Synthesis and Topological Trapping of Cyclic Poly(alkylene phosphates)

Nov 17, 2014 - monomers has proven a versatile strategy for the synthesis of well-defined poly(esters),2 poly(carbonates),2,4 poly-. (siloxanes),5−7...
0 downloads 0 Views 1MB Size
Download PDF
Article pubs.acs.org/Macromolecules

Synthesis and Topological Trapping of Cyclic Poly(alkylene phosphates) Tyler S. Stukenbroeker, Diego Solis-Ibarra, and Robert M. Waymouth* Department of Chemistry, Stanford University, Stanford, California 94305, United States S Supporting Information *

ABSTRACT: The zwitterionic ring-opening polymerization of 2isopropoxy-2-oxo-1,3,2-dioxaphospholane (iPP) with N-heterocyclic carbenes (NHC) generates poly(alkylene phosphate)s with molecular weights of Mn = 55000−202000 Da. MALDI-TOF mass spectrometry provided clear evidence for cyclic poly(alkylene phosphate)s (poly(iPP)) for lower molecular weight fractions (m/z ≤ 3000). The cyclic topology of the higher molecular weight fractions was inferred by trapping of poly(iPP) in cross-linked 2-hydroxyethyl methacrylate (HEMA) hydrogels. Cross-linked HEMA hydrogels were generated in the presence of a high molecular weight (Mn = 202000 Da) poly(iPP) generated from the zwitterionic ring-opening polymerization of iPP with the NHC 1,3diisopropyl-4,5-dimethylimidazol-2-ylidene 2. Extraction of the resulting gel with methanol for 11 days revealed that 36% of the poly(iPP) was retained in the gel, whereas a linear poly(iPP) was completely extracted under similar conditions. The retention of the poly(iPP)s in the gels is attributed to topological trapping of the cyclic poly(iPP) in the cross-linked network.

■

other classes of monomers11 to generate cyclic polymers,14−18 we report herein the zwitterionic ring-opening polymerization of cyclic phosphate monomers to macrocyclic poly(alkylene phosphates) and their entrapment in cross-linked hydrogels. The ring-opening polymerization of cyclic phosphates with metal alkoxide catalysts as a strategy to generate poly(alkylene phosphates) was investigated extensively by Penzcek.19−21 Poly(alkylene phosphates), which share the phosphoester backbone of polynucleic acids, are biodegradable and biocompatible.22 These attributes have engendered considerable interest as biomedical materials.23−26 The organocatalytic ring-opening polymerization of cyclic phosphates was recently investigated by Iwasaki,8 Jérôme,9 Wooley,10,27 and others28 utilizing the guanidine 1,5,7-triazabicyclo[4.4.0]undec-5-ene (TBD), the amidine 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or a combination of DBU and a thiourea as catalysts. For the generation of linear poly(alkylene phosphates), the DBU/TU system was observed to exhibit the highest level of control9 and, in analogy to that proposed for the ring-opening polymerization of lactones,2 was proposed to occur by a combination of H-bond activation of the cyclic phosphate by the thiourea and general-base activation of the alcohol by DBU.9 The zwitterionic ring-opening polymerization11 of cyclic phosphates in the absence of alcohol initiators would require a

INTRODUCTION

Organocatalytic ring-opening polymerization1−3 of cyclic monomers has proven a versatile strategy for the synthesis of well-defined poly(esters), 2 poly(carbonates), 2,4 poly(siloxanes),5−7 and poly(alkylene phosphates).8−10 Organic catalysts can mediate ring-opening by a variety of mechanisms, including acid-catalysis, H-bonding catalysis, general base catalysis, and nucleophilic pathways.1,2 Nucleophiles can mediate the ring-opening polymerization of lactones or carbosiloxanes by a zwitterionic ring-opening polymerization mechanism to generate cyclic polyesters or cyclic poly(carbosiloxanes) (Figure 1).2,6,11 As part of our interest in extending zwitterionic12,13 ring-opening polymerization with

Received: August 26, 2014 Revised: October 30, 2014

Figure 1. Zwitterionic ring-opening polymerization of iPP. © XXXX American Chemical Society

A

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

Table 1. Representative Polymerizations of iPPa entry

[iPP]0 (M)

catalyst

catalyst conc (M)

1 2 3 4 5 6 7c 8d

1.0 1.0 0.7 1.0 1.0 1.0 2.0 neat

2 2 2 1 1 3 DBU/TU TBD

0.020 0.020 0.008 0.020 0.010 0.028 0.10 1.0e

initiator

initiator conc (M)

BnOH

0.010

EtOH BnOH

0.020 1.0e

solvent

time (min)

conversion (%)

