2-(Methylthio)ethyl Methacrylate: A Versatile Monomer for Stimuli

Oct 24, 2017 - 2-(Methylthio)ethyl Methacrylate: A Versatile Monomer for Stimuli Responsiveness and Polymerization-Induced Self-Assembly in the Presen...
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Letter Cite This: ACS Macro Lett. 2017, 6, 1237-1244

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2‑(Methylthio)ethyl Methacrylate: A Versatile Monomer for Stimuli Responsiveness and Polymerization-Induced Self-Assembly in the Presence of Air Sihao Xu,† Gervase Ng,† Jiangtao Xu,† Rhiannon P. Kuchel,‡ Jonathan Yeow,*,† and Cyrille Boyer*,† †

Centre for Advanced Macromolecular Design and Australian Centre for NanoMedicine, School of Chemical Engineering, and Electron Microscope Unit, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney NSW 2052, Australia

‡

S Supporting Information *

ABSTRACT: In this communication, we investigate the photoinduced electron/energy transfer−reversible addition− fragmentation chain transfer (PET-RAFT) polymerization of 2-(methylthio)ethyl methacrylate (MTEMA) using 5,10,15,20tetraphenylporphine zinc (ZnTPP) as a photocatalyst under visible red light (λmax = 635 nm). Interestingly, the polymerization kinetics were not affected by the presence of air as near identical polymerization kinetics were observed for nondeoxygenated and deoxygenated systems, which is attributed to the singlet oxygen quenching ability of MTEMA. In both cases, well-defined polymers were obtained with good control over the molecular weight and molecular weight distribution (MWD). Furthermore, we have demonstrated that MTEMA can undergo the polymerization-induced self-assembly (PISA) process from a poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) macromolecular chain transfer agent (macro-CTA) to yield well-defined polymeric nanoparticles of various morphologies. These nanoparticles were rapidly disassembled after exposure to visible light due to the formation of singlet oxygen by the encapsulated ZnTPP and subsequent rapid oxidation of the thioether group.

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RAFT polymerization, oxygen can be removed by a number of methods, including employing an excess of radical initiator to form unreactive peroxy radicals,19−21 employing oxidase enzymes to convert oxygen into hydrogen peroxide3,22−24 or reacting photosensitized oxygen species with suitable quenching species.4,25−28 Some of these approaches have also recently been implemented in RAFT dispersion polymerization for the synthesis of polymeric nanoparticles using a polymerizationinduced self-assembly (PISA) approach. The PISA approach is a highly versatile and robust approach for the synthesis of selfassembled nanoparticles of various morphologies and can be performed at high particle concentrations (10−50 wt %).29−32 Recently, our group4,26 and others33 have demonstrated that a PET-RAFT initiated PISA process can occur without deoxygenation due to the quenching of photosensitized oxygen by exogenous quenchers. Alternatively, Tan’s group34 building on previous works by Stevens 3,22 and Yagci, 35 have demonstrated that the addition of an oxidase enzyme (and oxidizable substrate) can be employed to allow for a photoinitiated PISA process to be conducted without prior deoxygenation.

t is well-known that free radical polymerizations can be hampered by the rapid quenching of initiating and propagating radicals by molecular oxygen.1,2 In controlled/ living radical polymerizations (CLRP), such as atom transfer radical polymerization (ATRP) or reversible addition− fragmentation chain transfer (RAFT) polymerization, oxygen quenching can be particularly problematic since oxygen can lead to not only inhibitory behavior, but also affect the livingness of the polymerization.1 To overcome this limitation, conventional CLRP is performed in the absence of oxygen by employing techniques such as inert gas sparging or freeze− pump−thaw cycling. However, these techniques require specialist equipment, such as vacuum pumps and an inert gas source, which may hinder the general applicability of CLRP. Alternatively, oxygen tolerant CLRP techniques have been proposed as a method to simplify a typical reaction setup and enable CLRP to be conducted under a broader range of conditions, such as in microtiter wellplates3,4 or even automated synthesizers.5,6 A number of mechanisms have been proposed to impart oxygen tolerance to CLRP. For example, Matyjaszewski,7−9 Percec,10−12 and others have demonstrated that ATRP/SETLRP can be performed with limited amounts of air due to the consumption of oxygen by oxidation of the transition metal catalyst and its subsequent regeneration by a reducing agent,13−15 light,16,17 or electrochemical means.18 During © XXXX American Chemical Society

