Rapid Oxygen Tolerant Aqueous RAFT Photopolymerization in

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Rapid Oxygen Tolerant Aqueous RAFT Photopolymerization in Continuous Flow Reactors Neomy Zaquen,†,‡,§ Ak M. N. B. P. H. A. Kadir,† Afiq Iasa,† Nathaniel Corrigan,†,‡ Tanja Junkers,*,§,∥ Per B. Zetterlund,*,† and Cyrille Boyer*,†,‡ †

Centre for Advanced Macromolecular Design (CAMD) and ‡Australian Centre for Nanomedicine, The University of New South Wales, 2052 Kensington, Sydney, Australia § Organic and Bio-Polymer Chemistry (OBPC), Universiteit Hasselt, Agoralaan Building D, 3590 Diepenbeek, Belgium ∥ Polymer Reaction Design Group, School of Chemistry, Monash University, VIC 3800 Melbourne, Australia Macromolecules Downloaded from pubs.acs.org by TULANE UNIV on 02/07/19. For personal use only.

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ABSTRACT: Recently, new controlled polymerization pathways have emerged for the synthesis of functional polymer materials. The use of light, particularly visible light, to generate radicals has shown to be beneficial over thermal induction due to the high control over reaction parameters as well as spatiotemporal control. Although numerous photopolymerizations have been performed in batch, additional initiators or activators are often needed to increase the overall yield, making this process time-consuming and costly; optical path lengths directly correlate with achievable space-time yields. The use of flow reactors is in this case advantageous. In this work, new synthetic protocols are demonstrated for the synthesis of di- and triblock copolymers in tubular reactors via photoinduced electron/energy transfer-reversible addition−fragmentation chain transfer (PET-RAFT) polymerization. Within just 10 min of polymerization time, full monomer conversion was reached for a variety of acrylamides and acrylates, and polymers with molecular weights up to 100000 g mol−1 and high end-group fidelity were obtained. Changing the flow rates, concentrations, and light intensity allowed alteration of the molecular weights, and several diand triblock copolymers were synthesized, indicating the high level of control over the polymerization. In addition, multiple flow reactors were coupled to allow the synthesis of triblock copolymers in a reactor cascade process without the need for intermediate purification. The attractiveness of this approach is illustrated by considering that a PDMAA-b-PDMAA-b-PDMAA triblock copolymer with a number-average molecular weight of 3200 g mol−1 and dispersity of 1.24 could be theoretically obtained at a rate of 300 g/day.

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INTRODUCTION Reversible deactivation radical polymerization (RDRP) techniques, such as atom transfer radical polymerization (ATRP),1−3 nitroxide-mediated polymerization (NMP),4,5 and reversible addition−fragmentation chain transfer (RAFT) polymerization,6−9 have emerged as efficient tools for synthesis of complex macromolecular structures, leading to the employment of RDRP in numerous high-end applications.10,11 Significant progress has been achieved in terms of the ability to control RDRP reactions through the use of external stimuli.12 Among the various stimuli available, light can be considered the ideal candidate; it is easily accessible and abundant as well as inexpensive and has inherent spatiotem© XXXX American Chemical Society

poral characteristics. Moreover, photochemical reactions can be performed in a “green” and environmentally friendly fashion, thereby reducing the environmental footprint.13,14 A variety of photomediated RDRP techniques have been developed with numerous examples that use either a photoredox catalyst, photoinitiator, or direct photoactivation (photoiniferter) pathways.15−18 Although classical radical photoinitiators have been used in RDRP,18 more recent systems have utilized catalytic initiating systems to increase the Received: December 10, 2018 Revised: January 24, 2019

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DOI: 10.1021/acs.macromol.8b02628 Macromolecules XXXX, XXX, XXX−XXX

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Scheme 1. Degenerative Chain Transfer via Reductive Photoinduced Electron/Energy Transfer-Reversible Addition− Fragmentation Chain Transfer (PET-RAFT) for Access to Acrylamide/Acrylate Diblock Copolymers Using Microflow Reactor Technology (Top); Proposed Photopolymerization Mechanism When EY Is Excited under Visible Light and Reduced by an Amine, Leading to a PET-RAFT Mechanism (Bottom)

