the behavior observed in buffers.
A
B
Fig. 3. Cyclic voltammetry of 0.2 mM PhOH. (A) Peak potential as a function of 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 of pD, see SI Appendix); gray crosses, simulation according to a Nernstian EPT mechanism. (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.
Costentin et al.
2.2. The H2O–CPET Pathway. As the first wave vanishes upon
decreasing the pH, a question arises concerning the nature of the oxidative dehydrodimerization mechanism at the henceforth predominating second wave. Because the PET pathway is shut down, the only remaining possibilities are the stepwise EPT pathway and the concerted CPET pathway. It is interesting to note that once the first wave has completely disappeared, the location of the second wave remains the same down to pH ⫽ 4, with a peak potential (black stars in Fig. 3A) well above its value in buffered media, until it catches up to the buffered medium (59-mV slope, straight line in Fig. 3A). This behavior is a consequence of the absence of buffering, whatever the reaction mechanism, reversible electron and proton transfers within an EPT pathway or reversible concerted proton–electron transfer in a CPET pathway. In both cases, the generation of protons upon electron transfer decreases the local pH. The evacuation of the protons produced by diffusion from the electrode thus becomes a crucial rate-controlling factor. In this context, phenol concentration is an important parameter because it is a measure of the maximal amount of protons produced. Upon decreasing the pH, the amount of protons generated by the oxidation becomes small as compared with the concentration of protons already present, leading to the same behavior observed in the buffered media of the same pH. This effect is not mechanism-discriminating, but the EPT mechanism can be ruled out for the following kinetic reasons. In the successive steps of this reaction sequence recalled in Scheme 1, the ratio of the deprotonation and protonation rate constants, K⫺p ⫽ k⫺p/k⫹p ⫽ 100 (see pKs in Fig. 1C). To give this pathway the best chance to compete, we selected for simulation of cyclic voltammetric responses, a very rapid electron transfer so as to obtain a Nernstian behavior and the maximal conceivable value, 1013 s⫺1, for the deprotonation rate constant by water. We see in Fig. 3A that the simulated peak potentials are much too positive as compared with the experimental peak potentials and, in Fig. 3B, that the voltammogram shapes do not agree. The reason for this behavior is that the deprotonation/protonation step is not at equilibrium because the reprotonation step is not much faster than the follow-up dimerization and diffusion of the phenoxyl radical. The result is that the protonation step interferes in the kinetics of the overall process, making it occur at a potential more positive than if the deprotonation/protonation step were at equilibrium. These observations unambiguously establish the occurrence of the CPET mechanism. Repeating the cyclic voltammetric analysis in heavy water led to the results reported in Fig. 3A (gray stars). In the CPET potential domain, the peak potentials are more positive in D2O PNAS 兩 October 27, 2009 兩 vol. 106 兩 no. 43 兩 18145
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2.1. The OHⴚ–PET Pathway. The only base in the unbuffered medium able to deprotonate the phenol and thus launch the PET pathway is the OH⫺ ion. Above the phenol pK, the phenoxide ion predominates, and the reaction simply consists in its oxidation yielding the phenoxyl radical, which dimerizes eventually. As the pH decreases below the pK, fast deprotonation of phenol by the OH⫺ ions still present continues to produce the phenoxide ion and hence the radical and the dimer in the framework of the CE mechanism (36) that we have named the PET pathway. Because on the one hand the medium is not buffered and, on the other, deprotonation is very fast, diffusion of OH⫺ ions toward the electrode becomes the most important rate-controlling factor. Phenol concentration is another essential parameter because it determines the amount of proton equivalents that are generated upon oxidation, making the pH decrease during the course of the cyclic voltammogram. These various factors can be put together within a kinetic model that leads to an integral equation 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.