Received: September 19, 2017 Accepted: October 17, 2017

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DOI: 10.1021/acsmacrolett.7b00731 ACS Macro Lett. 2017, 6, 1237−1244

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ACS Macro Letters

Figure 1. (A) Scheme demonstrating the PET-RAFT polymerization of MTEMA in the presence of ZnTPP and CDTPA as photocatalyst and RAFT agent, respectively. PET-RAFT homopolymerization kinetics were performed with and without deoxygenation in DMF and under red light (λmax = 635 nm, 3.0 mW/cm2) using a [MTEMA]/[CDTPA]/[ZnTPP] = 200:1:0.01. Variation of (B) ln([M]0/[M]t) with irradiation time and (C) GPC derived molecular weight and dispersity with conversion. Corresponding MWDs at different irradiation times for polymerizations conducted (D) with and (E) without prior deoxygenation.

1B). Furthermore, regardless of whether prior deoxygenation was applied, the GPC derived molecular weight values were observed to increase linearly with monomer conversion and the molecular weight distributions (MWDs) remained narrow (Đ < 1.4) and unimodal throughout the polymerization, suggesting the controlled/living nature of the polymerization (Figure 1C− E; SI, Table S1).45 However, in both cases, a slight deviation between the experimental and theoretical molecular weight values was observed at low monomer conversion, which we attributed to the slow addition/fragmentation process in RAFT mediated methacrylate polymerizations at low temperatures and monomer conversions (particularly for trithiocarbonates) (see SI, Figure S1).26,46,47 Nonetheless, the unusual kinetic behavior of MTEMA suggests the efficiency with which molecular oxygen is removed from the system, since the presence of oxygen in conventional RAFT polymerization generally leads to an increased inhibition period.19 To investigate whether this degree of oxygen tolerance was specific to MTEMA, we attempted to polymerize MMA under the same polymerization conditions (SI, Figure S1). In comparison with MTEMA, the PET-RAFT polymerization of MMA in DMF without deoxygenation exhibited a long inhibition period (>200 min) and slower polymerization rate compared to the deoxygenated polymerization which presented a minimal inhibition period (SI, Figure S1A). Previously, we have demonstrated that the observed tolerance to oxygen in PET-RAFT polymerization can be attributed to the photosensitization of molecular oxygen by ZnTPP into singlet oxygen which is then rapidly quenched by reaction with quenchers such as DMSO48 (as a solvent) or exogenous additives such as 9,10-dimethylanthracene.26 We hypothesized that the oxygen tolerance of MTEMA under PET-RAFT conditions (in the absence of exogenous quenchers) was due to the oxidation of the thioether functionality of MTEMA into the corresponding sulfoxide (or sulfone) which effectively removes molecular oxygen from the polymerization mixture. 1H NMR analysis confirmed the oxidation of the thioether moiety in the crude nondeoxygenated polymerization mixture with the presence of a minor population (94%) were obtained within 24 h and good evidence of controlled/living behavior was observed (Figure 3A,C), indicating the minimal impact of oxygen on the PET-RAFT dispersion polymerization process. It is well known that the thioether group can be readily oxidized by reactive oxygen species (ROS), such as singlet oxygen and hydrogen peroxide.36,58 In recent years, ROS reactive polymers have attracted increasing interest owing to the upregulation of ROS in certain diseases, including cancer, diabetes, and various cardiovascular and degenerative diseases.59-60 Although a range of stimuli responsive PISA-derived nanoparticles have been developed,56,61-72 to date there have been no reports of ROS responsive nanoparticles synthesized using the PISA approach. We hypothesized that these PMTEMA based nanoparticles could exhibit oxidation sensitive

We varied the target degree of polymerization (DP) of MTEMA to study the effect of block length on nanoparticle formation, while maintaining a [POEGMA]/[ZnTPP] = 1:0.01 and a total solids content of 15 wt %. To negate the potential effect of the oxidized (P)MTEMA on nanoparticle morphology, these polymerizations were performed after deoxygenation with nitrogen. Under red light irradiation (λmax = 635 nm, 1.7 mW/ cm2), high monomer conversions (>93%) were achieved within 24 h, and the observed polymer dispersities remained low in all cases (Đ < 1.32; Figure 3A,B). Importantly, as the polymerization was conducted under vigorous stirring, we observed that the dispersions remained colloidally stable. Using transmission electron microscopy (TEM), we observed the evolution of the nanoparticle morphology from spheres (DP = 30, PISA-1), to worms (DP = 50, PISA-2), and finally vesicles (DP = 120, PISA-3; Figure 3D). Interestingly, similar to other PISA systems, the formation of the worm morphology was also accompanied by a significant increase in the viscosity of the dispersion which is usually associated with the onset of interworm contacts.56,57 To investigate whether the presence of oxygen could affect the nanoparticle morphology, we conducted the same PISA process without prior deoxygenation. 1240