level of control.19 A recent development in the field of photoinduced RAFT polymerization is the use of photoredox catalysts to activate polymerization through a photoinduced electron/energy transfer-RAFT (PET-RAFT) mechanism.20−23 In this process, a photoredox catalyst activates RAFT polymerization by transferring an electron or energy from the photocatalyst to the RAFT agent, which subsequently results in C−S bond cleavage and radical generation. Until recently, metal catalysts such as fac-[Ir(ppy)3], Ru(bpy)3Cl2, and ZnTTP were primarily employed for PET-RAFT polymerization. However, organic dyes such as Eosin Y (EY) can also be used to activate RAFT agents as efficient photoredox catalysts for PET-RAFT in polar solvents.15,24−26 Although PET-RAFT can proceed in the presence of oxygen, lower apparent propagation rates (kpapp = 0.03 h−1 with oxygen vs kpapp = 0.07 without oxygen) are usually obtained when using EY as photocatalyst.15,25 The addition of a reducing agent, e.g., triethylamine (TEA), can increase the polymerization rate significantly by acting as an electron donor to EY to yield an EY radical anion (EY−). EY− can then reduce oxygen to generate superoxide or transfer an electron to the RAFT agent to generate propagating radicals for chain growth (Scheme 1).25 This robust photoRDRP technique is compatible with a wide range of monomers even in the presence of oxygen. The development of these deoxygenation methods simplifies the polymerization process and also allows for convenient high-throughput screening of materials.27,28 Although significant advances toward oxygen tolerant polymerization have been made, there are still serious issues regarding scalability. Most photopolymerizations are limited to milligram-scale production of material and are subject to batch-to-batch variations due to optical pathway limitations. Because of the absorption of light by the chromophores, the light intensity drops quickly, and reactors are typically only illuminated efficiently within the first centimeter of light incidence. Hence, in any larger reactor polymerizations will only occur at the reactor wall, requiring strong stirring of the reactor and concomitantly extending the reaction time significantly. Recently, the use of microplates in which reactions are performed at microgram scale has gained interest,

leading to high throughput screening processes for a plethora of reaction conditions to generate polymer libraries.24,26,29−33 However, upscaling these polymerizations for commercialization is a significant issue in regards to reproducibility. Microreactor technology has also gained interest over the years as an elegant solution to these problems on both lab and industrial scales.13,34−37 Commonly used microreactors are easy to setup, have low maintenance costs, and can produce materials on kilogram scales.34,38,39 The high surface to volume ratio of the microreactor channels results in excellent control over the polymerization, improved reproducibility, and fewer side reactions. The combination of microreactors with photopolymerization is of high interest due to the favorable light penetration, leading to uniform irradiation throughout the reactor. This significantly accelerates photochemical reactions, leading to well-defined materials with high reproducibility. Although the field of photopolymerization was for a long time limited to coatings, over the past few years significant advances have been made in the field of controlled photopolymerization in flow.39−45 Recently, a flow protocol for the synthesis of methacrylate (block) copolymers in DMSO via trithiocarbonate (TTC) photoiniferter polymerization under blue light was reported.45 As the polymerization was not oxygen tolerant, degassing prior to polymerization was necessary to obtain welldefined polymer materials. Progress in photoflow polymerization has also been made by polymerizing diethylacrylamide (DEAA) via PET-RAFT using ZnTPP as catalyst in DMSO.43 Within 1 h of residence time, full monomer conversion was obtained, and number-average molecular weights (Mn) of 20000 g mol −1 were reached without the need for degassing.43,44 However, a metal photoredox catalyst combined with an organic solvent was needed to perform the polymerization. Herein, we present a highly efficient and well-controlled aqueous polymerization of acrylates and acrylamides in a continuous flow reactor via a reductive PET-RAFT process under air, which yields full monomer conversion in few minutes. A green light source was used in combination with an organic dye (EY) and a reducing agent (triethanolamine; TEtOHA) to initiate the polymerization. N,N-DimethylacryB

DOI: 10.1021/acs.macromol.8b02628 Macromolecules XXXX, XXX, XXX−XXX

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Figure 1. Schematic representation of the photoflow reactor setup for the synthesis of block copolymers in a continuous flow reactor under green light. BPR = back-pressure regulator. syringes (Adelab Australia). In the second part of this work a reactor cascade was built consisting of two separate reactors (1 and 3 mL) wrapped around the same metal framework and illuminated by the same light source. Efficient mixing between the output stage of reactor 1 and the additional monomer solution was enabled by using a static micromixing tee (PEEK static mixing tee for 1/16 in. o.d. tubing, Upchurch, Figures 2 and 3). Synthesis of triblock copolymers was

lamide (DMAA) was used as monomer to optimize the system in flow, leading to well-defined polymers with high end-group fidelity in a few minutes. Remarkably, full monomer conversion was reached within only 10 min of residence time, and polymers with molecular weights as high as 100000 g mol−1 were obtained. This is the first example of photoflow polymerization which was achieved without prior deoxygenation to yield polymers in 20000 g mol−1) in flow. DPs of 100−1000 were targeted at a 4 M concentration of DMAA (similar to the concentration used so far) with a residence time 10 min; this resulted in clear shifts of MWDs to higher MWs with increasing target DPs but were accompanied by increased Đ values up to 1.81 for DP = 1000. Still, all MWDs remained unimodal and symmetrical (Table 2 and Figure S7). These

