Dynamic Self-Assembly and Synthesis of Polylactide Bearing 5

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Dynamic Self-Assembly and Synthesis of Polylactide Bearing 5-Hydroxymethylfurfural Chain Ends Kai Kan, Mitsuru Akashi, and Hiroharu Ajiro ACS Appl. Polym. Mater., Just Accepted Manuscript • DOI: 10.1021/acsapm.8b00185 • Publication Date (Web): 27 Dec 2018 Downloaded from http://pubs.acs.org on January 1, 2019

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is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

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ACS Applied Polymer Materials

Dynamic Self-Assembly and Synthesis of Polylactide Bearing 5-Hydroxymethylfurfural Chain Ends Kai Kan, †, ⊥* Mitsuru Akashi, § Hiroharu Ajiro†, ⊥* †

Division of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama-

cho, Ikoma, Nara, 630-0192, Japan ⊥

Institute for Research Initiatives, Division for Research Strategy, Nara Institute of Science and

Technology, 8916-5, Takayama-cho, Ikoma, Nara, 630-0192, Japan. §

Graduate School of Frontier Biosciences, Osaka University, 2-1 Yamada-oka, Suita, 565-0871,

Japan.

KEYWORDS

Stereocomplex,

Dynamic

Interaction,

Self-Assembly,

Quartz

Crystal

Microbalance (QCM), Imine, 5-Hydroxymethyl furfural, Heat resistance

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ABSTRACT

In regards to addition of functionality into polylactide, the chemical modification method is a promising approach. Herein, we selected 5-hydroxymethylfurfural (HMF) as initiator to introduce the chain end of polylactide. HMF is a valuable biomass produced from glucosefructose via dehydration. The structure of HMF contains aldehyde and alkyl alcohol, which resembles benzyl alcohol. This polymer was able to control the molecular weight. This meant that the polymerization initiated from HMF showed effective initiation for the polymerization, compared with vanillin in previous research. The present polymer improved the thermal properties by stereocomplex formation with both enantiomeric homopolymer. Subsequently, the terminal group of aldehyde of HMF undergoes bonding/removing as a dynamic formation with hydrophilic amine under equilibrium conditions. This phenomenon self-assembled interesting nano structured morphology, and also able to form self-assembled monolayer (SAM). By using this SAM, the decomposition speed under various pH buffer was evaluated by quartz crystal microbalance.

1. Introduction Bio-based polymers from renewable resources are significant prospects for the contribution of sustainable future and low carbon society.1 Among the various biomass candidates, transformation of lignocellulosic biomass is one of the most valuable platform2-8 to replace from petroleum-based chemicals. In particular, polylactide (PLA) is derived from glucose by bacterial fermentation. PLAs have been widely studied and developed as green sustainable materials, such as biomedical9-13 and environmental packaging applications,14-17 in order to replace petroleum2 ACS Paragon Plus Environment

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based polymers over the past decades because of their superior biocompatibility and biodegradability. However, they are limited its wide use in applications because of poor thermal and less functionality. Therefore, the functionalization of bio-based polymers is significant to create new generation materials toward sustainable society. It is known that the stereocomplex PLA formed from the mixture of poly(L,L-lactide) (PLLA) and poly(D,D-lactide) (PDLA) results in reinforcement of thermal and mechanical characteristics.18-20 Since stereocomplex formation was caused by polymer–polymer interaction toward the main chain of PLA, the chemical modification is preferred method to add another functionalization. Until now, stereocomplex PLA formation from linear stereoblock-type PLAs,21-22 branched PLAs using polyglycidol,23 three armed PLAs,24 star-shape PLAs,25 DielsAlder coupling stereoblock-type PLAs,26 and triblock typed PLAs27-29 was reported to improve physical properties. Related to these studies, our group have also designed various stereocomplex type PLA materials by chain-end modification to add further functionalities. At first, we modified PLAs by conjugation with both aromatic cinnamic acid derivatives to improve thermal degradation temperature and melting temperature.30-32 Subsequently, we have created this type polymer by layer-by-layer stereocomplex formation from an inkjet system.33 Moreover, we introduced catechin34 to ring-opening polymerization of PLAs to show not only controlling thermal property but also another antibacterial properties function to utilize as biomaterial application. From this aspect, our approach to chain-end modifications of PLA is one possible way to develop high performance green plastics because it is possible to add other functionalization to improve thermal properties and contribute to biomaterial applications.