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Figure 4. (A) 1H NMR spectra (acquired in DMSO-d6) of aqueous POEGMA-b-PMTEMA vesicles (PISA-7, 0.5 wt%) after irradiation with visible light (λmax = 560 nm, 9.7 mW/cm2) in the presence of oxygen. For clarity, only the range from 2.05 to 2.80 ppm is shown here, for the full 1H NMR spectrum see SI, Figure S8. (B) Conversion of thioether groups with irradiation time as quantified using the 1H NMR peak at 2.15 ppm. (C) Digital photographs showing the change in turbidity with increasing irradiation time.

completely transparent indicating disassembly of the polymeric vesicles (SI, Scheme S1). In order to investigate this disassembly process further, we monitored the transmittance of 500 nm light through a 0.05 wt % vesicle solution (PISA-7) during irradiation. Under visible light irradiation (λmax = 560 nm, 9.7 mW/cm2), the solution transmittance increased over a period of 3 h indicating the disassembly of these vesicles under visible light (SI, Figure S10A,B). Alternatively, the addition of a chemical stimulus, H2O2, could also be used to trigger disassembly of these thioether functionalized nanoparticles due to oxidation of the PMTEMA block to PMSEMA49,73 (SI, Figure S10C,D). After addition of H2O2 (30 wt%), the transmittance increased over a period of 3 h to ∼90 % indicating almost complete disassembly of the thioether functionalized vesicles. 1H NMR analysis after the addition of H2O2 revealed the presence of the same PMSEMA peaks that are observed under the action of singlet oxygen (SI, Figure S9). We have successfully demonstrated that PET-RAFT polymerization of MTEMA proceeds without the need for deoxygenation of the polymerization mixture due to the singlet oxygen quenching properties of the monomer itself. Furthermore, MTEMA was polymerized under PET-RAFT dispersion polymerization conditions in methanol allowing for the fabrication of nanoparticles with various morphologies according to a PISA approach. These nanoparticles were rapidly disassembled after exposure to visible light in the presence of air due to the singlet oxygen mediated oxidation of the thioether moiety to the corresponding hydrophilic sulfoxide. To the best of our knowledge, this process demonstrates, for the first time, ROS (and visible light) responsive nanoparticles synthesized using a PISA approach.

behavior due to the high water solubility of the corresponding polymeric sulfoxide, poly(methylsulfinyl)ethyl methacrylate (PMSEMA).42 To test this hypothesis, we first synthesized POEGMA-b-PMTEMA nanoparticles with a high concentration of ZnTPP ([POEGMA]/[ZnTPP = 1:0.06]; Figure 3A, PISA-7). To reduce the formation of dead polymer chains, a lower light intensity (λmax = 635 nm, 1.0 mW/cm2) was employed enabling a narrow MWD (Đ = 1.32) to be obtained. Importantly, TEM analysis indicated the formation of a pure vesicle morphology in accordance with the corresponding experiment performed with a lower concentration of photocatalyst (SI, Figure S6). Finally, the nanoparticles were dialyzed directly against water to obtain a 0.5 wt% vesicle dispersion. Furthermore, the resultant aqueous dispersion was colored, which suggests the encapsulation of the catalyst within the hydrophobic core of the nanoparticles due to its strong aqueous insolubility. UV−vis spectra obtained directly in water or after disassembly of the nanoparticles in DMSO confirmed the presence of the characteristic Soret (∼428 nm) and Q (500 650 nm) bands of ZnTPP (SI, Figure S7A,B) which was quantified by comparison with a calibration curve to give a ZnTPP loading of 0.15 wt% relative to polymer with an encapsulation efficiency of approximately 85 % (see SI, Experimental Section). To determine whether the encapsulated ZnTPP retained its ability to generate singlet oxygen, we irradiated a 0.5 wt% solution of ZnTPP loaded vesicles (Figure 3, PISA-7) with visible light (λmax = 560 nm, 9.7 mW/cm2) and monitored the solution via 1H NMR. As the irradiation time increased, we observed a decrease in the PMTEMA peaks at 2.15 and 2.75 ppm corresponding to the methyl (CH3-S-CH2) and methylene (CH3-S-CH2) protons adjacent to the sulfur atom, respectively (Figure 4A, SI, Figures S8 and S9). Simultaneously, downfield peaks at 2.8−3.2, 2.65, and 4.30 ppm appeared, indicating the formation of PMSEMA via the oxidation of the PMTEMA block. Monitoring of the thioether peak at 2.15 ppm revealed that more than 70 % of PMTEMA was converted to PMSEMA after 5 h of visible light irradiation (Figure 4B). In addition, visual inspection revealed a decreasing turbidity of the reaction mixture over time which was attributed to the increased water solubility of PMSEMA compared to PMTEMA (Figure 4C). After 5 h irradiation, the initially cloudy reaction mixture was