Table 1. Summary of Optimization Parameters for Photopolymerization of DMAA in Flow Reactor parameters deoxygenation [RAFT]:[TEtOHA] amine [RAFT]:[EY] RAFT agent light intensity [DMAA]

variations degassed vs nondegassed 1:2, 1, 0.5, 0.1, 0.01 TEA, DMA, TEtOHA 1:0.05, 0.01, 0.005 CDTPA, BTPA, CPADB 0.286−0.057 mW cm−2 4, 3, 2, 1, 0.5 M

optimized resulta

entry

nondegassed

A1−A17

1:1 TEtOHA

B1−B31 C1−C11

1:0.01 BTPA

D1−D20 E1−E20

0.286 mW cm−2 2.5 M

F1−F8

Table 2. Polymerization Conditions for Aqueous PETRAFT Polymerization of DMAA under Green LED Irradiation for Varying Degrees of Polymerizationa entryb

DP theory

α (%)

Mn,th (g mol−1)

H1 H2 H3 H4 H5 H6 H7 H8 H9 H10

100 200 300 400 500 600 700 800 900 1000

81 85 87 84 79 76 81 81 88 83

8400 17400 26500 34000 37800 46000 57100 65200 79600 83400

G1−G5

a

A variety of reaction parameters were tested as stated under “parameters”. Optimized results refer to highest control over the polymerization by (i) best agreement between Mn and Mn,th and (ii) lowest dispersity (Đ) values.

conversions (α ≈ 95%) were achieved within only 10 min, and the polymer showed a good agreement between experimental and theoretical molecular weights (Mn ≈ Mn,th; Figure S1). However, the MWDs prepared in the absence or presence of oxygen had an average dispersity (Đ) of ∼1.3, which is higher than expected for a typical photoactivated RAFT polymerization of acrylamides.22−29 These higher than expected dispersities were attributed to small variations in the reaction temperature during the reaction (25 ± 2 °C), but more importantly the presence of different initiation pathways as demonstrated by Figg et al.25 Indeed, the addition of a tertiary amine results in a reductive PET-RAFT mechanism as well as direct initiation of DMAA by EY under green light. As such, small differences between theoretical and experimental Mn values and slightly broader MWDs were obtained. As the use of EY in combination with TEtOHA did not show significant difference when reactions were deoxygenated, it was decided to perform the reactions under air for the remainder of this work. The protocol was further optimized to obtain better control over the polymerization by varying the type of amine compounds and concentration. Despite varying [RAFT]: [TEtOHA] (Table S2, entries B1−B31), exploring different types of amines (Table S3, entries C1−C11), [RAFT]:[EY] ratios (Table S4, entries D1−D20), and various RAFT agents, the dispersity remained around 1.3 (Tables S2−S5 and Figures S2−S5). In some cases, Đ values >1.3 and even up to 2 were obtained. The latter was observed when using CDTPA, presumably due to direct activation (or photolysis) of CDTPA under green light via an iniferter pathway46 in addition to photoredox activation, which may have led to excessive activation and thus increased levels of termination. Furthermore, a reduced polymerization rate was observed in some cases (at low TEtOHA or EY content) even after optimization of the light intensity(Table S6, entries F1−F7, and Figure S6) or the DMAA concentration (Table S7, entries G1−G5, and Figure S8). Considering the above results, the following parameters were chosen for the majority of this work: [DMAA]:[BTPA]:[EY]:[TEtOHA] with a ratio of 200:1:0.01:1 with a residence time of 10 min. Under these optimized conditions, high monomer conversion (α > 95%) and good control over the polymerization were achieved (Mn ≈ Mn,th and Đ < 1.3) with Mn ≈ 20000 g mol−1. The success of the above flow process was further demonstrated by synthesizing higher molecular weight

Mn Mp (g mol−1) (g mol−1) 9500 14200 22500 27400 30500 33300 34200 41000 42100 41000

