Synthesis of Novel Amphiphilic Polyisocyanate Block Copolymer with

Feb 25, 2014 - Chae, Seo, Bak, and Lee. 2018 51 (3), pp 697–704. Abstract: To achieve molecular packing of protic-functionalized helical polymers in...
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Synthesis of Novel Amphiphilic Polyisocyanate Block Copolymer with Hydroxyl Side Group Chang-Geun Chae, Priyank N. Shah, Joonkeun Min, Ho-Bin Seo, and Jae-Suk Lee* Department of Nanobio Materials and Electronics, School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), 123 Cheomdangwagi-ro, Buk-gu, Gwangju 500-712, Republic of Korea S Supporting Information *

ABSTRACT: A novel amphiphilic polyisocyanate block copolymer with hydroxyl side groups was synthesized by a combination of living anionic polymerization and thiol−ene click chemistry. First, the living anionic block copolymerization of allyl isocyanate (AIC) and n-hexyl isocyanate (HIC) produced a well-defined block copolymer (PAIC-b-PHIC) as a precursor. The subsequent free-radical-mediated thiol−ene click reaction of this polymer with 2-mercaptoethanol at room temperature quantitatively converted the allyl side groups of the PAIC domain to hydroxyl groups, finally creating PAIC(OH)-bPHIC. The amphiphilicity of PAIC(OH)-b-PHIC led to lamellar and cylindrical phase separations in the thin films cast from different solvents (THF and toluene). The functionalities and phase separation behaviors of PAIC(OH)-b-PHIC were characterized by NMR, SEC-MALLS, and TEM analysis.

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creating artificial liposome structures.13 Unfortunately, normal polyisocyanates do not possess protic functionalities and exhibit a lack of structural similarities to biological systems. The preparation of well-defined protic-functionalized polyisocyanates via in situ living polymerization remains a challenge due to the chain transfer of active sites during the polymerization. Polyisocyanates bearing amido (−CONHR) and carbamate (−NHCO2R) groups have been moderately controlled by anionic polymerization, but cross-linked portions were not avoided entirely due to the chain transfer of the living anion.14 We previously reported the living nature of the anionic polymerization of carbamate isocyanates using additives or a weak anionic initiator.15 Consequently, the monomers bearing bulky or longer side groups protected the carbamate group from the proton abstraction. The protection/deprotection method16 used for the functionalization of vinyl polymers is undesirable for polyisocyanates because the severely acidic deprotection conditions promote the consecutive degradation of the polyisocyanates to cyclic trimers, thereby lowering the molecular weight.2b,17 Recently, the postpolymerization modification that combines living polymerization and click chemistry18 has rapidly given rise to the ability to incorporate diverse functionalities into well-defined polymers retaining targeted molecular properties. The click reaction not only satisfies the need for tolerance of a diverse range of functionalities but also can be implemented in a modular manner even under mild conditions. Notably, the “alkyne−azide reaction” and “Diels−Alder reaction” have

INTRODUCTION Polyisocyanates are a class of rod-type polymers that adopt dynamic helical conformations.1 Since their discovery in synthesis,2 their distinct helical and morphological features have been found to be of great importance in potential applications such as optical switches,3 nanocarriers,4 liquid crystals,5 photonic crystals,6 and biomimetics.7 In particular, their biomimetic structures are beneficial for a good understanding of the relationship between the structures and biological functions of biomolecules, such as DNA, RNA, and proteins,8 and for simulating the behaviors of biomolecules in a physiological environment. Inspired by this fact, we have made efforts to investigate the conformational properties of polyisocyanates. For instance, on the basis of Green’s pioneering works,9 we developed long-range control of the single-handed helix in poly(n-hexyl isocyanate) by introducing remote chiral units.10 We also found that poly(n-hexyl isocyanate) produces α-helix- and β-sheet-like structures that are reversible in the thin films cast from different solvents.11 The development of water-soluble polyisocyanates12 is expected to enable this transition in aqueous media. Protein conformations including primary to quaternary structures mainly result from intramolecular hydrogen bonding, which is a different originating process than that of polyisocyanate’s chain conformation. Indeed, the introduction of protic functionalities into the polyisocyanate’s side groups, such as hydroxyl (−OH), amino (−NH2), carboxyl (−COOH), and amino acid (−CH(NH2)COOH) groups, may play a decisive role in constructing newer helicity models. Moreover, these functionalities grant hydrophilicity and water solubility to polymer chains. Amphiphilic helical block copolymers can be utilized as stimuli-responsive vehicles for drug delivery by © 2014 American Chemical Society

