Current-controlled ‘plug-and-play’ electrochemical atom transfer radical polymerization of acrylamides in water

Aqueous electrochemical atom transfer radical polymerisation (eATRP) can be challenging due to deleterious side reactions leading to the loss of the ω-chain end, increased rates of activation ( k act ) leading to higher [P n ˙], increased rates of termination, and the lability of the X-Cu II /L bond to hydrolysis leading to poor control. Herein, we build on recent advances in eATRP methodology to develop a simplified current-controlled eATRP of acrylamides in water. The simplification arises from the use of commercial, standardised reaction hardware which enables the polymerisations to be performed in a 2-electrode, ‘plug-and-play’, undivided electrochemical cell configuration. Further simplification is afforded by the design of a single stepwise current profile ( I app vs time) capable of mediating current-controlled eATRP of N - hydroethylacrylamide (HEAm). At room temperature, polymerisation of HEAm to target degrees of polymerisation (DP n ,th ) of 20 – 100 proceeds with good control ( Ɖ ≤ 1.50). Loss of control when targeting higher DP n at room temperature is circumvented by lowering the reaction temperature (RT to 0 °C), increasing the stirring rate (400 rpm to 800 rpm) and increasing the catalyst concentration. Using the best conditions, a linear increase in M n,SEC with DP n (up to DP n = 320) and low dispersity values (DP n ,th = 40 – 160; Ɖ = 1.26 – 1.38) were obtained. Furthermore, the current profile and reaction conditions can support the polymerisation of other primary and secondary acrylamides and the retention of the ω-Br chain end is exemplified by a short in situ chain extension. Overall, this represents further simplification of aqueous eATRP with respect to reaction set up and experimental parameters


INTRODUCTION
Atom transfer radical polymerisation (ATRP) 1, 2 is a popular technique for polymer synthesis as it enables excellent control over polymer composition, end groups and architecture. 3 Through careful consideration of the reaction conditions and catalyst choice, it has been applied to polymerise a variety of functional monomers and to prepare polymers with a range of architectures, including telechelic, 4 star, 5 brush, 6 and graft copolymers, 7 for instance.
In early ATRP, 8,9 the active catalysts (typically a copper (Cu) complex; Cu I /L) was used directly to activate dormant alkyl (R-X) or macromolecular (P n -X) halides and generating radicals (R˙ / P n˙) capable of reacting with vinyl monomers. The activation process occurs via simultaneous electron transfer process and halogen abstraction in which the Cu I /L complex is oxidised to X-Cu II /L and a reactive carbon-centred radical is formed. The radicals can undergo propagation until they are deactivated by a second electron transfer and halogen abstraction process in which the X-Cu II /L is reduced back to Cu I /L and propagating radical chain ends are oxidised back to the dormant alkyl halide chain ends (P n -X). Control over the polymerisation was conferred by accumulation of X-Cu II /L, through unavoidable radical termination reactions.
This promoted deactivation of propagating radicals (P n˙) via reformation of dormant polymer chains (P n -X) and established the activation-deactivation equilibrium (K ATRP ) that governs the control over all ATRP reactions. 10 It was important to perform the reactions under strict deoxygenated conditions due to the propensity of the Cu I /L complex to undergo oxidation thus removing the activating complex from the reaction system.
In recent years, advances in ATRP methodology have shown that the redox mechanism can be manipulated and controlled using external stimuli including light, 11 sound, 12 mechanical force 13 and (bio)chemical intervention using reducing agents. 14 These advances negated the need to directly use oxidatively labile Cu I /L, using the external stimulus to generate it in-situ from more oxidatively stable Cu II /L complexes. 15 The ability to control the relative [Cu I /L] and [Cu II /L] provides fine control over K ATRP and the polymerisation as a whole. In 2011, electricity was also shown to be an excellent external stimulus leading the development of electrochemical ATRP (eATRP). 16,17 The voltage and current can be readily controlled using a potentiostat or simple current generator which helps to easily alter important reaction parameters such as applied potential (E app ) or applied current (I app ). 18 Such parameters allow the number, and relative energy of electrons involved in the reaction to be controlled. 19,20 The direct use of electrons, which can be generated from sustainable/renewable energy sources, significantly improves the sustainability and reduces the carbon footprint of electrochemical reactions compared to the analogous chemically-driven processes/reactions that often require stoichiometric amounts of chemical oxidants and reductants.