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsmacrolett.7b00731. Additional experimental and characterization data, as well as Figures S1−S10, Table S1, and Scheme S1 (PDF). 1241

DOI: 10.1021/acsmacrolett.7b00731 ACS Macro Lett. 2017, 6, 1237−1244

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methacrylate in dimethyl sulfoxide. Polym. Chem. 2015, 6 (13), 2523− 2530. (17) Yang, Q.; Lalevée, J.; Poly, J. Development of a Robust Photocatalyzed ATRP Mechanism Exhibiting Good Tolerance to Oxygen and Inhibitors. Macromolecules 2016, 49 (20), 7653−7666. (18) Li, B.; Yu, B.; Huck, W. T. S.; Zhou, F.; Liu, W. Electrochemically Induced Surface-Initiated Atom-Transfer Radical Polymerization. Angew. Chem. 2012, 124 (21), 5182−5185. (19) Gody, G.; Barbey, R.; Danial, M.; Perrier, S. Ultrafast RAFT polymerization: multiblock copolymers within minutes. Polym. Chem. 2015, 6 (9), 1502−1511. (20) Cosson, S.; Danial, M.; Saint-Amans, J. R.; Cooper-White, J. 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 (8), 1600780. (21) Wu, H.; Yang, L.; Tao, L. Polymer Synthesis by Mimicking Nature’s Strategy: combination of ultra-fast RAFT and the Biginelli reaction. Polym. Chem. 2017, 8, 5679−5687. (22) Chapman, R.; Gormley, A. J.; Herpoldt, K.-l.; Stevens, M. M. Highly Controlled Open Vessel RAFT Polymerizations by Enzyme Degassing. Macromolecules 2014, 47 (24), 8541−8547. (23) Zhang, B.; Wang, X.; Zhu, A.; Ma, K.; Lv, Y.; Wang, X.; An, Z. Enzyme-Initiated Reversible Addition−Fragmentation Chain Transfer Polymerization. Macromolecules 2015, 48 (21), 7792−7802. (24) Lv, Y.; Liu, Z.; Zhu, A.; An, Z. Glucose Oxidase Deoxygenation Redox Initiation for RAFT Polymerization in Air. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 164−174. (25) Shanmugam, S.; Xu, J.; Boyer, C. Exploiting Metalloporphyrins for Selective Living Radical Polymerization Tunable over Visible Wavelengths. J. Am. Chem. Soc. 2015, 137 (28), 9174−9185. (26) Ng, G.; Yeow, J.; Xu, J.; Boyer, C. Application of oxygen tolerant PET-RAFT to polymerization-induced self-assembly. Polym. Chem. 2017, 8, 2841. (27) Yeow, J.; Shanmugam, S.; Corrigan, N.; Kuchel, R. P.; Xu, J.; Boyer, C. A Polymerization-Induced Self-Assembly Approach to Nanoparticles Loaded with Singlet Oxygen Generators. Macromolecules 2016, 49 (19), 7277−7285. (28) 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 (9), 1519− 1526. (29) Warren, N. J.; Armes, S. P. Polymerization-Induced SelfAssembly of Block Copolymer Nano-objects via RAFT Aqueous Dispersion Polymerization. J. Am. Chem. Soc. 2014, 136 (29), 10174− 10185. (30) Sun, J.-T.; Hong, C.-Y.; Pan, C.-Y. Recent advances in RAFT dispersion polymerization for preparation of block copolymer aggregates. Polym. Chem. 2013, 4 (4), 873−881. (31) Rieger, J. Guidelines for the Synthesis of Block Copolymer Particles of Various Morphologies by RAFT Dispersion Polymerization. Macromol. Rapid Commun. 2015, 36 (16), 1458−1471. (32) Yeow, J.; Boyer, C. Photoinitiated Polymerization-Induced SelfAssembly (Photo-PISA): New Insights and Opportunities. Adv. Sci. 2017, 4 (7), 1700137. (33) Ren, K.; Perez-Mercader, J. Thermoresponsive gels directly obtained via visible light-mediated polymerization-induced selfassembly with oxygen tolerance. Polym. Chem. 2017, 8 (23), 3548− 3552. (34) Tan, J.; Liu, D.; Bai, Y.; Huang, C.; Li, X.; He, J.; Xu, Q.; Zhang, L. Enzyme-Assisted Photoinitiated Polymerization-Induced SelfAssembly: An Oxygen-Tolerant Method for Preparing Block Copolymer Nano-Objects in Open Vessels and Multiwell Plates. Macromolecules 2017, 50 (15), 5798−5806. (35) Oytun, F.; Kahveci, M. U.; Yagci, Y. Sugar overcomes oxygen inhibition in photoinitiated free radical polymerization. J. Polym. Sci., Part A: Polym. Chem. 2013, 51 (8), 1685−1689. (36) Ghogare, A. A.; Greer, A. Using Singlet Oxygen to Synthesize Natural Products and Drugs. Chem. Rev. 2016, 116 (17), 9994−10034.