Mnb

Mw/Mnb

THF THF PhMe THF THF THF PhMe

2 2 1 10 12 16 h 165 20

78 89 65 27 90 0 82 64

202000 113000 80000 55000 23000

1.25 1.05 1.14 1.19 1.08

16000 11000

1.10 1.44

a

Carried out at ambient T, except where noted, DBU = 1,8-diazabicycloundec-7-ene, TU = 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea, TBD = triazabicyclodecene. bDetermined by light scattering. cReaction conducted at 0 °C. dBecame too viscous for stirring. eMol percent relative to initial monomer concentration.

nucleophilic mechanism for phosphoester transesterification. Nucleophilic transesterification mechanisms at phosphorus centers are known and have been invoked for phosphoryl transfer mediated by enzymes such as the histidine kinases and nucleoside diphosphate kinases (NDPK).29 Herein we report that N-heterocyclic carbenes30 can mediate the zwitterionic ring-opening polymerization of 2-isopropoxy-2-oxo-1,3,2-dioxaphospholane-based (iPP) to generate cyclic poly(alkylene phosphates). We also demonstrate that the cyclic polymers poly(iPP) can be entrapped31,32 in poly(HEMA) hydrogels (HEMA = hydroxyethyl methacrylate) to generate novel double-network hydrogels.33,34

■

RESULTS AND DISCUSSION The zwitterionic ring-opening polymerization of the isopropoxy phospholane iPP8 with N-heterocyclic carbenes (NHCs) 1,3,4,5-tetramethylimidazol-2-ylidene 1 and 1,3-diisopropyl4,5-dimethylimidazol-2-ylidene 2 in the absence of alcohol initiators was rapid, reaching high conversion within minutes to afford clear, amorphous polymers (Table 1, runs 1−5, see also Table S1, Supporting Information). The less nucleophilic carbene 3 (IMes) showed no conversion over the course of several hours (Table 1, entry 6). Analysis of the reaction mixtures by 1H NMR indicated conversion to polymer with no side products and no signals attributable to end groups. MALDI-TOF MS of the poly(iPP) generated with carbene 2 (Table 1, entry 2) yielded ions corresponding to the sodium adducts of cyclic oligomers (Figure 2). Minor peaks indicated exchange of an isopropoxy group for a proton. No end group signals were observed in either the 1H or 31P NMR spectra. The molecular weight of poly(iPP) synthesized via ZROP ranged from 50 to 200 kDa with Mw/Mn < 1.3. While the polydispersities are relatively narrow, the molecular weights are significantly higher than that predicted from the initial monomer to NHC ratio ([iPP]0/[NHC]0). The absence of observable end groups by NMR spectroscopy and the MALDI spectrum of Figure 2 indicate that the ring-opening of iPP generates cyclic structures (Figure 1). Because the MALDI only samples lower molecular weight fractions, it is possible that the cyclic poly(iPP)s evident in this spectrum are not representative of the sample (Mn = 113000 Da) but are a minor fraction of cyclic oligomers generated by intramolecular “backbiting”35 of the growing chains. As the topology of the higher molecular weight fractions can be investigated by comparison of the intrinsic viscosity of linear and cyclic chains,36 we sought to generate linear poly(iPP)s with comparable molecular weights to those of entries 1−4 (Table 1).

Figure 2. MALDI-TOF MS spectrum of poly(iPP) synthesized with ZROP (Table 1, entry 2).

A series of linear poly(iPP)s were generated in the presence of alcohol initiators with N-heterocyclic carbene 1 (Table 1, entry 5), with DBU/TU (Table 1, entry 7), with TBD (Table 1, entry 8), and with Sn(Oct)2 or Al(OMe)Et2 (Table S1, Supporting Information). Linear samples generated with carbene 1 or DBU/TU9 afforded poly(iPP) with molecular weights Mw ≤ 25 000 Da with monomodal and narrow molecular weight distributions (Mw/Mn ≤ 1.1). However, efforts to generate linear poly(iPP)s with comparable molecular weights to those generated in the zwitterionic ring-opening polymerization (Table 1, entries 1−4) were unsuccessful, even with the DBU/TU catalyst system.9 Attempts to obtain higher molecular weight poly(iPP) with the DBU/TU catalyst system by increasing the monomer to initiator ratio gave bimodal molecular weight distributions, where the higher molecular weight fraction did not exhibit a UV absorption indicative of the pyrene end group (Table S1, run G, Supporting Information). It is likely that at very low alcohol concentrations (i.e., high M/I ratios), the amidine DBU can mediate a competitive nucleophilic zwitterionic polymerization to generate higher molecular weight cyclic (UV-inactive) chains, as recently observed for the ring-opening of lactide with DBU in the absence of alcohol initiators.37 Attempts to generate higher molecular weight linear poly(iPP) with Sn(Oct)2 or Al(OMe)Et2 afforded only low molecular weight polymers with broad molecular weight distributions (Mw/Mn = 1.37−2.57), which exhibited multiple resonances in the 31P NMR spectra, consistent with extensive P-OR transesterification. B