13200 19800 31900 41800 49800 54700 63900 71700 78500 82700

Đ

DP

1.33 1.36 1.41 1.52 1.60 1.61 1.77 1.70 1.77 1.81

81 170 261 336 395 456 567 648 792 830

a

Experimental conditions: solvent = water; light source = green LED light (λmax = 530 nm, 0.3 mW cm−2), [DMAA]:[BTPA]:[TEtOHA]: [EY] = variable: 1:1:0.01 with a total concentration of monomer = 4 M and a polymerization time of 10 min. bSamples synthesized with varying [DMAA]:[BTPA] ratio from 100 to 1000 equiv.

results show that the flow protocol allowed very rapid polymerization of DMAA; high monomer conversion was reached within just 10 min residence time without any inhibition period, making the photoflow process highly efficient. Polymerization protocols reported so far have required longer reaction times to reach full monomer conversion−acrylate polymerization using UV light required up to 20 min residence time,40 and the use of green light took 30 min to reach full conversion.43 Moreover, the simplicity of the present protocol, including the fact that no deoxygenation is required, makes upscaling facile and cost-effective. Versatility of the Flow Process. The versatility of the flow process developed above was demonstrated by applying the optimized protocol ([M]:[BTPA]:[EY]:[TEtOHA] ratio of 200:1:0.01:1 in water) to a broader range of acrylamide and acrylate monomers. Results are shown in Tables 3 and 4 as well as Figures S8−S10 for N,N-diethylacrylamide (DEAA), hydroxyethylacrylamide (HEAA), 4-acryloylmorpholine (NAM), N-isopropylacrylamide (NIPAM), poly(ethylene glycol) methyl ether acrylate (POEGA), and 2-hydroxyethyl acrylate (HEA). Polymerization of HEA proceeded in a controlled fashion with a linear increase in Mn with increasing monomer conversion and Mn ≈ Mn,th provided that the initial monomer concentration [M]0 was as low as 0.5 M (Table 3, entries K1− K8). NIPAM, HEAA, and NAM showed excellent control up to a starting monomer concentration of 4 M with relatively low dispersity values over the entire polymerization process with Đ = 1.3−1.5 at full monomer conversion (Table 3 and Table S8). These results demonstrate a highly efficient aqueous RDRP photoflow process for HEA, HEAA, NIPAM, and NAM monomers. All acrylamide and acrylate monomers exhibited similarly high polymerization rates as DMAA, reaching full conversion in 99 89 86 61 >99 >99 75 >99 74 35 >99 >99 >99 >99 >99 >99 >99 >99

9900 15100 20000 27800 19100 16200 23200 20600 9300 19300 18400 12900 23400 20900 9900 15100 20000 1200 2200 3200

9100 15500 20600 26000 17800 15700 24200 33100 7500 21800 16400 10900 23500 28900 9800 15200 19600 1400 2600 3700

1.38 1.40 1.52 1.79 1.47 1.38 1.38 2.19 1.42 1.64 1.62 1.31 1.82 2.44 1.34 1.29 1.39 1.15 1.16 1.24

98 50 100 180 86 57 100 100 75 100 74 35 100 100 100 150 200 10 20 30

Experimental conditions: solvent = water; light source = green LED light (λmax = 530 nm, 0.3 mW cm−2), [M]:[BTPA]:[TEtOHA]:[EY] = 4:1:1:0.01. bSample L1 was synthesized as homopolymer and used for chain extension; samples L2−L4 were synthesized with a DP of 50, 100, and 200 respectively; samples L5−L8 were synthesized by chain extending PDMAA with DEAA, HEAA, NAM, and HEA respectively; sample L9 was synthesized as homopolymer and used for chain extension; samples L10−L14 were synthesized by chain extending PDEAA with DMAA, DEAA, HEAA, NAM, and HEA respectively; samples L15−L17 were synthesized with a DP of 100, 50, and 50 respectively; samples L18−L20 were synthesized with a DP of 10, 10, and 10, respectively. a

