synthesis of polymethylacrylamide carrying r-phenylglycine pendant groups and effect of hydrogen...

European Polymer Journal xxx (2013) xxx–xxx

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European Polymer Journal

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Synthesis of polymethylacrylamide carrying R-phenylglycinependant groups and effect of hydrogen bonds on main chainhelicity

0014-3057/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.eurpolymj.2013.10.032

⇑ Corresponding authors. Tel./fax: +86 451 82589543 (J. Bai), Tel./fax:+86 451 82589540 (W. Liu).

E-mail addresses: [email protected] (J. Bai), [email protected] (W.Liu).

Please cite this article in press as: Bai J et al. Synthesis of polymethylacrylamide carrying R-phenylglycine pendant groups and ehydrogen bonds on main chain helicity. Eur Polym J (2013), http://dx.doi.org/10.1016/j.eurpolymj.2013.10.032

Jianwei Bai ⇑, Chunhong Zhang, Lijia Liu, Wenbin Liu ⇑, Xiande Shen, Xiaodong Xu, Luan FanPolymer Materials Research Center, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin 150001, ChinaKey Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, HarbinEngineering University, Harbin 150001, China

a r t i c l e i n f o

Article history:Received 31 August 2013Received in revised form 30 October 2013Accepted 31 October 2013Available online xxxx

Keywords:Chiral vinyl monomerFree radical polymerizationOptical activity polymerSecondary structure

a b s t r a c t

A series of chiral methacrylamide derivatives, RR-PEBM, RS-PEBM, and R-PMBM, wereseparately synthesized and radically polymerized to obtain the corresponding polymers(poly(RR-PEBM)s, poly(RS-PEBM)s, and poly(R-PMBM)s) in the present study. An interest-ing effect of the chiral carbon atom, which was away from the backbone, on the formationsof the hydrogen bonds between the amide groups and chiroptical properties of polymerswas observed. The chiroptical properties of the resulting polymers were investigated indetail by polarimetry, circular dichroism (CD), and UV–Vis spectroscopies. The specificoptical rotation of poly(RS-PEBM) and poly(R-PMBM) showed a slight dependence on thesolvent polarity, but in contrast, the polarity of the polymerization solvents clearly affectedthe values of the specific rotation of the poly(RR-PEBM)s. The polymers prepared in toluenedisplayed a larger optical rotation and stronger cotton effects than the one prepared inmethanol. These results indicated that the hydrogen bonds formed between the amidegroups in the polymers played an important role in both the polymerization process andthe formation of the partial helical structure of the polymer. The secondary structure ofpoly(RR-PEBM) was relatively stable upon heating but unstable in THF by adding MeOH.

� 2013 Elsevier Ltd. All rights reserved.

1. Introduction group [15,16]. The optically active polymers, characterized

In recent decades, significant interest has focused onoptically active polymers due to their unique functionssuch as molecular recognition, catalytic activity inasymmetric transformations and also the opticalresolution for racemates [1–10]. The polymerization of achiral monomer is one of the most frequently used strate-gies to prepare optically active polymers [11–14]. In orderto increase the asymmetric coupling between the stereo-center in the side group and main chain, the chiral atomis usually directly linked to (or close to) the polymerizable

in the side-chain by the presence of an asymmetric carbonatom with a single chirality, may induce the backbone toassume a dissymmetric conformation with a prevailinghandedness, at least for sections [17].

Meanwhile, amino acids are constitutional componentsof peptides and proteins, which are able to produce highly-ordered hierarchical structures through intra- and inter-chain hydrogen bonds. The incorporation of a high degreeof amino acid chirality in polymer chains can enhance thepotential to form secondary structures or higher-orderedstructures. Amino acid- and peptide-based optically activepolymers, especially poly[(meth)acrylamide]s [18,19] andpoly[(meth)acrylates]s [20], exhibit biocompatibility, bio-degradability, and unique optical properties [21–23]. Aminoacids were introduced into helical polymers as side groupsby Endo’s [24–26] and Masuda’s groups [27–29]. Both

ffect of

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2 J. Bai et al. / European Polymer Journal xxx (2013) xxx–xxx

groups found that H-bonds between the side group residuesplayed an important role in the stabilization of the resultanthelical conformation. Wan et al. also reported that H-bondsbetween amino acid residues of alanine-bearing vinylter-phenyl helical polymers stabilized the helical conformationas well as steric repulsion of the bulky side groups, but it wassensitive to the solvent and pH value [30]. Although the H-bonds of the amino acid have been considered to stabilizethe conformation of polymers, more helical polymerscontaining amino acid residues are needed to further under-stand their impacts on the formation mechanism of thepolymer helical chains.

We now report the synthesis and optical properties of aseries of phenylglycine-bearing optically active polymers,poly{N-[(R)-((R)-1-phenylethylaminocarbonyl)-benzyl]methacrylamide} (poly(RR-PEBM), poly{N-[(R)-((S)-1-phe-nylethylaminocarbonyl)-benzyl]methacrylamide} (poly(RS-PEBM)), and poly{N-[(R)-phenylmethylaminocarbon-ylbenzyl]methacrylamide} (poly-(R-PMBM)). The effects ofthe polymerization solvents on the chiroptical propertiesof the obtained polymers were examined on the basis ofthe circular dichroism and specific optical rotation. It is con-vincible that the chiral carbon atom, which is away from thebackbone, has an obvious influence on the connection modeof the hydrogen bonds between the amino acid residues inthese polymers. Hydrogen bonds in these polymers have apositive effect on the stability of their conformation. There-fore, they are sensitive to the solvent and the chiropticalproperties of the polymers could be tuned by externalstimuli.