Received: January 20, 2014 Revised: February 17, 2014 Published: February 25, 2014 1563

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Scheme 1. Synthesis of PAIC(OH)-b-PHIC via Living Anionic Polymerization and Thiol−Ene Click Reaction

polymerized by mixing with the initiator solution. The living PAIC solution exhibited a light yellow color. The polymerization was terminated by adding an excess of acetyl chloride, an end-capping reagent, in pyridine. The resulting polymer was precipitated in a large amount of methanol, filtered, and dried under vacuum for characterization. The methanol-soluble portion concentrated by evaporating the solvent was analyzed by 1H NMR to check the presence of remaining monomers or trimers. dn/dc = 0.086 mL/g (in THF at 40 °C). 1H NMR (CDCl3, 400 MHz), δ (ppm): 5.83−5.71 (br m, 1H, −CH), 5.31−5.12 (br q, 2H, CH2), 4.50−4.06 (br, 2H, −NCH2−). 13C NMR (CDCl3, 100 MHz), δ (ppm): 131.87, 116.96, 49.99. The carbonyl carbon peak of the polymer was not detected due to the limited solubility of PAIC in CDCl3, as reported previously.21 Synthesis of PAIC-b-PHIC. AIC (2.46 mmol) in THF (9.4 mL) was polymerized by mixing with Na-BA (0.19 mmol) in THF (3.9 mL) at −98 °C. After the homopolymerization, HIC (2.19 mmol) in THF (6.0 mL) was added to the living PAIC solution. The polymerization was terminated by adding an excess of acetyl chloride, an end-capping reagent, in pyridine. The resulting polymer was precipitated in a large amount of methanol, filtered, and dried under vacuum for characterization. The methanol-soluble portion concentrated by evaporating the solvent was analyzed by 1H NMR to check the presence of remaining monomers or trimers. dn/dc = 0.090 mL/g (in THF at 40 °C). 1H NMR (CDCl3, 400 MHz), δ (ppm): 5.83−5.71 (br m, 1H, −CH), 5.31−5.12 (br q, 2H, CH2), 4.50−4.06 (br, 2H, −NCH2− of PAIC), 3.92−3.44 (br, 2H, −NCH2− of PHIC), 1.75−1.50 (br s, 2H, −NCH2CH2−), 1.38−1.20 (br s, 6H, −NCH2CH2(CH2)3−), 0.93−0.82 (br s, 3H, −CH3). 13C NMR (CDCl3, 100 MHz), δ (ppm): 156.76, 131.87, 116.96, 49.99, 48.54, 31.49, 28.38, 26.22, 22.55, 13.95. Synthesis of PAIC(OH)-b-PHIC via Thiol−Ene Click Reaction. To a glass reactor, PAIC-b-PHIC (200 mg), 5 equiv of 2mercaptoethanol, and 0.5 equiv of V-70 radical initiator were dissolved in dry THF (2 mL). The mixture was degassed by three freeze− pump−thaw cycles under high vacuum (10−6 Torr), flame-sealed, and stirred at room temperature for 6 h. After the reaction, the modified polymer was precipitated in a large amount of methanol, filtered, and dried under vacuum for characterization. dn/dc = 0.090 mL/g (in THF at 40 °C). 1H NMR (CDCl3, 400 MHz), δ (ppm): 3.92−3.44 (br, 6H, −NCH2−, −CH2OH), 2.93−2.39 (br, 4H, −CH2SCH2−), 1.97−1.82 (br s, 2H, −NCH2CH2− of PAIC(OH)), 1.75−1.50 (br s, 2H, −NCH2CH2− of PHIC), 1.38−1.20 (br s, 6H, −NCH2CH2(CH2)3−), 0.93−0.82 (br s, 3H, −CH3). 13C NMR (CDCl3, 100 MHz), δ (ppm): 156.76, 61.18, 48.54, 34.87, 31.49, 28.38, 26.22, 22.55, 13.95. Preparation of TEM Samples for Phase Separation and SelfAssembly of PAIC(OH)-b-PHIC. PAIC(OH)-b-PHIC solutions (1 mg/mL) in THF, toluene, and THF/methanol (v/v = 4/6, 3/7, 2/8, and 1/9) were drop-cast on a carbon-coated copper grid and annealed