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

As our efforts to generate linear poly(iPP)s with molecular weights ≥80 kDa were unsuccessful, we could not utilize the relative intrinsic viscosities14,16 to provide evidence for high molecular weight cyclic structures. We thus sought an alternative method to probe the topology of these materials and reasoned that a “topological entrapment” method might provide evidence for the presence of cyclic structures. This approach entails the generation of a cross-linked gel in the presence of both linear and cyclic poly(iPP); if a significant fraction of the cyclic structures were to be threaded by the chains of the network, the cyclic structures would be entrapped by the gel whereas the linear chains would be free to diffuse out of the gel. Semlyen31,32 had previously investigated the entrapment of cyclic polyesters and cyclic PDMS (≤10 kDa) in cross-linked polymers and had measured the entrapment efficiencies with solvent extraction. Hydroxyethyl methacrylate polymers cross-linked with methacrylate functionalized polyethylene glycol served as a convenient cross-linked network that was both chemically compatible with the poly(iPP) and would swell suitably in organic solvent to release the embedded macromolecules. The generation of hydrogels was carried out by radical polymerization (AIBN) of 2-hydroxyethyl methacrylate (HEMA) and a telechelic PEG-diacrylate (1.2 mol %, PEG Mn = 400) in the presence of either linear or cyclic poly(iPP). A small amount of DMF was added to help solvate both components throughout polymerization and minimize polymerization-induced phase separation.38 Methanol was chosen as an extraction solvent as it swells the gel and is an excellent solvent for poly(iPP). Methanol was added to the hydrogels containing cyclic poly(iPP) (Mn = 202 kDa), linear poly(iPP) (Mn = 16 kDa), or linear poly(N,Ndimethylacrylamide) (PDMAA, Mn = 117 kDa) and were left to soak at 25 °C with gentle stirring for varying amounts of time. The methanol was then removed by syringe, and the methanol washings were evaporated, suspended in dichloromethane, then filtered and dried under high vacuum. NMR analysis of the residue extracted from the gels showed it was greater than 95% poly(iPP). Shown in Figure 3 is a graph of the weight percentage of entrapped polymers that were extracted from the methanolswollen HEMA gels as a function of extraction time. As seen in this figure, 98% of the linear poly(iPP) (Mn = 16 kDa) was extracted from the gel after 11 days, whereas only 64% of the poly(iPP) generated from carbene 2 (Mn = 202 kDa) was extracted under similar conditions. These data indicate that 36% of poly(iPP) generated from carbene 2 (Table 1, entry 1) remains entrapped in the gel under conditions where a linear poly(iPP) is completely extracted from the gel. These data are consistent with a cyclic topology for the entrapped poly(iPP)31,32 as cyclic chains that are threaded into the network would be unable to diffuse out of the gel. The observation that high molecular weight linear poly(N,Ndimethylacrylamide) (PDMAA, Mn = 117 kDa) also extracted with ≥90% efficiency after 11 days implies that the lower extraction efficiency (or greater entrapment percentage) of the cyclic poly(iPP) is not simply due to differences in the molecular weights. Furthermore, competitive extraction of equal portions linear and cyclic poly(iPP) entrapped in the same gel showed that the relative rates of extraction remained constant, suggesting the different molecular weights are not the root cause of the selectivity. The observation that the linear poly(iPP) was efficiently extracted implies that the trapping of

Figure 3. Weight % of cyclic poly(iPP) (circles, Mn = 202 kDa), linear poly(iPP) (squares, Mn = 16 kDa), or linear PDMAA (triangles, Mn = 117 kDa) recovered from HEMA hydrogels as a function of extraction time (% relative to original mass of entrapped polymer). Lack of error bars indicates the standard deviation is smaller than the size of the marker.

the cyclic poly(iPP) is not due to the formation of covalent bonds between the HEMA gel and the poly(iPP) created during the radical polymerization. This is supported by a separate control experiment which demonstrated that when methyl methacrylate is polymerized in the presence of poly(iPP) under the same conditions that the gel is synthesized, no shift or broadening of the poly(iPP) peak was observed (Figure S2, Supporting Information). The HEMA gels containing entrapped poly(iPP) were analyzed by FT-IR spectroscopy to provide evidence for the entrapped poly(iPP). FT-IR spectra of the gels was obtained by slicing the gels and using a diamond ATR to analyze the center portion of the gel (Figure S12, Supporting Info). FTIR spectra of gels generated in the presence of either linear or cyclic poly(iPP) revealed the presence of both HEMA-derived carbonyl stretches and phosphate-derived stretches (Figure S12a,b, Supporting Information). After extraction with methanol, FTIR spectra of the HEMA gels containing entrapped cyclic poly(iPP) showed clear absorbances associated with the entrapped poly(iPP). In contrast, HEMA gels from which the linear poly(iPP) were extracted did not evidence any signal for residual poly(iPP) (Figure S12c,d, Supporting Information). The FTIR data and extraction data provide evidence that the zwitterionic ring-opening polymerization of iPP with carbene 2 generates poly(iPP) that remains entrapped in HEMA crosslinked networks after methanol extraction for 11 days. On the basis of Semlyen’s work,32 these data strongly imply that the poly(iPP) generated under these conditions have a cyclic topology. The relatively modest trapping efficiency of 36% (11 day extraction) for poly(iPP) could be due to several factors: (a) incomplete threading of the cyclic poly(iPP) into the crosslinked network, (b) methanolic degradation of the poly(iPP) after extraction with methanol, or (c) the poly(iPP) generated from the zwitterionic ring-opening of iPP contains a mixture of linear and cyclic chains. Our current data do not allow us to completely discriminate among these possibilities, but molecular weight analysis of the extracted poly(iPP) provide evidence that methanolytic degradation of the poly(iPP) is in part responsible for the low trapping efficiencies. Shown in Figure 4 are GPC traces of the poly(iPP) extracted from HEMA gels C

