Stereoregular Glycine-Bearing Polymers from

Dec 15, 2016 - Moreover, 3-substituted polymers with high trans-HT regularity exhibit much bigger water contact angle and higher cloud point than its ...
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Crystalline Regio-/Stereoregular Glycine-Bearing Polymers from ROMP: Effect of Microstructures on Materials Performances Maosheng Li,†,§ Fengchao Cui,‡ Yunqi Li,‡ Youhua Tao,*,† and Xianhong Wang† †

Key Laboratory of Polymer Ecomaterials and ‡Key Laboratory of Synthetic Rubber, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Renmin Street 5625, Changchun 130022, People’s Republic of China § University of Chinese Academy of Sciences, Beijing 100039, People’s Republic of China S Supporting Information *

ABSTRACT: Synthesis of amino acid or peptide-bearing polymers with controlled microstructures is still a long-going challenge in polymer chemistry in contrast to natural biopolymers with exactly controlled microstructures like proteins and DNA. Here, a series of new glycine-substituted cyclooctenes monomers were designed and synthesized. Ring-opening metathesis polymerizations (ROMP) of all 3-substituted monomers with Grubbs second-generation catalyst afford glycine-bearing polymers with high head-to-tail regioregularity and high trans-stereoregularity, whereas ROMP of 5-substituted monomers is neither regio- nor stereoselective. Theoretical study revealed that sterically cumbersome glycine substituent in the 3-position is crucial for the high regio- and stereochemistry in the polymerization. Of importance, differential scanning calorimetry and wideangle X-ray scattering measurements show that unsaturated 3-substituted polymers are semicrystalline due to their high degrees of structure regularity and the strong hydrogen-bonding interactions between glycine side-chains. Such obvious crystallization behaviors before the saturation of the backbone will facilitate its future applications as biomimetic materials. Moreover, 3substituted polymers with high trans-HT regularity exhibit much bigger water contact angle and higher cloud point than its random 5-substituted analogues, indicating that structure regularity of these glycine-bearing polymers can decide the surface hydrophilicity and thermoresponsive behaviors. These results demonstrate the dependence of glycine-bearing polymer properties on their microstructures. Finally, the less reactive internal trans-double bonds of the polymers undergo thiol−ene addition effectively, allowing the preparation of regiospecific glycine-bearing polymers with a range of features in a facile way.

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INTRODUCTION The design of biocompatible and biomimetic polymers, which can mimic natural compounds with various biological activities, is a significant field of research.1−9 Amino acids and peptides bearing polymers are a class of biomimetic materials that definitely become important because of their remarkable performances such as biocompatibility and biological activities.10−29 Several examples have been reported in the design of polymers that have an abiological backbone but amino acids or peptides as side groups to mimic biological systems including cellular adhesion and bacterial chemotaxis.30 The most common and efficient method for synthesis of polymers with amino acid moieties as pendant groups is accomplished by the controlled/living radical polymerization (CRP). Recent researches have specifically focused on synthesizing polymers © XXXX American Chemical Society

with controlled molecular weight and well-defined architecture.31−39 However, the precise control of microstructures (i.e., monomer sequence, regio- and stereochemistry) of these polymers, which may rival those of natural biopolymers, is still one of the tough pending goals because of the intrinsic character of radical polymerization. Alternatively, by utilizing a unique methodology, acyclic diene metathesis (ADMET) polymerization, Wagener reported the first examples of polyolefins with precisely spaced amino acids branches through polymerization of symmetrically substistuted α,ω-dienes.40−45 Received: October 15, 2016 Revised: December 3, 2016