Before embarking on synthesis of triblock copolymers, a series of diblock copolymers were prepared. Polymerization of DMAA in the first reactor was followed by chain extension with DMAA at various targeted DPs (50, 100, and 200), leading to high monomer conversions in each case (α > 89%) (Figure 5). In addition, good correlation between Mn and Mn,th was observed, with somewhat higher dispersity values (Đ = 1.8) for the highest targeted DP of 200. Similarly good results were obtained when PDMAA was chain extended with NAM (Table 5, Figure 5, Figures S11 and S12), leading to welldefined PDMAA-b-PNAM block copolymers with Mn values of 20000 g mol−1. Chain extension with HEA showed full monomer conversion; however, Mn and Mn,th were not in close agreement, and a high dispersity was observed (Đ = 2.2, Table 5, entry L8). This result is most probably due to smaller fractions of cross-linker present in commercial HEA. Chain extension with DEAA or HEAA, on the other hand, resulted in lower polymerization rates with only 61% conversion in the case of HEEA (Table 5). Polymerization of DEAA as the first block showed only 75% monomer conversion in the first reactor. As such, all chain extensions performed on PDAA resulted in statistical copolymers or quasi-block copolymers instead of pure block copolymers. As a proof of the high livingness, we decided to investigate multiple chain extensions using DMAA as a model monomer to yield PDMAA100-b-PDMAA50-b-PDMAA50 (total DP = 200) and PDMAA10-b-PDMAA10-b-PDMAA10 (total DP = 30) “triblock” copolymers in one step by coupling three reactors in series without intermediate purification. The initial monomer concentration in the first reactor stage was 4 M, leading to 1 M at the injection point of reactor 3. High monomer conversions (α > 99%) for each step were reached with Đ values below 1.4

(total DP = 200) and even below 1.25 (total DP = 30) obtained within just 30 min of total residence time. Controlled synthesis of multiblocks in flow has been reported previously, with synthesis up to hexablocks using thermal initiation47,48 or diblocks using either UV40 or visible light.43,45 However, in these cases longer reaction times were successively required for each chain extension due to the dilution. In the present case, full monomer conversion was reached within 10 min of polymerization time in each reactor stage, resulting in three successful chain extensions in 30 min without intermediate purification. This is a remarkable finding as we would expect a significant decrease in polymerization rate in the last reactor due to the decrease in the concentration of the RAFT agents and Eosin Y and amine (catalyst and cocatalyst). Looking closely into the kinetics of PDMAA (Table S1), high monomer conversion (α = 84%) was achieved within 2.5 min, while full monomer conversion was reached within 5 min when targeting a DP of 200. As a polymerization time of 10 min was chosen for each chain extension, a high monomer conversion was maintained through the three steps. Using this process in theory, we could prepare 300 g of PDMAA triblock copolymer in 24 h without the need for intermediate purification (this value was calculated based on the amount of triblock copolymer obtained after 10 min of reaction if we would allow this reaction to run for 24 h). As a comparison, in batch this would take over 2 h, and only small quantities (a few grams) will be produced per reaction.

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CONCLUSIONS In this work, synthesis of di- and triblock copolymers in tubular reactors via rapid PET-RAFT polymerization under air using either a single or coupled reactors was demonstrated. I

DOI: 10.1021/acs.macromol.8b02628 Macromolecules XXXX, XXX, XXX−XXX

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acrylate; HEAA, N-hydroxyethylacrylamide; λmax, wavelength at maximum absorbance; min., minutes; MRT, microreactor technology; [Mt], total molar concentration; NAM, 4acryloylmorpholine; NIPAM, N-isopropylacrylamide; NMR, nuclear magnetic resonance; POEGA, poly(ethylene glycol) methyl ether acrylate; RAFT, reversible addition−fragmentation chain transfer; RDRP, reversible-deactivation radical polymerizations; SEC, size exclusion chromatography; TEA, triethylamine; TEtOHA, triethanolamine.

Polymerization of acrylates and acrylamides was induced by green light in combination with an organic dye (EY) and a reducing agent (triethanolamine; TEtOHA). Full conversion was reached within just 10 min with molecular weights up to 100000 g mol−1, high end-group fidelity, and dispersities typically in the range of 1.3. This procedure was then applied to different acrylamide and acrylate monomers to demonstrate its versatility. Di- and triblock copolymers were subsequently targeted in one pass by coupling multiple reactors in series, without the need for intermediate purification. It is important to note here that block extension does not lead to increased dispersity values, indicating the high level of control over the polymerization. These results highlight the versatility of this flow process and provide a convenient synthetic route to polymer libraries of triblock copolymers. By simply changing the monomer and ratios used, a variation of block copolymers can be synthesized. The potential for scale-up was illustrated by demonstrating that, in theory, a well-defined triblock copolymer could be synthesized in a straightforward fashion, at rates of 300 g/day using this methodology.