With regards to the addition of functionality, the reversible property by dynamic covalent chemistry approach has attracted much attention to create polymer building block architecture. 3537

For example, aldehyde is found to be a reversible linkage because it can form imine bonds

with amines under mild conditions.38-40 This approach can organize self-assembled monolayer (SAM) of different alkanethiols on Au interface,41,42 and used as a platform for the development of biomedical materials.43-45 Indeed, the quartz crystal microbalance (QCM) is a versatile technique, which gives response of adsorption and desorption molecules on an interface based on the amount of mass deposited on the quartz crystal surface.46,47 In this meaning, we can get the information of desorption as degradation kinetics of PLA and derivatives.48,49 Recently, we expanded the chain-end modifications approach to introduce dual dynamic functionality by a natural aromatic aldehyde, such as vanillin, at the chain end of PLA.50,51 We achieved nanostructure control between turning hydrophilic/hydrophobic balance due to the transformation of aldehyde of vanillin moiety at hydrophobic PLA chain end to imine with hydrophilic amino compounds. Among aldehyde terminated PLA, there was only used for reaction intermediate to reductive amination.52 In this meaning there are no reports about controlling nanostructure and reversible nature except for our study between aldehyde and amine. However, the initiator derived from vanillin is not efficient. We thought that the initiator of phenolic hydroxyl group in not efficient compared with alkyl alcohol such as benzyl alcohol. Therefore, the proper initiator possessing aldehyde is required. In this study, we selected 5-hydroxymethylfurfural (HMF) as an initiator to synthesize poly(L,L-lactide) and poly(D,D-lactide) in order to utilize an effective initiator for high selectivity of ring-opening polymerization of lactide. HMF is a valuable lignocellulosic biomass produced from glucose-fructose via dehydration.53 The structure of HMF contains aldehyde and 4 ACS Paragon Plus Environment

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alkyl alcohol. The aldehyde moiety would make possible to selectively undergo dynamic bonding/removing under equilibrium conditions, as well as the alkyl alcohol moiety would contribute to the molecular weight control that would make possible to form stereocomplex easily. We apply this imine-based dynamic bond through SAM formation under equilibrium conditions to detect pH-responsive reversible moiety evidenced by QCM analysis (Figure 1). This thermal resistance and nanostructure control could be contributed for not only environmental use but also biomedical application such as thermal sterilization. 2. Experimental 2.1. Materials L,L-lactide (LLA; Musashino Chemical Laboratory, Ltd., Japan) and D,D-lactide (DLA; Musashino Chemical Laboratory, Ltd., Japan) were recrystallized from ethyl acetate/n-hexane and then dried under vacuum at room temperature. HMF (Wako Pure Chemical Industries, Ltd., Japan) was used without purification. 2.2. Characterization The molecular weight of PLAs was calculated by gel permeation chromatography (GPC) on JASCO Chem NAV system with two columns (TSKgel SuperH4000 and TSKgel GMHXL) in tetrahydrofuran (THF) calibrated with polystyrene standards at 40 oC. The polymer structure was detected by 1H NMR spectra on JEOL ECA-600 spectrometer (600 MHz, chloroform-d) and Mass spectrum (MS) spectra by Autoflex II (Bruker Daltonics). The formation of PLA and stereocomplex was confirmed from Fourie transformed infrared (FT-IR) using IRAffinity-1S (Shimadzu), X-ray diffraction (XRD) by Rigaku RINT-TTRIII/NM using CuK (50 kV, 300 5 ACS Paragon Plus Environment


