SuFEx Postpolymerization Modification Kinetics and Reactivity in

Article Cite This: Macromolecules XXXX, XXX, XXX−XXX

SuFEx Postpolymerization Modification Kinetics and Reactivity in Polymer Brushes Karson Brooks,† Jeremy Yatvin,† Marina Kovaliov,‡ Grant H. Crane,† Jessica Horn,† Saadyah Averick,‡ and Jason Locklin*,† †

Department of Chemistry and College of Engineering, University of Georgia, 220 Riverbend Road, Athens, Georgia 30602, United States ‡ Laboratory for Biomolecular Medicine, Allegheny Health Network Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, United States S Supporting Information *

ABSTRACT: Since its introduction in 2014, the sulfur(VI) fluoride exchange (SuFEx) reaction has emerged as a promising new reaction in the field of polymer chemistry, in both polymerization of diverse polymer backbones and postpolymerization modification (PPM). Previously, we successfully reported the use of SuFEx chemistry as a method for surface derivatization through the PPM of sulfonyl fluoride containing polymer brushes. However, with the diversity of conditions, substrate scope, and catalyst selection afforded by this reaction, it is advantageous to expand the use of SuFEx for PPM on polymer brushes to discern the advantages and limitations of this reaction in surface conjugation. In this work, we used three different polymer brush systemsalkyl sulfonyl fluorides, aromatic sulfonyl fluorides, and aromatic fluorosulfonatesand each was reacted with three different silyl ether derivatives (aryl, alkyl, and benzyl). Each of these reactions was subjected to different catalysts, and herein, we present rates, conditions, and side products for PPM of polymer brushes using SuFEx chemistry. In addition, we explored the use of TBDMS brushes and their reaction with fluorosulfonate derivatives, where surprisingly no surface reaction occurs. With these studies, we are able to better understand the rates and limitations of this click reaction in the context of surface derivatization.

1. INTRODUCTION Since the introduction of the copper-catalyzed azide−alkyne cycloaddition click reaction in 2002, click and click-like reactions have become staples in small molecule synthesis, postpolymerization modification (PPM), and conjugation of both simple and complex molecules to various scaffolds.1−9 By definition, true click reactions must meet several criteria, including being high yielding, fast, modular, wide in scope, and simple to purify and have flexibility in synthetic design.1,10 In 2014, a new click-like reaction, sulfur(VI) fluoride exchange chemistry (SuFEx), was introduced by Sharpless.11 This reaction couples inert sulfonyl fluorides and fluorosulfonates to silyl ethers in the presence of strong guanidine bases or fluoride containing catalysts.12,13 Since its emergence, SuFEx has already found use in small molecule synthesis, protein labeling, polymer synthesis, and surface derivatization.11,14−20 Additionally, studies have been conducted on expanded base and reactant selections in order to broaden the scope of the reaction.21−23 This expansion affords evidence leading to both an understanding of the reaction mechanism and an understanding of reaction limitations and advantages. These studies, however, have only explored reactions in solution. With the potential of SuFEx for interfacial modifications (surface coupling, PPM of polymer supports, hydrogel modifications, © XXXX American Chemical Society

heterogeneous catalysis, etc.), it is our goal to investigate the factors influencing the rate of reaction and side product formation as well as study limitations of SuFEx with varying reactants and bases, when reactions are conducted at interfaces.14,15 Polymer brushes provide an excellent platform to investigate PPM at interfaces because of both their unique physiochemical properties and their high density of reactive moieties.24,25 We have previously reported PPM rates and conditions for SuFEx on the surface, using alkyl sulfonyl fluoride polymer brushes with a variety of silyl ether derivatives catalyzed by guanidine superbases.14 However, with the diversity of SuFEx in terms of reactant type and catalyst selection, it is advantageous to expand these studies to further understand the limitations of this reaction for interfacial modification. In this work, we report the kinetic rates, conditions, and observed side products using both sulfonyl fluoride and fluorosulfonate polymer brushes reacted with a variety of catalysts and silyl ether derivatives. This work provides the framework for a better understanding of the SuFEx reaction at interfaces. Received: November 8, 2017 Revised: December 21, 2017

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DOI: 10.1021/acs.macromol.7b02372 Macromolecules XXXX, XXX, XXX−XXX

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Macromolecules

Scheme 1. Synthetic Scheme for the Fabrication of Polymer Brushes Made from (A) PEFA, (B) VPSF, and (C) FSPMA

