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Chapter 7
Electrochemical Procedures To Determine Thermodynamic and Kinetic Parameters of Atom Transfer Radical Polymerization Francesca Lorandi,1 Marco Fantin,2 Francesco De Bon,1 Abdirisak A. Isse,1 and Armando Gennaro*,1 1Department
of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy 2Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States *E-mail:
[email protected].
Electrochemical investigation provides information about the stability, activity and halidophilicity of catalysts for Atom Transfer Radical Polymerization (ATRP). Moreover, several electrochemical tools were developed to measure thermodynamic and kinetic parameters of ATRP. These techniques enabled to determine activation rate constants spanning over 12 orders of magnitude. ATRP equilibrium constant and relevant side reactions concerning the catalyst were also examined by electrochemical methods. As such, electrochemistry enables to build a database of kinetic and thermodynamic constants of ATRP and related reactions of copper complexes.
Introduction In atom transfer radical polymerization (ATRP), the equilibrium between propagating radicals and dormant species is governed by the redox couple XCuIIL+/CuIL+ (L = polydentate amine, X = halogen). CuIL+ generates radicals by reductive cleavage of the C−X bond in the initiator (RX) or dormant chain (PnX). The C−X cleavage is coupled with atom transfer to the Cu complex (Scheme 1). The ensuing oxidized form of the catalyst XCuIIL+ deactivates radicals after they add to few monomer (M) molecules (1). © 2018 American Chemical Society
Scheme 1. General ATRP Mechanism
The equilibrium constant of ATRP is defined by the ratio between the activation and deactivation rate constants, i.e. KATRP = kact/kdeact. These quantities are related to the rate of polymerization (Rp) and to the dispersity of the obtained polymer (Eq. 1 and Eq. 2, respectively).
where kp is the propagation rate constant, DP is the degree of polymerization and p is the monomer conversion. kp depends on temperature and on the nature of monomer and solvent. kp is typically measured by well-established techniques such as pulsed laser initiated polymerization coupled with size exclusion chromatography (PLP-SEC), whereas PLP combined with time-resolved near-infrared spectroscopy (2), in the single pulse (SP)-PLP method, provides accurate values of the termination rate constant (kt) of polymer chains (3). KATRP, kact, and kdeact values are affected by temperature and by nature of catalyst, initiator, solvent, monomer, and the monomer/solvent ratio. ATRP equilibrium constants were determined by GC or UV-Vis spectroscopy (4, 5). Activation rate constants were measured by gas-chromatography, HPLC, NMR, or UV-Vis spectroscopy (6–8). These techniques are compatible only with moderately slow reactions, thus stopped-flow methods were adopted for faster systems (9, 10). kdeact values are generally very high, approaching the diffusion-controlled limit, therefore only few experimental methods were developed for their direct determination. Some kdeact values were obtained from EPR measurements (11) or from radical clock reactions with radical trapping agents (7). More commonly, kdeact was determined by independently measuring kact and KATRP. In the last decade, several electrochemical tools were developed to measure kact, kdeact, and KATRP over a large range of values spanning several orders of magnitude. Minimal amount of reactants are required, and highly accurate values are generally determined within a short measurement time. The most modern and active complexes can be easily investigated by voltammetric techniques. These methods are presented in this chapter. The contribution of electrochemistry to ATRP has created a large database of kinetic and thermodynamic data that has enhanced the comprehension of the polymerization process, providing tools to 162
select the appropriate experimental conditions for the desired polymerization result.
Mechanism of ATRP Activation In ATRP, three possible pathways can describe the formation of the propagating radical: i) outer-sphere electron transfer generating intermediate RX•− (OSET-SW), ii) OSET concerted with C−X bond rupture (OSET-C), and iii) inner-sphere electron transfer or atom transfer (ISET-AT) (inset in Figure 1).
Figure 1. Comparison of free energies during ISET-AT and OSET-C processes for the reaction of bromoacetonitrile with CuITPMA+ in acetonitrile at 25 °C Inset: possible mechanisms of electron transfer in ATRP. Reprinted with permission from ref. (12). Copyright 2008 American Chemical Society.