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

displacement29 of chloride by the NHC, followed by attack of chloride on the phospholane ring in an Arbuzov reaction.40 The solid-state structure of 4 reveals a slightly distorted tetrahedral geometry at phosphorus with a P(1)−C(4) distance of 1.8568(12) Å, terminal P−O distances of 1.4762(9) Å (P(1)−O(3)) and 1.4814(9) Å (P(1)−O(2)), and P-OR distance of 1.6076(9) Å (P(1)−O(3)) (Figure 6). This

Figure 4. GPC traces of extracted cyclic IPP. (a) Poly(iPP) generated from 2 (Table 1, entry 1), (b) poly(iPP) extracted from gel after 8 h, (c) poly(iPP) extracted from gel after 11 d.

after 8 h (Figure 4b) and 11 days (Figure 4c). Whereas the GPC traces of poly(iPP) generated from carbene 2 are monomodal (Figure 4a), the GPC trace of poly(iPP) extracted after 11 days shows both a low molecular weight peak and a high molecular weight shoulder. The presence of a low molecular fraction in the extracted poly(iPP) that was not present in the original sample suggests that under the extraction conditions, some of the poly(iPP) was degraded under the extraction conditions. The origin of the high molecular weight shoulder is not clear but could be due to the methanolytic ringbreaking of the cyclic poly(iPP) to linear topology, which would be expected to elute at a shorter retention time.39 Mechanistic Studies. To provide evidence for a nucleophilic transesterification mechanism, model studies were carried out with NHC 2 and 2-chloro-2-oxo-1,3,2dioxaphospholane. A cooled toluene solution of the chlorophospholane was treated with NHC 2 at −78 °C and slowly warmed to room temperature to afford a white cloudy solution. Isolation of the solid revealed 2-chloroethyl-(1,3-diisopropyl4,5-dimethyl-imidazolium)-phosphonate 4 in 39% yield, and recrystallization from CH2Cl2 afforded X-ray quality crystals (Figure 5). The imidazolium phosphonate 4 was characterized by 1H, 13C, 31P NMR, ESI mass spectrometry, and single-crystal X-ray analysis.

Figure 6. X-ray crystal structure of the imidazolium phosphonate 4. Thermal ellipsoids are set to 50% probability. Selected bond distances (Å) and angles (deg): P1−C4, 1.8568(12); P1−O3, 1.4762(9); P1− O2, 1.4814(9); P1−O1, 1.6076(9); O3−P1−O2, 122.01(5)°; O1− P1−C4, 100.82(5)°; O3−P1−C4, 106.69(5)°, O2−P1−C4, 107.83(5)°, O3−P1−O1, 106.68(5)°; O2−P1−O1, 110.71(5)°.

structure is analogous to that of the NHC, oxophosphorane 2-(diphenylphosphoryl)-1,3-dimesityl-4,5-dihydro-1H-imidazol-3-ium, recently reported by Stephan.41 Related NHC P(III) and P(V) compounds are also known.42−44 Shown in Figure 7 is a proposed mechanism for the zwitterionic ring-opening polymerization (ZROP) of iPP to generate cyclic poly(iPP). Nucleophilic attack of the NHC on iPP would generate a zwitterion that upon addition of further monomer would generate a macrozwitterion that could cyclize to generate the cyclic polymer. In analogy to other zwitterionic ring-opening polymerizations of lactones,11,42,45−47 it is likely that the initiation step is inefficient such that only a small fraction of carbenes transform to active zwitterions, which propagate rapidly.47 This is consistent with the observation that the molecular weights are much higher than that predicted based on the initial ratio of [iPP]0/[NHC]0. The fast rates and high molecular weights observed imply that propagation is rapid and faster than cyclization48 to liberate the cyclic poly(alkylene phosphate). The relatively narrow polydispersities are likely due to the inability of the liberated carbenes to reinitiate chains, as a consequence of the low initiation efficiency, especially at higher conversions.42,47 The fast rates for the ZROP of iPP with NHCs 2 and 3 impeded our initial attempts to investigate the kinetics or evolution of molecular weight with conversion, but further studies are underway to investigate the mechanism of these reactions.