5.38 (dd, 1H). 13C NMR (126 MHz; CDCl3): δ 149.3, 138.2, 135.0, 127.9, 120.9, 116.0. Synthesis of TBDMS−Pyrenemethanol. 2-Pyrenemethanol was synthesized from pyrene-1-carboxaldehyde through reduction with NaBH4 using previously reported methods.26 0.37 g (1.61 mmol) of 2pyrenemethanol, 0.24 g (3.53 mmol) of imidazole, and 0.26 g (1.69 mmol) of tert-butyldimethylchlorosilane were dissolved in 20 mL of dichloromethane (DCM), and the reaction was allowed to stir overnight. The mixture was extracted with water two times and brine once and dried with MgSO4. DCM was removed under reduced pressure to yield 0.41 g (73%) of a brown solid. 1H NMR (300 MHz, CDCl3): δ 8.14 (m, 9H), 5.48 (s, 2H), 0.99 (s, 9H), 0.16 (s, 6H). 13C NMR δ: 134.54, 131.32, 130.81, 130.62, 128.03, 127.85, 127.52, 127.32, 126.94, 125.95, 125.79, 125.24, 125.00, 124.81, 124.66, 122.97, 63.82, 26.02, 18.49, −5.08. Synthesis of TBDMS−Azobenzene. 1.00 g (5.04 mmol) of 4(phenylazo)phenol, 0.76 g (11.10 mmol) of imidazole, and 0.80 g (5.29 mmol) of tert-butyldimethylchlorosilane were dissolved in 40 mL of dichloromethane (DCM), and the reaction was allowed to stir overnight. The mixture was extracted with water two times and brine once and dried with MgSO4. DCM was removed under reduced pressure to yield 1.03 g (65%) of a dark red oil. 1H NMR (300 MHz, CDCl3) δ: 7.86 (m, 4H), 7.47 (d, 3H), 6.96 (d, 2H), 1.01 (s, 9H), 0.25 (s, 6H). 13C NMR δ: 158.62, 152.76, 147.41, 130.36, 129.00, 124.57, 122.55, 120.46, 25.64, 18.27, −4.36. Synthesis of TBDMS−Tyramine. 4.00 g (29.2 mmol) of tyramine hydrochloride, 4.37 g (64.2 mmol) of imidazole, and 4.63 g (30.7 mmol) of tert-butyldimethylchlorosilane were dissolved in 100 mL of dichloromethane (DCM), and the reaction was allowed to stir overnight. The mixture was extracted with water two times and brine. The brown liquid was dried with MgSO4, and DCM was removed under reduced pressure to yield 4.36 g (59%) of an off-white solid. 1H NMR (300 MHz, CDCl3) δ: 7.06 (d, 2H), 6.77 (d, 2H), 3.03 (t, 2H), 2.81 (t, 2H), 0.97 (s, 9H), 0.18 (s, 6H). 13C NMR δ: 130.79, 129.68, 120.19, 117.92, 42.61, 36.58, 25.66, 18.16, −4.45. Synthesis of 4-(Phenyldiazenyl)Phenyl Sulfurofluoridate. 4(Phenyldiazenyl)phenol (1.0 g, 5.04 mmol) and trimethylamine (0.61 g, 6.05 mmol) were dissolved in DCM (200 mL) in a 500 mL roundbottom flask equipped with a stir bar. The headspace of the flask was evacuated under light vacuum and filled with sulfuryl fluoride gas from a balloon. The reaction was allowed to stir at room temperature for 12 h. The reaction was washed sequentially with 100 mL of 0.6 M HCl, 200 mL of H2O two times, and 200 mL of brine and then dried over Na2SO4. DCM was evaporated under reduced pressure. Purification through flash chromatography yielded 1.34 g (95%) of an orange powder. 19F NMR (300 MHz, CDCl3) δ: 38.17. 1H NMR (500 MHz,

2. MATERIALS AND METHODS Materials. Silicon wafers (orientation , native oxide) were purchased from University Wafer, and quartz substrates were purchased from AdValue Technologies. Acetonitrile was distilled from CaH2, and all other solvents were purified and dried via a solvent purification system (MB-SPS). TBDMS−Disperse red 1 was synthesized following previously reported methods.14 All other reagents were purchased from Sigma-Aldrich, TCI, or VWR and used as received unless noted. All NMR spectra were recorded in CDCl3 unless otherwise noted using a 300 MHz instrument. Synthesis of 4-Vinylphenyl Sulfofluoridate. 4-Vinylphenol. 4Acetoxystyrene (10.00 g, 61 mmol) was diluted with THF (100 mL) in a round-bottom flask equipped with a magnetic stir bar and then chilled in an ice bath. NaOH (6.02 g, 150 mmol, 2.5 equiv) was dissolved in 30 mL of water and then added dropwise over 5 min to the vigorously stirred solution of 4-acetoxystyrene. After 4 h, 30 mL of 1.5 M HCl chilled in an ice bath was added dropwise over 15 min to the cold, yellow reaction mixture, which was then further diluted with 200 mL of cold water. The mixture was extracted with diethyl ether (2 × 200 mL). The organic phase was collected and dried with MgSO4, and the majority of the solvent was removed under reduced pressure. Ethanol (100 mL, anhydrous) was then added to the product solution, and the majority of the solvent was again evaporated to remove remaining THF and acetic acid. (Note: some ethanol (ca. 10 mL) was allowed to remain to prevent autoinitiation of the monomer.) The yield, as determined by NMR spectroscopy, was quantitative (7.32 g), and the product was immediately used in the next step without any further purification or storage. 1H NMR (500 MHz, DMSO-d6, δ [ppm]): 9.52 (s, 1H), 7.31−7.25 (m, 2H), 6.76−6.70 (m, 2H), 6.61 (dd, 1H), 5.58 (dd, 1H), 5.04 (dd, 1H). 4-Vinylphenyl Sulfofluoridate. 4-Vinylphenol (10 g, 51.6 mmol) and triethylamine (20.0 mL, 144 mmol) were dissolved in dichloromethane (120 mL). The reaction flask was sealed with a rubber stopper, and most air inside the flask was gently removed by vacuum. Sulfuryl fluoride gas was introduced through a balloon with a needle, and the reaction was stirred vigorously at room temperature overnight. The solvent was removed under reduced pressure. Ethyl acetate (100 mL) was then added, and the mixture was washed with a saturated solution of Na2CO3 and brine. The organic layers were combined and dried over MgSO4. The solvent was removed under reduced pressure to give 5.7 g (52%) as a light brown oil. Before use in polymerization, the compound was flushed through a plug of neutral alumina with DCM to remove any residual impurities. 19F NMR (500 MHz, DMSO-d6): δ/ppm = +38.4. 1H NMR (300 MHz, DMSO-d6): δ 7.53−7.50 (m, 2H), 7.33−7.30 (m, 2H), 6.74 (dd, 1H), 5.80 (dd, 1H), B