A

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Macromolecules Because of the remarkable functional group tolerance of ruthenium catalysts, ring-opening metathesis polymerization (ROMP) of amino acid/peptide functionalized norbornenes and oxa-norbornenes monomers has attracted considerable research attentions in the past few years.46−53 For example, Grubbs reported that norbornene monomers bearing peptide glycine−arginine−glycine−aspartic acid undergo ROMP to give biomimetic materials with cell-adhesive property.54−56 Masuda employed ROMP of amino acid-substituted norbornene monomers to synthesize block copolymers with the unique ability to form reverse micelles.57 Using ROMP, Sampson prepared norbornyl polymers bearing multivalent fertilin β oligopeptides to inhibit adhesion of sperm to the egg plasma membrane.53 However, polymerization of 5-substituted norbornene and oxanorbornene monomers using rutheniumbased catalysts provides internally heterogeneous polymers due to the lack of complete regio- and stereocontrol in the polymerization.58 In general, natural proteins are copolymers derived from a lot of different amino acids, and the precisely controlled microstructures determine the conformation and biological activity of the generated protein. Toward the development of more realistic mimics of biopolymers, we desired to synthesize amino acid or peptide-bearing polymers with precisely controlled microstructures, in which structural ambiguities were minimized. Recently, Hillmyer published a series of papers demonstrating that ROMP of cyclooctene (COE) with substituent at the 3-position could afford polymers having high head-to-tail regioregularity and trans-stereoregularity with the use of Grubbs second (G2) or third (G3) generation catalyst.59−64 Kobayashi also carried out the ROMP of 3alkoxy-substituted cyclooctenes with G2 to yield polymers with high regioregularity and trans-stereoregularity.65 Very recently, Kobayashi synthesized highly regio-/stereoregular ROMP polymers with amide side chains.66 Despite these remarkable efforts, due to the synthetic difficulties of the amino acidsubstituted cyclooctenes monomers, the synthesis of regio- and stereospecific amino acid-containing ROMP polymers still remains a challenge, and further systematical exploration on the influence of microstructures on the properties of these amino acid-containing polymers is also highly desired. In addition, though unsaturated poly(COE) with high trans double-bond shows a melting endothermic peak, indicating a certain level of crystallization.67,68 Because of the steric congestion along the polymer backbone, thus inhibiting crystallization of the polymers,59,62,65 there have been few reports of crystalline unsaturated poly(RCOE) with substituent in the side chain.66 Indeed, producing durable materials which could be shaped into useful biologically active structures requires polymers that either have a high glass temperature or a reasonable degree of crystallization.45 We hypothesized that the combination of regio- and stereoselective ROMP and amino acid side chains would produce crystalline unsaturated poly(RCOE), which would facilitate its future applications as biomimetic materials. In this contribution, we designed and synthesized a series of new glycine-substituted cyclooctenes monomers, designated as 3GlyxCOE and 5GlyxCOE, where x (= 0, 1, 2, 3, and 4) represents the numbers of CH2CH2O moieties at the side chain (Scheme 1). Polymerizations of all 3-substituted monomers 3Gly0COE-3Gly4COE with G2 afforded polymers with high head-to-tail regioregularity and high trans-stereoregularity, whereas ROMP of 5-substituted monomers 5Gly0COE5Gly4COE was neither regio- nor stereoselective (Scheme 1).

Scheme 1. Synthesis of Regio-/Stereoregular GlycineBearing Polymers via ROMP

In particular, the crystallization behavior, surface hydrophilicity, and temperature responsiveness of the resultant polymers were systematically investigated to estimate the influence of polymer microstructures on materials properties. To the best of our knowledge, few such studies have been reported so far. Finally, the thiol−ene addition of 2-mercaptoacetate to the less reactive internal trans-double bonds of the polymers was quantitative, and achieved >99% conversion, allowing the preparation of regiospecific glycine-bearing polymers with a range of features in a facile way.