In the context of Cu-mediated eATRP electrons delivered from a working electrode (WE) are used to reduce Cu II /L to the active Cu I /L on demand to regulate the polymer synthesis through controlling the relative [Cu I /L] and [Cu II /L] which allows the overall radical concentration to be accurately controlled. 21 Furthermore, the use of oxidatively stable Cu II /L negates the need for stringent deoxygenation since the reducing voltages/current applied throughout the polymerisation ensures a constant supply of the Cu I /L activator complex. The once complex reaction set up of eATRP has been simplified over the last 10 years, to a point where eATRP can performed in a 'plug-and-play' configuration using commercial, standardised equipment (IKA ElectraSyn). 22,23 Furthermore, it can be run in 2-electrode configuration, by virtue of the use of sacrificial counter electrodes (CE), in an undivided electrochemical cell using cheap and easy to operate current generators in simplified eATRP (seATRP) under galvanostatic (constant current) conditions. 24 Both potentiostatic (constant potential) and galvanostatic eATRP have been mainly used for the controlled polymerisation of (meth)acrylates, in both organic [25][26][27] and aqueous [28][29][30] media.
In potentiostatic eATRP a constant potential, selected based on the redox potential of the Cucomplex used, is applied to reduce inactive Cu II /L to active Cu I /L resulting in generation of a current that in the presence of P n -X rapidly decays to a steady state as the eATRP equilibrium is established. The potential is set relative to a reference electrode and the corresponding current (I) is maintained as long as there is Cu II /L and P n -X present. This configuration is attractive because it can be highly selective for a particular complex and the current output (I vs t), can be used to qualitatively monitor the retention of Cu II /L and P n -X throughout the reaction. Integration of the I vs t plots provides the total charge passed during a given eATRP reaction and from this a much simpler, 2-electrode configuration, through which a simple galvanostat, can be used to enable galvanostatic eATRP. Based on the total charged passed, a current profile is set; the potential output, which is reductive and measured at the cathode in this case, changes until it reaches the redox potential of the Cu-complex employed. At a given resistance, the potential output is constant as long as there is sufficient Cu II /L (at the electrode surface) and P n -X (in bulk). The galvanostatic configuration is attractive from an industrial point of view due to the lack of need for a reference electrode.
The polymerisation of acrylamides in aqueous solutions is best achieved by Cu(0)-mediated single electron transfer radical polymerisation (SET-LRP). 31,32 Aqueous ATRP of acrylamides is more difficult to control due to issues such as hydrolysis and/or elimination of the ω-chain end, 33 increased rates of activation (k act ) leading to higher [P n˙] and increased rates of termination and lability of the X-Cu II /L bond to hydrolysis. 34 40 Using the current vs time (I v t) plot generated from these reactions, the total charge passed during potentiostatic polymerisation was calculated and used to derive a current profile for galvanostatic eATRP of DMAm.
Herein, we report the potentiostatic eATRP of N-hydroxyethylacrylamide (HEAm) from which we have designed a current profile that enables the current-controlled eATRP of HEAm with good control. Moreover, the entire current-controlled investigation has been performed using a single current profile to probe the effects of temperature, degree of polymerisation (DP n ), DMF SEC: Agilent Infinity II MDS instrument equipped with differential refractive index (DRI), viscometry (VS), dual angle light scatter (LS) and variable wavelength UV detectors.
The system was equipped with 2 x Agilent Polargel columns (300 x 7.5 mm) and a Polargel 5 µm guard column. The eluent is DMF with 0.01% LiBr additive. Samples were run at 1 ml /min at 50 °C. Poly(methyl methacrylate) standards (Agilent EasiVials) were used for calibration, and the calibration range was 600 -870,000 gmol -1 . Analyte samples were filtered through a Nylon membrane with 0.22 μm pore size before injection. Respectively, experimental number average molecular weights (M n , SEC ) and dispersity (Đ m ) values of synthesized polymers were determined by conventional calibration using Agilent GPC/SEC software.
Cyclic voltammetry (CV): CV was conducted on a CH-Instruments 600 E potentiostat using a 3 mm glassy carbon disc electrode. The electrode was polished with 0.05 µm alumina powder, and then sonicated in MilliQ water for 30 seconds between each use. The counter electrode was a platinum wire coil. The reference electrode was Ag/AgCl, and the silver wire was rinsed in MilliQ water placed into a glass capillary tube fitted with a vycor frit and filled with 3 M KCl solution. Before all CVs, the reaction cell was purged with N 2 for 10 minutes. The supporting electrolyte KNO 3 (0.111 g, 1.1 mmol) and water (11 mL) were mixed as background electrolyte, and used to perform background CVs. Background CVs were taken before any measurements to exclude the possibility of impurities adsorbed to the glassy carbon electrode.