2. Experimental

2.1. Materials

2,20-Azobis-isobutyronitrile(AIBN) was purchased fromTianjin Kermel Chemical Co., Ltd. and used after recrystal-lization. (R)-Phenylglycine was purchased from AldrichChemical Co., Inc. and used without any further purifica-tion. (R)-1-phenethylamine and (S)-1-phenethylaminewere purchased from Shanghai Jingchun Chemical Co.,Ltd. Methacryloyl chloride (MAC) was purchased fromTianjin Kermel Chemical Co., Ltd. and freshly distilled be-fore use. l-ethyl-3-(3-dimethylaminopropy1)carbodiimidehydrochloride (EDCl) and 1-hydroxybenzotriazole(HOBt)was purchased from J&K Chemical Co., Ltd. THF, CHCl3,CH2Cl2 and toluene were distilled over calcium hydride.MeOH was distilled over calcium oxide. Other reagentswere commercially available and used without furtherpurification.

2.2. Measurements

The 1H and 13C NMR spectra were collected in CDCl3 orDMSO-d6 solution on a Bruker 500 MHz spectrometer. Thechemical shifts were recorded in ppm(d) relative to tetra-methylsilane. The weight- and number-average molecularweights (Mw and Mn, respectively) were estimated by a gelpermeation chromatography (GPC) apparatus equipped

Please cite this article in press as: Bai J et al. Synthesis of polymethylahydrogen bonds on main chain helicity. Eur Polym J (2013), http://dx.d

with a Waters 2414 refractive-index detector and a Water600 pump. The CD and UV–Vis spectra were measured in a1 mm path length using a Jasco J-815 spectropolarimeter.The sample solution was kept at the desired temperaturewith a PTC-423S/15 controller. Optical rotations (OR) weremeasured using a PerkinElmer 341 polarimeter. Fouriertransform infrared (FT-IR) spectra were recorded on aPerkinElmer Spectrum 100. Elemental analyses were per-formed on an Elementar Analyses system GmbH Vario ELinstrument.

2.3. Synthesis of novel chiral methacrylamide derivatives

2.3.1. N-[(R)-carboxylbenzyl]methacrylamide (R-CBM)Methacryloyl chloride (33 mmol) was added dropwised

into a solution of (R)-Phenylglycine (33 mmol) and NaOH(66 mmol) in H2O (60 ml) at 0 �C. The mixture was stirredat 0 �C for 3 h, and react overnight at room temperature.The solution was acidified with HCl (1 mol/L) to pH 2and extracted with CHCl3. Evaporation of the organic layerunder vacuum at room temperature gave a residue. Purifi-cation with recrystallization in toluene afforded the prod-uct as white solid (5.0 g). Yield 69%. 1H NMR (500 MHz,CDCl3, d(ppm)): 1.96 (s, 3H, ACH3), 5.61–5.62 (d, 1H,ANCH), 5.40 (s, 1H, @CH2), 5.78 (s, 1H, @CH2), 6.80–6.82(d, 1H, ANH), 7.33–7.41 (m, 5H, phenyl ring), 10.04 (s,1H ACOOH). mp: 125.0–125.8; ½a�25

365 ¼ �668�

ðc ¼ 1 mg=mL;THFÞ.

2.3.2. N-{(R)-[(R)-1-phenylethylaminocarbonyl]benzyl}methacrylamide (RR-PEBM)

(R)-CBM (8 mmol) was dissolved in anhydrous CH2Cl2

(200 ml) and the resulting solution was cooled to 0 �C.(R)-1-phenethylamine (8 mmol) was added and solutionwas stirred at 0 �C for 15 min. Triethylamine (16 mmol)was added and the solution was stirred at 0 �C for10 min. EDCl (12.8 mmol) was added, followed by HOBt(12 mmol) at 0 �C. The reaction mixture was allowed to stirfor 20 min at 0 �C and then warmed to rt and stirred over-night. The mixture was washed twice with saturatedNaHCO3 and brine respectively. The organic layer wasdried over anhydrous Na2SO4 and concentrated. The resi-due was purified by column chromatography on silica gel(chloroform/acetone (20/1, v/v) as eluent) to give 1.3 g ofproduct as white solid. Yield 65%. 1H NMR (500 MHz,CDCl3, d(ppm)): 1.44–1.46 (d, 3H, ACH(CH3)), 1.96 (s, 3H,ACH3), 5.63–5.64 (d, 1H, ANCH), 5.35 (s, 1H, @CH2), 5.77(s, 1H, @CH2), 6.98–6.99 (d, 2H, ANH), 5.05–5.08 (m, 1H,ACH(CH3)) 6.37–7.34 (m, 10H, phenyl ring). IR (KBr)3307 (NAH), 3280 (NAH), 1648 (C@O), 2973 (CAH),1607, 1495 (phenyl), 1681 (C@C); Anal. Calcd. ForC20H22N2O2: C, 74.53; H, 6.83; N, 8.70. Found: C, 74.48;H, 7.08; N, 8.55; MS: m/z = 322 (Calcd. 322.40);½a�25

365 ¼ �165�ðc ¼ 1 mg=mL;THFÞ.