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(1) Matyjaszewski, K.; Wang, J.-S. Controlled/“Living” Radical Polymerization. Atom Transfer Radical Polymerization in the Presence of Transition-Metal Complexes. J. Am. Chem. Soc. 1995, 117, 5614−5614. (2) Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura, T. Polymerization of Methyl Methacrylate with the Carbon Tetrachloride/Dichlorotris(triphenylphosphine)ruthenium(II)/ Methylaluminum Bis(2,6-di-ferf-butylphenoxide) Initiating System: Possibility of Living Radical Polymerization. Macromolecules 1995, 28, 1721− 1723. (3) Matyjaszewski, K.; Tsarevsky, N. V. Macromolecular engineering by atom transfer radical polymerization. J. Am. Chem. Soc. 2014, 136, 6513−33. (4) Nicolas, J.; Guillaneuf, Y.; Lefay, C.; Bertin, D.; Gigmes, D.; Charleux, B. Nitroxide-mediated polymerization. Prog. Polym. Sci. 2013, 38, 63−235. (5) Hawker, C. J.; Bosman, A. W.; Harth, E. New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations. Chem. Rev. 2001, 101, 3661−3668. (6) Moad, G.; et al. Living Free-Radical Polymerization by Reversible Addition-Fragmentation Chain Transfer: The RAFT Process. Macromolecules 1998, 31, 5559−5562. (7) Mayadunne, R. T. A.; Rizzardo, E.; Chiefari, J.; Chong, Y. K.; Moad, G.; Thang, S. H. Living Radical Polymerization with Reversible Addition-Fragmentation Chain Transfer (RAFT Polymerization) Using Dithiocarbamates as Chain Transfer Agents. Macromolecules 1999, 32, 6977−6980. (8) Moad, G. RAFT Polymerization − Then and Now. In Controlled Radical Polymerization: Mechanisms, 2015; pp 211−246. (9) Moad, G.; Rizzardo, E.; Thang, S. H. Radical addition− fragmentation chemistry in polymer synthesis. Polymer 2008, 49, 1079−1131. (10) Stuart, M. A.; Huck, W. T.; Genzer, J.; Muller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukruk, V. V.; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S. Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 2010, 9, 101−13. (11) Matyjaszewski, K.; Müller, A. H. E. Controlled and Living Polymerizations. From Mechanisms to Applications; John Wiley & Sons: New York, 2009. (12) Leibfarth, F. A.; Mattson, K. M.; Fors, B. P.; Collins, H. A.; Hawker, C. J. External regulation of controlled polymerizations. Angew. Chem., Int. Ed. 2013, 52, 199−210. (13) Cambie, D.; Bottecchia, C.; Straathof, N. J.; Hessel, V.; Noel, T. Applications of Continuous-Flow Photochemistry in Organic Synthesis, Material Science, and Water Treatment. Chem. Rev. 2016, 116, 10276−341. (14) Xiao, P.; Zhang, J.; Dumur, F.; Tehfe, M. A.; Morlet-Savary, F.; Graff, B.; Gigmes, D.; Fouassier, J. P.; Lalevée, J. Visible light sensitive photoinitiating systems: Recent progress in cationic and radical photopolymerization reactions under soft conditions. Prog. Polym. Sci. 2015, 41, 32−66. (15) Xu, J.; Shanmugam, S.; Duong, H. T.; Boyer, C. Organophotocatalysts for photoinduced electron transfer-reversible additionfragmentation chain transfer (PET-RAFT) polymerization. Polym. Chem. 2015, 6, 5615−5624. (16) Xu, J.; Atme, A.; Marques Martins, A. F.; Jung, K.; Boyer, C. Photoredox catalyst-mediated atom transfer radical addition for

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.8b02628. (i) Experimental part in which all materials used, characterization methods, and protocols are described; (ii) all results obtained upon optimization of the flow protocol; (iii) results concerning the polymerization of all monomers except DMAA; (iv) multiblock copolymer synthesis results (PDF)

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REFERENCES

AUTHOR INFORMATION

Corresponding Authors

*E-mail [email protected]. *E-mail [email protected]. *E-mail [email protected]. ORCID

Tanja Junkers: 0000-0002-6825-5777 Per B. Zetterlund: 0000-0003-3149-4464 Cyrille Boyer: 0000-0002-4564-4702 Funding

MCSC-IF-GF applicant no. 12U1717N. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We acknowledge The European Union Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 665501 with the research Foundation Flanders (FWO) (N.Z.).