AUTHOR INFORMATION

Corresponding Authors

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

Jiangtao Xu: 0000-0002-9020-7018 Cyrille Boyer: 0000-0002-4564-4702 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS C.B. and J.X. acknowledge Australian Research Council (ARC) for their Future Fellowships (FT12010096 and FT160100095, respectively).

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REFERENCES

(1) Bhanu, V. A.; Kishore, K. Role of Oxygen in Polymerization Reactions. Chem. Rev. 1991, 91 (2), 99−117. (2) Ligon, S. C.; Husár, B.; Wutzel, H.; Holman, R.; Liska, R. Strategies to Reduce Oxygen Inhibition in Photoinduced Polymerization. Chem. Rev. 2014, 114 (1), 557−589. (3) Chapman, R.; Gormley, A. J.; Stenzel, M. H.; Stevens, M. M. Combinatorial low-volume synthesis of well-defined polymers by enzyme degassing. Angew. Chem. 2016, 128 (14), 4576−4579. (4) Yeow, J.; Chapman, R.; Xu, J.; Boyer, C. Oxygen tolerant photopolymerization for ultralow volumes. Polym. Chem. 2017, 8, 5012−5022. (5) 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 (10), 2740−2743. (6) Siegwart, D. J.; Leiendecker, M.; Langer, R.; Anderson, D. G. Automated ARGET ATRP Accelerates Catalyst Optimization for the Synthesis of Thiol-Functionalized Polymers. Macromolecules 2012, 45 (3), 1254−1261. (7) Jakubowski, W.; Min, K.; Matyjaszewski, K. Activators Regenerated by Electron Transfer for Atom Transfer Radical Polymerization of Styrene. Macromolecules 2006, 39 (1), 39−45. (8) Matyjaszewski, K.; Coca, S.; Gaynor, S. G.; Wei, M.; Woodworth, B. E. Controlled Radical Polymerization in the Presence of Oxygen. Macromolecules 1998, 31 (17), 5967−5969. (9) Min, K.; Jakubowski, W.; Matyjaszewski, K. AGET ATRP in the Presence of Air in Miniemulsion and in Bulk. Macromol. Rapid Commun. 2006, 27 (8), 594−598. (10) Fleischmann, S.; Percec, V. SET-LRP of methyl methacrylate initiated with CCl4 in the presence and absence of air. J. Polym. Sci., Part A: Polym. Chem. 2010, 48 (10), 2243−2250. (11) Fleischmann, S.; Rosen, B. M.; Percec, V. SET-LRP of acrylates in air. J. Polym. Sci., Part A: Polym. Chem. 2010, 48 (5), 1190−1196. (12) Jiang, X.; Rosen, B. M.; Percec, V. Immortal SET−LRP mediated by Cu(0) wire. J. Polym. Sci., Part A: Polym. Chem. 2010, 48 (12), 2716−2721. (13) Gnanou, Y.; Hizal, G. Effect of phenol and derivatives on atom transfer radical polymerization in the presence of air. J. Polym. Sci., Part A: Polym. Chem. 2004, 42 (2), 351−359. (14) Wang, Y.; Li, X.; Du, F.; Yu, H.; Jin, B.; Bai, R. Use of alcohols as reducing agents for synthesis of well-defined polymers by AGETATRP. Chem. Commun. 2012, 48 (22), 2800−2802. (15) Bai, L.; Zhang, L.; Pan, J.; Zhu, J.; Cheng, Z.; Zhu, X. Developing a Synthetic Approach with Thermoregulated PhaseTransfer Catalysis: Facile Access to Metal-Mediated Living Radical Polymerization of Methyl Methacrylate in Aqueous/Organic Biphasic System. Macromolecules 2013, 46 (6), 2060−2066. (16) Mosnacek, J.; Eckstein-Andicsova, A.; Borska, K. Ligand effect and oxygen tolerance studies in photochemically induced copper mediated reversible deactivation radical polymerization of methyl 1242