Solutions were prepared for CV and simplified eATRP as shown below.
Electrolysis reaction set-up: Potentiostatic and galvanstatic electrolyses were performed using an ElectraSyn 2.0 device. The IKA electrochemical cell consisted of a reaction vial and an electrode head to which working, counter and reference electrodes were attached. An IKA manufacture Pt-coated electrode was used as the working electrode (cathode). The sacrificial counter electrode (anode) was initially Al wire (Alfa-Aesar, length = 15 cm, diameter = 1.0 mm, annealed) manipulated to a size similar to the IKA Pt-coated electrode as reported in our previous work. 22 This was replaced during the investigation by an IKA manufacture Al electrode, which was used for the majority of the experiments. An IKA manufacture Ag/AgCl (using 3 M KCl) reference electrode was included for potentiostatic reactions. For reactions performed in an ice bath, an ElectraSyn GoGo module was used enabling the reaction vial to be placed in an ice bath on a stirrer hotplate adjacent to the ElectraSyn 2.0 ( Fig S1), which was still used to deliver the required potential or current. Stirring rates of 400 rpm or 800 rpm were used depending on the experiment.

Potentiostatic seATRP of N-hydroxyethyl acrylamide
Initially, cyclic voltammetry (CV) was performed to determine standard reduction potential (E θ ≈ E 1/2 = (E pc + E pa ) / 2) of the Cu II /TPMA complex in the reaction solution (10 wt% . The E 1/2 was found to be -0.13 V (vs Ag/AgCl, Fig 1A) which is similar to values reported in the literature of Cu II /TPMA in aqueous solutions of other water soluble acrylamides and (meth)acrylates. 28,42 The initiator, 2-hydroxyethyl-2-bromoisobutyrate (HEBiB), was then added to the reaction solution and CV was repeated to determine changes in the redox activity of the Cu II /TPMA complex and the activation behaviour of HEBiB ( Fig   1B). A large current enhancement in the cathodic scan (E pc ) and a significant reduction in current in the anodic scan (E pa ) was observed when HEBiB was present in the reaction solution. This is consistent with our previous work and the work of others with Cu II /TPMA complexes in related reaction systems. 22,24 During the cathodic scan, Cu II /TPMA is reduced to Cu I /TPMA, which in the presence of HEBiB undergoes rapid activation of the HEBiB via one-electron transfer to form a carbon-based radical and reform Cu II /TPMA, thus leading to a current enhancement. If the activation process occurs faster than the timescale of the of CV scan, there is significantly less, or no, Cu I /TPMA present during the anodic scan which diminishes or removes the anodic current. 43 hours. Pseudo-first order kinetics were observed, with a k p app = 1.07 x 10 -4 s -1 and M n,SEC increasing linearly with conversion, which was indicative of a controlled polymerisation (Fig   2). This was further supported by the low dispersity obtained ( whilst deviations between the M n,SEC (8400 g.mol -1 ) and M n,th (3700 g.mol -1 ) suggest poor initiation efficiency or -more likely -gradual loss of the ω-Br chain end, which has been reported previously in Cu-mediated RDRP of acrylamides. 33 Applying more reducing potentials (E app = E 1/2 -0.06 / -0.12 V) resulted in slower reactions, lower conversions, bimodal SEC traces and higher dispersities, indicating that the polymerisations were not well controlled (Table 1, entries 2-3, Fig S2). The loss of control at more reducing potentials is not uncommon 16,28,44 and can be attributed to higher [Cu I /TPMA], which results in higher radical concentrations due to the high activity of the Cu I /TPMA species.   (Fig S3). This profile was expected for an electrochemical reduction (Cu II /TPMA to Cu I /TPMA), which is coupled to a chemical activation process (R-X/P n -X by Cu I /TPMA to form R˙/P n˙ and Cu II /TPMA), and has been previously reported for eATRP reactions. 24,28 Integration of this gave the total charge passed (Q) during the potentiostatic reaction and enabled a 6-step current profile to be designed with I app gradually decreasing from -4.0 mA to -0.8 mA. This would then be applied to the subsequent current-controlled reactions.  (Table 1, entry 5; Ɖ m = 1.39, Fig S4). To simplify the reaction set-up, the Al-wire counter electrode was replaced with a commercial, standardised IKA Al electrode. In this configuration, the polymerisation reached 86% conversion within 2 hours (Table 1, entry 6, Fig S5). The reaction exhibited pseudo-first order kinetics, and a linear increase of M n,SEC with conversion indicative of a well-controlled eATRP (M n,SEC = 11000 g.mol -1 , Ɖ m = 1.32, Fig 3).