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Macromolecules Scheme 2. Fabrication of TBDMS−Tyramine Brushes from the Aminolysis of Poly(PFPA)

Scheme 3. Synthetic Scheme for SuFEx Postpolymerization Modification on Aryl Sulfonyl Fluoride, Aryl Fluorosulfonate, and Alkyl Sulfonyl Fluoride Polymer Brushes

CDCl3) δ: 8.02, 8.04 (d, 2H), 7.93, 7.94 (d 2H), 7.49−7.56 (m, 5H). 13 C NMR δ: 152.30, 151.93, 151.08, 131.80, 129.21, 124.74, 123.13, 121.69. Aromatic Sulfonyl Fluoride Brush Fabrication. Silicon dioxide and quartz substrates functionalized with PEFABLOC SC (4-(2aminoethyl)benzenesulfonyl fluoride hydrochloride) (PEFA) were prepared from postpolymerization modification of poly(pentafluorophenyl acrylate) (poly(PFPA)) brushes (Scheme 1A). Poly(PFPA) brushes were prepared from freshly synthesized PFPA and substrates functionalized with an AIBN−silane initiator using previously reported methods.27 Once fabricated, poly(PFPA) brushes were placed in a 15 mM solution of PEFABLOC SC in anhydrous DMF with 30 mM trimethylamine for 20 min.15 The slides were subsequently removed from the solution, washed with DMF, and dried under a stream of nitrogen. Upon functionalization, the brushes were characterized via spectroscopic ellipsometry and FTIR. Aromatic Fluorosulfonate Brush Fabrication. Poly(4-vinylphenyl sulfofluoridate) (VPSF) brushes on both silicon dioxide wafers and quartz were prepared via surface-initiated free radical polymerization (Scheme 1B). VPSF was degassed with argon at 0 °C and transferred to an inert atmosphere glovebox (MBraun Labstar) along with a substrate functionalized with an AIBN−silane initiator. The substrate was then placed on a microscope slide (Fisherbrand precleaned microscope slide), and 300 μL of VPSF was pipetted onto the substrate. Another microscope slide was then placed on top of the substrate and clamped with four binder clips. A hand-held UV lamp was then placed over the substrate (350 nm, 4.15 W/cm2) and

allowed to polymerize for 45 min. Once the polymerization was complete, the substrate was removed, washed with tetrahydrofuran (THF), and dried under a stream of nitrogen. Alkyl Sulfonyl Fluoride Brush Fabrication. 3-(Fluorosulfonyl)propyl methacrylate was synthesized using previously reported methods.14 Brushes were prepared using the same conditions as used for poly(VPSF) brush fabrication (Scheme 1C). TBDMS−Tyramine Brush Fabrication. Poly(PFPA) brushes were placed in a 40 mM solution of TBDMS−tyramine in anhydrous DMF with 80 mM trimethylamine for 20 min (Scheme 2). The slides were subsequently removed from the solution, washed with DMF, and dried under a stream of nitrogen. Upon functionalization, the brushes were characterized via spectroscopic ellipsometry and FTIR. UV/Vis Kinetic Traces. Sulfonyl fluoride and fluorosulfonate brushes on quartz substrates were measured on a UV−vis spectrometer using a slide holder with a sample window area of 19.6 mm2. The substrates were then immersed in a solution of 0.1 mmol TBDMS (TBDMS−azobenzene, TBDMS−pyrenemethanol, and TBDMS-Disperse red 1) with 0.02 mmol of base or 0.002 mmol of [HFH−] in anhydrous MeCN for a specified amount of time. The slides were then rinsed with MeCN and dried under a stream of nitrogen, and the spectra were recorded. The rate of reaction was collected by monitoring the appearance and intensity of absorbance peaks in the spectra over time (λmax = 485 nm for TBDMS-Disperse red 1, 346 nm for TBDMS−pyrenemethanol, and 323 nm for TBDMS−azobenzene). A pseudo-first-order kinetic plot was genC


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Macromolecules

Figure 1. (top) Pseudo-first-order kinetic plots for (A) VPSF, (B) FSPMA, and (C) PEFA polymer brushes reacting with TBDMS−azobenzene and TBDMS−Disperse red 1 catalyzed by DBU and TBD. (bottom) Pseudo-first-order rate constants for TBDMS−Disperse Red 1 and TBDMS− azobenzene for each brush system catalyzed by TBD and DBU.

Figure 2. Absorbance spectra for (A) VPSF catalyzed by TBD, (B) VPSF catalyzed by DBU, (C) FSPMA catalyzed by TBD, (D) FSPMA catalyzed by DBU, (E) PEFA catalyzed by TBD, and (F) PEFA catalyzed by DBU.