Table 1. Simulation parameters Parameters
Values
Potentials (V vs. NHE)
dim 0 0 ⫽ 0.714, EPET ⫽ 0.803, EEPT ⫽ 1.519, EPET 0 0 ECPET(H2O) ⫽ 1.400, ECPET(D2O) ⫽ 1.421
Diffusion coefficients ⫻105 (cm2 s⫺1) Standard rate constants (cm s⫺1) Rate constants (M⫺1 s⫺1 or s⫺1)
DPhOH ⫽ 3.7, DOH⫺ ⫽ 5.4, DH⫹ ⫽ 9.3, DD⫹ ⫽ 6.6 (41), DPO4H2⫺ ⫽ 1 kCPET (H) ⫽ 25 ⫾ 5, kCPET (D) ⫽ 10 ⫾ 2 S S 2kdim ⫽ 2.6 ⫻ 109, kp ⫽ 1011, k⫺p ⫽ 1013
than in H2O, indicating a significant H/D isotope effect. This observation suggests the interference of the CPET kinetics in addition to proton diffusion. To characterize the kinetics of the CPET reaction, additional experiments were carried out as a function of the scan rate at pH 7.2, right in the middle of the pH range of interest. The results are shown in Fig. 4A. The following kinetic model may be used to simulate the cyclic voltammograms and derive the standard rate constant of the CPET 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. Because water is the solvent, its activity and concentration are considered as constant and may be removed from the expression of the equilibrium and kinetic laws. As discussed previously (43, 44), the rate law for an electrochemical CPET reaction may be approximated by a Butler–Volmer relationship with a transfer coefficient equal to 0.5: 0 i/FS ⫽ kSCPET exp关共F/2RT兲共E ⫺ E CPET 兲兴兵关ArOH兴 0 0 ⫺ 共关ArO•兴 0关H⫹兴 0/C S兲exp关⫺共F/RT兲共E ⫺ E CPET 兲兴其,
where the []0 are the concentrations at the electrode surface in mol/L. Cs is the standard concentration that we take equal to 1 0 mol/L. ECPET , the standard potential governing the CPET pathway, has the value indicated in Fig. 1C. Determination of kCPET , the corresponding standard rate constant, is the main S objective of the kinetic analysis of the system. This value leads to the integral equation of the CPET wave (see SI Appendix), which depends on the parameter kSCPET共C 0/C S兲 1/2 , p⫽ 1/4 共D ArOH兲 共D H⫹兲 1/4共Fv/RT兲 1/3共4k dimC 0/3兲 1/6
between pH 6 and 8—leads to the following value of the standard rate constant: kCPET (D) ⫽ 10 ⫾ 2 cm s⫺1. The H/D S kinetic isotopic effect is therefore equal to 2.5, a value expected for an adiabatic or quasiadiabatic CPET electrochemical reaction (26). One may wonder why such high values of an electrochemical standard rate constant could be reached at very moderate scan rates. The reason for this is that the follow-up dimerization tends to make the preceding electron transfer the rate-determining step in unbuffered as well as in buffered media. This tendency is 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 parameter would have in buffered media (45): p⫽
共D ArOH兲
1/2
kSCPET . 共Fv/RT兲 1/3共4k dimC 0/3兲 1/6
With the values listed in Table 1, p ⫽ 0.5 at 0.2 V/s in unbuffered water, indicating a mixed kinetic control by electron transfer and dimerization, allowing the determination of the standard rate constant. In the corresponding buffer medium p ⫽ 200, leaving no chance for electron transfer to participate in the kinetic control. 3. Passage from Unbuffered to Buffered Media. Additional Concerted or PET Pathways? Once the mechanisms taking place in complete
absence of buffer have been established, it is interesting to
A
B
[2]
which measures the competition between the CPET reaction and the follow-up dimerization for the kinetic control of the whole process (p30 and p3⬁, respectively). Simulation of the experimental voltammograms shown in Fig. 4B led to a quite satisfactory fit for kCPET ⫽ 25 ⫾ 5 cm s⫺1. S A similar approach was also used to derive the value of kCPET S in heavy water. Simulation (Table 1) of the peak potential in the zone where it is constant and equal to 1.140 V vs. NHE—
A
B
Fig. 4. Cyclic voltammetry of 0.2 mM PhOH in unbuffered water at pH ⫽ 7.2 as 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. 18146 兩 www.pnas.org兾cgi兾doi兾10.1073兾pnas.0910065106
C
D
Fig. 5. Passage from unbuffered to buffered media. Cyclic voltammetry of 0.2 mM PhOH at pH 7.2 in phosphate buffer at 0.2 V/s as a function of buffer concentration. (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) 7 in 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, prediction for the PO4H2⫺–PET mechanism (see section 3). (D) Variation of the peak potential with Z0. Dots, experimental data; line, prediction for the PO4H2⫺– PET mechanism (see section 3).
Costentin et al.
Concluding Remarks. The most important finding of this work is the demonstration that a concerted proton–electron transfer mechanism is operating in the electrochemical oxidation of phenol. To our knowledge, the identification of such a reaction pathway in the electrochemical dehydrodimerizations of phenols in which water acts as the proton acceptor is a previously undescribed finding. The use of unbuffered media was essential in this venture. It indeed allows for the rapid shutting-down of the PET (proton transfer first followed by electron transfer) pathway at pHs close to the phenol pK. A large pH domain is thus open for investigating the other pathways, making it possible to identify unambiguously the concerted pathway, to determine the corresponding standard rate constant, and to measure the H/D kinetic isotope effect. Reaching these unambiguous conclusions required a careful estimation of the scan rate and concentration conditions under which self-inhibition can be trimmed down to negligible. These efforts also led to an accurate determination of the thermodynamics of the reaction, providing an essential framework for mechanism analysis. It is also worth noting that, thanks to the use of unbuffered media at intermediate pHs, cyclic voltammetry allowed a straight visualization of the competition between the PET and CPET pathway. Another point worth emphasizing is the inability of the EPT pathway to compete efficiently with the CPET pathway, illustrating the avoidance of high-energy intermediates on the reaction pathway. The electrochemical H2O-CPET reaction is characterized by an exceptionally large standard rate constant. It would be interesting to see whether the ensuing expectation of a similarly large intrinsic rate constant in homogeneous phenol oxidation is indeed observed, opening the appending question of activation control vs. the forward and reverse diffusion. Another finding that will be interesting to compare with homogeneous processes is the fact that the addition of a buffer base-like PO4H2⫺, drives the system toward a PET pathway rather than toward a CPET pathway.