Figure 5. Generation of imidazolium chloroethoxy phosphonate and proposed intermediate.

The generation of the imidazolium phosphonate 4 indicates that nucleophilic attack at phosphorus by an NHC is a viable process and indirectly supports a nucleophilic mechanism for phosphoester transesterification (Figure 7). We were unable to observe any intermediates in this process, but a reasonable mechanism for the formation of 4 is the nucleophilic D

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

Figure 7. Proposed mechanism for the zwitterionic ring-opening polymerization of iPP.

■

Synthesis of 2-Isoproxy-1,3,2-dioxophospholane 2-oxide.8 First, 2.54 g of 2-choloro-1,3,2-dioxophospholane 2-oxide (TCI America, FW = 142.48) was dissolved in 35 mL of tetrahydrofuran. Then 2.74 mL (0.129 mol) of triethylamine (FW = 101.2, d = 0.726) was added dropwise at 0 °C, followed by 1.40 mL (0.111 mol) of 2propanol (FW = 60.1, d = 0.786). After 11 h, the reaction was filtered over Celite and solvent removed. The product distilled under vacuum at 140 °C. Yield = 1.76 g (59%). Spectra matched that of literature.8 1 H NMR (CDCl3): δ 4.67 (m, 1H), 4.32 (m, 4H), 1.29 (d, 6H). 31P NMR (CDCl3): δ 17.3 (s) Synthesis of Imidazolium Phosphonate 4. First, 42.7 mg of 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene (FW = 180.29) was dissolved in toluene and cooled in Schlenk flask to −78 °C. Then a solution of 33.7 mg of 2-chloro-2-oxo-1,3,2-dioxaphospholane (TCI America, FW = 142.48) was added dropwise with stirring. Upon warming to RT, a white suspension formed. the solid portion was isolated and dried under vacuum. Yield = 29.9 mg (39%). NMR and MS were conducted in acetonitrile. 1H NMR (CD3CN): δ 1.5 (12H, d), 2.3 (6H, s), 3.7 (2H, t), 4.0 (2H, m), 6.4 (2H, br). 13C NMR (CD3CN): δ 10.4 (s), 20.7 (s), 22.1 (s), 44.6 (d JCP = 7.6 Hz), 50.4 (s), 51.0 (s), 65.5 (d, JCP = 6.1 Hz). 31P (CD3CN): δ −8.8 (s) m/z: 323.2, 281.1, 239.1. Product was dissolved in minimum amount of anhydrous DCM and sealed in a vial containing diethyl ether. After 1 week in −10 °C freezer, large colorless crystals suitable for X-ray analysis were obtained. ZROP Polymerization of iPP with NHC 2. First, 10.9 mg of 2 (FW = 180.29) was dissolved in 3.02 mL of THF and than added to 502 mg of iPP (FW = 166.11) with stirring [iPP]0:[2] = 50:1. [iPP]0 = 1 M quenched with approximately 30 mg of 4-nitrophenol after 2 min. After 30 min, solvent was removed under vacuum. NMR showed 77% conversion. GPC (LS): Mn = 144.3 kDa, Mw/Mn = 1.07. ZROP polymerization with carbenes 1 and 3 were conducted in a similar manner. Polymerization of iPP with 1 and BnOH. First, 1.00g of iPP (FW = 166.11) was added into a vial along with 6.5 mg of benzyl alcohol (FW = 108.14) via a stock solution in THF. A solution of 7.8 mg of 1 (FW = 124.2) in THF was added to the stirring monomer. The reaction was a clear rose color. After 12 min, approximately 20 mg of 4-nitrophenol were added to the reaction and allowed to stir for 1 h. Solvent was removed under vacuum. NMR showed 90% conversion. GPC sample (LS): 23320, Mw/Mn = 1.08 Polymerization of iPP with EtOH, DBU/TU. First, 45.4 mg of TU (FW = 370.36) were added to 407 mg of iPP (FW = 166.11) in 1.22 mL of toluene. Then 1.4 μL of ethanol (FW = 46.07, d = 0.789) was added, followed by 18.6 mg DBU (FW = 152.24). Reaction

SUMMARY In conclusion, the zwitterionic ring-opening polymerization of the cyclic phosphate iPP with NHCs in the absence of alcohols occurs rapidly to generate high molecular weight poly(iPP) with low polydispersity. The poly(alkylene phosphates) generated under these conditions can be entrapped in HEMA cross-linked gels with efficiencies of up to 36%, implying that a significant fraction of the high molecular weight poly(iPP) generated under these conditions consist of cyclic macromolecules. Moreover, the cyclic-infused gels generated by this strategy constitute an intriguing class of double-network gels33,34 whose properties are currently under investigation.