2.3.3. N-{(R)-[(S)-1-phenylethylaminocarbonyl]benzyl}methacrylamide (RS-PEBM)

Yield 58%. 1H NMR (500 MHz, CDCl3, d(ppm)): 1.96 (s,3H, ACH3), 5.63–5.64 (d, 1H, ANCH), 5.36 (s, 1H, @CH2),5.71 (s, 1H, @CH2), 6.92–6.93 (d, 2H, ANH), 5.01–5.10

crylamide carrying R-phenylglycine pendant groups and effect ofoi.org/10.1016/j.eurpolymj.2013.10.032


J. Bai et al. / European Polymer Journal xxx (2013) xxx–xxx 3

(m, 1H, ACH(CH3)) 6.37–7.35 (m, 10H, phenyl ring). IR(KBr) 3306 (NAH), 3283 (NAH), 1648 (C@O), 2973(CAH), 1607, 1493 (phenyl), 1682 (C@C); Anal. Calcd. ForC20H22N2O2: C, 74.53; H, 6.83; N, 8.70. Found: C, 74.49;H, 7.03; N, 8.60; MS: m/z = 322 (Calcd. 322.40);½a�25

365 ¼ �404�ðc ¼ 1 mg=ml;THFÞ

2.3.4. N-[(R)-phenylmethylaminocarbonylbenzyl]methacrylamide (R-PMBM)

Yield 50.5%. 1H NMR (500 MHz, CDCl3, d(ppm)): 1.91 (s,3H, ACH3), 5.67–5.69 (d, 1H, ANCH), 5.33 (s, 1H, @CH2),5.71 (s, 1H, @CH2), 6.72 (s, 1H, ACHNH), 7.09 (s, 1H, ACH2-

NH), 4.40–4.41 (d, 2H, ANHCH2) 7.11–7.42 (m, 10H, phenylring). IR (KBr) 3306 (NAH), 3280 (NAH), 1648 (C@O), 2973(CAH), 1608, 1491 (phenyl), 1682 (C@C); Anal. Calcd. ForC19H20N2O2: C, 74.03; H, 6.49; N, 9.09. Found: C, 73.99;H, 6.69; N, 8.99; MS: m/z = 322 (Calcd. 322.40)½a�25

365 ¼ �290�ðc ¼ 1 mg=mL;THFÞ.

2.4. Radical polymerization

The radical polymerizations of the monomers werecarried out in various solvents, such as CHCl3, THF, CH3OHand toluene, under dry nitrogen atmosphere in glass tubeusing AIBN as an initiator at 60 �C. After the polymeriza-tions were completed, the reaction mixtures were pouredinto a large amount of mixed CH3OH/H2O (2/1, v/v) toprecipitate the products. The collected polymers werepurified by reprecipitate from a CH3OH/H2O system inthree cycles and dried under reduced pressure at 60 �Cfor 12 h.

2.5. Polymer by acid treatment

The P4 (0.15 mmol) was dissolve in mixed THF/CH3-

COOH (1/9, v/v) (100 ml) and the resulting solution wasallowed to stir for 12 h at room temperature. Then, thereaction mixtures were poured into a large amount ofH2O to precipitate the products. The P40 was obtainedunder reduced pressure at 60 �C for 12 h.

Scheme 1. Synthesis of monomers RR-PEBM, RS-PEBM, and R-PMBM and t(R-PMBM).


3. Results and discussion

3.1. Synthesis and polymerization of monomers

The synthetic procedures for the three monomers, RR-PEBM, RS-PEBM, and R-PMBM, are illustrated in Scheme 1.The key intermediate, N-[(R)-carboxylbenzyl]methacryla-mide, was prepared according to previous publications[31]. The amidation reaction by chiral 1-phenylethylamineunder basic conditions produced the desired monomers.The chemical structures of the monomers were confirmedby 1H NMR, FT-IR spectroscopy, and elemental analysis.

The free radical polymerizations of the three mono-mers were carried out in solution with AIBN as theinitiator at 60 �C. The results are summarized in Table 1.The polymerizations in THF and CHCl3 homogeneouslyproceeded, while in the case of toluene and methanolused as the solvent, the formed polymers gradually pre-cipitated with the progress of the reaction. The polymeryields were found to be lower in toluene as compared tothe THF system under the same conditions. This may bedue to the poor solubility of the monomers and growingpolymers in toluene. In fact, these polymers were solublein THF, DMF, CHCl3, and DMSO, but insoluble in n-hex-ane, diethyl ether, toluene, and MeOH. In addition, vari-ous solvents were used to investigate the effect of thepolymerization solvent on the chiroptical properties ofthe resultant polymers. The data in Table 1 indicate thatthere is an increase in the absolute values of the specificrotation with the polymerization solvents in the order ofMeOH < THF < CHCl3 < Toluene for these polymers. Thepoly(RR-PEBM) obtained in toluene has a maximummolecular weight with a relatively low polydispersity,and it exhibites the highest positive specific rotation of½a�25

365 ¼ þ192�ðP4Þ. Moreover, when toluene is selected

as the solvent, poly(RS-PEBM) shows highest negativespecific rotation of ½a�25

365 ¼ �187�ðP8Þ, probably because

the monomer itself in toluene favors the formation ofhydrogen bonds. When MeOH is selected as the solvent,the intramolecular and intermolecular H-bonds in themonomer may be replaced by the methanol moleculesduring polymerization process (Scheme 2c).

heir corresponding polymers poly(RR-PEBM), poly(RS-PEBM), and poly



Table 1Radical polymerization of monomers using AIBN as initiator at various conditions.a