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ABBREVIATIONS BTPA, n-butyltrithiocarbonate)propionic acid; °C, degrees Celsius; CDTPA, 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]; CPADB, 4-cyanopentanoic acid dithiobenzoate; D2O, deuterium oxide; DMA, dimethylaniline; DMAA, N,Ndimethylacrylamide; DMAc, N,N-dimethylacetamide; DEAA, N,N-diethylacrylamide; DI, deionized (DI); DMSO, dimethyl sulfoxide; EY, Eosin Y disodium salt; HEA, 2-hydroxyethyl J

DOI: 10.1021/acs.macromol.8b02628 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules polymer functionalization under visible light. Polym. Chem. 2014, 5, 3321−3325. (17) McKenzie, T. G.; Fu, Q.; Wong, E. H. H.; Dunstan, D. E.; Qiao, G. G. Visible Light Mediated Controlled Radical Polymerization in the Absence of Exogenous Radical Sources or Catalysts. Macromolecules 2015, 48, 3864−3872. (18) McKenzie, T. G.; Fu, Q.; Uchiyama, M.; Satoh, K.; Xu, J.; Boyer, C.; Kamigaito, M.; Qiao, G. G. Beyond Traditional RAFT: Alternative Activation of Thiocarbonylthio Compounds for Controlled Polymerization. Adv. Sci. 2016, 3, 1500394−1500401. (19) Corrigan, N.; Yeow, J.; Judzewitsch, P.; Xu, J.; Boyer, C. Seeing the Light: Advancing Materials Chemistry through Photopolymerization. Angew. Chem., Int. Ed. 2018, DOI: 10.1002/anie.201805473. (20) Shanmugam, S.; Xu, J.; Boyer, C. Photoinduced Electron Transfer-Reversible Addition-Fragmentation Chain Transfer (PETRAFT) Polymerization of Vinyl Acetate and N-Vinylpyrrolidinone: Kinetic and Oxygen Tolerance Study. Macromolecules 2014, 47, 4930−4942. (21) Shanmugam, S.; Boyer, C. Stereo-, Temporal and Chemical Control through Photoactivation of Living Radical Polymerization: Synthesis of Block and Gradient Copolymers. J. Am. Chem. Soc. 2015, 137, 9988−9999. (22) Shanmugam, S.; Xu, J.; Boyer, C. Exploiting Metalloporphyrins for Selective Living Radical Polymerization Tunable over Visible Wavelengths. J. Am. Chem. Soc. 2015, 137, 9174−9185. (23) Shanmugam, S.; Xu, J.; Boyer, C. Light-Regulated Polymerization under Near-Infrared/Far-Red Irradiation Catalyzed by Bacteriochlorophyll a. Angew. Chem., Int. Ed. 2016, 55, 1036−1040. (24) Yeow, J.; Chapman, R.; Xu, J.; Boyer, C. Oxygen tolerant photopolymerization for ultralow volumes. Polym. Chem. 2017, 8, 5012−5022. (25) Figg, C. A.; Hickman, J. D.; Scheutz, G. M.; Shanmugam, S.; Carmean, R. N.; Tucker, B. S.; Boyer, C.; Sumerlin, B. S. ColorCoding Visible Light Polymerizations To Elucidate the Activation of Trithiocarbonates Using Eosin Y. Macromolecules 2018, 51, 1370− 1376. (26) Fu, Q.; Xie, K.; McKenzie, T. G.; Qiao, G. G. Trithiocarbonates as intrinsic photoredox catalysts and RAFT agents for oxygen tolerant controlled radical polymerization. Polym. Chem. 2017, 8, 1519−1526. (27) Hook, A. L.; Anderson, D. G.; Langer, R.; Williams, P.; Davies, M. C.; Alexander, M. R. High throughput methods applied in biomaterial development and discovery. Biomaterials 2010, 31, 187− 98. (28) Meier, M. A. R.; Hoogenboom, R.; Schubert, U. S. Combinatorial Methods, Automated Synthesis and High-Throughput Screening in Polymer Research: The Evolution Continues. Macromol. Rapid Commun. 2004, 25, 21−33. (29) Yeow, J.; Joshi, S.; Chapman, R.; Boyer, C. A Self-Reporting Photocatalyst for Online Fluorescence Monitoring of High Throughput RAFT Polymerization. Angew. Chem., Int. Ed. 2018, 57, 10102−10106. (30) Chapman, R.; Gormley, A. J.; Stenzel, M. H.; Stevens, M. M. Combinatorial Low-Volume Synthesis of Well-Defined Polymers by Enzyme Degassing. Angew. Chem., Int. Ed. 2016, 55, 4500−4503. (31) Gormley, A. J.; Yeow, J.; Ng, G.; Conway, O.; Boyer, C.; Chapman, R. An Oxygen-Tolerant PET-RAFT Polymerization for Screening Structure-Activity Relationships. Angew. Chem., Int. Ed. 2018, 57, 1557−1562. (32) Cosson, S.; Danial, M.; Saint-Amans, J. R.; Cooper-White, J. Accelerated Combinatorial High Throughput Star Polymer Synthesis via a Rapid One-Pot Sequential Aqueous RAFT (rosa-RAFT) Polymerization Scheme. Macromol. Rapid Commun. 2017, 38, 1600780−1600788. (33) Pan, X.; Lathwal, S.; Mack, S.; Yan, J.; Das, S. R.; Matyjaszewski, K. Automated Synthesis of Well-Defined Polymers and Biohybrids by Atom Transfer Radical Polymerization Using a DNA Synthesizer. Angew. Chem., Int. Ed. 2017, 56, 2740−2743.