D


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Macromolecules Table 1. Thicknesses (in nm) before and after PPM for Each Brush System with TBD and DBU VPSF azobenzene Disperse red 1 pyrenemethanol

before after before after before after

FSPMA

PEFA

TBD

DBU

TBD

DBU

TBD

DBU

52.3 76.8 47.3 66.7 48.0 88.6

46.1 66.0 40.7 69.9 49.1 92.1

107.0 155.9 107.5 146.8 101.9 169.6

105.9 153.1 98.5 143.5 101.7 154.2

99.5 121.0 95.3 121.1 93.9 126.8

91.6 135.6 102.3 135.7 94.5 125.1

erated from the linear portion of the absorbance plot and fit to obtain rate constants. Characterization. Thicknesses were measured using a M-2000 spectroscopic ellipsometer (J.A. Woollam Co., Inc.) with a white light source at three angles of incidence (65°, 70°, and 75°) to the silicon wafer normal. The data were modeled using a Cauchy layer, fitting thickness, extinction coefficient, and refractive index of the polymer brush layer. For the in-situ measurements of the TBDMS−tyramine, a surface outfitted with a liquid cell from J.A. Woollam (0.5 mL) was used, and the solvent of interest was injected into the cell. The data were fit using a Cauchy model, fitting thickness, extinction coefficient, and refractive index with the ambient environment defined as the optical properties of the solvent, which was measured prior to the experiment. For MeCN, the refractive index at 632.8 nm and 25 °C was 1.3452, and the refractive index of water at 632.8 nm and 25 °C was 1.3389 under our experimental conditions. Infrared spectra were taken using a Nicolet model 6700 with a grazing angle attenuated total reflectance accessory at 64 scans with a 4 cm−1 resolution.

collected kinetics traces (Figure S1), pseudo-first-order reaction rates were calculated (Figure 1). With TBDMS−Disperse Red 1 and TBDMS−azobenzene, pseudo-first-order rate constants were easily calculated from the reaction trace, as the absorbance increased continuously until eventually plateauing. However, with the benzyl derivative (TBDMS−pyrenemethanol), the absorbance at 346 nm constantly varied in all brush systems with both TBD and DBU, increasing and decreasing between each spectrum. Additionally, the absorbance of TBDMS− pyrenemethanol in each brush system was observed to be lower than that of the other two silyl ether reactants (Figure 2), the result of which is a lower concentration of pyrene through PPM. This low absorbance along with constant fluctuation in the absorbance intensity with reaction time is a result of the αhydrogens adjacent to the pyrene ring, which are susceptible to attack by either the basic catalyst, fluoride anion, or adventitious water, the consequence of which is the formation of sulfonic acid derivative (Scheme S1).21 From Figure 1, it is clear that the reaction rates show a dependence in catalyst choice, silyl ether substitution, and brush system. The reactivity of the sulfur fluoride derivative plays a large role in reaction rate, with the trend following aromatic sulfonyl fluoride > alkyl sulfonyl fluoride > aromatic fluorosulfonate with both the aromatic and aliphatic silyl ethers. Also, throughout each brush system, the aryl silyl ether consistently had a slower reaction rate than alkyl silyl ether. Finally, the reactions with TBD as a catalyst were always at least 1 order of magnitude faster than DBU, which correlates with previous studies performed by our group with FSPMA brushes.14 While the exact mechanism for the SuFEx reaction still remains unknown, several observations from these studies are important to note. First, TBD is a stronger base than DBU (pKb of 26.03 vs 24.34 in MeCN) as well as more nucleophilic serving as a bifunctional catalyst in reactions requiring nucleophilic attack, such as the ring-opening of lactones.28,29 This greater basicity as well as increased nucleophilicity likely contributes to the faster reaction kinetics.30−32 The role of basicity has also been shown previously with weaker bases such as 4-(dimethylamino)pyridine (DMAP), which were observed to have no catalytic activity toward SuFEx.13 Additionally, in the different brush systems, the different rates may be a result of electronics of the sulfonyl fluoride/fluorosulfonate brush, with the more electron-deficient PEFA brushes reacting faster than the less electron-withdrawn FSPMA and VPSF brushes. It has been previously shown with the strong electron-withdrawing nonaflyl fluoride that DBU readily reacts with the sulfonyl fluoride and displaces the fluorine, as evidenced by the in-situ formation of DBU·(HF)n, resulting in the conversion of an primary or secondary alcohol to an inverted alkyl fluoride33,34 These studies illustrate the importance of catalyst basicity as well as the role of electronics of the sulfonyl fluoride/

3. RESULTS AND DISCUSSION Polymer brushes were synthesized using free radical polymerization of azo-based silane initiator monolayers on both quartz and silicon dioxide surfaces.27 To fabricate aryl sulfonyl fluoride brushes, poly(pentafluorophenyl acrylate) (p(PFPA)) brushes were first synthesized and reacted with PEFA, a commercially available amine-bearing sulfonyl fluoride (Scheme 1A). Aryl fluorosulfonate brushes were polymerized directly from 4vinylphenyl sulfofluoridate (VPSF) using photoinitiated polymerization, yielding poly(VPSF) brushes (Scheme 1B). Alkyl sulfonyl fluoride brushes were directly polymerized from 3(fluorosulfonyl)propyl methacrylate (FSPMA) which provides poly(FSPMA) brushes (Scheme 1C).14 The three different brush platforms were each reacted with three tert-butyldimethylsilyl (TBDMS) protected reactants: TBDMS−pyrenemethanol, a benzyl derivative; TBDMS−azobenzene, an aryl derivative; and TBDMS−Disperse red 1, an alkyl derivative (Scheme 3). These three molecules were chosen for PPM to investigate the reaction scope of SuFEx on the surface. It has been shown previously that more electron-withdrawn species can form unstable sulfonate linkages, resulting in either substitution/elimination or hydrolysis of the adduct. Using these three TBDMS derivatives, we are able to investigate and characterize the stability of the formed sulfonate/sulfate linkages. Three different catalysts were examined for each reaction pair: triazabicylcodecene (TBD), diazabicycloundec-7ene (DBU), and tetrabutylammonium bifluoride (TBABF). These catalysts are all known to facilitate SuFEx, but vary in regard to basicity, which may lead to differences in the mechanistic course of action. For each brush system, pseudo-first-order reaction rates were calculated with each guanidine base and each silyl ether. A UV− vis spectrophotometer equipped with a custom-made slide holder was used to monitor reaction kinetics. From the E