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RESULTS AND DISCUSSION Monomer Synthesis. As shown in Scheme 2, synthesis of 3-carboxylic acid-substituted cyclooctene was accomplished through an addition reaction between ninhydrin and cyclooctene, followed by oxidative cleavage of ninhydrin−cyclooctene adducts. Monomer 3Gly0COE was then synthesized by the reaction of 3-carboxyl-substituted cyclooctene with Lglycine methyl ester hydrochloride in 77.8% yield. 1-Ethyl-3-(3(dimethylamino)propyl)carbodiimide hydrochloride (EDC· HCl) was used as a condensation agent because the urea derivative could be readily removed from the reaction mixture. Monomers 3Gly1COE-3Gly4COE were prepared via hydrolysis of 3Gly0COE in the presence of lithium hydroxide, followed by condensation with commercially available monomethoxyoligo(ethylene glycol). The 5-glycine-substituted cyclooctenes synthesis began from the commercially available cyclooctadiene. The addition with HBr resulted in 5-bromocyclooctene, which subsequently reacted with magnesium to prepare Grinard reagent and then reacted with CO2 to give 5-carboxylic acid-substituted cyclooctene. Direct condensation of this intermediate with L-glycine methyl ester hydrochloride generated monomer 5Gly0COE. Subsequent hydrolysis and condensation with monomethoxy oligo (ethylene glycol) provided monomers 5Gly1COE5Gly4COE. The structures of the monomers were confirmed by 1H and 13 C NMR (see Supporting Information, Figures S6−S29). Figure 1 shows the typical 1H NMR spectra of 3Gly4COE and 5Gly4COE, which showed characteristic resonances of glycine and oligo(ethylene glycol) moieties. The resonance at 4.1 ppm is attributed to protons of methylene groups in glycine. Peak at 4.3 ppm is methylene protons next to ester bond. The 13C B

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Macromolecules Scheme 2. Synthesis of 3-Glycine-Substituted and 5-Glycine-Substituted Cyclooctenesa

Reagents and conditions: (i) ninhydrin, toluene, refluxed, 48 h, 86%; (ii) H5IO6, 0−10 °C, Et2O, 85%; (iii) EDC·HCl, DMAP, DCM, Et3N, 0 °C− rt,70−88%; (iv) 1 M LiOH, dioxane/H2O = 1:1 (v/v), rt, 95%; (v) HBr/CH3CO2H, rt, overnight, 79−85%; (vi) Mg, THF, I2, refluxed, 12 h, CO2 bubbled 48 h, then 1 M HCl acidification, 65%. a

polymerized slower than 5Gly4COE (Figure S1). One reason for this phenomenon was due to the steric effect of 3substituted monomers, which would restrict the coordination between monomer double bond and the catalytic center of G2.63 To obtain the polymers in high yield, a high catalyst loading ([M]0/[G2]0 = 2000:4) was used for 3Gly0COE3Gly4COE (Table 1, entries 1−6). As shown in Table 1, the molecular weight of the resultant polymers determined by size exclusion chromatography (SEC) using polystyrene (PS) as standards was higher than the calculated value. This is probably because of the hydrodynamic volume difference between the resultant polymers and PS standards. In addition, the Mn,NMR of the polymers can also be determined from the peak intensity ratio of the monomer to the end group via 1H NMR spectroscopy. The Mn,NMR from the peak intensity ratio was close to the calculated value Mn,calc, indicating that the molecular weight of the resultant polymers was controlled to a comparable value by using cis-4-octene as a CTA. Though the SEC curve showed a symmetric single peak, the molecular weight distribution was broad (Đ = 1.5−2.7), in consistent with the representative values for the ROMP/CT system.69 We have thus demonstrated that ROMP of glycinesubstituted monomers with G2 provides an effective approach toward biomimetic polymers with amide side-chains. The regio- and stereostructures of all ten glycine-substituted ROMP polymers were carefully characterized by 1H, 13C, and 1 H−1H-cosy NMR, and by FTIR spectroscopies. The 13C NMR spectra of poly(3Gly4COE) are shown in Figure 2A. There were two groups of olefinic signals located at 128.4 and 133.9 ppm as opposed to eight signals from the six possible regio- and stereoisomeric structures,70 which strongly confirmed high regioregularity of the resulting polymer [head-totail (HT) or alternating head to head (HH) and tail-to-tail (TT)]. Further analysis of the 1H−1H correlated spectra (Figure 3) showed the correlation between the olefinic signals Ha and Hb in the poly(3Gly4COE), which was strongly supportive of highly HT regioregularity. In addition, as can be seen in Figure 3, the coupling constant for double bond protons was 15.3 Hz for poly(3Gly4COE), indicating a trans configuration of the double bond. FTIR spectra of poly(3Gly4COE) exhibited strong absorptions at 972 cm−1 (Figure

Figure 1. 1H NMR spectra of (A) 3Gly4COE and (B) 5Gly4COE in CDCl3 at room temperature.