Theoretical and electrochemical analysis of the activation process of a wide series of alkyl halides, mimicking the chain end of the macromolecular dormant species, enabled to define the real mechanism of the activation reaction (12). The OSET-SW pathway was discarded because it was experimentally proved that reductive cleavage of alkyl halides used as initiators in ATRP follows a concerted mechanism. ISET-AT and OSET-C have similar thermodynamic requirements; therefore, they were discriminated by considering their relative transition state energies. The rate constant of the hypothetical OSET-C reaction between bromoacetonitrile and CuITPMA+ complex was estimated using Marcus theory for ET with correction for in-cage interactions of ion-dipole fragments (the sticky model) (13, 14). The calculated kOSET-C ≈ 10-11 M-1 s-1 was more than 12 orders of magnitude smaller than the experimental value (kact ≈ 82 M-1 s-1 at 25 °C in CH3CN), pointing out that the correct activation mechanism is via ISET-AT. 163
This conclusion was confirmed by measuring the activation rate constants of reduction of some alkyl halide initiators by outer sphere electron donors (i.e. electrogenerated organic radical anions, A•−), and by comparing them with kact by some CuIL+ complexes (15).
Figure 2. A comparison between rate constants, k, of RX activation by aromatic radical ions (dots) and CuIL+ complexes (squares), measured in CH3CN + 0.1 M Et4NBF4 at 25 °C. The lines are the best-fitting curves for dissociative electron transfer by A•−. Reprinted with permission from ref. (15). Copyright 2013 Elsevier.
Figure 2 shows a comparison of kact values measured obtained for three CuIL+ complexes. In all cases, activation orders of magnitude faster than activation by outer-sphere the same standard potential of the copper catalysts, which mechanism for Cu complexes.
for A•− with those by CuIL+ was 7-10 electron donors of confirms the ISET
Cyclic Voltammetry of ATRP Catalysts Cyclic voltammetry (CV) is a versatile screening tool for ATRP catalysts and initiators. Binary Cu/L and ternary X/Cu/L complexes exhibit a quasi-reversible voltammetric peak couple from which their standard reduction potential is measured as the semi-sum of cathodic (Epc) and anodic (Epa) peak potentials: E ≈ E1/2 = (Epc + Epa)/2. E of X/Cu/L is generally more negative than E of the corresponding Cu/L (Figure 3a), and both are considerably more negative than E .
of the solvated Cu(II) salt: 164
As a rule, the more negative E, the higher the catalytic activity of the complex in ATRP (5). E generally shifts to more positive values if the temperature is raised, resulting in a decrease of the reducing power of the catalyst (16). However, monomer propagation is favored at high T, thus ATRP rate increases with T. CV conducted in water at different pHs showed that common amine ligands may be protonated by decreasing the pH, thus losing their ability to stabilize the copper center. Instead, the CuIIL(OH)+ complex forms at basic pH (Figure 3b) (17) because OH– binds copper more strongly than X−.
Figure 3. (a) Cyclic voltammetry (CV) of 1 mM CuIIMe6TREN2+ in the absence and presence of 2 mM Et4NBr or Et4NCl, in DMSO + 0.1 M Et4NBF4, v = 0.2 V s-1, T = 25 °C. (b) CV of 1 mM CuIITPMA2+ at different pH, in water + 0.1 M Et4NBF4, v = 0.2 V s-1, T = 25 °C. Adapted with permission from ref. (17). Copyright 2015 American Chemical Society. (c) CV of 1 mM CuIIMe6TREN2+, CuIITPMA2+, CuIIPMDETA2+ in [BMIm][OTf], v = 0.1 V s-1, T = 50 °C. Adapted with permission from ref. (18). Copyright 2017 Elsevier. (d) CV of 1 mM BrCuIITPMA2+ with increasing amount of sodium dodecyl sulfate (SDS) in water + 0.1 M NaBr. v = 0.1 V s-1, T = 65 °C. Adapted with permission from ref. (19). Copyright 2017 American Chemical Society. 165
Electrochemical analysis in Ionic Liquids (ILs) can be performed without adding a supporting electrolyte, because of the relatively high ionic conductivity of these media. CV of common ATRP catalysts and initiators in 1-butyl-3-methylimidazolium trifluoromethanesulfonate showed similar features to the ones observed in traditional organic solvents (Figure 3c) (18). Voltammetric studies were carried out also in an oil-in-water miniemulsion, formed with sodium dodecyl sulfate (SDS) surfactant. E of BrCuIITPMA+ in the miniemulsion shifted to more negative values, compared to pure water, while the peak currents decreased (19). A similar effect was found in water, when adding increasing amounts of SDS (Figure 3d), suggesting that this surfactant interacted with the catalyst, enhancing the stabilization of the CuII species. CVs of alkyl halides used as ATRP initiators show an irreversible bi-electronic reduction peak, with a peak potential Ep reversible peak couple due to the reduction of the remaining CuIIL2+ molecules not involved in the catalytic process. The position of the prepeak is directly correlated to kact (Eq. 14).