■

EXPERIMENTAL SECTION

General Considerations. All polymerizations were conducted in a dry nitrogen glovebox. Tetrahydrofuran (THF) and toluene were distilled from sodium/benzophenone and stored under nitrogen. Dichloromethane (DCM) used for polymerizations was stirred over calcium hydride and distilled. All chemicals were purchased from Sigma-Aldrich unless otherwise specified. Polystyrene calibrated molecular weights were obtained on a Viscotek GPCMax with two Waters columns (300 mm by 7.7 mm) in THF at 35 °C at a flow rate of 1 mL/min and Viscotek S3580 refractive index detector. Monodisperse polystyrene calibrants ranged from Mp = 500 to 275000. Light-scattering (LS) molecular weights were determined on an Agilent 1260 Infinity SEC pump with two Agilent polypore columns (300 mm by 7.7 mm) in DMF at 70 °C at a flow rate of 0.6 mL/min and Wyatt Heleos II 8-angle light scattering detector and Wyatt T-rex refractive index detector. NMR data was collected on 300, 400, and 500 MHz Varian instruments. Synthetic Procedures. 1,3,4,5-Tetramethylimidazol-2-ylidene (1) was prepared by synthesizing and deprotonating the imidazolium salt according to the literature.49 1,3-Diisopropyl-4,5-dimethylimidazol-2ylidene (2) was prepared by reducing 1,3-diisopropyl-4,5-dimethyl1H-imidazole-2(3H)-thione according to the literature.5 1,3-Bis(2,4,6trimethylphenyl)imidazol-2-ylidene (3) was prepared by deprotonating the 1,3-dimesityl-1H-imidazol-3-ium chloride purchased from Strem according to the literature.50 1-(3,5-Bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) was synthesized according to the literature.51 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7triazabicyclo[4.4.0]undec-5-ene (TBD) were purchased and purified by distillation and sublimation, respectively. E

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

■

proceeded at 0 °C for 4 h, 20 min. Quenched with acetic acid outside of glovebox. NMR showed 82% conversion. GPC sample (LS): Mn = 16490, Mw/Mn = 1.10. Linear polymerization with sparteine was conducted by substituting (−)-sparteine for DBU in this procedure. Polymerization of iPP with BnOH, TBD. First, 11.2 mg of benzyl alcohol was added to 1.66 g of iPP. Then 13.5 mg of TBD was added with stirring in a vial. After 20 min, the clear reaction became too viscous for magnetic stirbar. NMR showed 64% conversion, and the reaction was added to ether to precipitate the polymer. GPC sample (PS calibration): Mn = 7416, Mw/Mn = 1.18 Purification of Poly(iPP). The solid polymer obtained from THF was redissolved in methylene chloride and precipitated twice in diethyl ether at 0 °C. The sample was dissolved in methylene chloride and layered with water and one drop of triethylamine. This was mixed vigorously with shaking and then separated via centrifuge. The organic layer was isolated and washed twice more with DI water and separated via centrifuge. The organic layer was dried with sodium sulfate, filtered, and solvent removed under vacuum to give a colorless, amorphous polymer. NMR showed monomer, catalyst(s), and quenching agent had been removed. 1H NMR (CDCl3): δ 4.7 (oct, 1H), 4.2 (t, 4H), 1.3 (d, 6H). 31P (CDCl3): δ −1.1. Sample Preparation: MALDI-TOF MS. Polymer samples (for example, Table S1, entry 2, Supporting Information) were analyzed by an Applied Biosystems Sciex TF4800 MALDI-TOF at the Molecular Foundry, a part of Lawrence Berkeley National Laboratory. Samples were prepared by dissolving combining a 20 mg/mL solution of dithranol (Aldrich) with 10 mg/mL polymer and 0.1 M NaI (Aldrich) in a 10:10:1 ratio. Synthesis of poly(iPP) Embedded Gels. First, 152 mg of 2hydroxyethyl methacrylate (Aldrich, distilled, FW = 130.14) was combined with 8 mg of poly(ethylene glycol) dimethacrylate (Polymer Sciences, PEG Mn = 400; 5 wt % = 1.2 mol % = 1 cross-link/40 HEMA units) and 0.4 mL of dimethylformamide in a plastic vial. This mixture was vortexed for 10 min and then added to 40 mg of a poly(iPP) sample. To this mixture was added 1.6 mg of AIBN (Aldrich, recrystallized, FW = 164.21); the resulting solution was purged with argon and placed in a 75 °C bath for 30 min. The gel was removed and dried at 60 °C overnight in a vacuum oven to give a transparent, sticky gel. Synthesis of Poly(N,N-dimethylacrylamide) (PDMAA) Embedded Gels. These gels were prepared analogously but with 40 mg of PDMAA (Polymer Source, stated Mn = 117 kDa, Mw/Mn = 1.5). Gel Extractions with Methanol. The polymer-embedded gels were extracted by adding 5 mL of methanol to a vial containing the gel and a stir bar. With gentle stirring, the sample was allowed to soak for a given amount of time and then the methanol was removed via syringe. The methanol washings were dried, and then 3 mL of dichloromethane was added and briefly sonicated to extract soluble products. The washings were syringe filtered and dried under high vacuum. The PDMAA washings were less soluble than poly(iPP) in dichloromethane, so instead they were analyzed by NMR in methanold4 to determine oligomeric HEMA impurities and reported masses were adjusted accordingly.