NMR spectra also showed the expected resonance and further confirmed successful synthesis of target molecules. Polymerization of Glycine-Bearing Monomers with G2. Glycine-bearing monomers were polymerized in chloroform at 40 °C using G2, which was tolerant to amide group. In order to regulate the molecular weight of the polymers, cis-4octene was used as a chain transfer agent (CTA). The polymerization system was homogeneous, and the polymerization was quenched by ethyl vinyl ether. Initially, the ratio of [M]0/[G2]0 was fixed at 2000:1, and the monomer conversion was up to 100% for 5Gly0COE-5Gly4COE (Table 1, entries 7− 11); however, the conversion was only 60% for monomer 3Gly4COE even after 72 h of polymerization (Table S1, entry 2). The kinetic experiments confirmed that 3Gly4COE C

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Macromolecules Table 1. Ring-Opening Metathesis Polymerizations of Monomers with G2 Catalysta entry

polymers

[M]0/[G2]/[CTA]

convb (%)

Mn,calcc (kg/mol)

Mn,NMRd (kg/mol)

Mn,SECe (kg/mol)

Đe

t-HTf (%)

1 2 3 4 5 6 7 8 9 10 11 12

poly(3Gly0COE) poly(3Gly1COE) poly(3Gly2COE) poly(3Gly3COE) poly(3Gly4COE) poly(3Gly4COE) poly(5Gly0COE) poly(5Gly1COE) poly(5Gly2COE) poly(5Gly3COE) poly(5Gly4COE) poly(5Gly4COE)

2000:4:50 2000:4:50 2000:4:50 2000:4:50 2000:4:50 2000:4:200 2000:1:50 2000:1:50 2000:1:50 2000:1:50 2000:1:50 2000:1:200

94 96 88 87 89 90 100 100 100 100 100 100

7.8 9.6 10.2 11.5 13.2 3.6 8.8 10.6 12.3 14.0 15.7 4.0

6.8 8.1 9.4 10.2 11.5 4.1 6.7 8.0 9.2 10.7 11.5 3.9

16.8 22.2 26.8 14.2 22.8 12.3 14.7 19.4 20.6 17.7 15.8 8.9

1.8 1.9 2.0 1.8 1.8 1.5 2.1 2.4 2.5 1.9 2.7 1.9

98 98 98 97 98 −g −g −g −g −g −g −g

Conditions: [M]0 ≈ 1M, CTA= cis-4-octene, solvent = CHCl3, 40 °C oil bath, 24 h. bDetermined by 1H NMR analysis of the reaction mixture. Mn,calc = M(monomer) × [M]0/([G2] + [CTA]) × conversion (monomer). dMn,NMR = M(monomer) × AH(j)/AH(o) × 3. eDetermined by SEC in DMF (0.01 M LiBr), polystyrene as standard. fThe content of trans-HT was determined by 1H NMR analysis. gNot determined. a c

a trans-HT regioregular sequence for all other poly(3GlyxCOE)s (Figures S30−S45). These results indicated that the polymers from 3GlyxCOE monomers have markedly high trans-HT regularity in all cases. On the contrary, the olefinic signals (Ca and Cb) and a-positon of carboxyl (Ce) in the 13C NMR spectra (Figure 2B, Figures S51, S55, S59, and S63) for all of the poly(5GlyxCOE)s showed multiple peaks, indicating that HH, TT, and HT structures existed in the polymers. Moreover, the E/Z ratio of poly(5GlyxCOE)s was approximately equal to that of poly(COE) by ROMP of the unsubstituted monomer using G2, as evidenced by 1H NMR and FTIR data (Figures S50, S53, S54, S57, S58, S61, S62, S65, S66, and S69, Supporting Information). In brief, the ROMP of 3GlyxCOE monomers is indeed a very powerful method for the synthesis of precision amino acid-bearing polymers. Quantum Chemical Calculations. In Cramer and Hillmyer’s previous work,60 mechanistic details of the ROMP of 3substituted-cyclooctenes (3RCOEs) were systematically investigated with quantum chemical calculations, while those of 5RCOEs have not been studied. To better understand the effect of glycine substitutions at different positions of COE for stereo- and regioselectivity of the polymerization, we described the profiles of potential energy surfaces (PES) for polymerization pathways of 3Gly0COE and 5Gly0COE with quantum chemical calculations, respectively. Because of the existence of CC on the COE ring, both cis and trans stereoisomers could be produced. Meanwhile, the introduction of glycine substitution on COE ring could produce two different conformational production with the substituent being distal or proximal to the N-heterocyclic carbine (NHC) ligand. Therefore, we respectively characterized four possible polymerization pathways for 3Gly0COE and 5Gly0COE, based on the lowest energy conformers. The calculated results showed that the initiation reactions of ROMP were divided into two steps, and the second step (retro-[2 + 2] TS structure, TS2) was the rate-limiting step (RLS), as depicted in Figure 4. PESs producing cis and trans productions in the distal polymerization pathways are shown in Figure S2 as an example. Although the TS2 Gibbs free energy barriers of the cis production pathway was slightly higher than the trans one with 1.3 kcal/mol, the energy of the Dewar−Chatt−Duncanson adducts (Add) in the cis production pathway was 5.2 kcal/mol higher than the trans one and the first step reaction in the cis production pathway was obviously more difficult than the trans one. This indicated