Sample code Monomer Solvent Yieldb (%) Mnc (�104) Mw/Mn

c ½a�25365 (�)d

P1 RR-PEBM MeOH 81 0.9 2.16 +101P2 RR-PEBM CHCl3 88 1.5 1.94 +165P3 RR-PEBM THF 97 1.3 2.77 +157P4 RR-PEBM Toluene 72 2.3 2.03 +192P5 RS-PEBM MeOH 86 0.5 2.16 �171P6 RS-PEBM CHCl3 93 0.7 1.90 �180P7 RS-PEBM THF 91 1.6 2.57 �183P8 RS-PEBM Toluene 81 1.5 2.41 �187P9 R-PMBM MeOH 92 0.8 1.89 �38P10 R-PMBM CHCl3 88 1.8 1.94 �41P11 R-PMBM THF 91 1.5 2.37 �42P12 R-PMBM Toluene 89 1.6 1.83 �44

a Polymerization conditions: [monomer]0 = 0.5 mol/L; [initiator]0 = 0.02 mol/L; temperature, 60 �C; time, 24 h.b Diethyl ether- and water-insoluble part.c Determined by GPC on the basis of a calibration of polystyrene standards and using THF as eleuent at 35 �C.d Specific optical rotation (½a�25

365) of polymers were measured in a 1 dm cell at a concentration of ca.1 mg/mL in THF.


3.2. Hydrogen-bond interaction

It is well-known that amino acids and peptides in bio-logical systems favor the formation of hydrogen bonds[32,33]. To elucidate the influence of the hydrogen bondon the conformation of these polymers, we performed a1H NMR titration experiment on the monomer RS-PEBM,in which RS-PEBM was used as a model compound of thepolymers, because the highly broadened signals in the 1HNMR spectrum of the polymer were expected to provideno useful information. Fig. 1 shows the 1H NMR spectraof the RS-PEBM solutions in deuteriochloroform of differ-ent concentrations at room temperature. The position ofthe resonance peak of its amide proton changes with thevariation in the concentration in the aprotic solvent. Thedilute solution of RS-PEBM (50 mg/mL) exhibits a reso-nance peak of the amide proton (ACONH) at �6.05 ppm(marked by the asterisk in Fig. 1A). When the solution con-centration is gradually increased, the amide signals areprogressively downfield shifted. At a concentration of300 mg/mL, the amide signal of RS-PEBM is downfieldshifted to �6.92 ppm. As the solution concentration in-creases to 330 mg/mL, the resonance peak of the amideproton overlaps with the resonance peak of the phenyl.When the solution concentration is 600 mg/mL, the reso-nance peak of the amide proton is shifted to �7.54 ppm.

a bScheme 2. Schematic diagram of intramolecular hydrogen-bonding formationbonding formation between monomer and monomer (b) or MeOH (c) molecule


In addition, the peaks of the amide protons of the polymerslightly broaden (Fig. 1J). Noting that chloroform is anaprotic solvent, the downfield shift of the amide peakshould be due to the formation of a hydrogen bond. Whena proton is involved in the hydrogen bond, its electron isshared by two electronegative elements and its electrondensity is decreased. As a result, the proton is deshieldedand comes into resonance at a lower field [30,32]. The ef-fect of the H-bonds on the adjacent proton is also revealedby the downfield shift in the resonance peak of the pro-ton(ANCH). Plotting the NMR data reveals that the peakposition of the amide resonance downfield shifts with anincrease in the concentration of the chloroform solutionin a linear fashion (Fig. 2). That is to say, the populationof the hydrogen bonding complexes of RS-PEBM linearlyincreases with the concentration. The result indicates thatRS-PEBM forms molecular clusters in solution due tostrong self-association via the formation of hydrogenbonds between the NAH group of one molecule and theC@O group of the other. Upon binding to another electro-negative element of oxygen, the amide proton is deshield-ed, leading to the observed downfield shift in its resonancesignal as illustrated in Scheme 2a or b.

Moreover, the solvent effect on the hydrogen bondingwas investigated by gradually varying the solvent naturein both binary mixture of DMSO/chloroform. Because

cbetween residue group of monomer (a) and intermolecular hydrogen-

s.



Fig. 1. 1H NMR spectra of chloroform-d solutions of the monomer RS-PEBM with varying concentrations (mg/mL): (A) 50, (B) 100, (C) 150, (D)200, (E) 250, (F) 300, (G) 330, (H) 360, (I) 400, and (J) 600. The resonancepeaks of the amide proton (CONH) are marked with asterisk (*) and uparrow ("). The resonance peaks of the proton (ANCH), which is close tothe vinyl, are marked with down arrow (;).

Fig. 2. Concentration dependence of the chemical shift of the resonancepeak of the amide proton of RS-PEBM (marked by the asterisk in Fig. 1) asa function of concentration.

Fig. 3. 1H NMR spectra of DMSO-d6/chloroform-d solutions of RS-PEBM(50 mg/mL) with varying ratios of DMSO-d6 (vol%): (A) 0, (B) 15, (C) 30,(D) 50, (E) 70, and (F) 100. The resonance peaks of the amide proton(CONH) are marked with asterisk (�) and up arrow ("). The resonancepeaks of chloroform are marked with down arrow (;).


DMSO is capable of hydrogen-bonding solvent and can beused as a heterocomplexation probe. we performed a 1HNMR experiment on RS-PEBM in deuterated DMSO/chloro-form mixtures. With the addition of DMSO fraction, twodownfield shifts are observed in the signals of the amideprotons of RS-PEBM (Fig. 3). These low field shift are obvi-ously caused by the formation of intermolecular H-bondsbetween the NAH group of RS-PEBM and the S@O groupof DMSO.