By applying Eq. 14, kact was calculated directly from CVs recorded at various CRX and/or scan rates. The effect of these two parameters on the voltammetric response is depicted in Figure 6. The intensity of the prepeak increased and Ep shifted toward more negative values by either increasing CRX or v. Under the total catalysis regime, a slope of about -30 mV was obtained by plotting Ep vs. logCRX or vs. logv, in agreement with Eq. 14.
Figure 6. Cyclic voltammetry of 10−3 M CuIITPMA2+ recorded in H2O + 0.1 M Et4NBF4 at: a) 0.05 V s−1 in the absence and presence of 2-hydroxyethyl-2-bromoisobutyrate (HEBiB) with CHEBiB = 2 × 10−4, 3 × 10−4, 5 × 10−4 and 7 × 10−4 M; b) different scan rates 0.01, 0.02, 0.03, 0.05, 0.07, and 0.1 V s−1 in the presence of 5 × 10−4 M HEBiB. Insets: variation of prepeak potential, Ep, with log CHEBiB or log v. Adapted with permission from ref. (20). Copyright 2017 American Chemical Society.
The total catalysis technique does not require a radical scavenger, because all RX molecules are rapidly converted to radicals in a thin layer close to the electrode surface, thus the termination rate is enhanced and the activation process becomes irreversible. However, this simple method requires clear and well-reproducible voltammetric responses. 177
CV under total catalysis conditions was used in water (Table 4) to measure kact values as high as 2.6 × 107 M-1 s-1, and very recently to study the activation of ethyl α-bromoisobutyrate in acetonitrile by the extremely active, new ATRP catalyst CuII(TPMANMe2) (30).
Table 4. Activation Rate Constants of Various Catalyst/Initiator Systems Measured by Cyclic Voltammetry under Total Catalysis Conditions, T = 25 °C RX
Ligand
a
Solvent
kact (M-1 s-1)
Ref.
Me6TREN
HEBiBa
H2O
2.6 × 107
(20)
TPMA
HEBiBa
H2O
5.4 × 106
(20)
TPMANMe2
ethyl α-bromoisobutyrate
CH3CN
7.2 × 106
(30)
2-hydroxyethyl-2-bromoisobutyrate.
Figure 7. Background-subtracted experimental and simulated voltammograms of CuIIMe6TREN2+ in the presence of bromoacetonitrile recorded at 0.5 and 1, in CH3CN + 0.1 M Et4NBF4 at 25 °C. Adapted with permission from ref. (24). Copyright 2017 Elsevier. 178
d. Cyclic Voltammetry with Digital Simulation kact of both slow and fast ATRP systems was measured by digital simulations of CV (20, 24, 31). Experimental and digital CVs have been overlapped, having previously subtracted the background in the experimental signals (20, 24). The set of reactions required to simulate the electrochemical response is identical to the one used for the HRC method (Scheme 2), thus all parameters, except kact, should be measured independently, or be available in the literature. If some parameters are not easily accessible, they can be left as adjustable variables in the simulation together with kact, although at the expense of a greater uncertainty over the obtained kact values. This technique requires the presence of TEMPO, at least for slow activation processes. An example of a good match obtained by overlapping experimental and digital CVs is reported in Figure 7.
Table 5. Activation Rate Constants of Various Catalyst/Initiator Systems Measured by Cyclic Voltammetry with Digital Simulation, T = 25 °C Ligand
TPMA
Me6TREN
RX
Solvent
H2O
oligo(ethylene oxide) 2bromopropionate ethyl α-bromoisobutyrate
1.3 × 105
CH3CN
3.7 × 104
DMSO
8.7 × 104
(20)
(31)
2.4 × 103
methyl 2-bromopropionate
DMSO
2.5 × 102
(32)
4.5 × 101
benzyl bromide
Me6TREN
Ref.