Figure 2. 13C NMR spectra of (A) poly(3Gly4COE) and (B) poly(5Gly4COE) in CDCl3 at room temperature.

Figure 3. 1H−1H correlated spectrum of poly(3Gly4COE) in CDCl3 at room temperature.

S49), also suggesting the predominance of trans stereochemistry. NMR and FTIR measurement results also revealed D

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Figure 5. Optimized TS2 structures of the proximal and distal polymerization pathways with the productions of trans conformers for 3Gly0COE (upper panel) and 5 Gly0COE (lower panel).

Figure 4. 298 K Gibbs free energies and enthalpies (kcal/mol, enthalpies in parentheses) profiles of distal and proximal polymerization pathways with the productions of trans conformers for 3Gly0COE (A) and 5Gly0COE (B) in THF.

that the trans conformers could be dominant production, in consistent with the experimental results. Consequently, in the following text, the trans production pathways of 3Gly0COE and 5Gly0COE ROMP were further analyzed and discussed. Figure 4 depicts respectively the 298 K Gibbs free energies and enthalpies profiles of the proximal and distal polymerization pathways with the productions of trans conformers for 3Gly0COE and 5Gly0COE. It showed that the distal pathways for 3Gly0COE was preferred over the proximal one due to lower Gibbs free energies barrier of RLS with 14.6 kcal/mol versus 21.11 kcal/mol, while the polymerization pathways for 5Gly0COE did not have significantly prone to the distal approaches or the proximal one. These conclusions were better agreement with our experimental results, and the preference of the distal pathway for 3Gly0COE was also consistent with the previously reported results.60 The propensity of the distal approach for 3Gly0COE mainly attributed to the less steric hindrance between the mesityl group of catalyst and glycine substituent than that of the proximal one (Figure 5, upper panel). However, for 5Gly0COE, there were no apparent steric interactions between the mesityl group of catalyst and glycine substituent (Figure 5, lower panel) whether the initiation reactions proceeded by the distal or proximal approaches, resulting that the ROMP of 5Gly0COE did not have any regioselectivity. Consequently, the investigation of 5Gly0COE also confirmed that the steric hindrance between the mesityl group of catalyst and substituents at different position of COE ring played a vital role in the regioselectivity of ROMP. Effect of Microstructures on Materials Properties. The effect of precise microstructure control on the polymer properties was first investigated in terms of crystallization behavior of the polymers. Figure 6, Figure S3, and Table 2 show the differential scanning calorimetry (DSC) data for the series of unsaturated glycine-bearing polymers. All five 5-

Figure 6. DSC profiles of poly(3Gly0COE) (1), poly(3Gly1COE) (2), poly(5Gly0COE) (3), and poly(5Gly1COE) (4) at a heating rate of 10 °C/min.