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mA;  = 0.154 nm) as the X-ray source. The thermal property of PLAs were analyzed by Thermogravimetry analysis (TGA) by TG/DTA 6200 (10 oC/min, N2) and Differential scanning calorimetry (DSC) by SEIKO Instruments EXSTAR DSC6200 (5 oC/min, N2). Optical rotation of PLAs was obtained from JASCO digital polarimeter P-1020 (589 nm, 1 mg/mL in CHCl3, 23 o

C). Dynamic transformations of PLAs were measured by Dynamic light scattering (DLS) on

Malvern ZEN 3600 Zetasizer Nano ZS by monochromatic coherent He−Ne laser fixed at 633 nm in 20 oC, and Scanning electron microscopy (SEM) by Hitachi SU-6600. The transformation behavior of PLAs sample for SEM was as follows. Firstly, the samples of PLLA-imine (10) in CDCl3 were reprecipitated by methanol, and corrected by centrifugation method at 4 oC, 3500 rpm, for 20 min. Then the polymer suspension was corrected for DLS. This polymer suspension 10 was added in 5M HCl to correct precipitate sample (PLLA-HMF (1)) for measurement of SEM. The SEM samples of polymer suspension 10 or precipitated solution 1 were dropped on aluminum foil, and dry at room temperature. Quartz crystal microbalance (QCM) was monitored by Ageilent HP53181A 225 MHz. 2.3. Synthesis of poly(L,L-lactide)-HMF (PLLA-HMF) and poly(D,D-lactide)-HMF (PDLA-HMF) The PLLA-HMF and PDLA-HMF (1, 2, 3, 4) and PLA-benzylalcohol (5, 6) were prepared according to our previously reference of PLA-benzyl alcohol30,31 and PLA-vanillin.50,51 Herein the typical procedure of PLLA-HMF (1) was described as follows. In a round-bottom flask, LLA (1.0 g, 6.9 mmol), 3.5 mL of 0.1 molL-1 of HMF in dry toluene and 2.2 mL of 1 vol% SnOct2 (69 mol) in dry toluene were mixed and mechanically stirred to react at 110 oC for 2h. Then, the


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product was purified using reprecipitation method over methanol three times, and dried at room temperature. 2.4. Synthesis of stereocomplex-HMF (9) The corresponding amount of PLLA-HMF (1) and PDLA-HMF (2) were dissolved in acetonitrile (5 mg mL-1), and mixed at room temperature for 24h. After 24h, the precipitates appeared, and purified by centrifuged to collect, and dried at room temperature. 2.5. Synthesis of PLLA-imine (10) The PLLA-imine (10) was prepared according to our previously reference of PLA-vanillin.50 2-(2-aminoethoxy) ethanol diluted by chloroform (0.165 mL) was slowly added to 30 mg of PLLA-HMF (1) in 0.635 mL CDCl3. After 24h at room temperature, traced by 1H NMR. Then we used this PLLA-imine (10) to study hydrolysis behaviors under 1 mL of 5M HCl. This solution was extracted with distilled water and chloroform for three times, evaporated to get PLLA-HMF (1) by 1H NMR. 2.6. Preparation of PLLA-imine monolayer (11) on the QCM Before measurements, QCM electrodes were treated with a piranha solution (H2SO4 : H2O2 = 3 : 1) for 5 min, followed by rinsing with deionized water, methanol and drying with N2 gas in each solvent to clean the surface at room temperature. Then clean QCM electrodes were immersed in a 1 mM cysteamine in ethanol solution for 20h at room temperature. After 20h, the QCM electrodes were rinsing with methanol, chloroform, and drying with N2 gas in each step. Next, the QCM electrodes were exposed to a 3.33 x 10-4 M solution of PLLA-HMF (1) in chloroform. After that in each adsorption, the surfaces of QCM were rinsed with chloroform, 7 ACS Paragon Plus Environment