DOI: 10.1021/acsmacrolett.7b00731 ACS Macro Lett. 2017, 6, 1237−1244

Letter

ACS Macro Letters (37) Xu, J.; Ypma, M.; Chiarelli, P. A.; Park, J.; Ellenbogen, R. G.; Stayton, P. S.; Mourad, P. D.; Lee, D.; Convertine, A. J.; Kievit, F. M. Theranostic Oxygen Reactive Polymers for Treatment of Traumatic Brain Injury. Adv. Funct. Mater. 2016, 26 (23), 4124−4133. (38) Kramer, J. R.; Deming, T. J. Glycopolypeptides with a RedoxTriggered Helix-to-Coil Transition. J. Am. Chem. Soc. 2012, 134 (9), 4112−4115. (39) Hussain, I.; Graham, S.; Wang, Z.; Tan, B.; Sherrington, D. C.; Rannard, S. P.; Cooper, A. I.; Brust, M. Size-Controlled Synthesis of Near-Monodisperse Gold Nanoparticles in the 1−4 nm Range Using Polymeric Stabilizers. J. Am. Chem. Soc. 2005, 127 (47), 16398−16399. (40) Hemp, S. T.; Allen, M. H.; Smith, A. E.; Long, T. E. Synthesis and Properties of Sulfonium Polyelectrolytes for Biological Applications. ACS Macro Lett. 2013, 2 (8), 731−735. (41) Mackenzie, M. C.; Shrivats, A. R.; Konkolewicz, D.; Averick, S. E.; McDermott, M. C.; Hollinger, J. O.; Matyjaszewski, K. Synthesis of Poly(meth)acrylates with Thioether and Tertiary Sulfonium Groups by ARGET ATRP and Their Use as siRNA Delivery Agents. Biomacromolecules 2015, 16 (1), 236−245. (42) Li, S.; Chung, H. S.; Simakova, A.; Wang, Z.; Park, S.; Fu, L.; Cohen-Karni, D.; Averick, S.; Matyjaszewski, K. Biocompatible Polymeric Analogues of DMSO Prepared by Atom Transfer Radical Polymerization. Biomacromolecules 2017, 18 (2), 475−482. (43) Fu, C.; Herbst, S.; Zhang, C.; Whittaker, A. K. Polymeric 19F MRI agents responsive to reactive oxygen species. Polym. Chem. 2017, 8 (31), 4585−4595. (44) Discekici, E. H.; Pester, C. W.; Treat, N. J.; Lawrence, J.; Mattson, K. M.; Narupai, B.; Toumayan, E. P.; Luo, Y.; McGrath, A. J.; Clark, P. G.; Read de Alaniz, J.; Hawker, C. J. Simple Benchtop Approach to Polymer Brush Nanostructures Using Visible-LightMediated Metal-Free Atom Transfer Radical Polymerization. ACS Macro Lett. 2016, 5 (2), 258−262. (45) Goto, A.; Fukuda, T. Kinetics of living radical polymerization. Prog. Polym. Sci. 2004, 29 (4), 329−385. (46) Feldermann, A.; Stenzel, M. H.; Davis, T. P.; Vana, P.; BarnerKowollik, C. Facile Access to Chain Length Dependent Termination Rate Coefficients via Reversible Addition−Fragmentation Chain Transfer (RAFT) Polymerization: Influence of the RAFT Agent Structure. Macromolecules 2004, 37 (7), 2404−2410. (47) Barner-Kowollik, C.; Quinn, J. F.; Nguyen, T. L. U.; Heuts, J. P. A.; Davis, T. P. Kinetic Investigations of Reversible Addition Fragmentation Chain Transfer Polymerizations: Cumyl Phenyldithioacetate Mediated Homopolymerizations of Styrene and Methyl Methacrylate. Macromolecules 2001, 34 (22), 7849−7857. (48) 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 (18), 6779−6789. (49) Rodriguez, A. R.; Kramer, J. R.; Deming, T. J. Enzyme-Triggered Cargo Release from Methionine Sulfoxide Containing Copolypeptide Vesicles. Biomacromolecules 2013, 14 (10), 3610−3614. (50) Gou, L.; Coretsopoulos, C. N.; Scranton, A. B. Measurement of the dissolved oxygen concentration in acrylate monomers with a novel photochemical method. J. Polym. Sci., Part A: Polym. Chem. 2004, 42 (5), 1285−1292. (51) Figg, C. A.; Simula, A.; Gebre, K. A.; Tucker, B. S.; Haddleton, D. M.; Sumerlin, B. S. Polymerization-induced thermal self-assembly (PITSA). Chem. Sci. 2015, 6 (2), 1230−1236. (52) Zhou, W.; Qu, Q.; Xu, Y.; An, Z. Aqueous PolymerizationInduced Self-Assembly for the Synthesis of Ketone-Functionalized Nano-Objects with Low Polydispersity. ACS Macro Lett. 2015, 4 (5), 495−499. (53) Blanazs, A.; Madsen, J.; Battaglia, G.; Ryan, A. J.; Armes, S. P. Mechanistic Insights for Block Copolymer Morphologies: How Do Worms Form Vesicles? J. Am. Chem. Soc. 2011, 133 (41), 16581− 16587. (54) Derry, M. J.; Fielding, L. A.; Armes, S. P. Industrially-relevant polymerization-induced self-assembly formulations in non-polar