The current-control over the reaction was then investigated in an experiment, wherein the current profile was applied and removed at regular intervals during the course of the reaction (Fig 4).  DP n,th , was varied. When DP n,th was decreased to 40 the polymerisation reached 74% conversion within 2 hours yielding PHEAm with M n,SEC = 8200 g.mol -1 and Ɖ m = 1. 35  only 52% in 2 hours and dispersity values increased reaching Ɖ = 1.7 when DP n,th = 320. A plot of M n,SEC vs DP n revealed that M n,SEC increased linearly with DP n up to DP n,th = 100 but then plateaued suggesting that the polymerisations were well controlled up to DP n,th =100 ( Fig   5A). This is supported by the SEC traces which show that the molecular weight distributions working electrode was observed, whilst no electrodeposition was observed when DP n,th = 40 -100. At the lower [I] values used when targeting higher DP n,th , more reducing potentials were required to reach and maintain I app (Fig S7). At these reducing potentials, electrodeposition of Cu 0 can occur more readily which removes Cu from reaction media, thus decreasing [Cu I /TPMA] and [Cu II /TPMA] to the detriment of the reaction rate and control over the polymerisation.

Current-controlled seATRP of N-hydroxyethyl acrylamide at 0 °C
To investigate the effect of temperature on the current-controlled eATRP of HEAm, we decided to perform a series of reactions at 0 °C using the current profile established at room temperature. Initially, the current profile with regimes of I app = -4 mA (5 min Table 2, entry 1), and the dispersity of the PHEAm obtained was too high for a controlled polymerisation (Ɖ m = 2.32). As well as reducing the rate of deleterious side reactions, lowering the reaction temperature was having an effect on the rate of polymerisation and also the rate of mass transport to and from the electrode interfaces 46 and the activity coefficients 47 of the Cu II ions present. This led to higher effective resistance in the electrochemical cell and significant electrodeposition being observed, due to the highly reducing potentials required to maintain I app .
The reaction was repeated under identical conditions, except for the stirring rate which was increased from 400 rpm and 800 rpm ( Table 2, entry 2). The conversion increased to 56% after 4 hours, and the control over the polymerisation was improved (M n,SEC = 15900 g.mol -1 , M n,th = 10700 g.mol -1 , Ɖ m = 1.49). Kinetic analysis of the reactions performed at 400 rpm and 800 rpm revealed the rate of the reaction increased at the higher stirring rate (k p app,400 = 2.2 x 10 -5 s -1 , k p app,800 = 5.6 x 10 -5 s -1 , Fig 6A). M n,SEC increased linearly with conversion at 800 rpm ( Fig   6B), which was not the case at 400 rpm, and the SEC trace of the final polymer obtained at 800 rpm was more symmetrical than the one obtained at 400 rpm ( Fig 6C). However, the dispersity obtained was still higher than expected for a polymer synthesised by RDRP and electrodeposition at the working electrode was still prevalent. In an attempt to improve the control over the polymerisation at 0°C, the [ control over the polymerisation (Fig 7A). This was supported by good agreement between Mn,SEC (17700 g.mol -1 ) and M n,th (14400 g.mol -1 ) and the lowest dispersity (Ɖ m = 1.38) when targeting DP n,th = 160 (Fig S9). To determine if the increased [Cu II /TPMA] could be applied to target shorter and longer chain lengths, reactions in which the DP n,th was varied were performed at 0 °C, 800 rpm and [Cu II /TPMA] = 6.90 mM (Fig 7B). When DP n,th was decreased to 40, the polymerisation reached 91% conversion within 4 hours, yielding PHEAm with M n,SEC = 8000 g.mol -1 (M n,th = 4400 g.mol -1 ) and Ɖ m = 1.26, which is an improvement on the analogous reaction performed at room temperature (77% in 2 hours, M n,SEC = 8200 g.mol -1 , M n,th = 3600 g.mol -1 , Ɖ m = 1.35).
