Open-to-Air RAFT Polymerization in Complex Solvents: From Whisky

Mar 15, 2018 - Department of Chemistry, University of Minnesota , Minneapolis ... in a wide range of complex aqueous solvents, including, beer, wine, ...
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Letter Cite This: ACS Macro Lett. 2018, 7, 406−411

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Open-to-Air RAFT Polymerization in Complex Solvents: From Whisky to Fermentation Broth Deborah K. Schneiderman,† Jeffrey M. Ting,†,‡ Anatolii A. Purchel,§ Ron Miranda, Jr.,† Matthew V. Tirrell,†,‡ Theresa M. Reineke,§ and Stuart J. Rowan*,†,‡,∥ †

Institute for Molecular Engineering, University of Chicago, Chicago, Illinois 60637, United States Argonne National Laboratory, Lemont, Illinois 60439, United States § Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States ∥ Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States ‡

S Supporting Information *

ABSTRACT: We investigate the use of in situ enzyme degassing to facilitate the open-to-air reversible addition− fragmentation chain transfer (RAFT) polymerization of hydroxyethyl acrylate (HEA) in a wide range of complex aqueous solvents, including, beer, wine, liquor, and fermentation broth. This enzyme-assisted polymerization procedure is impressively robust, and poly(HEA) was attained with good control over molecular weight and a narrow dispersity in nearly all of the solvents tested. Kinetics experiments on HEA polymerization in whisky and spectroscopic analysis of the purified polymers suggest high end-group fidelity, as does the successful chain extension of a poly(HEA) macro chain transfer agent with narrow dispersity. These results suggest enzyme-assisted RAFT may be a powerful and underutilized tool for high-throughput screening and materials discovery and may simplify the synthesis of well-defined polymers in complex conditions.

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limit the utility of light-driven polymerizations, particularly for opaque reactions (e.g., suspension/emulsion polymerizations, or in media with high cell density). Enzyme-assisted RAFT (EnzA-RAFT), where polymerization is conducted in tandem with enzyme-mediated reactions, may offer one potential solution to these challenges. Seminal work by Derango et al. and Iwata et al. demonstrated the ability of oxidoreductase enzymes to initiate the free radical polymerization of (meth)acrylate monomers.16,17 More recently, enzymes have been used to assist RDRP reactions.18,19 For instance, Stevens and co-workers have shown that the glucose oxidase (GOx) enzyme, which catalyzes the coupled conversion of oxygen and glucose to gluconolactone and hydrogen peroxide, can degas open-to-air aqueous RAFT polymerizations (Scheme 1).19 Hydrogen peroxide from this reaction has also been employed as an initiator in the presence of iron, copper, or horseradish peroxidase at low temperatures.20−23 By eliminating exogenous initiators and degassing steps, the addition of enzymes like GOx may improve scalability of controlled polymerization processes and facilitate high throughput materials screening.20 Conceivably, EnzA-RAFT

ver the last two decades, transformative advances in synthetic polymer chemistry have enabled the facile synthesis of functional macromolecules with precise control over architecture, molar mass, and dispersity.1,2 In particular, reversible deactivation radical polymerization (RDRP) methods, such as reversible addition−fragmentation chain transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP), are powerful synthetic tools that allow the synthesis of bespoke polymers for a wide range of applications (e.g., block polymers for bioapplications).3−5 Compared to conventional living anionic polymerization, one chief advantage of RDRP is a greater tolerance against impurities, such as moisture.6,7 This versatility has been exploited for the controlled synthesis of well-defined polymers in a wide variety of complex chemical environments via both ATRP and RAFT polymerization.8−10 Still, there is an inexorable drive to develop aqueous polymerization protocols that are even milder and more robust. For example, photoredox catalysts11,12 have been exploited to eliminate oxygen from radical polymerizations, obviating the need for prior degassing (i.e., using inert gas sparging or freeze−pump−thaw). Exceptionally mild polymerization conditions can also be leveraged for emerging specialized applications, for example, the synthesis of living bioconjugates.13−15 Unfortunately, biocompatibility and scalability may © XXXX American Chemical Society

Received: January 24, 2018 Accepted: March 9, 2018

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DOI: 10.1021/acsmacrolett.8b00069 ACS Macro Lett. 2018, 7, 406−411