BecauseRR-PEBM andRS-PEBM have two electron-acceptor groups (NAH) and two electron-donor groups(C@O), we compared the FT-IR spectra of RR-PEBM andRS-PEBM to clarify the effect of the H-bonds on the confor-mation of the monomers under different conditions. It iswell-known that the stretching vibration of the carbonylin the free amide (amide I) is present at 1670 cm�1, but


it can be influenced by hydrogen bonding [34]. The absorp-tion peaks in the FT-IR spectra of two monomers are shownin Fig. 3. Their FT-IR spectra appear two main peaks (peak Iand peak II) for amide I. The absorption peak I in the twomonomers appears at the same wave number(1671 cm�1) in the solid state and in the chloroform solu-tion of varying concentrations. In contrast to this, there aredifferent wave numbers for peak II in the monomers. In the1 mg/mL solution, the signals of peak II are present at1647 cm�1 for the two monomers.

While in the solid, the characteristic peak II of RR-PEBMand RS-PEBM are present at 1638 and 1643 cm�1, respec-tively, suggesting that amide I assigned peak I to theC@O group intramolecular H-bonds and peakII to theC@O group intermolecular H-bonds for the monomers.Moreover, Fig. 4a shows that the intensity of peak I isstronger than that of peak II of RR-PEBM in the liquid andsolid state, indicating that the binding mode in RR-PEBMis dominated by the intramolecular H-bond, and the modeof intermolecular H-bond is minor (Scheme 2a). However,for RS-PEBM, the intensity of peak II gradually increasesand exceeds that of peak I with the concentration of RS-PEBM increases as shown in Fig. 4b. It implies that thebinding mode of the intermolecular H-bonds dominate inRS-PEBM versus the intramolecular H-bonds.(Scheme 2b). This result illustrates that the configurationof chiral carbon atom, which is away from the backbone,drives the connection mode of the hydrogen bonds be-tween the amino acid residues in the monomers.

Since the 1H NMR signals of the polymers are broad, itcould not be used to probe the H-bonds. Therefore, theirH-bonding interaction was investigated by FT-IR spectros-copy. Fig. 5 shows the FT-IR spectra of poly(RR-PEBM) andpoly(RS-PEBM) in the solid state and in a solution at vary-ing concentrations. The characteristic peak I and peak II ofamide I are assigned to the intramolecular H-bonds andintermolecular H-bonds of the polymers, respectively.With an increase in the concentrations from 1 to 160 mg/mL, the hydrogen bonds are mostly intermolecular in the



Fig. 4. FT-IR spectra of (a) RR-PEBM in the solid state and its solution in CHCl3 at different concentrations (1�160 mg/mL) and (b) RS-PEBM in the solid stateand its solution in CHCl3 at varying concentrations (1�160 mg/mL).

Fig. 5. FT-IR spectra of (a) P4 in the solid state and its solution in CHCl3 at different concentrations (1�160 mg/mL) and (b) P8 in the solid state and itssolution in CHCl3 at varying concentrations (1�160 mg/mL).


polymers, probably because the formation of intermolecu-lar H-bonds between NAH and the carbonyl groups occurnot only along the polymer main chain but also interchainin polymers. However, Their results are similar to themonomer, the intramolecular H-bonds in poly(RR-PEBM)are of significant proportion compared to that in poly(RS-PEBM).

3.3. Conformation of polymers in solution

The chiroptical properties of the monomers and the cor-responding polymers were examined by polarimetry. Forpoly(RS-PEBM) and poly(R-PMBM), the maximum valuesof ½a�25

365 are, respectively, �171o and �38o, which are big-ger than that of their monomers (�404o and �290o). Espe-cially, a remarkable change in the optical activity isobserved during the transformation from RR-PEBM(½a�25

365 ¼ �163�) to the corresponding polymers

(½a�25365 ¼ þ101

�to þ 192

�). The opposite sign of poly(RR-


PEBM) compared to the monomer from which it is formedindicates that the optical activity of the poly(RR-PEBM)does not solely arise from the chirality of the side groups,but also from the chiral secondary structure, most likelywith a helical conformation, when the polymer main chainis generated [35–37]. Apparently, the formation of thehelical main-chain should be attributable to the asymmet-ric induction of the chiral pendants in the monomer unitsduring polymerization. However, the polarity of the poly-merization solvents clearly affects the values of the specificrotation of the resulting polymers (Fig. 6). The absolutevalues of the specific rotation increase with the polymeri-zation solvents in the order of MeOH < THF < CHCl3 < Tolu-ene for the polymers. Based on a comparison to thecorresponding poly(RS-PEBM)s and poly(R-PMBM)s, obvi-ous changes could be observed in values of the specificrotation for poly(RR-PEBM)s in the opposite direction. Inaddition, The specific optical rotation of poly(RS-PEBM)and poly(R-PMBM) show a slight dependence on the



Fig. 6. Dependence of specific optical rotation ½a�25365 on the polymeriza-

tion solvents for (j) poly(RR-PEBM), (N) poly(R-PMBM), and (d) poly(RS-PEBM) in THF(c = 1 mg/mL), respectively.