5.4 × 106
2-hydroxyethyl-2bromoisobutyrate
ethyl α-bromoisobutyrate PMDETA
kact (M-1 s-1)
bromoacetonitrile
CH3CN
1.0 × 105
bromoacetonitrile
DMSO
3.6 × 105
chloroacetonitrile
CH3CN
5.9 × 102
CH3CN
4.0 × 104
DMSO
1.8 × 104
CH3CN
3.6 × 104
DMSO
2.4 × 104
bromoacetonitrile TPMA ethyl α-bromoisobutyrate
(33)
(33)
Digital simulation of CV has been applied to both slow and fast activation reactions, measuring kact in the range 10-108 M-1s-1, in water, acetonitrile, and DMSO (Table 5). In contrast, the total catalysis method was valid in a limited range of kact, CRX, and v values. 179
Electrochemical Determination of kdeact The accurate measurement of the ATRP deactivation rate constant is difficult because of its high value, generally close to the diffusion-controlled limit. An electrochemical method based on comparing experimental catalytic CVs with simulated voltammograms was used to measure few kdeact values in DMSO (32). First, cyclic voltammetry in the presence of TEMPO, coupled with digital simulation enabled to determine kact, as described in the previous section. The set of reactions reported in Scheme 2 was used in the simulations, with kact as the only unknown parameter. The value of kdeact had no effect on this experiment, because TEMPO quenched all available radicals. The same experiment was then repeated in the absence of TEMPO and simulated by using the just calculated kact, while refining the kdeact value. Indeed, when no radical scavenger was added, the deactivation reaction occurred and the recorded catalytic current Ip decreased, due to the backward reaction between XCuIIL2+ and radicals. The same set of scan rates and ratios was used in both experiments, thus the only difference was the absence or presence of the deactivation process. The procedure was used on 3 different initiators, with BrCuIIPMDETA2+ as catalyst, in DMSO (Table 6) (32).
Table 6. Deactivation Rate Constants Measured by Cyclic Voltammetry with Digital Simulation in DMSO, T = 25 °C RX
Ligand
PMDETA
kdeact (M-1 s-1)
Ethyl α-bromoisobutyrate
1.8 × 106
Methyl 2-bromopropionate
7.6 × 106
Benzyl bromide
8.6 × 105
It must be considered that side reactions may hamper these kinetic analysis. In particular, the CuI catalyzed radical termination (CRT, Scheme 3) should be considered (34).
Scheme 3. Mechanism of CuI Catalyzed Radical Termination (CRT) The CRT mechanism involves the reversible formation of an organometallic adduct, R-CuII, followed by termination with a second radical species. If TEMPO is present, CRT has no effect, because radicals are trapped before forming the organometallic intermediate. However, in the absence of any radical scavenger, CRT can significantly alter the shape and peak current of the voltammetric 180
response. Therefore, reported kdeact values should be refined considering the influence of CRT on primary and secondary alkyl radicals, whereas tertiary radicals are substantially unaffected by this reaction (33, 35).
Electrochemical Determination of KATRP Chronoamperometry at a rotating disk electrode was used to determine KATRP, by monitoring the disappearance of CuIL+ during the reaction between CuIL+ and RX, and by applying a modified Fischer’s equation (23). This equation relates the concentration of XCuIIL+ to the ATRP equilibrium constant:
where Y is the concentration of the “persistent radical” XCuIIL+, C0 and I0 are the initial concentrations of CuIL+ and RX, and c′ and c″ are constants. Eq. 15 is valid for C0 ≠ I0, whereas it reduces to Eq. 16 if C0 = I0 (36). The experimental procedure was identical to the one reported for kact determination via RDE, except that TEMPO was not added to the solution. Therefore, activation, deactivation, and radical termination occur during the measurement of KATRP. Side reactions, and particularly CRT, must be avoided. The ratio between the rates of radical-radical termination (RT) and CRT is given by Eq. 17.