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10. Webster RD (2007) New insights into the oxidative electrochemistry of vitamin E. Acc Chem Res 40:251–257. 11. Ralph J, et al. (2004) Lignins: Natural polymers from oxidative coupling of 4-hydroxyphenyl-propanoids. Phytochem Rev 3:29 – 60. 12. Vanholme R, Morreel K, Ralph J, Boerjan W (2008) Lignin engineering. Curr Opin Plant Biol 11:278 –285. 13. Morrow GW (2001) Anodic oxidation of oxygen-containing compounds. Organic Electrochemistry, eds Lund H, Hammerich O (Marcel Dekker, New York) 4th Ed, pp 589 – 620. 14. Rhile IJ, et al. (2006) Concerted proton-electron transfer in the oxidation of hydrogenbonded phenols. J Am Chem Soc 128:6075– 6088. 15. Costentin C, Robert M, Save´ant JM (2006) Electrochemical and homogeneous protoncoupled electron transfers: Concerted pathways in the one-electron oxidation of a phenol coupled with an intramolecular amine-driven proton transfer. J Am Chem Soc 128:4552– 4553. 16. Markle TF, Rhile IJ, DiPasquale AG, Mayer JM (2008) Probing concerted protonelectron transfer in phenol-imidazoles. Proc Natl Acad Sci USA 105:8185– 8190. 17. Costentin C, Robert M, Save´ant JM (2007) Adiabatic and non-adiabatic concerted proton-electron transfers. Temperature effects in the oxidation of intramolecularly hydrogen-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.
Materials and Methods The electrochemical kinetics were obtained from cyclic voltammetric experiments on a glassy carbon electrode carefully polished before each run. Details on the methods and materials used are given in the SI Appendix. Experimental Details. The effects of self-inhibition, a quantitative analysis of the OH⫺–PET, H2O–CPET, H2O–EPT, PO4H2⫺–PET and PO4H2⫺–CPET mechanisms, and procedures for numerical simulations can be found in the SI Appendix. ACKNOWLEDGMENTS. Partial financial support from the Agence Nationale de la Recherche (Program blanc PROTOCOLE) is gratefully acknowledged.
PNAS 兩 October 27, 2009 兩 vol. 106 兩 no. 43 兩 18147
CHEMISTRY
investigate what happens upon progressive addition of a buffer to the solution. Selecting the PO4H2⫺/PO4H2⫺ couple as a representative example, successive additions of the two members in equal amounts—so as to maintain the pH ⫽ 7.2—resulted in the appearance of a new wave in front of the H2O-CPET wave, which grows at the expense of the latter (Fig. 5A) until it reaches a steady value, the wave being then identical to that observed in a buffered medium at the same pH. Two different mechanisms may be acting in the passage from an unbuffered to a buffered medium. One is the PET mechanism shown in Scheme 1, in which again Z ⫽ PO4H2⫺ (Z0 is then the bulk concentration of PO4H2⫺); Fig. 5 C and D illustrate the good adherence to experimental data of predictions based on the PO4H2⫺–PET mechanism (see SI Appendix), both in terms of peak current and potential with the parameter values. A PO4H2⫺–CPET pathway should also be envisaged because it benefits from a better driving force than the H2O–CPET pathway. Indeed, although the driving force of the CPET reactions do not depend on pH (21), the standard potential defining the driving force of the reaction is obtained from the apparent standard potential at a pH equal to the pK of the proton acceptor under consideration. It thus appears from Fig. 1C that the PO4H2⫺–CPET pathway has a driving force advantage of 0.425 eV over the H2O–CPET pathway. Although the characteristic equations are not exactly the same, the predictions for the PO4H2⫺–CPET pathway would involve, as for the PO4H2⫺–PET pathway, a variation with buffer concentration similar to Fig. 5C. Discrimination from the PO4H2⫺–PET mechanism, rather, derives from the absence of the H/D isotope effect as 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 the experiment in Fig. 5B was carried out, the rate-determining step should be the CPET reaction. In fact, at this buffer concentraCPET tion, kS,PO4 H2⫺ should be as large as 140–240 cm s⫺1 for the kinetic control to pass from electron transfer to dimerization CPET (see SI Appendix). Because kS,PO4 H2⫺ is obviously much smaller CPET ⫽ 25 cm s⫺1, i.e., 0.5 cm s⫺1 per water (compare with kS,H 2O molecule), we may conclude that the reaction is kinetically controlled by the CPET electron transfer step and should therefore exhibit a significant H/D isotope effect. Its absence, at the level of the PO4H2⫺-triggered oxidation wave (first wave in Fig. 5B), consequently rules out this mechanism at the benefit of the PO4H2⫺–PET pathway, which is not expected to show any significant H/D isotope effect (see SI Appendix).
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