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methanol, and dried under a stream of dry nitrogen. We used this PLLA-imine monolayer (11) to study hydrolysis behaviors under 5M HCl, pH 5 buffer, and pH7.4 TBS buffer. 3. Results and discussion Recently, we successfully conjugated the benzyl alcohol30,31 and vanillin50,51 into PLLA and PDLA at chain ends. Since vanillin is a phenolic hydroxyl initiator, the initiator is not efficient compared with benzyl alcohol (Figure S1). This result revealed that it was difficult to control molecular weight by GPC compared with theoretical values (Table 1, run 7). Therefore, we selected a more proper initiator possessing aldehyde. Herein, PLLA-HMF and PDLA-HMF were synthesized by ring-opening polymerization of both enantiomeric lactides using initiators as HMF (Scheme 1). To confirm the molecular weight control, the terminal group of HMF was analysed by 1H NMR, GPC, and MALDI-TOF MS. From 1H NMR spectrum, HMF combined with PLLA by aldehyde peak was observed (Figure 2a). The small impurity around 2-4 ppm might be the residue of HMF reacted itself. (Figuer 2a and S2-S4) From the integral ratios of terminal and main chain peaks were calculated Mn as 4500. The molecular weight by GPC trace was 3800 (Figure 2b). About the MALDI-TOF-MS spectrum, a single series of peaks was founded. It meant the peak interval was almost the same as lactic acid mass (MW = 72), and each peak mass is expected HMF introduced in PLLA (Figure 2c). Additionally, from the MALDITOF MS, only one population of lactic acid mass peak appearance meant esterification was not yet completed due to the catalyst system.54 These results indicate that the polymerization initiated from HMF and the initiator efficiency was improved during polymerization. Then we investigated thermal properties of stereocomplexes by using these PLAs. Firstly, we studied the formation of stereocomplex by X-ray diffraction (XRD) and FT-IR. From XRD patterns of PLLA-HMF (1) and PDLA-HMF (2) showed peaks at 2 = 14.7o, 16.6o, 18.9o, and 22.3o. Then 8 ACS Paragon Plus Environment

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stereocomplex-HMF (9) showed at 2 = 11.9o, 20.7o, and 23.9o, corresponding to the previous report, and totally formed (99%) (Figure 3 and Figure S9).18 Additionally, the FT-IR spectra showed the C=O stretching band of the ester group had shifted from 1755 cm-1 for 1 and 2 and 1742 cm-1 for precipitate. This result indicated stereocomplex formation due to the formation of interaction between the C=O and CH3 groups55 (Figure 4). Then we investigated the thermal property by TGA and DSC. From the TGA results, the T10 of 1 and 2 showed at 234 and 233 oC, and 9 yielded at 255 oC (Figure 5). The increase of heat resistance by T10 is due to polymer-polymer interaction occurred by stereocomplex. Similarly, from DSC results, the Tm of 1 and 2 was around 140 and 143 oC, whereas the Tm for the 9 was 210 oC (Figure 6). These results proved that high heat resistance depending on the stereocomplex formation, and the chain end of HMF did not prevent polymer-polymer interaction, as reported in previous research.50 Next, we investigate the reversible transformation from imine because it can be hydrolysed to starting material under acidic conditions. Here, hydrophilic amine such as 2-(2-aminoethoxy) ethanol was selected to form imine. To prove this transformation, 1 (Figure 7a) and 2-(2aminoethoxy) ethanol (1:1eq.) were mixed in CDCl3 at room temperature. After 24h, imine formed around 63% (Figure S7). This showed the reaction conversion from starting material to form imine bond was improved compared with previous research of vanillin as an initiator that is not formed imine50 due to improvement of initiator efficiency of HMF. Then, we changed the molar ratio of 1 and 2-(2-aminoethoxy) ethanol (1:10 eq.) in CDCl3 at room temperature (Figure 7 and Figure S8). After 24h, PLLA-imine (10) was almost converted to imine more than 99% (Figure 7b and Figure S5). Thus imine was totally formed by 1 and 2(2-aminoethoxy) ethanol. Then imine was cleaved by acid hydrolysis. This meant the addition of 9 ACS Paragon Plus Environment