■

ACKNOWLEDGMENTS This material is based on work supported by the National Science Foundation (DMR-1407658). T.S.S. acknowledges a National Defense Science and Engineering Graduate Fellowship. Work at the Molecular Foundry (MALDI-TOF MS) was supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under contract no. DE-AC02-05CH11231.

■

REFERENCES

(1) Kamber, N. E.; Jeong, W.; Waymouth, R. M.; Pratt, R. C.; Lohmeijer, B. G. G.; Hedrick, J. L. Chem. Rev. 2007, 107, 5813−5840. (2) Kiesewetter, M. K.; Shin, E. J.; Hedrick, J. L.; Waymouth, R. M. Macromolecules 2010, 43, 2093−2107. (3) Fevre, M.; Pinaud, J.; Gnanou, Y.; Vignolle, J.; Taton, D. Chem. Soc. Rev. 2013, 42, 2142−2172. (4) Tempelaar, S.; Mespouille, L.; Coulembier, O.; Dubois, P.; Dove, A. P. Chem. Soc. Rev. 2013, 42, 1312−1336. (5) Lohmeijer, B. G. G.; Dubois, G.; Leibfarth, F.; Pratt, R. C.; Nederberg, F.; Nelson, A.; Waymouth, R. M.; Wade, C.; Hedrick, J. L. Org. Lett. 2006, 8, 4683−4686. (6) Brown, H. A.; Chang, Y. A.; Waymouth, R. M. J. Am. Chem. Soc. 2013, 135, 18738−18741. (7) Rodriguez, M.; Marrot, S.; Kato, T.; Stérin, S.; Fleury, E.; Baceiredo, A. J. Organomet. Chem. 2007, 692, 705−708. (8) Iwasaki, Y.; Yamaguchi, E. Macromolecules 2010, 43, 2664−2666. (9) Clément, B.; Grignard, B.; Koole, L.; Jérôme, C.; Lecomte, P. Macromolecules 2012, 45, 4476−4486. (10) Zhang, S.; Wang, H.; Shen, Y.; Zhang, F.; Seetho, K.; Zou, J.; Taylor, J.-S. A.; Dove, A. P.; Wooley, K. L. Macromolecules 2013, 46, 5141−5149. (11) Brown, H. A.; Waymouth, R. M. Acc. Chem. Res. 2013, 46, 2585−2596. (12) Johnston, D. S. Adv. Polym. Sci. 1982, 42, 51−106. (13) Suzuki, M. In Encyclopedia of Polymer Science and Technology; 4th ed.; John Wiley & Sons, Inc.: New York, 2013. (14) Cyclic Polymers; 2nd ed.; Semlyen, J. A., Ed.; Kluwer: Dordrecht, The Netherlands, 2000. (15) Hoskins, J. N.; Grayson, S. M. Polym. Chem. 2011, 2, 289−299. (16) Topological Polymer Chemistry: Progress of Cyclic Polymers in Synthesis, Properties and Functions; Tezuka, Y., Ed.; World Scientific Publishing: Singapore, 2013. (17) Jia, Z. F.; Monteiro, M. J. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 2085−2097. (18) Kricheldorf, H. R. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 251−284. (19) Klosinski, P.; Penczek, S. Macromolecules 1983, 16, 316−320. (20) Penczek, S.; Biela, T.; Klosinski, P.; Lapienis, G. Makromol. Chem., Macromol. Symp. 1986, 6, 123−153. (21) Penczek, S.; Libiszowski, J. Makromol. Chem. 1988, 189, 1765− 1785. (22) Wang, Y.-C.; Yuan, Y.-Y.; Du, J.-Z.; Yang, X.-Z.; Wang, J. Macromol. Biosci. 2009, 9, 1154−1164. (23) Du, J.-Z.; Du, X.-J.; Mao, C.-Q.; Wang, J. J. Am. Chem. Soc. 2011, 133, 17560−17563. (24) Zhao, Z.; Wang, J.; Mao, H. Q.; Leong, K. W. Adv. Drug Delivery Rev. 2003, 55, 483−499. (25) Mao, H. Q.; Leong, K. W. In Advances in Genetics: Non-Viral Vectors for Gene Therapy, Part 1, 2nd ed.; Huang, L., Hung, M.-C., Wagner, E., Ed.; Academic Press: New York, 2005; Vol 53, pp 275− 306. (26) Wu, X. L.; Kim, J. H.; Koo, H.; Bae, S. M.; Shin, H.; Kim, M. S.; Lee, B.-H.; Park, R.-W.; Kim, I.-S.; Choi, K.; Kwon, I. C.; Kim, K.; Lee, D. S. Bioconjugate Chem. 2010, 21, 208−213. (27) Zhang, S.; Li, A.; Zou, J.; Lin, L. Y.; Wooley, K. L. ACS Macro Lett. 2012, 1, 328−333. (28) Steinbach, T.; Ritz, S.; Wurm, F. R. ACS Macro Lett. 2014, 3, 244−248.