proven to be sufficient to modify the end and side groups of polyisocyanates.19 As another important click reaction, the “thiol−ene reaction”, which involves the conjugation of a thiol with an unsaturated CC bond (hydrothiolation), has the remarkable ability to introduce protic functionalities into alkene-functionalized polymers using functionalized thiols.20 Here, we report the modular and precise synthesis of a novel polyisocyanate block copolymer with hydroxyl side groups via living anionic polymerization and a thiol−ene click reaction (Scheme 1). Poly(allyl isocyanate)-b-poly(n-hexyl isocyanate) (PAIC-b-PHIC) as a precursor polymer was prepared via living anionic block copolymerization of AIC and HIC. The allyl side groups comprising the PAIC domain of the block copolymer were quantitatively transformed into hydroxyl side groups after the subsequent thiol−ene click reaction with 2-mercaptoethanol under mild conditions to create a novel block copolymer, PAIC(OH)-b-PHIC. The optimized synthetic procedure provided molecular weight (MW) precision, narrow molecular weight distribution (MWD), and modular hydroxyl functionalities. Furthermore, the phase separation behaviors of PAIC(OH)-b-PHIC clearly showed its amphiphilic character.

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EXPERIMENTAL SECTION

Materials. Reagents were purchased from Aldrich and used as received unless otherwise noted. Tetrahydrofuran (THF, Fisher Scientific, GR grade) was distilled under N2 after refluxing with sodium (Na, 99%) and then distilled from sodium naphthalenide solution under high vacuum (10−6 Torr). Allyl isocyanate (AIC, 98%), n-hexyl isocyanate (HIC, 97%), acetyl chloride (98%), and pyridine (99.5%) were distilled over calcium hydride (CaH2, Junsei, 95%) under reduced pressure and then redistilled over CaH2 under high vacuum (10−6 Torr). The distilled reagents were appropriately diluted with dry THF and divided in pure glass ampules equipped with breakseals under high vacuum. Benzanilide (98%) was recrystallized from ethanol three times. 2-Mercaptoethanol (99%) and 2,2′-azobis(4methoxy-2,4-dimethylvaleronitrile) (V-70, Wako Pure Chemical Industries, Ltd.) were used without further purification. Sodium benzanilide (Na-BA) as an initiator was synthesized by a previously reported procedure.10c Anionic Polymerization of AIC. All anionic polymerizations were carried out under 10−6 Torr in a sealed glass reactor equipped with break-seals using the break-seal technique. The reactor was prewashed with Na-Naph solution prior to the polymerization. The typical polymerization procedure was as follows: Na-BA (0.16 mmol) in THF (3.8 mL) was transferred into a reactor and then cooled to −98 °C in a frozen methanol bath. AIC (4.33 mmol) in THF (10.4 mL) was 1564

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Table 1. Anionic Polymerization of AIC Using Na-BA Initiator in THF at −98 °C under 10−6 Torr Mn (kDa) run

Na-BA (mmol)

AIC (mmol)

time (min)

calcd

SEC-MALLSa

Mw/Mna

A-1 A-2 A-3 A-4 A-5 A-6 A-7 A-8 A-9

0.08 0.48 0.16 0.09 0.09 0.08 0.09 0.13 0.11

5.77 5.27 4.33 3.79 5.03 5.77 5.02 4.08 3.91

2 5 5 5 5 5 10 20 30

6.1 1.1 2.4 3.7 4.8 6.2 4.4 2.3 2.2

29.9 5.10 12.8 18.9 21.7 28.0 21.1 10.5 7.30

1.07 1.07 1.05 1.04 1.06 1.07 1.07 1.14 1.38

yield (%) 98 98 98 99 98 99 91 82 70

(2)b

(9)b (18)b (30)b

a Mn (SEC‑MALLS) and Mw/Mn were measured by size exclusion chromatography-multiangle laser light scattering (SEC-MALLS) in THF with 2 vol % Et3N at 40 °C. bThe amount of remaining monomer is presented in parentheses. cThe yield of the trimer is presented in parentheses.