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HCl aq to imine 10 led to form aldehyde and result in disappearance of imine (Figure 7c and Figure S6) due to reversibility through aldehyde-imine transformation. Then we use this dynamic nature to demonstrate controlling the different morphology through the amphiphilic property of this chain-end hydrophilic modification. Here we perform Tyndall effect observation by red light laser, dynamic light scattering (DLS), and scanning electron microscopy (SEM) to control the nanostructure. As shown in Figure 8a, 10 was precipitated from chloroform to methanol, and 5M HCl was added 10 to make 1. From the observation with naked eye, 10 was made the turbidity, but 1 was transparent. This is because precipitation in solution by addition of 5M HCl. Moreover, Tyndall effects were clearly observed of 10 (Figure 8b), resulting in colloidal aggregates remaining in 10. On the other hand, 1 was not confirmed of Tyndall effects because of clear supernatant after the aggregates precipitated. From the DLS measurements, the average size of 10 was about 160 nm (Figure 8c). However, it was difficult to measure 1 in DLS because the clear solution and most of aggregates precipitated. We then control the different morphology by microscopic observation SEM. As seen in SEM images of 10 in Figure 8, spherical nano sized particle with an average diameter of 120-160 nm was observed. We called this morphology as rain drop-like morphology in previously reported (Figure 8d).50 Otherwise, 1 formed fibrous morphology as well as previously reported (Figure 8d).50 This nano-sized particle approximately 100 nm in average diameter of 10 correlates with the result from DLS. These transformation was might be able to take hydrophobic-hydrophilic change as externalstimuli. The reason we thought this change is because hydrophilic moiety (i.e. hydroxyl group) on the outside of 10 self-assembled to nanoparticle. After the addition of acid to 10, the interface of hydrophilic component was breakage induced by acid hydrolysis to change hydrophobic nature 1. Thus hydrophobic component was instable in solution to aggregate during precipitation. 10 ACS Paragon Plus Environment

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This precipitate self-assembled to become fibril formation from the interface of the broken nanoparticles. Finally, we study this imine-aldyhyde transformation by formation self-assemble monolayer (SAM) from PLLA-imine monolayer (11) by QCM analysis. The dynamic building moiety could possibly play an important role for biomedical applications such as drug delivery systems (DDS) due to control of degradation speed by pH buffer. We form 11 from cysteamine as amineterminated SAMs on a gold substrate of QCM and 1 under ambient condition. Then we study the decomposition behavior in 5M HCl, pH5 buffer, and pH7.4 TBS buffer. In 5M HCl condition, the 11 rapidly lost weight to amine-terminated monolayer within 1 min by QCM (Figure 9a). Compared to HCl condition, pH 5 is slightly changed (Figure 9b), and pH7.4 buffer is stable of imine structure for 1 day on the surface (Figure 9b). Then the rapid detachment of 11 was confirmed when switching from pH 7.4 to HCl. We conclude this system was able to control imine detachment speed accelerated at a low pH. Conclusions In conclusion, HMF was employed as an initiator for PLA, which was able to control molecular weight compared with vanillin. Then the modified polymer also improved thermal properties by stereocomplex formation (T10 = 255 oC, Tm = 210 oC). Furthermore, the terminal group of HMF with hydrophilic amine could transform to imine high yield and decomposition confirmed by 1H NMR. This reversibility formed a nano-structure morphology change confirmed by Tyndall effect, DLS, and SEM. Then this character was applied to SAM formation and able to control the decomposition speed under various pH solution. Thus, this polymer could be used as environment

and

biomedical

applications.