Table 2The specific optical rotations (½a�25

365=�) of polymers in various solvents.a

Polymerb CHCl3 DMF Acetone DMSO CH3COOHc

P4 184 160 156 152 200P8 �180 �182 �175 �184 �186

a Specific optical rotations in unit of degree were measured in a 1 dmcell at a concentration of ca. 1 mg/mL at 25 �C.

b The polymers were obtained in toluene.c 10% THF were added to make the sample dissolve completely.


solvent polarity, but in contrast, the polarity of the poly-merization solvents clearly affect the values of the specificrotation of the poly(RR-PEBM)s. It implies that the chiralcarbon atom, which is away from the backbone, has anobvious influence on both the polymerization processand the optical activity of the obtained polymers.

The results described above led to the hypothesis thatthe hydrogen bonding networks between the pendantamide groups may have an effect on the conformation ofthe polymers. Therefore, various solvents were used toprobe the relationship between the H-bonds and confor-mation of the polymers. The ½a�25

365 of poly(RR-PEBM) (P4)and poly(RS-PEBM) (P8) were measured in various solvents

Fig. 7. The CD (up) and UV–Vis (down) spectra of (a) RR-PEBM, P4, and P40 in THMeOH with various compositions (100/0–40/60 v/v) at r.t. (c = 0.5 mg/mL).


(Table 2). It can be seen that no essential change is ob-served on the optical values of poly(RS-PEBM)s under thedifferent conditions. However, in solvents as H-bondacceptors, such as DMF, acetone, and DMSO, relativelylower values of the specific rotation are observed forpoly(RR-PEBM). While in CHCl3, the higher ½a�25

365 of 184o

is observed. A higher optical value is also observed in aceticacid. The reason for this is that the acetic acid break theintramolecular H-bonds of poly(RR-PEBM), and it producesan acetate salt of the amide. The electrostatic repulsion ofthe ionic amide would result in maintaining the helicalconformation of poly(RR-PEBM) in acetic acid [27]. Whenthe poly(RR-PEBM) dissolved in acetic acid/THF (1/9 v/v)was poured into a large amount of H2O to precipitate thepolymer (P40), which showed a significant decrease in theoptical value (½a�25

365 ¼ 58�) than the original one

(½a�25365 ¼ 200

�). These results indicate that after removing

the acetic acid molecules in the system, the one-handedhelical conformation of the original polymer could not bemaintained and the reformed H-bonds in the polymercould not retain the original conformation of the polymer,which it may be caused by the steric effect of the bulkypendent groups.

Fig. 7a shows the CD and UV–Vis spectra of the monomer(RR-PEBM) and polymers (P4 and P40) in THF. They exhibitalmost similar UV–Vis spectral patterns. However, thereare considerable differences in the CD fashions among them.While RR-PEBM only shows a CD signal at 228 nm, P4 exhib-its a plus CD signal at 218 nm and minus CD signal at230 nm. These prove that it adopts a helical conformationwith a preferred screw sense. In comparison to the corre-sponding P4, obvious changes could be observed in the CDsignals of P40. Both of them have a plus CD signal at around218 nm and minus CD signal at around 232 nm, but signifi-cant changes take place in the CD signal intensity of thepolymers. The changes are attributed to a recombinantintramolecular hydrogen bond and their reduced effectiveconjugation length inside the polymers. That is to say, thehelix stability of the polymer depends on the orderedarrangement of the chiral derivative along the polymerbackbone through the formation of hydrogen bonds, thebreakage of which will trigger a helix–coil transition.

The conformations of the optically active helicalpolymers and biomolecules are usually sensitive to

F and (b) P4 in THF at different temperatures and (c) P4 measured in THF/




temperature changes [38]. When the temperature exceedstheir tolerable limit, their unique helical conformationscan be destroyed and random coils formed [39]. Thus,poly(RR-PEBM) was measured at different temperaturesto study its conformational stability. Fig. 7b depicts thetemperature dependence of the CD and UV–Vis spectra ofpoly(RR-PEBM) measured in THF. These observations re-veal that heating a THF solution of poly(RR-PEBM) led toonly a slight decrease in the intensity of the cotton effect.This enhanced thermal stability is in contrast to the insta-bility of the helical conformation of polymers from mono-substituted acetylenes [40]; that is, the chiropticalproperties of the helical polyacetylenes drastically de-crease with the increasing temperature unless they possessbulky substituents [41,42].

Fig. 7c displays the CD and UV–Vis spectra of poly(RR-PEBM) measured in mixtures of THF/MeOH with variouscompositions at room temperature. While the UV–Visabsorption of poly(RR-PEBM) does not change with anincreasing fraction of methanol in THF, the CD signals ataround 230 nm sharply decrease. This means that the con-formational transition took place from the helix to randomcoil, which should stem from the loss of the intramolecularhydrogen bonds by adding methanol. It can be assumedthat methanol, a protic solvent, effectively destroys theintramolecular hydrogen bonds between the amide groupsof the side chains. Based on these results, we can concludethat the hydrogen bonds are especially affected by polarsolvents, resulting in deformation of the helical structure.

4. Conclusions

We reported the synthesis of a series of (R)-phenylgly-cine-modified N-phenylmethacrylamide derivatives andtheir corresponding polymers, poly(RR-PEBM), poly(RS-PEBM), and poly(R-PMBM), via radial polymerization. Themolecular weight and the specific optical rotation of theresultant polymers significantly depended on the polymer-ization solvents. In most cases, the polymerizationperformed in toluene produced a higher molecular weightas compared to the methanol system. When toluene wasapplied, the absolute values of the specific optical rotationsof poly(RR-PEBM), poly(RS-PEBM), and poly(R-PMBM)reached their respective maxima under certain conditions.However, the chiral carbon atom, which is away from thebackbone, has an obvious influence on both the polymeri-zation process and the optical activity of the obtained poly-mers. The molecular interaction of the hydrogen bondsbetween the amino acid residues in the polymer chainsare verified by the 1H NMR studies through the indirectspectral measurement using the monomer as a modelcompound. The IR results of the monomers and polymershave led us to conclude that intermolecular H-bonds be-tween the amide of amino residues is the major character-istic in RS-PEBM. In contrast, RR-PEBM in solventsprimarily form intramolecular H-bonds, which may resultin the formation of a partial helical conformation of thecorresponding polymers. The secondary structure ofpoly(RR-PEBM) is relatively stable upon heating, but unsta-ble in THF by adding MeOH.