Since kt and kCRT are generally of the order of 109 M-1s-1 and 104 M-1s-1 (34), respectively, whereas KATRP for active catalysts in polar solvents is in the range ratio is required to suppress CRT. Therefore, a large 10-4-10-6, a high CRX excess of RX with respect to the initial amount of CuI was used to minimize the = 50, contribution of CRT. KATRP values in Table 7 were obtained using which ensured CRX > 50, especially during the initial stages of the reaction (36). KATRP values of CuIMe6TREN+ and CuITPMA+ with methyl 2-bromopropionate (acrylate mimic) were measured in CH3CN, DMF, and mixtures with butyl acrylate (Table 7). The presence of the monomer did not alter the reaction scheme because with such active catalysts and no deactivators most radicals terminated immediately and monomer conversion was negligible. Interestingly, for relatively slow systems it was possible to determine KATRP and kact in one experiment, by monitoring first the reaction between CuIL+ and RX, and then adding a concentrated solution of TEMPO to trap all radicals and isolate the activation step by suppressing deactivation. 181
It should be noticed that literature values for KATRP (36) were generally smaller than the ones determined by RDE (23). This is likely due to the presence of Br− or Cl− ions in previous measurements. These halide ions bind to CuI by formation of species, thus decreasing the amount of the active catalyst, inactive XCuIL or CuIX2−. The presence of these species slows down the process. Therefore, absolute values of KATRP and kact should be measured in the absence of halide ions. The simplicity and high reproducibility (5-10 % error) of this technique offer a valuable tool to investigate various catalyst/initiator systems, thus increasing the understanding of the ATRP mechanism.
Table 7. ATRP Equilibrium Constants of Various Systems Measured by Rotating Disk Electrode, T = 25 °C Ligand
Me6TREN
RX
methyl 2-bromopropionate
ethyl 2-chloropropionate
TPMA
methyl 2-bromopropionate
Solvent
KATRP
CH3CN
1.1 × 10-5
CHCH3CN /BA 1/1 v/v
7.2 × 10-6
DMF
1.3 × 10-4
DMF/BA 1/1 v/v
1.9 × 10-5
CH3CN
2.3 × 10-6
CH3CN
3.5 × 10-6
CHCH3CN/BA 1/1 v/v
1.8 × 10-6
DMF
1.6 × 10-5
DMF/BA 1/1 v/v
1.7 × 10-6
Estimation of Halidophilicity Constants from ATRP Measurements If halogen ions are present during kinetic analysis of the ATRP process, the measured parameter is an apparent constant, whose value depends on . were measured with increasing under Indeed, decreasing values of otherwise identical conditions (Figure 8a). The drop in the overall rate of current decay is due to the reduced availability of CuIL+ owing to the speciation of CuI involving both active CuIL+ and inactive XCuIL (at higher ratios, additional inactive halogenated CuI species are formed). Therefore, the decrease values can be used to measure the halidophilicity constant for CuIL+, of by correlating KATRP to This procedure was validated by using the value of = 186 M-1, previously measured by potentiometry for CuIMe6TREN+ in CH3CN (22). Then it was applied to CuITPMA+ in CH3CN, obtaining = 389 M-1 (Figure 8b). 182
Figure 8. a) vs. time for the reaction of CuIL+ with 2-methyl bromopropionate in the presence of different amounts of Br−, measured at an RDE in CH3CN + 0.1 M Et4NBF4, T = 25 °C. b) Experimental KATRP values, in the presence of increasing and fitting of data to obtain . Adapted with permission from ref. (23). Copyright 2018 Elsevier.
Electrochemical Determination of kdisp The rotating disk electrode was also used to measure the rate constant of CuI disproportionation, kdisp (17, 27):
The experimental procedure is the same as previously described for kact determination, except that neither RX nor radical scavenger is added. The recorded current, IL, is proportional to which is easily calculated by Eq. 10. The extent of disproportionation mainly depends on the nature of ligand and solvent, and halide ions if present. Indeed, in the presence of X-, additional equilibria for CuI speciation and disproportionation of XCuIL, CuIX2- and CuIX should be considered. The equilibrium constant of CuIL+ disproportionation in Eq. 18 can be expressed by the following relation (21):
or alternatively
where
is the disproportionation constant of solvated Cu+ ions:
Thus, the disproportionation process strongly depends on the extent of stabilization provided by the ligand to the metallic center. 183
values between 10-4 and 102 were calculated from Eq. 20 in water (17), with TPMA providing the greatest stability for CuI, whereas smaller values were reported in organic solvents (10-2-10-7) (29). In acetonitrile, the disproportionation of CuI is negligible. Regarding disproportionation kinetics, relatively high kdisp values, ranging from 1 to 102 M-1s-1, were measured in water, generally increasing with pH and exhibiting a good correlation with the corresponding Kdisp (17). kdisp values between 10-2 and 1 M-1s-1 were measured in organic solvents and solvent/monomer combinations (27).