under reduced pressure at room temperature for 24 h. The annealed samples were stained with I2 vapor for 8 h, and the excess I2 was removed under reduced pressure at room temperature for 24 h. Characterization. The 1H and 13C NMR spectra were recorded using a JEOL JNM-ECX400 spectrometer in CDCl3 at 25 °C. Chemical shifts were expressed with reference to tetramethylsilane (TMS) (δ = 0 ppm) as an internal standard. The molecular weight and polydispersity were determined by a size exclusion chromatography− multiangle laser light scattering (SEC-MALLS) system equipped with four columns (HR 0.5, HR 1, HR 3, and HR 4; Waters Styragel columns ran in series with a column pore size of 50, 100, 500, and 1000 Å, respectively), an Optilab DSP interferometric refractometer (Wyatt Technology), and a DAWN EOS laser photometer (Wyatt Technology). THF with 2 vol % triethylamine (Et3N) was used as an eluent at a flow rate of 1.0 mL/min at 40 °C. The dn/dc value for each polymer in THF at 40 °C was calculated by detecting the refractive indices for five different concentrations of the polymer samples with an LED (Optilab DSP) source. The SEC analysis using CHCl3 eluent was also performed on a Shimadzu LC-20A Prominence Series equipped with a RID-10A refractive index detector and a Shodex LF-804 column (pore size of 3000 Å) at a flow rate of 1.0 mL/min at 40 °C. The transmission electron microscope (TEM) images were recorded using a Tecnai G2 S-Twin.

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not complete. A small amount of N-(methoxycarbonyl)-2propenylamine was observed in the methanol-soluble portion by 1H NMR spectroscopy, which indicates the reaction of the remaining AIC monomer with methanol. The polymerization yield eventually reached 99% after 5 min, and no remaining monomers or trimers were detected. As the polymerization time increased beyond 5 min, the yield of the polymer decreased in inverse proportion to the increasing trimer formation. The chemical structure of the resulting polymer was confirmed by 1H and 13C NMR (Figure 1). The allyl side

RESULTS AND DISCUSSION

Anionic Polymerization of AIC. PAIC has been reported to be synthesized by the organotitanium(IV)-catalyzed coordination polymerization of AIC.21 In the present study, we decided to use an anionic polymerization method using NaBA as an initiator to obtain the living PAIC. This method has shown the best control of the molecular properties such as a predictable MW and narrow MWD. The living mechanism stabilizes the living chain end by the additive effect to prevent the backbiting depolymerization reaction which forms isocyanurate as a cyclic trimer.22 Na-BA molecules are formed into approximately five-membered self-aggregates in THF at −98 °C.22c This aggregate performs the dual function of initiating the polymerization of isocyanates through one molecule and protecting the living chain end through the other four molecules. Therefore, this system gives a MW corresponding to 20% of the initiation efficiency. An end-capping reaction using acetyl chloride and pyridine catalyst22c was implemented after the polymerization to prevent any additional depolymerization that may occur during the subsequent polymer modification. To determine the time required for the reaction to reach completion, the polymerization time was varied. The results are summarized in Table 1. Most of the AIC monomers were converted into polymer after 2 min, but the polymerization was

Figure 1. (a) 1H NMR and (b) 13C NMR spectra of PAIC (A-2) in CDCl3.

groups of PAIC remained completely intact after the anionic polymerization. In the 1H NMR spectrum of PAIC (A-2), three broad proton peaks corresponding to the allyl group (−CH2− CHCH2) were clearly observed at 5.83−5.71, 5.31−5.12, and 4.50−4.06 ppm (Figure 1a). In the 13C NMR spectrum, three characteristic carbon peaks corresponding to the allyl group were also present at 131.87, 116.96, and 49.99 ppm (Figure 1b). These spectra showed no peaks indicating side reactions of 1565