Acknowledgments

This work was financially supported by the NationalNatural Science Foundation of China (No. 51103030), theFundamental Research Funds for the Central Universities(Nos. HEUCFT1009, HEUCF201310009, HEUCF201310004and HEUCFR1227) and Daicel Corporation (Tokyo, Japan).

The authors are grateful to Professor Y. Okamoto for hissuggestions on this work.

References

[1] Okamoto Y, Nakano T. Asymmetric polymerization. Chem Rev1994;94(2):349–72.

[2] Aoki T, Shinohara K-i, Kaneko T, Oikawa E. Enantioselectivepermeation of various racemates through an optically activepoly{1-[dimethyl(10-pinanyl)silyl]-1-propyne} membrane.Macromolecules 1996;29(12):4192–8.

[3] Itsuno S, Paul DK, Salam MA, Haraguchi N. Main-chain ionic chiralpolymers: synthesis of optically active quaternary ammoniumsulfonate polymers and their application in asymmetric catalysis. JAm Chem Soc 2010;132(9):2864–5.

[4] Xi X, Liu G, Lu W, Jiang L, Sun W, Shen Z. Optically active copolymersof N-(oxazolinyl)phenylmaleimides with methyl methacrylate:synthesis and chiral recognition ability. Polymer 2009;50(2):404–9.

[5] Luo M, Zhang J, Wan XH. A novel chiral polyacetylene containinganthraquinone imide and its near-infrared properties. Acta PolymSin 2013;4:443–9.

[6] Nakano T. Optically active synthetic polymers as chiral stationaryphases in HPLC. J Chromatogr A 2001;906(1–2):205–25.

[7] Tang Z, Iida H, Hu H-Y, Yashima E. Remarkable enhancement of theenantioselectivity of an organocatalyzed asymmetric henry reactionassisted by Helical poly(phenylacetylene)s bearing cinchona alkaloidpendants via an amide linkage. ACS Macro Lett 2012;1(2):261–5.

[8] Song C, Zhang C, Wang F, Yang W, Deng J. Chiral polymericmicrospheres grafted with optically active helical polymer chains:a new class of materials for chiral recognition and chirally controlledrelease. Polym Chem 2013;4(3):645–52.

[9] Haraguchi N, Kiyono H, Takemura Y, Itsuno S. Design of main-chainpolymers of chiral imidazolidinone for asymmetric organocatalysisapplication. Chem Commun 2012;48(33):4011–3.

[10] Iida H, Iwahana S, Mizoguchi T, Yashima E. Main-chain opticallyactive riboflavin polymer for asymmetric catalysis and itsvapochromic behavior. J Am Chem Soc 2012;134(36):15103–13.

[11] Cheuk KKL, Lam JWY, Li BS, Xie Y, Tang BZ. Decorating conjugatedpolymer chains with naturally occurring molecules: synthesis,solvatochromism, chain helicity, and biological activity ofsugar-containing poly(phenylacetylene)s. Macromolecules2007;40(8):2633–42.

[12] Green MM, Jha SK. The road to chiral amplification in polymersoriginated in Italy. Chirality 1997;9(5–6):424–7.

[13] Schlitzer DS, Novak BM. Trapped kinetic states, chiral amplificationand molecular chaperoning in synthetic polymers: chiral inductionin polyguanidines through ion pair interactions. J Am Chem Soc1998;120(9):2196–7.

[14] Aoki T, Ohshima M, Shinohara K-i, Kaneko T, Oikawa E.Enantioselective permeation of racemates through a solid (+)-poly{{2-[dimethyl(10-pinanyl)silyl]norbornadiene}} membrane.Polymer 1997;38(1):235–8.

[15] Sakai R, Sakai N, Satoh T, Li W, Zhang A, Kakuchi T. Strict sizespecificity in colorimetric anion detection based onpoly(phenylacetylene) receptor bearing second generation lysinedendrons. Macromolecules 2011;44(11):4249–57.

[16] Xu XD, Zhu YQ, Li H, Feng SW, Dai HC, Shen XD, et al. Stereospecificradical polymerization of optically active (meth)acrylamides: studyon the mechanism of stereocontrol. Acta Polym Sin 2013;3:274–80.

[17] Zhi J, Zhu Z, Liu A, Cui J, Wan X, Zhou Q. Odd�even effect in free radicalpolymerization of optically active 2,5-bis[(40-alkoxycarbonyl)-phenyl]styrene. Macromolecules 2008;41(5):1594–7.

[18] Hopkins TE, Wagener KB. Chiral polyolefins. Adv Mater 2002;14(23):1703–15.

[19] Xu X, Feng S, Zhu Y, Li H, Shen X, Zhang C, et al. Stereospecific radicalpolymerization of optically active (S)-N-(2-hydroxy-1-phenylethyl)methacrylamide catalyzed by Lewis acids. Eur Polym J 2013;49(11):3673–80.


http://refhub.elsevier.com/S0014-3057(13)00524-7/h0005



































































[20] Bush SM, North M. Synthesis of addition polymers derived fromenantiomerically pure amino acids. Polymer 1998;39(4):933–41.