The Interplay between Activation and Disproportionation: SARA-ATRP or SET-LRP? The measurement of kdisp gave an important contribution to the mechanistic analysis of Reversible-Deactivation Radical Polymerizations (RDRP) in the presence of Cu0 (Scheme 4). Percec et al. proposed a mechanism, called Single Electron Transfer – Living Radical Polymerization (SET-LRP), which i) considered Cu0 as the only activator of RX (or PnX), through an outer sphere electron transfer process, and ii) assumed fast and complete disproportionation of CuI species (37). In contrast, Matyjaszewski et al. proposed the Supplemental Activator Reducing Agent (SARA)-ATRP mechanism, based on CuI/CuII activation/deactivation, with Cu0 acting as a supplemental activator of RX, and reducing agent by comproportionation with CuII complex, thus re-generating CuI (38).
Scheme 4. SET-LRP versus SARA-ATRP Mechanism. Adapted with permission from ref. (27). Copyright 2015 Elsevier. The RDE technique provided low kdisp values in DMSO and DMSO/methyl acrylate mixtures, for both CuI/TPMA and CuI/Me6TREN catalysts (10-2-100 M1s-1) (27). The presence of the monomer and/or halide ions decreased the value of kdisp for a fixed complex. In the presence of a Cu0 wire the disproportionation was only slightly faster than in the absence of Cu0, with kdisp increasing with the length of the wire. kact of RX with different reactivity was measured via RDE for the aforementioned systems. The obtained values (1 < kact < 103 M-1s-1) show that generally kact > kdisp. In particular, under typical conditions of RDRP in the 184
presence of Cu0 (i.e. Cu/Me6TREN in DMSO/methyl acrylate, with very reactive RX), kact was more than 3 orders of magnitude higher than kdisp. It follows that CuI is mainly consumed by the activation reaction, thus the extent of its disproportionation is negligible. The ratio between the rates of activation and disproportionation can be evaluated (Eq. 22). Considering that generally CRX , it results that ract >> rdisp. >>
Hence, SARA-ATRP mechanism was confirmed because i) CuI disproportionation was slow, even negligible, ii) CuI rapidly activated RX, thus Cu0 cannot be the sole activator. Similarly, electrochemical determination of high kact values in aqueous media, by using CV and digital simulations, provided further confirmation of the SARA mechanism (29). Indeed, in pure water CuIMe6TREN+ activates OEOBP and HEBiB with rate constants kact = 6.6 × 105 M-1s-1 and 2.6 × 107 M-1s-1, respectively, whereas kdisp = 1.25 × 102 M-1s-1. In water/monomer mixtures (e.g. 18 vol% OEOA), kact decreased by about one order of magnitude, but the reactivity of CuI toward RX activation was still much higher than that of Cu0. It was estimated that at least 400 m of Cu0 wire were required to match the activity of 10-6 M CuIMe6TREN+, in the same system.
Electrochemical Investigation of Organo-Copper Complexes in ATRP A complete mechanistic understanding of ATRP requires to identify side-reactions and measure their kinetic and thermodynamic parameters. CuI catalyzed radical termination (CRT) plays an important role in ATRP, particularly for acrylate monomers. However, the mechanism of CRT is not fully defined. As previously reported in Scheme 3, CuI species reacts with radicals by forming CuII-R species, with an equilibrium constant KOMRP (where OMRP = organometallic mediated radical polymerization) (35). Then, free radicals react with the organometallic complex, with a rate constant kCRT, leading to radical termination and re-generation of CuI. It is likely that termination proceeds by a disproportionation-like pathway, giving products with the same molecular weight of the original polymeric radicals (39). Zerk and Bernhardt exploited the use of cyclic voltammetry combined to digital simulations to analyze the interplay between ATRP and OMRP (33). TPMA and Me6TREN were used as ligands, CH3CN and DMSO as solvents, and bromoacetonitrile (BrAN) and ethyl α-bromoisobutyrate (EBiB) as initiators. The voltammetric analysis was conducted in the absence of radical traps such as TEMPO. The two initiators gave distinct responses. When RX was EBiB, a single reduction peak was observed in most cases (Figure 9a,c). In contrast, in the presence of BrAN a second reduction peak appeared at more negative potentials (Figure 9b,d). 185
Figure 9. Cyclic voltammetry of 1.0 mM BrCuIITPMA+ + RX in DMSO (A and B) or CH3CN (C and D) + 0.1 M Et4NClO4, at v = 200 mV s−1. Experimental data in solid curves, simulated data in dashed curves. Adapted with permission from ref. (33). Copyright 2017 American Chemical Society.