Table 2. Thermal Characteristics of Polymers

a b

polymer

Tga (°C)

Tma (°C)

poly(3Gly0COE) poly(3Gly1COE) poly(3Gly2COE) poly(3Gly3COE) poly(3Gly4COE) poly(5Gly0COE) poly(5Gly1COE) poly(5Gly2COE) poly(5Gly3COE) poly(5Gly4COE)

23.3 −1.3 −15.5 −26.8 −32.3 22.7 2.3 −15.8 −28.6 −36.7

105.4 102.0 −b −b −b −b −b −b −b −b

Determined by DSC on the second heating cycle at 10 °C/min. Amorphous polymer.

substituted polymers were completely amorphous, and Tg was decreased from 22.7 to −36.7 °C, with an increase number of CH2CH2O moieties in the substituent group. Conversely, we E

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Macromolecules were delighted to find that the unsaturated poly(3Gly0COE) and poly(3Gly1COE) were semicrystalline polymers, and DSC profiles displayed obvious endothermic peaks at 105.4 and 102 °C, respectively (curves 1 and 2 in Figure 6). Such obvious melting and crystallization behaviors before the saturation of the backbone have not been observed in the previously reported alkyl- and ether-substituted regioregular ROMP polymers with even short side chains.59,62,65 Both the structure regularities coupled with the strong hydrogen-bonding interactions between glycine side chains are responsible for the crystallization behavior we observed. The promotion of crystallization by hydrogen-bonding interactions between side chains was further confirmed by Kobayashi’s paper that appeared during peer review of this paper.66 It reports the synthesis of highly regio-/stereoregular ROMP polymers with amide side chains, and the unsaturated polymers with a small substituent at the amide nitrogen displayed crystallinity.66 Besides the major melting transition, the shoulder peaks were also observed for poly(3Gly0COE) and poly(3Gly1COE), indicating there existed more than one type of crystal structure.61 DSC of the precision poly(3Gly2COE), poly(3Gly3COE), or poly(3Gly4COE) only showed glass transitions. The longer side chains suppressed polymer’s crystallinity, leading to an amorphous polymer as seen in other systems.59,62,65,67 Figure 7 shows the wide-angle X-ray diffraction (WAXD) profiles of the formed copolymers with different structure

crystallinity of the polymers. In addition, the distance (d) of crystalline planes in the polymers can be calculated by Bragg’s equation (2d sin θ = nλ). The calculated values of d are 4.52 and 4.09 Å, corresponding to two scattering peaks. The degree of crystallinity (Xc) of poly(3Gly0COE) and poly(3Gly1COE) was 21% and 35%, respectively, as estimated by the XRD profile. The effect of microstructure on the surface hydrophilicity of glycine-bearing polymers was then evaluated by water contact angle measurement. As shown in Figure 8, with increasing

Figure 8. Water contact angles of poly(3GlyxCOE)s (●) and poly(5GlyxCOE)s (◆); x represents the number of CH2CH2O moieties.

number of CH2CH2O moieties in the substituent group, the water contact angle monotonically decreased from 100° to 44° for poly(3GlyxCOE)s, and 89° to 18° for poly(5GlyxCOE)s, respectively. Moreover, poly(3GlyxCOE) with high trans-HT regularity exhibited much bigger water contact angle than its random 5-substituted analogues (e.g., 44° for poly(3Gly4COE) and 18° for poly(5Gly5COE)). The disparity in surface hydrophilicity between 3- and 5-substituted polymers was due to the structural variation. Obviously, precise microstructures facilitated the aggregation of polymer chains in an ordered manner on the substrate surface, leading to decreased surface free energy at the air−polymer interface;71 consequently, its water contact angle increased. This result suggests that regioand stereostructures are crucial for determining the surface hydrophilicity behaviors of the glycine-bearing polymers and that the surface hydrophilicity can be gradually changed by the regio- and stereostructures of the polymers. The resultant poly(3Gly4COE) and poly(5Gly4COE) were soluble in cold water at neutral pH. The thermoresponsiveness of these polymers was also investigated. Heating of the aqueous solution led to a fast transition from clear solution to turbid emulsion (Figure 9A). The thermoresponsive behavior in water was investigated at varying temperatures by measuring the light transmittance of the polymer solutions at a wavelength of 500 nm. To see the main effect of microstructure, the thermoresponsive was compared for poly(3Gly4COE) and poly(5Gly4COE) with the same degree of polymerization (DP) but different microstructural regularity (Table 1, entries 5, 6 and 11, 12). As shown in Figure 9B, when the DP for the glycine-bearing ROMP polymers was fixed at 40, precision poly(3Gly4COE) with high trans-HT regularity was more