Letter

ACS Macro Letters Scheme 1. Aqueous RAFT Polymerization of HEA with Simultaneous Enzyme-Catalyzed Degassing

could be applied to the aqueous EnzA-RAFT polymerization of renewable monomers (e.g., in fermentation broth), perhaps eliminating arduous purification steps. However, to do so demands an understanding of the tolerance of both GOx and RAFT to a range of aqueous impurities. Previously, it has been shown that the copper-mediated RDRP polymerization of Nisopropylacrylamide can be carried out in a variety of commercial water−alcohol mixtures; however, those polymerizations were conducted under air-free conditions (degassed by sparging or freeze−pump−thaw, in the case of carbonated solvents). 10 To probe the applicability, tolerance, and limitations of EnzA-RAFT Polymerization, we studied opento-air polymerization in a variety of complex aqueous solvents. As an initial control, degassed, closed vessel RAFT polymerizations of hydroxyethyl acrylate (HEA) using the water-soluble chain transfer agent (CTA) 2-(propylthiocarbonothioylthio)-2-methylpropionoic acid (PPA) and the commercial radical initiator VA-044 were carried out in three different solvents: (i) aqueous methanol (40%, v/v), (ii) aqueous ethanol (40%, v/v), and (iii) House of Stuart whisky (HoSt, nominally 40% alcohol by volume, ABV). In each case, the polymerization solution was thoroughly degassed by nitrogen sparging and conducted in a closed flask. The starting ratio of HEA monomer to PPA CTA, was adjusted to target a theoretical molar mass (Mn, theo) of ∼15 kg mol−1. All three polymerizations exhibited similarly high conversion (∼90%), as determined by proton nuclear magnetic resonance spectroscopy (1H NMR) after 3 h at 50 °C, while importantly for this study, open-to-air control reactions did not polymerize (Figure S2). 1H NMR end group analysis (Figure S3) of each dialyzed sample revealed a number-average molar mass (Mn) similar to both the calculated theoretical value and the absolute molar mass determined by size-exclusion chromatography with multiangle light scattering (SEC-MALS). As shown in Figure 1A, SEC-MALS also revealed consistently low dispersity (Đ < 1.1) for each sample. Finally, the poly(HEA) glass transition and degradation temperatures (Figures 1B,C) were similar, regardless of the solvent used. Together, these results suggested the myriad of flavor compounds present in the whisky24 had an inconsequential impact on the polymer structure and endgroup fidelity. Next, the open-to-air EnzA-RAFT experiments were investigated to determine whether the trace chemicals present in whisky would inhibit the ability of to GOx to effectively degas the reaction. Accordingly, excess GOx and glucose were added to the reaction solution containing HEA, VA-044, PPA CTA, and HoSt whisky.20 For polymerization conducted in an open test tube at 45 °C, an induction period of ∼40 min was observed, after which the monomer conversion increased

Figure 1. Poly(HEA) were prepared indicated degassed solvent: aqueous methanol (MeOH, 40% v/v), aqueous ethanol (EtOH, 40% v/v), and whisky (HoSt). (A) SEC refractive index chromatograms. (B) Overlay of differential scanning calorimetry thermographs. The data were collected on the second heating cycle at a ramp rate of 10 °C min−1. The full range of these data are shown in Figure S4. (C) Thermogravimetric analysis (TGA) thermographs, showing degradation temperatures (5% mass loss) for heating under nitrogen at a ramp rate of 10 °C min−1.

monotonically, plateauing after a period of about 25 h (Figure 2A). As expected, in control reactions lacking either enzyme or glucose, there was no evidence of polymerization under otherwise identical conditions. Subsequent work (detailed in Table S5 of the Supporting Information) revealed that a variety of other monomers could also be polymerized in HoSt. The open-to-air EnzA-RAFT polymerization of HEA in HoSt whisky compared favorably to the closed flask controls run in nitrogen-sparged aqueous ethanol (40% v/v) and nitrogensparged HoSt whisky (Figures 2A, S26, and 27). Although the final monomer conversion after 25 h was slightly lower for the open HoSt reaction (92%) than the closed controls (98% and 97% for ethanol and HoSt, respectively), at early time points (