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resulting polymers showed narrow and unimodal MWDs and predictable MW values (Table 2 and Figure 3a). The molar

the allyl group. These results show that the anionic polymerization of AIC using Na-BA yielded the living polymer without any undesired side reactions. When PAICs were synthesized with different feed ratios of monomer to initiator, the MW values determined by SECMALLS (Mn = 5.1−28.0 kDa) were approximately 5 times higher than the calculated values (Table 1). Because the initiation efficiency of Na-BA is 20%, these results well agreed with the typical MW prediction of anionic polymerization using Na-BA. The obtained PAICs possessed narrow and unimodal MWDs (Mw/Mn = 1.04−1.07) (Table 1 and Figure 2). The precise MW properties indicate that the polymerization of AIC proceeded in a living manner.

Figure 3. RI-detected SEC curves of the PAIC-b-PHIC block copolymers in THF: (a) AH-1 and (b) HA-1.

fraction of the PAIC block determined by 1H NMR ( f PAIC(NMR)) also exhibited good agreement with the calculated value (f PAIC(calcd)). In each RI-detected SEC curve of AH-1 and AH-2, a small curve (a fraction of 3−5%) was detected in a very high MW region (Figure 3a). This curve was magnified considerably in the MALLS detection. This peak originates from aggregates that formed due to the low solubility of the PAIC block in THF. This minor curve disappeared when using a different SEC instrument with a CHCl3 eluent (Figure S1 in the Supporting Information). The reverse monomer addition order (HIC first) precluded the living block copolymerization with AIC. The obtained block copolymers, HA-1 and HA-2, showed bimodal MWDs (Table 2 and Figure 3b). These results imply that there is a difference in reactivity between the two monomers. AIC with a very short aliphatic side group appears to be less electrophilic toward the living PHIC anion, which results in heterogeneous chain growth. Synthesis of PAIC(OH)-b-PHIC via Thiol−Ene Click Reaction. To conjugate the hydroxyl functionality to the side chain of the polyisocyanate, a practical modification was attempted via free radical-mediated thiol−ene reaction of the allyl groups of PAIC-b-PHIC with a hydroxyl thiol using a thermal radical initiator. In this reaction, high temperatures must be avoided due to the PAIC’s thermal fragility. Therefore, 2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile) (V-70) as a low temperature-decomposable radical initiator was used for this modification. Its strong dissociation ability accomplishes

Figure 2. RI-detected SEC curve of PAIC (A-2) in THF.

The limited solubility of PAIC homopolymer in typical organic solvents precluded the radical-mediated reaction. While the living PAIC anion remained soluble in THF, the terminated polymer did not (the precipitation occurred rapidly upon termination.). Although PAIC could be quite dissolved in CH2Cl2 and CHCl3, the mixture of PAIC and 2-mercaptoethanol was not compatible to each other (the precipitation happened in CHCl3 and even in mixed solvent). For easy processing, thus, we decided to replace with organic-soluble PAIC-b-PHIC block copolymer as a precursor polymer for thiol−ene click reaction. Synthesis of PAIC-b-PHIC. To obtain the living precursor diblock copolymer, the sequential block copolymerization of AIC and HIC monomers was carried out under the same conditions as the homopolymerization of AIC and HIC. In the anionic block copolymerization, changing the order of monomer addition should be conducted to confirm the homogeneity of the block copolymerization. The polymerization time for AIC and HIC was determined to be 5 and 60 min, respectively. The results of the block copolymerization are summarized in Table 2. When adding AIC first and HIC second, the block copolymerization afforded the living PAIC-b-PHIC block copolymer with a homogeneous molecular composition. The

Table 2. Anionic Block Copolymerization of AIC with HIC Using Na-BA Initiator in THF at −98 °C under 10−6 Torra Mn (kDa)

monomer

f PAIC

run

Na-BA (mmol)

1st (mmol)