Figure 7. Wide-angle X-ray diffraction (WAXD) of poly(3Gly0COE), poly(3Gly1COE), poly(5Gly0COE), and poly(5Gly1COE).

regularities. No diffraction was observed in the poly(5Gly0COE) and poly(5Gly1COE) with low structure regularity, confirming their amorphous nature. On the contrary, for poly(3Gly0COE) and poly(3Gly1COE) with high trans-HT regularity, sharp diffraction peaks were observed at 2θ values of 19.6° and 21.7°, demonstrating that the precision glycinebearing polymer is a semicrystalline polymer. These results illuminate that the precise microstructure control can affect the F

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Figure 9. (A) Visual turbidity change of poly(3Gly4COE) upon heating the aqueous solution. (B) Temperature dependence of transmittance for the aqueous solutions (2 mg/mL) of poly(3Gly4COE) and poly(5Gly4COE) with different DP (500 nm, heating at a rate of 1 °C min−1).

poly(3Gly4COE) and poly(5Gly4COE) upon heating is ascribed to the weakened hydrogen bonding between the (CH2CH2O)4CH3 moieties with water.72−74 It has already been demonstrated that the alternating copolymer was more soluble than the random copolymer in acidic water,75 which may be responsible for the higher Tc of poly(3Gly4COE). Indeed, the interaction preference between polymer chain and water might be changed depending on the placement fashion of hydrophilic side chain (precisely or random). Postpolymerization Modification of Regio-/Stereoregular Glycine-Bearing ROMP Polymers. Another notable feature of the regio-/stereospecific glycine-bearing polymers that were obtained by ROMP is the presence of internal transdouble bonds in the main chains. Because of the steric hindrance, internal trans-double bonds are less reactive than pendant double bonds, reported by Hoyle et al.76,77 Therefore, efficient and quantitative thiol−ene reaction of internal transdouble bonds still remains a challenge. Here, we investigated the thiol−ene reaction of methyl 2-mercaptoacetate, tert-butyl (2-mercaptoethyl)carbamate, 2-mercaptoethan-1-ol, and butane-1-thiol onto poly(3Gly4COE) via radical addition pathways by using 2,2-dimethoxy-2-phenylacetophenone (DMPA) as a radical photoinitiator and a thiol/olefin ratio of 50:1 (Scheme 3 and Table 3). After 4 h of exposure to UV light, the

soluble than irregular counterparts poly(5Gly4COE): it became turbid at Tc = 26.0 °C (Tc: cloud point), whereas poly(5Gly4COE) did so at a lower temperature, Tc = 24.7 °C. This phenomenon was also observed with polymers having lower DP (e.g., DP = 10), where poly(3Gly4COE) also exhibited higher Tc than that of poly(5Gly4COE). This indicates important differences in the thermoresponsive behavior of the glycine-bearing polymers with different microstructural regularity, despite having the same chemical composition and molecular weight. To gain deep insight into the phase transition of these glycine-bearing polymers, the temperature-variable 1H NMR analysis of the phase transition of the 2 mg/mL poly(3Gly4COE) and poly(5Gly4COE) solution was performed. At 20 °C, the protons of methoxy (m, δ = 3.3 ppm) and methylene (l, δ = 3.6 ppm) were clearly observed for poly(3Gly4COE) and poly(5Gly4COE) (Figure 10). Starting

Scheme 3. Thiol−Ene Addition of Poly(3Gly4COE)

Figure 10. 1H NMR spectra of poly(3Gly4COE)40 (A) and poly(5Gly4COE)40 (B) in D2O at various temperatures.

resultant polymers were purified by precipitation into large amount of diethyl ether and analyzed by 1H NMR spectroscopy and SEC. Fortunately, the addition of 2-mercaptoacetate to the less reactive internal trans-double bonds achieved >99% conversion of all alkene groups, with the double-bond proton resonances (δ = 5.59 ppm) disappearing and two new resonances (δ = 3.24 and 3.30 ppm) appearing, attributed toSCH2COOCH3 (Figure S70). The SEC analysis showed a slightly decrease in molecular weight due to the disparity in

from 25 °C, with the increase of temperature, characteristic peaks of poly(3Gly4COE) weakened substantially, along with a broadening in width. However, for the poly(5Gly4COE) sample, the characteristic signals (m, l) showed distinct weakening between 20° and 25° (Figure 10B). These results are consistent with the LCST values measured by UV−vis. In addition, these results also indicate that the dehydration of G