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Macromolecules fluorosulfonate brush system. Our observed reaction rates along with the previous studies suggest that the strong base attacks the sulfonyl fluoride/fluorosulfonate moiety to either displace the fluorine or serve as a fluorine shuttle that goes on to further react with the silyl ether. To further confirm the successful reactions of TBDMS− Disperse Red 1 and TBDMS−azobenzene as well confirm the formation of sulfonic acid derivatives with TBDMS− pyrenemethanol, spectroscopic ellipsometry and FTIR were used to monitor changes in film thickness and surface chemistry. Polymer brushes on silicon dioxide surfaces were synthesized and reacted with the three TBDMS derivatives with TBD and DBU for the amount time specified by the kinetic traces. The polymer brush thickness was measured both before and after reaction, and these results are summarized in Table 1. In each brush system, an increase in thickness is observed after PPM. This is expected in the cases of TBDMS− azobenzene and TBDMS−Disperse red 1, since the molecular weight of the sides chains increases upon reaction with the chromophore.35 However, when TBDMS−pyrenemethanol was used, we still observed a thickness increase, even though the formation of the acid reduces the side-chain molecular weight. Here, it is likely that the strong polyelectrolyte brush leads to highly stretched conformation.36 The FTIR spectrum for the DBU-catalyzed reaction is shown in Figure 3, with the aromatic sulfonyl fluoride brush (PEFA) in Figure 3A, the aromatic fluorosulfonate brush (VPSF) in Figure 3B, and the alkyl sulfonyl fluoride (FSPMA) brush in Figure 3C. FTIR spectra of the TBD catalyzed reactions are also included in Figure S2. In the PEFA system, two characteristic stretches are observed at 1405 and 1214 cm−1, which are assigned to the symmetric and asymmetric SO stretches in the sulfonyl fluoride. Upon reaction with the silyl ether derivatives in the presence of DBU, these peaks disappear and new peaks are observed at 1373 and 1198 cm−1 in the TBDMS−azobenzene spectrum, corresponding to the formed sulfonate during the reaction. In the case of the TBDMS−pyrenemethanol, two new stretches are observed at 1035 and 1010 cm−1, which are characteristic of tosic acid (Figure S3). This provides further evidence of the inherent instability of this linkage. In the TBDMS−Disperse red 1 spectrum, stretches indicative of the formed sulfonate (1338 and 1191 cm−1) as well as tosic acid (1035 and 1010 cm−1) are observed, which points to a mixture of product formation and hydrolysis. This is further supported by the lower absorbance values for TBDMS−Disperse red 1 versus TBDMS−azobenzene in the absorbance spectra (Figure 2), indicating less dye per unit area on the PEFA brushes. This is evidence for a lower stability of the formed alkyl sulfonate linkage, which indicates a mixture of product formation and a small amount of hydrolysis. In Figure 3B, the VPSF brushes have characteristic stretches at 1451 and 1233 cm−1 , corresponding to the asymmetric and symmetric SO peaks, respectively. After reacting with DBU, the TBDMS− azobenzene spectrum has new stretches at 1407 and 1214 cm−1, respectively. These stretches are a result of the formation of a sulfate linkage and provide evidence for a complete reaction with the brush surface. With the TBDMS− pyrenemethanol, a new peak at 1043 and 1016 cm−1 appears, corresponding to the formation of the hydrogen sulfate derivative on the surface. Again, the TBDMS−Disperse red 1 spectrum shows a mixture of both sulfonate formation (1422 and 1207 cm−1) and hydrogen sulfate formation (1043 and

Figure 3. FTIR spectra for (A) PEFA, (B) VPSF, and (C) FSPMA brushes catalyzed by DBU in MeCN.

1016 cm−1). Finally, in Figure 3C, the FSPMA brushes have characteristic stretches at 1401 and 1202 cm−1 due to the SO bond, which is replaced upon reaction with a peak at 1373 and 1198 cm−1 when TBDMS−azobenzene is used. Upon reaction with TBDMS−pyrenemethanol, a new peak at 1038 and 1012 cm−1 appears, corresponding to degradation of the sulfonate linkage, and as with the other brush systems, there is a mixture in the TBDMS−Disperse red 1 spectrum with peaks at 1338, 1189, 1038, and 1012 cm−1. Reaction kinetics were also investigated using tetrabutylammonium bifluoride, a catalyst that was recently shown to be more efficient (in terms of catalyst loading and reaction kinetics) for SuFEx polymerization.21,23 The catalyst is also much milder in terms of basicity and nucleophilicity, allowing for polymerizations of high molecular weight backbones (alkyl sulfonyl fluorides coupled with aromatic silyl ethers) that were previously shown to be unstable in the presence of the other F