2nd (mmol)

calcd

SEC-MALLSb

Mw/Mnb

yield (%)

calcdc

NMRd

AH-1 AH-2 HA-1 HA-2

0.19 0.16 0.14 0.20

AIC, 2.46 AIC, 2.11 HIC, 2.43 HIC, 2.17

HIC, 2.19 HIC, 4.86 AIC, 2.62 AIC, 7.31

2.8 5.2 4.0 4.7

12.9 24.5 e e

1.06 1.08 e e

100 100 98 100

0.53 0.30

0.53 0.30

a Polymerization time was 5 min for AIC and 60 min for HIC. bMn(SEC‑MALLS) and Mw/Mn were measured by size exclusion chromatography− multiangle laser light scattering (SEC-MALLS) in THF with 2 vol % Et3N at 40 °C. cTheoretical molar fraction of the PAIC block was based on the feed ratio. dActual molar fraction of the PAIC block was determined from the 1H NMR spectrum. eA bimodal MWD was observed in the SEC curve.

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Table 3. Thiol−Ene Click Reaction of PAIC-b-PHIC with 2-Mercaptoethanol Using V-70 Radical Initiator in THF at Room Temperature under 10−6 Torr for 6 ha Mn (kDa) run

polymer

thiol

convb (%)

calcd

SEC-MALLSc

Mw/Mnc

AH-1(OH) AH-2(OH)

AH-1 ( f PAIC = 0.53) AH-2 ( f PAIC = 0.30)

2-mercaptoethanol 2-mercaptoethanol

>99 >99

18.0 29.5

18.2 29.8

1.06 1.06

a

[ene]0/[thiol]0/[V-70]0 = 1/5/0.5. bThe conversion was determined by observing the transition of the 1H NMR signal from the precursor polymer to the modified one. cMn(SEC‑MALLS) and Mw/Mn were measured by size exclusion chromatography−multiangle laser light scattering (SEC-MALLS) in THF with 2 vol % Et3N at 40 °C.

of the carbon peak, giving further evidence of the complete conversion by the thiol−ene reaction (Figure 4c,d). The MWs and MWDs of the polymers before and after the click reaction were compared by SEC-MALLS measurements. The PAIC(OH)-b-PHICs retained increased MWs, in agreement with the theoretical predictions, as well as their narrow MWDs (Table 3). The RI-detected SEC curves showed that while AH-1(OH) (f PAIC(OH) = 0.53) with a higher conjugation percentage has a higher hydrodynamic volume than AH-1 (Figure 5a), AH-2(OH) ( f PAIC(OH) = 0.30) shows little change

the initiation of the thiol−ene reaction even at room temperature. PAIC(OH)-b-PHIC was obtained by the thiol−ene reaction of PAIC-b-PHICs with different compositions and 2mercaptoethanol using V-70 in THF at room temperature under 10−6 Torr for 6 h. The click reaction accomplished over 99% conversion (Table 3). The quantitative functionalization was confirmed by the complete transition of the proton peaks in the 1H NMR spectra of the resulting polymers (Figure 4).

Figure 5. RI-detected SEC curves of PAIC-b-PHIC and PAIC(OH)-bPHIC in THF: (a) AH-1 and AH-1(OH) and (b) AH-2 and AH2(OH).

in the hydrodynamic volume in comparison with AH-2 (Figure 5b). Because these polymers have rigid-rod structures, a slight side group extension might not significantly influence the radius of gyration of the polymers in THF solution after modification. Interestingly, the aggregate portion detected in SEC curve of each PAIC-b-PHIC clearly disappeared after the click reaction (Figure 5). This implies the improved solubility of the PAIC(OH) block in THF conferred by the extended side group after the click reaction. Consideration on Phase Separation and Self-Assembly Behaviors of PAIC(OH)-b-PHIC. The TEM images of the PAIC(OH)-b-PHIC films cast from THF and toluene solutions (1 mg/mL) were used to define the phase separation tendency of the amphiphilic rod−rod diblock copolymer (Figure 6). The dark region is the PAIC(OH) domain, and the bright region is the PHIC domain. The PAIC(OH) domain was selectively stained by I2 doping. The AH-1(OH) (DPPHIC = 64) and AH2(OH) (DPPHIC = 149) films cast from a THF solution showed

Figure 4. 1H NMR spectra of (a) AH-1 and (b) AH-1(OH) and 13C NMR spectra of (c) AH-1 and (d) AH-1(OH).