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Macromolecules Table 3. Postpolymerization Modification of Regio-/Stereoregular Glycine-Bearing Polymersa entry

polymer

thiol added

convb (%)

Mn,SECc (kg/mol)

Mw,SECc (kg/mol)

Đc

1 2 3 4 5

poly(3Gly4COE) MMAPoly(3Gly4COE) BMECPoly(3Gly4COE) MEPoly(3Gly4COE) BTPoly(3Gly4COE)

CH3OOCCH2SH BocNHCH2CH2SH HOCH2CH2SH CH3CH2CH2CH2SH

>99 46 50 45

22.8 19.5 27.9 23.2 22.4

4o.1 37.2 46.5 41.4 41.9

1.8 1.9 1.7 1.8 1.9

a

Conditions: 4 h, rt, hv, 365 nm, 36 W; [RSH]:[double-bond] = 50:1; entries 2 and 4 were performed in bulk; entries 3 and 5 were performed in THF. bDetermined by 1H NMR analysis. cDetermined by SEC in DMF (0.01 M LiBr), PS as standards.

hydrodynamic volume between MMAPoly(3Gly4COE) and poly(3Gly4COE) (Table 3). Higher activity and good solubility of 2-mercaptoacetate toward poly(3Gly4COE) are responsible for the efficient thiol−ene addition we observed. Conversely, the thiol−ene addition of less active tert-butyl (2-mercaptoethyl)carbamate, 2-mercaptoethan-1-ol, and butane-1-thiol onto poly(3Gly4COE) achieved lower conversion (46%, 50%, and 45%, respectively) over 4 h.

Youhua Tao: 0000-0002-2138-2592 Author Contributions

M.L. and F.C. contributed equally. Notes

The authors declare no competing financial interest.

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REFERENCES

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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.6b02244. Experimental details and characterization data (PDF)

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ACKNOWLEDGMENTS

This work is supported by “The Hundred Talents Program” from the Chinese Academy of Sciences, the National Natural Science Foundation of China (Grants 21474101, 51673192, and 21504092), Jilin Science and Technology Bureau (Grant 20160414001GH). We thank Prof. Jingyao Liu in Jilin University to provide the Gaussian09 programs.

CONCLUSION In summary, several semicrystalline polymers are reported by ROMP of new glycine-substituted monomers using G2 catalyst. ROMP of all 3-substituted monomers was regio- and stereoselective and thus afforded precision glycine-bearing polymers with high trans-HT regularity. In comparison, ROMP of 5-substituted monomers was neither regio- nor stereoselective. The effects of regio- and stereostructures on the polymer properties were systematically investigated. Unsaturated 3-substituted polymers exhibited melting behavior because of their semicrystalline structures. Such melting and crystallization behaviors before the saturation of the backbone have not been observed in the previously reported alkyl- and ether-substituted regioregular ROMP polymers. Both the structure regularities and the strong hydrogen-bonding interactions between glycine side chains are responsible for such substantial crystallinity. Meanwhile, 5-substituted random analogues are completely amorphous. Furthermore, it was observed that the surface hydrophilicity and thermoresponsiveness were also dependent on the regio- and stereostructures of the glycine-bearing polymers. Finally, the successful addition of 2-mercaptoacetate to the less reactive internal trans-double bonds of the polymers allowed the preparation of regiospecific glycine-bearing polymers with a range of characteristics in a simple procedure. Indeed, this work not only offers an attractive strategy which can be applied to precision amino acidcontaining polymers but also affords us abundant information to correlate the structure−property relationship of biomimetic materials.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (Y.T.). ORCID

Yunqi Li: 0000-0002-5190-3037 H

DOI: 10.1021/acs.macromol.6b02244 Macromolecules XXXX, XXX, XXX−XXX

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