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Macromolecules strong base catalysts.37,38 Therefore, we hypothesized that the milder bifluoride catalyst could expand the utility of SuFEx on the surface, allowing for greater reactant choice and substrate scope, such as the ability to use TBDMS derivatives that are otherwise prone to deprotonation of the α-hydrogen.39 Solutions of TBDMS−azobenzene and TBDMS−pyrenemethanol (50 mM) with 2 mol % TBABF were prepared in acetonitrile, and kinetics were recorded for the PEFA brush on quartz. With TBDMS−azobenzene, the reaction was extremely slow (Figure 4A) when compared to the same system catalyzed

slight increase in thickness before and after reaction, the lack of change in the FTIR spectra provides evidence that the elevated temperature does not significantly increase the reaction kinetics of surface reactions catalyzed by TBABF. The reaction is still quite slow when compared to DBU and TBD catalysts, and increasing the rate of the reaction on the surface further may require higher catalyst loading than what was previously reported in successful solution studies (2%). These results indicate that at least for these surface reactions bifluoride catalysts are not superior to the strong guanidine bases, although a variety of bifluoride catalysts have not yet been explored. We also were interested in reversing the surface-bound reaction partner and first immobilizing silyl ether containing brushes and then subjecting them to SuFEx PPM. Silyl ether containing polymer brushes were fabricated through aminolysis with TBDMS−tyramine on poly(PFPA) brushes (Scheme 2). These brushes were reacted with 4-(phenyldiazenyl)phenyl sulfurofluoridate (50 mM in MeCN, 20 mol % TBD or DBU) for 3 days to ensure a complete reaction. However, even after long reaction times, there was no difference in either the IR spectra or any noticeable thickness changes for either substrate, which indicates no reaction (Table 2 and Figure 5A). This was also repeated on quartz slides with azobenzene via UV−vis spectroscopy (Figure 5B). Table 2. Thickness (in nm) of TBDMS−Tyramine Brushes Reacted with 4-(Phenyldiazenyl)phenyl Sulfurofluoridate and Catalyzed by TBD and DBU DBU TBD

TBDMS−tyramine

reacted

51.9 50.7

52.5 55.9

In the absorbance spectra, there is an absorbance peak at 280 nm, corresponding to the aromatic ring in tyramine. However, no azobenzene (λmax = 323 nm) was detected on the surface, which matches the FTIR and thickness data. This reaction was repeated with several other silyl ether containing polymer brush substrates and sulfonyl fluoride/fluorosulfonate reactants, and in every case, no reaction was observed. This result was surprising, especially when considering the success of the reactions with the diverse sulfonyl fluoride brush systems; however, this result may provide more evidence into the underlying mechanism of the reaction. To first test the accessibility of the silyl ether groups in the reaction environment, in-situ spectroscopic ellipsometry was used to measure the swelling behavior of the TBDMS−tyramine brush in MeCN. The data (Table S2) show an increase in thickness and a decrease in refractive index of the brush layer when immersed in MeCN. The refractive index decreases due to an increased volume of MeCN in the brush, which has a lower refractive index than the polymer film, indicating swelling of the polymer brush layer. In contrast, swelling was also measured in water to confirm the lack of brush swelling in an unfavorable solvent, and in this case, no swelling of the film occurred. Furthermore, in these surface reactions, there is a large concentration differential between reactants on the surface (nanomolar) and reactants in solution (millimolar). When the silyl ether has a much lower concentration than the sulfonyl fluoride/fluorosulfonate and base, no reaction occurs. However, when the sulfonyl fluoride/fluorosulfonate is first immobilized on the surface in lower concentration, the SuFEx reaction

Figure 4. (A) Kinetic trace for a PEFA brush reacted with TBDMS− azobenzene catalyzed by 2% TBABF in MeCN. (B) Absorbance spectra of PEFA brushes reacted with TBDMS−azobenzene and TBDMS−pyrene methanol catalyzed by 2% TBABF in MeCN.

by TBD or DBU, taking ∼500 h to reach full conversion. Additionally, the reaction with TBDMS−pyrenemethanol, like with DBU and TBD, resulted in a very low concentration of pyrene methanol on the surface, as evidenced by the absorbance spectra (Figure 4B). These results suggest hydrolysis of the benzyl substituent even in the presence of a milder catalyst. The use of a TBABF as a catalyst was further studied at elevated temperatures, as the polymerizations reported by Gao et al. using bifluoride based catalysts were all carried out at 130 °C. PEFA brushes on silicon dioxide wafers were placed in 50 mM solutions of TBDMS−azobenzene in N-methyl-2pyrrolidone (NMP) at both 130 and 25 °C for 3 h. After 3 h, the slides were removed, rinsed with NMP, and characterized via spectroscopic ellipsometry and FTIR. These results are summarized in Table S1 and Figure S4. In the FTIR, stretches at 1405 and 1214 cm−1 characteristic of PEFA starting material were still apparent in both cases. Although there was a very G


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increase the rate of reaction or allow for the formation of more unstable products in brush systems. Using this collected information, surface derivatization can be optimized for use in a wide array of applications to ensure full functionalization with high reliability and consistency. Moreover, information gathered from individual experiments may provide critical evidence in elucidating the mechanism of SuFEx on the surface in order to better understand and utilize this chemistry in the near future.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.7b02372. Kinetic traces, additional substrate characterization, and schemes (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail [email protected] (J.L.). ORCID

Saadyah Averick: 0000-0003-4775-2317 Jason Locklin: 0000-0001-9272-2403 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors acknowledge the National Science Foundation GRFP (1011RH252141) for funding this work.

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Figure 5. (A) FTIR and (B) absorbance spectra of TBDMS−tyramine brushes reacted with 4-(phenyldiazenyl)phenyl sulfurofluoridate catalyzed by DBU and TBD.