(34) Junkers, T. Precision Polymer Design in Microstructured Flow Reactors: Improved Control and First Upscale at Once. Macromol. Chem. Phys. 2017, 218, 1600421−1600430. (35) Li, X.; Mastan, E.; Wang, W.-J.; Li, B.-G.; Zhu, S. Progress in reactor engineering of controlled radical polymerization: a comprehensive review. React. Chem. Eng. 2016, 1, 23−59. (36) Britton, J.; Raston, C. L. Multi-step continuous-flow synthesis. Chem. Soc. Rev. 2017, 46, 1250−1271. (37) Plutschack, M. B.; Pieber, B.; Gilmore, K.; Seeberger, P. H. The Hitchhiker’s Guide to Flow Chemistry parallel. Chem. Rev. 2017, 117, 11796−11893. (38) Junkers, T. Precise macromolecular engineering via continuousflow synthesis techniques. J. Flow Chem. 2017, 7, 106−110. (39) Junkers, T.; Wenn, B. Continuous photoflow synthesis of precision polymers. React. Chem. Eng. 2016, 1, 60−64. (40) Wenn, B.; Junkers, T. Continuous Microflow PhotoRAFT Polymerization. Macromolecules 2016, 49, 6888−6895. (41) Chen, M.; Johnson, J. A. Improving photo-controlled living radical polymerization from trithiocarbonates through the use of continuous-flow techniques. Chem. Commun. 2015, 51, 6742−6745. (42) Ramsey, B. L.; Pearson, R. M.; Beck, L. R.; Miyake, G. M. Photoinduced Organocatalyzed Atom Transfer Radical Polymerization Using Continuous Flow. Macromolecules 2017, 50, 2668− 2674. (43) Corrigan, N.; Rosli, D.; Jones, J. W. J.; Xu, J.; Boyer, C. Oxygen Tolerance in Living Radical Polymerization: Investigation of Mechanism and Implementation in Continuous Flow Polymerization. Macromolecules 2016, 49, 6779−6789. (44) Corrigan, N.; Almasri, A.; Taillades, W.; Xu, J.; Boyer, C. Controlling Molecular Weight Distributions through Photoinduced Flow Polymerization. Macromolecules 2017, 50, 8438−8448. (45) Rubens, M.; Latsrisaeng, P.; Junkers, T. Visible light-induced iniferter polymerization of methacrylates enhanced by continuous flow. Polym. Chem. 2017, 8, 6496−6505. (46) Xu, J.; Shanmugam, S.; Corrigan, N. A.; Boyer, C. Catalyst-Free Visible Light-Induced RAFT Photopolymerization. In Controlled Radical Polymerization: Mechanisms, 2015; pp 247−267. (47) Baeten, E.; Haven, J.; Junkers, T. RAFT Multiblock Reactor Telescoping: From Monomers to Tetrablock Copolymers in a Continuous Multistage Reactor Cascade. Polym. Chem. 2017, 8, 3815−3824. (48) Kuroki, A.; Martinez-Botella, I.; Hornung, C.; Martin, L.; Williams, E. G. L.; Locock, K.; Hartlieb, M.; Perrier, S. Looped flow RAFT polymerization for multiblock copolymer synthesis. Polym. Chem. 2017, 8, 3249−3254.

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DOI: 10.1021/acs.macromol.8b02628 Macromolecules XXXX, XXX, XXX−XXX