ASSOCIATED CONTENT

S Supporting Information *

Additional synthetic details, NMR spectra, mass spectra, GPC chromatograms, FT-IR spectra and XRD details, CIF file. This material is available free of charge via the Internet at http:// pubs.acs.org.

■

Article

AUTHOR INFORMATION

Corresponding Author

*Phone: 650-723-4515. E-mail: [email protected]. Notes

The authors declare no competing financial interest. F

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX

Macromolecules

Article

(29) Admiraal, S. J.; Herschlag, D. J. Am. Chem. Soc. 1999, 121, 5837−5845. (30) Nolan had previously shown that N-heterocyclic carbenes can catalyze the transesterification of phosphate esters. Singh, R.; Nolan, S. P. Chem. Commun. 2005, 5456−5458. (31) Fyvie, T. J.; Frisch, H. L.; Semlyen, J. A.; Clarson, S. J.; Mark, J. E. J. Polym. Sci., Part A: Polym. Chem. 1987, 25, 2503−2509. (32) Wood, B. R.; Joyce, S. J.; Scrivens, G.; Semlyen, J. A.; Hodge, P.; O’Dell, R. Polymer 1993, 34, 3059−3063. (33) Gong, J. P.; Katsuyama, Y.; Kurokawa, T.; Osada, Y. Adv. Mater. 2003, 15, 1155−1158. (34) Waters, D. J.; Engberg, K.; Parke-Houben, R.; Ta, C. N.; Jackson, A. J.; Toney, M. F.; Frank, C. W. Macromolecules 2011, 44, 5776−5787. (35) Penczek, S.; Biela, T.; Duda, A. Macromol. Rapid Commun. 2000, 21, 941−950. (36) Roovers, J. In Cyclic Polymers, Snd ed.; Semlyen, J. A., Ed.; Kluwer Academic Publishers: Dordrecht, The Netherlands, 2000; pp 347−384. (37) Brown, H. A.; De Crisci, A. G.; Hedrick, J. L.; Waymouth, R. M. ACS Macro Lett. 2012, 1, 1113−1115. (38) Boots, H. M. J.; Kloosterboer, J. G.; Serbutoviez, C.; Touwslager, F. J. Macromolecules 1996, 29, 7683−7689. (39) Lee, H. C.; Lee, H.; Lee, W.; Chang, T. H.; Roovers, J. Macromolecules 2000, 33, 8119−8121. (40) Bhattacharya, A. K.; Thyagarajan, G. Chem. Rev. 1981, 81, 415− 430. (41) Holthausen, M. H.; Mehta, M.; Stephan, D. W. Angew. Chem., Int. Ed. 2014, 53, 6538−6541. (42) Brown, H. A.; Xiong, S. L.; Medvedev, G. A.; Chang, Y. A.; AbuOmar, M. M.; Caruthers, J. M.; Waymouth, R. M. Macromolecules 2014, 47, 2955−2963. (43) SAINT and SADABS; Bruker AXS Inc.: Madison, WI, 2007. (44) Abdellah, I.; Lepetit, C.; Canac, Y.; Duhayon, C.; Chauvin, R. Chem.Eur. J. 2010, 16, 13095−13108. (45) Zhang, X.; Waymouth, R. M. ACS Macro Lett. 2014, 3, 1024− 1028. (46) Acharya, A. K.; Chang, Y. A.; Jones, G. O.; Rice, J. E.; Hedrick, J. L.; Horn, H. W.; Waymouth, R. M. J. Phys. Chem. B 2014, 118, 6553− 6560. (47) Jeong, W.; Shin, E. J.; Culkin, D. A.; Hedrick, J. L.; Waymouth, R. M. J. Am. Chem. Soc. 2009, 131, 4884−4891. (48) Cyclization by an Arbuzov reaction at the imidazolium phosphonate terminus is also possible, but control experiments at high concentrations of NHC 2 did not provide any evidence for an isopropoxy imidazolium phosphonate analogous to 4. (49) Kamber, N. E.; Jeong, W.; Gonzalez, S.; Hedrick, J. L.; Waymouth, R. M. Macromolecules 2009, 42, 1634−1639. (50) Jeong, W.; Hedrick, J. L.; Waymouth, R. M. J. Am. Chem. Soc. 2007, 129, 8414−8416. (51) Pratt, R. C.; Lohmeijer, B. G. G.; Long, D. A.; Lundberg, P. N. P.; Dove, A. P.; Li, H.; Wade, C. G.; Waymouth, R. M.; Hedrick, J. L. Macromolecules 2006, 39, 7863−7871.

G

dx.doi.org/10.1021/ma501764c | Macromolecules XXXX, XXX, XXX−XXX