REFERENCES

(1) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem., Int. Ed. 2001, 40, 2004−2021. (2) Arnold, R. M.; Huddleston, N. E.; Locklin, J. Utilizing click chemistry to design functional interfaces through post-polymerization modification. J. Mater. Chem. 2012, 22, 19357−19365. (3) Arnold, R. M.; Patton, D. L.; Popik, V. V.; Locklin, J. A Dynamic Duo: Pairing Click Chemistry and Postpolymerization Modification To Design Complex Surfaces. Acc. Chem. Res. 2014, 47, 2999−3008. (4) Espeel, P.; Du Prez, F. E. Click”-Inspired Chemistry in Macromolecular Science: Matching Recent Progress and User Expectations. Macromolecules 2015, 48, 2−14. (5) Kolb, H. C.; Sharpless, K. B. The growing impact of click chemistry on drug discovery. Drug Discovery Today 2003, 8, 1128− 1137. (6) Nwe, K.; Brechbiel, M. W. Growing Applications of “Click Chemistry” for Bioconjugation in Contemporary Biomedical Research. Cancer Biother. Radiopharm. 2009, 24, 289−302. (7) Hein, C. D.; Liu, X.-M.; Wang, D. Click Chemistry, a Powerful Tool for Pharmaceutical Sciences. Pharm. Res. 2008, 25, 2216−2230. (8) Rodionov, V. O.; Fokin, V. V.; Finn, M. G. Mechanism of the Ligand-Free CuI-Catalyzed Azide−Alkyne Cycloaddition Reaction. Angew. Chem., Int. Ed. 2005, 44, 2210−2215. (9) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. Angew. Chem., Int. Ed. 2002, 41, 2596−2599. (10) Barner-Kowollik, C.; Du Prez, F. E.; Espeel, P.; Hawker, C. J.; Junkers, T.; Schlaad, H.; Van Camp, W. Clicking” Polymers or Just Efficient Linking: What Is the Difference? Angew. Chem., Int. Ed. 2011, 50, 60−62.

proceeds in every case. To test the effect of concentration on the surface reaction, tyramine−TBDMS brushes were immersed in solutions containing different concentrations of 4(phenyldiazenyl)phenyl sulfurofluoridate (0.5 mM and 5 μm; 20 mol % DBU or TBD in MeCN). After letting the reaction proceed for 3 days, no changes in the FTIR spectra (Figure S5) or film thickness (Table S2) were observed. The lack of reaction may be a result of several possibilities, such as deprotection of the silyl ether by excess base,40 steric hindrance in the brush system, or the reaction needing stoichiometric reactant equivalencies in order to proceed.

4. CONCLUSION In this work, we have extensively explored the scope and utility of SuFEx chemistry as a method for surface derivatization. Using different bases, reactants, and brush systems, kinetic rates, product identification, and possible side reactions were reported to better understand the advantages and limitations of SuFEx on the surface. We show that product stability is highly dependent on the nature of the TBDMS derivative and that reaction rate is dependent on base selection, with stronger guanidine bases yielding faster reaction rates. Additionally, when exploring other catalysts and brush systems, it was discovered that TBDMS brushes do not undergo surface conjugation, and more acidic catalysts like TBABF do not H


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Macromolecules

(31) Pratt, R. C.; Lohmeijer, B. G. G.; Long, D. A.; Waymouth, R. M.; Hedrick, J. L. Triazabicyclodecene: A Simple Bifunctional Organocatalyst for Acyl Transfer and Ring-Opening Polymerization of Cyclic Esters. J. Am. Chem. Soc. 2006, 128, 4556−4557. (32) Lohmeijer, B. G. G.; Pratt, R. C.; Leibfarth, F.; Logan, J. W.; Long, D. A.; Dove, A. P.; Nederberg, F.; Choi, J.; Wade, C.; Waymouth, R. M.; Hedrick, J. L. Guanidine and Amidine Organocatalysts for Ring-Opening Polymerization of Cyclic Esters. Macromolecules 2006, 39, 8574−8583. (33) Vorbrüggen, H.; Bennua-Skalmowski, B.; Klar, U. AmineInduced Decomposition of Perfluoroalkanesulfonyl Fluorides. Synthesis 2008, 2008, 1175−1178. (34) Vorbrüggen, H. The Conversion of Primary or Secondary Alcohols with Nonaflyl Fluoride into Their Corresponding Inverted Fluorides. Synthesis 2008, 2008, 1165−1174. (35) Murata, H.; Prucker, O.; Rühe, J. Synthesis of Functionalized Polymer Monolayers from Active Ester Brushes. Macromolecules 2007, 40, 5497−5503. (36) Seidel, C. Strongly Stretched Polyelectrolyte Brushes. Macromolecules 2003, 36, 2536−2543. (37) Subbarao, S. N.; Yun, Y. H.; Kershaw, R.; Dwight, K.; Wold, A. Electrical and optical properties of the system TiO2-xFx. Inorg. Chem. 1979, 18, 488−492. (38) Landini, D.; Maia, A.; Rampoldi, A. Dramatic effect of the specific solvation on the reactivity of quaternary ammonium fluorides and poly(hydrogen fluorides), (HF)n•F−, in media of low polarity. J. Org. Chem. 1989, 54, 328−332. (39) Shirota, Y.; Nagai, T.; Tokura, N. Reactions of alkanesulphonic acid derivatives with organoalkali metal compounds: Formation and reactivity of α-sulphonylcarbanions. Tetrahedron 1969, 25, 3193− 3204. (40) Yeom, C. E.; Kim, H. W.; Lee, S. Y.; Kim, B. M. DBU-mediated mild and chemoselective deprotection of aryl silyl ethers and tandem biaryl ether formation. Synlett 2007, 2007, 0146−0150.