Increasing DP n,th to 80 resulting in 79% conversion to PHEAm after 4 hours with control over the polymerisation retained (M n,SEC = 12500 g.mol -1 , M n,th = 7400 g.mol -1 , Ɖ m = 1.26). When the DP n,th was increased from 160 to 320 the control over the polymerisation was compromised, as previously observed in the room temperature reactions. The reaction conversion reached 53% in 4 hours, yielding PHEAm with M n,SEC = 24700 g.mol -1 (M n,th = 19600 g.mol -1 ) and Ɖ m = 1.52. Although the dispersity value is larger than we would expect for a true RDRP reaction, a plot of M n,SEC vs DP n revealed a linear correlation between M n,SEC and DP n,th , which represents an improvement on the analogous room temperature reactions (Fig 7C).  Repeating the polymerisation of secondary acrylamide HEAm resulted in 91% in 4 hours, M n,SEC = 8000 g.mol -1 (M n,th = 4400 g.mol -1 ), and Ɖ m = 1.25 (Fig S10). Secondary acrylamide NIPAm gave a comparable outcome with conversion reaching 96% in 4 hours. SEC analysis furnished a symmetrical molecular weight distribution with relatively good agreement between M n,SEC = 7300 g.mol -1 and M n,th = 4500 g.mol -1 , and low dispersity (Ɖ m = 1.31, Fig S11).
Tertiary acrylamides N-acryloylmorpholine (NAM) and DMAm did not polymerise well using our current profile under these reaction conditions. Conversions after 4 hours were limited to 29% for NAM, 49% for DMAm and control over the polymerisations was poor (Ɖ m ≥ 1.60, Fig S12-S13). The limited conversion indicates that the current profile, established for the polymerisation of secondary acrylamide HEAm was not appropriate for the tertiary acrylamide monomers. Furthermore, the loss of the ω-chain end during the aqueous Cu-mediated polymerisation of acrylamides is more prevalent with tertiary acrylamides than acrylamides, which could also contribute to loss of control during the polymerisation. 32,33 The monomer acrylamide, which contains a primary amide group was then subject to our current profile reaching 86% conversion within 4 hours. Aqueous SEC analysis revealed a highly symmetrical molecular weight distribution, with excellent agreement between the M n,SEC = 2200 g.mol -1 and M n,th = 2500 g.mol -1 and low dispersity (Ɖ = 1.27, Fig S14). Electrolysis was stopped and a second aliquot of NIPAm (DP n,th = 40) in water was added to the reaction mixture. The current profile with regimes of I app = -4 mA (5 min), -3.1 mA (5 min), reaction solution, resulting in 13% conversion within 3 hours at 0 °C. Despite the conversion being low, chain extension was evident via a shift in the mono-modal, symmetrical molecular weight distribution to higher molecular weight with M n,,SEC of chain extended PNIPAm increasing to 9400 g.mol -1 and low dispersity (Ɖ = 1.26) being retained (Fig 9). Thus, although chain extension is possible using our current profile, there is scope for improvement to enable higher conversions and application to block copolymerisation. This could be achieved by first performing the reactions under potentiostatic conditions to obtain a more bespoke current profile for the target polymerisation. it was not possible to target DP n,th > 100 and retain control of the polymerisation. To alleviate this, the reaction temperature was reduced to 0 °C to minimise deleterious reactions that can occur at the ω-chain end; the stirring rate was increased from 400 rpm to 800 rpm, to improve mass transfer and limit electrodeposition of Cu 0 on the working electrode that was found to occur at the lower temperature and stirring rates; and the concentration of Cu II /TPMA was increased to enhance the rate of reaction and improve control over the polymerisation. Under these conditions, the polymerisations were again shown to be under the control of I app whilst a plot of M n,SEC v DP n exhibited a linear increase up to DP n,th = 320. The control over the polymerisation was improved across the targeted DP n,th range, with lower Ɖ m values and more symmetrical SEC traces obtained at 0 °C compared to room temperature. Finally, the current profile was shown to enable the polymerisation of other secondary (NIPAm) and primary (AAm) acrylamides with very good control with retention of the ω-Br chain end in PNIPAm, prepared using our current profile, verified by a short in situ chain extension.
Thus, we have shown that it is possible to apply a single current profile, derived from a wellcontrolled potentiostatic eATRP reaction, to perform simplified, current-controlled eATRP of primary and secondary acrylamides. However, it should be noted that tertiary acrylamides (DMAm and NAM) suffered from low conversion and poor control when subjected to our current profile, indicating that it is not universal for the acrylamide monomer family. For the best results, bespoke current profiles should be obtained.

DATA AVAILABLITY
Additional data is presented in the supplementary information file. The raw/processed data from which this data was prepared is available upon request.