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FIGURES (a) Control of molecular weight

dehydration

Glucose

ferment

HMF

Poly(L,L-lactide)

5-(hydroxymethyl)-furfural (HMF)

L,L-lactide

(b) Functionalization of QCM to study dynamic formation and decomposition

cysteamine

Au surface of QCM

Formation of cysteamine monolayer

PLLA-HMF

pH buffer

Removal to cysteamine monolayer

Formation of PLLA-imine monolayer

Figure 1. The concept of this study. In this study we used chain end modification approach to get novel bio-based polymer; PLA-HMF. (a) The structure of this polymer could control the molecular weight due to alkyl alcohol initiator. (b) The dynamic functionality property could be applied to QCM study to know as controlling degradation speed by pH buffer. 12 ACS Paragon Plus Environment

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(a)

b

TMS

a

CHCl3

PLLA-HMF f

Monomer/Initiator = 20/1 Mn (theory) = 3000 Mn (NMR) = 4500 Mn (GPC) = 3800, PDI =1.45

ed 12 11 10 9

8

7

c 6

5

4

3

2

1

0 -1 -2 δ (ppm)

(c)

(b)

n =32 n =30 n =28 2454.70 2310.67 2166.63 n =33 n =25 n =31 2526.72 n =27 n =29 1949.59 n =22 2094.62 2238.65 2382.68 1733.54 n =24 n =26 1877.58 n =21 2021.60 n =23 1661.52 1805.55 n =20 72 1589.51

+

8

6

4 2 Log Mw (Polystyrene)

0

1500

1700

1900

2100

2300

2500

Mass (m/z) 1

Figure 2. Molar mass study of PLLA-HMF (1) by (a) H NMR spectra, (b) GPC and (c) MALDI-TOF MS.



(a)

16.6o

14.7o

5(b)

(c)

10

15

11.9o

10

18.9o 22.3o

16.6o

14.7o 5

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15

20

25

30

35

30

35

30

35

18.9o 22.3o 20

25

20.7o 23.9o 5

10

15

20

25

2θ (deg) Figure 3. XRD profiles of (a) PLLA-HMF (1), (b) PDLA-HMF (2), and (c) StereocomplexHMF (9). 14 ACS Paragon Plus Environment

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(a)

(b) 2000

(c)

2000

1755 cm-1 1800

1800

1600

1755 cm-1 1600

1400

1200

1000

1400

1200

1000

1742 cm-1 2000

2000

1800

1800

1600

1600

1400

1400

1200

1200

1000

1000

Wavenumber (cm-1) Figure 4. FT-IR spectra of (a) PLLA-HMF (1), (b) PDLA-HMF (2), and (c) StereocomplexHMF (9).



100 80

Weight (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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(a) 60

(b) (c)

40 20

0 50

150

250

Temperature (oC)

350

450

Figure 5. TGA charts of (a) Stereocomplex-HMF (9), (b) PLLA-HMF (1), and (c) PDLA- HMF (2).


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(a)

(b) 50

100

150

200

250

50

100

150

200

250

50

100

150

200

250

Endo

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(c)

50

100

150 200 o Temperature ( C)

250

Figure 6. DSC analyses of (a) PLLA-HMF (1), (b) PDLA- HMF (2), and (c) StereocomplexHMF (9).



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CDCl3

+ PLLA-HMF (1)

HCl 10 (Imine compound)

2-(2-aminoethoxy) ethanol

Ph-CHO

(a) PLLA-HMF (1)

(b) PLLA-HMF (1) / amine (1 eq. / 10 eq.) -CH=NConv. >99%

(c) (b) +HCl 11.8

11.5

11.0

10.5

10.0

9.5

9.0

8.5

8.0

δ (ppm)

Figure 7. 1H NMR spectra of (a) PLLA-HMF (1), (b) imine compound by 10 molar of amine, and (c) acidic hydrolysis of imine compound.