(11) Dong, J.; Krasnova, L.; Finn, M. G.; Sharpless, K. B. Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry. Angew. Chem., Int. Ed. 2014, 53, 9430−9448. (12) Yatvin, J.; Brooks, K.; Locklin, J. SuFEx Click: New Materials from SOxF and Silyl Ethers. Chem. - Eur. J. 2016, 22, 16348−16354. (13) Gembus, V.; Marsais, F.; Levacher, V. An efficient organocatalyzed interconversion of silyl ethers to tosylates using DBU and ptoluenesulfonyl fluoride. Synlett 2008, 2008, 1463−1466. (14) Yatvin, J.; Brooks, K.; Locklin, J. SuFEx on the Surface: A Flexible Platform for Postpolymerization Modification of Polymer Brushes. Angew. Chem., Int. Ed. 2015, 54, 13370−13373. (15) Brooks, K.; Yatvin, J.; McNitt, C. D.; Reese, R. A.; Jung, C.; Popik, V. V.; Locklin, J. Multifunctional Surface Manipulation Using Orthogonal Click Chemistry. Langmuir 2016, 32, 6600−6605. (16) Li, S.; Cohen-Karni, D.; Beringer, L. T.; Wu, C.; Kallick, E.; Edington, H.; Passineau, M. J.; Averick, S. Direct introduction of RSO2F moieties into proteins and protein-polymer conjugation using SuFEx chemistry. Polymer 2016, 99, 7−12. (17) Li, S.; Beringer, L. T.; Chen, S.; Averick, S. Combination of AGET ATRP and SuFEx for post-polymerization chain-end modifications. Polymer 2015, 78, 37−41. (18) Dong, J.; Sharpless, K. B.; Kwisnek, L.; Oakdale, J. S.; Fokin, V. V. SuFEx-Based Synthesis of Polysulfates. Angew. Chem., Int. Ed. 2014, 53, 9466−9470. (19) Oakdale, J. S.; Kwisnek, L.; Fokin, V. V. Selective and Orthogonal Post-Polymerization Modification using Sulfur(VI) Fluoride Exchange (SuFEx) and Copper-Catalyzed Azide−Alkyne Cycloaddition (CuAAC) Reactions. Macromolecules 2016, 49, 4473− 4479. (20) Brendel, J. C.; Martin, L.; Zhang, J.; Perrier, S. SuFEx - A selectively triggered chemistry for fast, efficient and equimolar polymer-polymer coupling reactions. Polym. Chem. 2017, 8, 7475. (21) Gao, B.; Zhang, L.; Zheng, Q.; Zhou, F.; Klivansky, L. M.; Lu, J.; Liu, Y.; Dong, J.; Wu, P.; Sharpless, K. B. Bifluoride-catalysed sulfur(VI) fluoride exchange reaction for the synthesis of polysulfates and polysulfonates. Nat. Chem. 2017, 9, 1083−1088. (22) Li, S.; Wu, P.; Moses, J. E.; Sharpless, K. B. Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF4 Hub. Angew. Chem., Int. Ed. 2017, 56, 2903−2908. (23) Wang, H.; Zhou, F.; Ren, G.; Zheng, Q.; Chen, H.; Gao, B.; Klivansky, L.; Liu, Y.; Wu, B.; Xu, Q.; Lu, J.; Sharpless, K. B.; Wu, P. SuFEx-Based Polysulfonate Formation from Ethenesulfonyl Fluoride− Amine Adducts. Angew. Chem., Int. Ed. 2017, 56, 11203−11208. (24) Brittain, W. J.; Minko, S. A structural definition of polymer brushes. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 3505−3512. (25) Orski, S.; Sheppard, G.; Arnold, R.; Grubbs, J.; Locklin, J. Postpolymerization Modification of Polymer Brushes. In Functional Polymers by Post-Polymerization Modification; Wiley-VCH Verlag GmbH & Co. KGaA: 2012; pp 353−369. (26) Vanjinathan, M.; Lin, H.-C.; Nasar, A. S. Synthesis, Characterization and Photophysical Properties of DCM-Based Light-Harvesting Dendrimers. Macromol. Chem. Phys. 2011, 212, 849−859. (27) Arnold, R. M.; Sheppard, G. R.; Locklin, J. Comparative Aminolysis Kinetics of Different Active Ester Polymer Brush Platforms in Postpolymerization Modification with Primary and Aromatic Amines. Macromolecules 2012, 45, 5444−5450. (28) Kaljurand, I.; Kütt, A.; Sooväli, L.; Rodima, T.; Mäemets, V.; Leito, I.; Koppel, I. A. Extension of the Self-Consistent Spectrophotometric Basicity Scale in Acetonitrile to a Full Span of 28 pKa Units: Unification of Different Basicity Scales. J. Org. Chem. 2005, 70, 1019− 1028. (29) Simón, L.; Goodman, J. M. The Mechanism of TBD-Catalyzed Ring-Opening Polymerization of Cyclic Esters. J. Org. Chem. 2007, 72, 9656−9662. (30) Kiesewetter, M. K.; Scholten, M. D.; Kirn, N.; Weber, R. L.; Hedrick, J. L.; Waymouth, R. M. Cyclic Guanidine Organic Catalysts: What Is Magic About Triazabicyclodecene? J. Org. Chem. 2009, 74, 9490−9496. I


SuFEx Postpolymerization Modification Kinetics and Reactivity in

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