solvents: RAFT dispersion polymerization of benzyl methacrylate. Polym. Chem. 2015, 6 (16), 3054−3062. (55) Blanazs, A.; Ryan, A. J.; Armes, S. P. Predictive Phase Diagrams for RAFT Aqueous Dispersion Polymerization: Effect of Block Copolymer Composition, Molecular Weight, and Copolymer Concentration. Macromolecules 2012, 45 (12), 5099−5107. (56) Blanazs, A.; Verber, R.; Mykhaylyk, O. O.; Ryan, A. J.; Heath, J. Z.; Douglas, C. W. I.; Armes, S. P. Sterilizable Gels from Thermoresponsive Block Copolymer Worms. J. Am. Chem. Soc. 2012, 134 (23), 9741−9748. (57) Fielding, L. A.; Lane, J. A.; Derry, M. J.; Mykhaylyk, O. O.; Armes, S. P. Thermo-responsive Diblock Copolymer Worm Gels in Non-polar Solvents. J. Am. Chem. Soc. 2014, 136 (15), 5790−5798. (58) Hulea, V.; Moreau, P.; Di Renzo, F. Thioether oxidation by hydrogen peroxide using titanium-containing zeolites as catalysts. J. Mol. Catal. A: Chem. 1996, 111 (3), 325−332. (59) Winterbourn, C. C. Reconciling the chemistry and biology of reactive oxygen species. Nat. Chem. Biol. 2008, 4 (5), 278−286. (60) Zhang, D.; Wei, Y.; Chen, K.; Zhang, X.; Xu, X.; Shi, Q.; Han, S.; Chen, X.; Gong, H.; Li, X.; Zhang, J. Biocompatible Reactive Oxygen Species (ROS)-Responsive Nanoparticles as Superior Drug Delivery Vehicles. Adv. Healthcare Mater. 2015, 4 (1), 69−76. (61) Derry, M. J.; Mykhaylyk, O. O.; Armes, S. P. A Vesicle-to-Worm Transition Provides a New High-Temperature Oil Thickening Mechanism. Angew. Chem. 2017, 129 (7), 1772−1776. (62) Lovett, J. R.; Warren, N. J.; Ratcliffe, L. P. D.; Kocik, M. K.; Armes, S. P. pH-Responsive Non-Ionic Diblock Copolymers: Ionization of Carboxylic Acid End-Groups Induces an Order−Order Morphological Transition. Angew. Chem., Int. Ed. 2015, 54 (4), 1279− 1283. (63) Tan, J.; Sun, H.; Yu, M.; Sumerlin, B. S.; Zhang, L. Photo-PISA: Shedding Light on Polymerization-Induced Self-Assembly. ACS Macro Lett. 2015, 4 (11), 1249−1253. (64) Tan, J.; Zhang, X.; Liu, D.; Bai, Y.; Huang, C.; Li, X.; Zhang, L. Facile Preparation of CO2-Responsive Polymer Nano-Objects via Aqueous Photoinitiated Polymerization-Induced Self-Assembly (Photo-PISA). Macromol. Rapid Commun. 