[21] Morioka K, Suito Y, Isobe Y, Habaue S, Okamoto Y. Synthesis andchiral recognition ability of optically active poly{N-[(R)-a-methoxycarbonylbenzyl]methacrylamide} with various tacticitiesby radical polymerization using Lewis acids. J Polym Sci, Part A:Polym Chem 2003;41(21):3354–60.

[22] Kakizawa Y, Harada A, Kataoka K. Glutathione-sensitive stabilizationof block copolymer micelles composed of antisense dna andthiolated poly(ethylene glycol)-block-poly(l-lysine): a potentialcarrier for systemic delivery of antisense DNA. Biomacromolecules2001;2(2):491–7.

[23] Barrera DA, Zylstra E, Lansbury PT, Langer R. Synthesis and RGDpeptide modification of a new biodegradable copolymer: poly(lacticacid-co-lysine). J Am Chem Soc 1993;115(23):11010–1.

[24] Kudo H, Sanda F, Endo T. Synthesis and radical polyaddition ofoptically active monomers derived from cysteine. Macromolecules1999;32(25):8370–5.

[25] Sanda F, Yokoi M, Kudo H, Endo T. Synthesis and reaction of b-hydroxyaspartic acid-based polymethacrylate. J Polym Sci, Part A:Polym Chem 2002;40(16):2782–8.

[26] Kudo H, Nagai A, Ishikawa J, Endo T. Synthesis and self-polyaddition ofoptically active monomers derived from tyrosine. Macromolecules2001;34(16):5355–7.

[27] Gao G, Sanda F, Masuda T. Synthesis and properties of amino acid-based polyacetylenes. Macromolecules 2003;36(11):3932–7.

[28] Zhao H, Sanda F, Masuda T. Synthesis and helical conformation ofpoly(N-propargylamides) carrying L-aspartic acid in the side chain. JPolym Sci, Part A: Polym Chem 2005;43(21):5168–76.

[29] Sanda F, Araki H, Masuda T. Synthesis and properties of Serine- andThreonine-based helical Polyacetylenes. Macromolecules2004;37(23):8510–6.

[30] Zhu Z, Cui J, Zhang J, Wan X. Hydrogen bonding of helical vinylpolymers containing alanine moieties: a stabilized interaction ofhelical conformation sensitive to solvents and pH. Polym Chem2012;3(3):668–78.

[31] Sanda F, Nakamura M, Endo T. Syntheses and radical polymerizationbehavior of novel optically active methacrylamides having (L)-leucine structure in the side chains. J Polym Sci, Part A: Polym Chem1998;36(15):2681–90.


[32] Cheuk KKL, Lam JWY, Lai LM, Dong Y, Tang BZ. Syntheses, hydrogen-bonding interactions, tunable chain helicities, and cooperativesupramolecular associations and dissociations ofpoly(phenylacetylene)s bearing l-valine pendants: toward thedevelopment of proteomimetic polyenes�. Macromolecules2003;36(26):9752–62.

[33] Fu W, Zhang R, Li B, Chen L. Hydrogen bond interaction anddynamics in PMMA/PVPh polymer blends as revealed by advancedsolid-state NMR. Polymer 2013;54(1):472–9.

[34] Lin SY, Chen KS, Liang RC. Thermal micro ATR/FT-IR spectroscopicsystem for quantitative study of the molecular structure of poly(N-isopropylacrylamide) in water. Polymer 1999;40(10):2619–24.

[35] Lai LM, Lam JWY, Tang BZ. Synthesis and chiroptical properties ofL-valine-containing poly(phenylacetylene)s with (a)chiral pendantterminal groups. J Polym Sci, Part A: Polym Chem 2006;44(6):2117–29.

[36] Nakano T, Okamoto Y, Hatada K. Asymmetric polymerization oftriphenylmethyl methacrylate leading to a one-handed helicalpolymer: mechanism of polymerization. J Am Chem Soc1992;114(4):1318–29.

[37] Chen JP, Gao JP, Wang ZY. Long-distance chirality transfer inpolymerization of isocyanides bearing a remote chiral group.Polym Int 1997;44(1):83–7.

[38] Tang HZ, Boyle PD, Novak BM. Chiroptical switching polyguanidinesynthesized by helix-sense-selective polymerization using [(R)-3,30-dibromo-2,20-binaphthoxy](di-tert-butoxy)-titanium(IV) catalyst. JAm Chem Soc 2005;127(7):2136–42.

[39] Zhang C, Liu F, Geng Q, Zhang S, Shen X, Kakuchi R, et al. Synthesis ofa novel one-handed helical poly(phenylacetylene) bearing poly(l-lactide) side chains. Eur Polym J 2011;47(10):1923–30.

[40] Bai JW, Shen XD, Liu WB, Zhang CH, Xiao H, Xu XD. Synthesis andchiral recognition ability of optically active poly(methacrylamide)with side chains. Acta Polym Sin 2013;4:419–25.

[41] Ciardelli F, Lanzillo S, Pieroni O. Optically active polymers of 1-alkynes. Macromolecules 1974;7(2):174–9.

[42] Yashima E, Huang S, Matsushima T, Okamoto Y. Synthesis andconformational study of optically active poly(phenylacetylene)derivatives bearing a bulky substituent. Macromolecules1995;28(12):4184–93.





















































































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