The second peak was attributed to the reduction of the organometallic complex R−CuIITPMA+ that formed after the generation of radicals by the activation process. When TEMPO was present, no second peak was observed; the scavenger immediately trapped the radicals, thus suppressing their reaction with the catalyst. The steric hindrance of tertiary radicals, such as that generated from EBiB, strongly disfavors the formation of the organometallic species. The formation of the organometallic species was supported by spectroelectrochemistry of BrCuIITPMA+ catalyst, in the presence of an 8-fold excess of BrAN initiator. A constant potential of about -900 mV vs Fc+/Fc was applied to generate R−CuIITPMA+, during which Vis-NIR spectra were recorded. The intensity of the peak corresponding to BrCuIITPMA+ progressively decreased, while a new peak appeared at a shorter wavelength. This new peak was assigned to CuII(TPMA)(CH2CN)+. EPR spectroscopy was used to prove the presence of two distinct copper complexes with trigonal-bipyramidal geometry, CuII(TPMA)(CH2CN)+ and BrCuIITPMA+. Spectroelectrochemistry was also applied to BrCuIIMe6TREN+ with BrAN in CH3CN and DMSO, and with ClAN in CH3CN. A similar hypsochromic shift was observed in each case. 186
CVs in Figure 9 were then simulated by using the set of reactions in Scheme 2 in addition to the reactions in Scheme 5, with the corresponding kinetic and thermodynamic parameters.
Scheme 5. Reactions and parameters required to simulate the OMRP equilibrium involving the ATRP catalyst: formation of the organometallic species (a), reduction of R-CuIIL+ (b), and dissociation of R-CuIIL+ (c). All kinetic and thermodynamic parameters in Scheme 5 as well as kdeact were set as adjustable during the CV simulation. Interestingly, the values obtained from the simulation indicated that the formation of the organometallic species was quite fast (1.6 × 107 < kd,OMRP < 3.6 × 107 M-1s-1), whereas its dissociation was much slower (ka,OMRP ≈ 10-1 s-1). The only exception was BrCuIITPMA+/EBiB in DMSO, where ka,OMRP ≈ 103 s-1 was found, which is in agreement with the larger steric hindrance of the ensuing tertiary radical. Therefore, the thermodynamic constant of the OMRP process was in the range 107-108 M-1 for the primary radical, whereas KOMRP = 104 M-1 for the tertiary one. It follows that a combination of high kact (i.e. fast radical generation) and high KOMRP (i.e. fast radical trapping) was required to observe an effect on the voltammetric response. Summarizing, CVs combined to digital simulations provided kinetic and thermodynamic information about the influence of the OMRP equilibrium on ATRP. Spectroelectrochemistry allowed a direct observation of R−CuIIL+ generation. However, it should be noticed that the series of reactions used in the simulation did not take into account the “true” CRT process, i.e. the termination reaction between R−CuIIL+ and a free radical (Eq. 23). Thus, more work is needed to obtain information about CRT in the overall mechanism of ATRP/OMRP.
Conclusions Information about the activity and stability of ATRP catalysts are readily accessible by performing cyclic voltammetry in the polymerization environment. The affinity of Cu species for halide ions can be also investigated. Other electrochemical tools, including chronoamperometry at a rotating disk electrode and voltammetric analysis combined with digital simulation, enabled the measurement of kact, kdeact, and KATRP. Slow catalytic systems as well as super active catalysts were successfully studied with these techniques. Finally, the disproportionation of CuI complexes and the formation of organocopper intermediates can be observed and quantified by electrochemical methods. In 187
brief, electrochemical analysis emerges as an essential tool to better understand ATRP, and predict the polymerization outcomes. Several efforts are being devoted to the synthesis of new ligands that convey specific properties to copper catalysts. Therefore, a database of redox properties of Cu/L complexes can guide the selection of appropriate catalyst to target specific macromolecular properties and structures. At present, electrochemical methods appear as the most versatile, allowing to analyze both low and extremely active ATRP catalysts.
Acknowledgments Financial support from the University of Padova (Grant CPDA150001) is gratefully acknowledged.
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