2017, 38 (13), 1600508. (65) Cunningham, V. J.; Ratcliffe, L. P. D.; Blanazs, A.; Warren, N. J.; Smith, A. J.; Mykhaylyk, O. O.; Armes, S. P. Tuning the critical gelation temperature of thermo-responsive diblock copolymer worm gels. Polym. Chem. 2014, 5 (21), 6307−6317. (66) Fu, W.; Luo, C.; Morin, E. A.; He, W.; Li, Z.; Zhao, B. UCSTType Thermosensitive Hairy Nanogels Synthesized by RAFT Polymerization-Induced Self-Assembly. ACS Macro Lett. 2017, 6 (2), 127−133. (67) Gao, P.; Cao, H.; Ding, Y.; Cai, M.; Cui, Z.; Lu, X.; Cai, Y. Synthesis of Hydrogen-Bonded Pore-Switchable Cylindrical Vesicles via Visible-Light-Mediated RAFT Room-Temperature Aqueous Dispersion Polymerization. ACS Macro Lett. 2016, 5 (12), 1327−1331. (68) Li, Q.; He, X.; Cui, Y.; Shi, P.; Li, S.; Zhang, W. Doubly thermoresponsive nanoparticles constructed with two diblock copolymers prepared through the two macro-RAFT agents co-mediated dispersion RAFT polymerization. Polym. Chem. 2015, 6 (1), 70−78. (69) Xu, Y.; Li, Y.; Cao, X.; Chen, Q.; An, Z. Versatile RAFT dispersion polymerization in cononsolvents for the synthesis of thermoresponsive nanogels with controlled composition, functionality and architecture. Polym. Chem. 2014, 5 (21), 6244−6255. (70) Zhang, W.-J.; Hong, C.-Y.; Pan, C.-Y. Fabrication of ReductiveResponsive Prodrug Nanoparticles with Superior Structural Stability by Polymerization-Induced Self-Assembly and Functional Nanoscopic Platform for Drug Delivery. Biomacromolecules 2016, 17 (9), 2992− 2999. (71) Zhang, W.-J.; Hong, C.-Y.; Pan, C.-Y. Efficient Fabrication of Photosensitive Polymeric Nano-objects via an Ingenious Formulation of RAFT Dispersion Polymerization and Their Application for Drug Delivery. Biomacromolecules 2017, 18 (4), 1210−1217. (72) Shi, P.; Qu, Y.; Liu, C.; Khan, H.; Sun, P.; Zhang, W. RedoxResponsive Multicompartment Vesicles of Ferrocene-Containing 1243

DOI: 10.1021/acsmacrolett.7b00731 ACS Macro Lett. 2017, 6, 1237−1244

Letter

ACS Macro Letters Triblock Terpolymer Exhibiting On−Off Switchable Pores. ACS Macro Lett. 2016, 5 (1), 88−93. (73) Petitdemange, R.; Garanger, E.; Bataille, L.; Dieryck, W.; Bathany, K.; Garbay, B.; Deming, T. J.; Lecommandoux, S. Selective Tuning of Elastin-like Polypeptide Properties via Methionine Oxidation. Biomacromolecules 2017, 18 (2), 544−550.

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DOI: 10.1021/acsmacrolett.7b00731 ACS Macro Lett. 2017, 6, 1237−1244