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(a)

(b)

HCl

PLLA-imine (10)

10

PLLA-HMF (1) (c) Intensity (%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1

(d)

15

10 10

1

(10) 160 nm

5 120-160 nm

0 1

10

100 1000 Diameter (nm)

10000

Figure 8. (a) Reaction scheme of imine (10) and PLLA-HMF (1). (b) Tyndall effect observation of 1 and 10 under red light laser. (c) DLS data of 10 at methanol, (d) SEM images of 1 and 10.



(b)

(a) 400

Frequency shift (-D) Hz

Frequency shift (-D) Hz

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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300

200

100

0 0

10

20

30

40

50

60

400

300

200

pH7.4

100

pH5 0 0

4

Time (s)

8

12

16

20

24

Time (h)

Figure 9. QCM analyses of dynamic reversible formation of the PLLA-imine (11) under (a) 5M HCl, (b) pH 5 buffer, and pH 7.4 TBS buffer.

SCHEMES. Scheme 1. Synthesis of PLLA-HMF (1) and PDLA-HMF (2)

L,L-Lactide

PLLA-HMF SnOct2

+

110 oC, 2h toluene

5-hydroxymethylfurfural (HMF) D,D-Lactide

PDLA-HMF


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TABLES. Table 1. The chain-end modified polylactides in this study

Run Product

[M]/[I]

th Yield Mn (%) (X103)a

1

PLLA-HMF (1)

20/1

96

3.0

3.8

1.45

-155±1

2

PDLA-HMF (2)

20/1

95

3.0

3.9

1.50

156±1

3

PLLA-HMF (3)

80/1

95

11.7

11.3

1.98

-157±1

4

PDLA-HMF (4)

80/1

87

11.7

11.8

1.86

167±2

5c

PLLA-benzylalcohol (5)

20/1

83

3.0

2.7

1.27

-148±2e

6c

PDLA-benzylalcohol (6)

20/1

84

3.0

2.8

1.26

148±3e

7d

PLLA-vanillin (7)

20/1

88

3.0

8.8

2.26

-155±1

8d

PDLA-vanillin (8)

20/1

85

3.0

10.6

2.27

148±1

a b

MnGPC (X103)b

PDI

b

[α]D23 (deg)

Theoretical molar mass. Experimental molar mass determined by GPC using PS standard in THF at 40 oC with UV-

detector. c

Followed reference 30 to prepare.

d

Data of Reference 50.

e

Data of Reference 30.

ASSOCIATED CONTENT Supporting Information. The following files are available free of charge. The molar mass study of PLLA-benzyl alcohol (5) and PLLA-vanillin (7) by GPC, 1H NMR study of additional molar ratio of PLLA-HMF and PDLA-HMF, 1H NMR trace study of PLLA21 ACS Paragon Plus Environment


imine (10), Peak fitting of XRD of stereocomplex-HMF (9) (file type, i.e., PDF)

AUTHOR INFORMATION Corresponding Author *Kai Kan. E-mail: [email protected]. TEL: +81-(0)887-57-2024. FAX: +81-(0)887-572520. *Hiroharu Ajiro. E-mail: [email protected]. TEL: +81-(0)743-72-5508. FAX: +81-(0)743-725509. ORCID Kai Kan: 0000-0002-4222-8033 Hiroharu Ajiro: 0000-0003-4091-6956 Present Addresses †Kai Kan: Kochi University of Technology. Notes The authors declare no competing financial interest. ACKNOWLEDGMENT This work was supported by the Sasakawa Scientific Research Grant from The Japan Science Society. We acknowledge Mr. Shohei Katao for help with XRD measurements, and Ms. Y. Nishikawa for help with MALDI-TOF MS measurements. We are also grateful to Prof. Michiya Fujiki for the fruitful discussion about optical rotation measurements. Moreover, we are grateful to Prof. Hironari Kamikubo and Dr. Yoichi Yamazaki for fruitful discussion about DLS 22 ACS Paragon Plus Environment

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+ Imine-based dynamic formation

Thermal resistance


Dynamic Self-Assembly and Synthesis of Polylactide Bearing 5

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