The allyl peaks at 5.83−5.71, 5.31−5.12, and 4.50−4.06 ppm clearly disappeared after the thiol−ene click reaction, while new methylene peaks corresponding to the thioether linkage, which was formed by the addition reaction of the unsaturated CC bond, appeared at 3.92−3.44, 3.94−2.39, and 1.97−1.82 ppm (Figure 4a,b). The 13C NMR spectra also showed the transition 1567

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Figure 6. TEM images of PAIC(OH)-b-PHIC: (a) AH-1(OH) in THF, (b) AH-2(OH) in THF, and (c) AH-2(OH) in toluene.

bonding and acid−base interactions utilizing protic side groups will be helpful for understanding molecular dynamics and functions of proteins24 (e.g., the infectious transformation from α-helices to β-sheets in prion proteins responsible for the fatal neurodegenerative diseases25). As an initial study for these goals, the relevant materials design and synthesis are now in progress.

a lamellar phase with different PHIC domain scales (Figure 6a,b), while AH-1(OH) was not dissolved in toluene, and the AH-2(OH) film cast from toluene showed a cylindrical phase (Figure 6c). Unlike THF which has a good affinity for both blocks, toluene as a nonpolar solvent has a good affinity to the hydrophobic PHIC block only. The denser aggregation and volume shrinkage of PAIC(OH) domain in toluene resulted in formation of a discontinuous cylindrical phase. To observe the self-assembly of PAIC(OH)-b-PHIC into micelles or vesicles in the solution state, the further DLS and TEM analysis were also carried out using the AH-1(OH) solutions (1 mg/mL) in THF/methanol (v/v = 4/6−1/9). Although a small amount of vesicles with a 400−500 nm diameter was found in the THF/methanol (v/v = 2/8) solution, most of the polymer chains were precipitated in a disordered state due to the relatively low hydrophilic fraction of AH-1(OH). For the complete vesicular formation, a block copolymer with a higher hydrophilic portion (>80 mol %) is needed, but the modification of PAIC-b-PHIC with a high fraction of PAIC block has been limited due to the low solubility of this polymer in organic solvents. In fact, the lengths and fractions of the hydrophilic block in the amphiphilic rod− rod diblock copolymers are crucial parameters to form stable nanoparticles in solution. Therefore, it is a primary prerequisite to prepare a soluble polyisocyanate with longer alkenyl side groups for in-depth studies on the self-assembly of amphiphilic polyisocyanate diblock copolymers. This synthesis is now ongoing by our group.

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ASSOCIATED CONTENT

* Supporting Information S

SEC curve of PAIC(OH)-b-PAIC (AH-1) in CHCl3. This material is available free of charge via the Internet at http:// pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail [email protected]; Tel (+82)-062-715-2306; Fax (+82)062-715-2304 (J.-S.L.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the “GIST-Caltech Research Collaboration” Project through a grant provided by GIST in 2014.

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CONCLUSIONS In summary, we successfully synthesized and characterized a novel polyisocyanate block copolymer with hydroxyl side groups. Living anionic polymerization enabled the control over the molecular size, composition, and distribution of the allylcontaining polyisocyanate homo- and block copolymers (PAIC and PAIC-b-PHIC, respectively). The following thiol−ene click reaction was proven to be an effective postfunctionalization method, resulting in the quantitative conversion of the allyl side group of PAIC-b-PHIC to hydroxyl groups while not reacting with the main chain. The obtained PAIC(OH)-b-PHIC showed a solvent-dependent phase separation transition (lamella to cylinder) caused by its amphiphilicity. To the best of our knowledge, this polymer is the first amphiphilic rod−rod block copolymer consisting of only helical polyisocyanate chains. The present results imply that more sophisticated structural design and synthesis may evolve the utility of polyisocyanates into biological nanostructures such as stimuli-responsive polymersomes13 and artificial cell membranes.23 Moreover, hydrogen 1568

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