An alternative approach for synthesizing polyglycolic acid copolymers

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An alternative approach for synthesizing polyglycolic acid copolymers from C1 feedstocks and fatty ester epoxides Yusuf Reyhanoglu, Ertugrul Sahmetlioglu, and Ersen Gokturk ACS Sustainable Chem. Eng., Just Accepted Manuscript • DOI: 10.1021/ acssuschemeng.8b05940 • Publication Date (Web): 08 Feb 2019 Downloaded from http://pubs.acs.org on February 8, 2019

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ACS Sustainable Chemistry & Engineering

An alternative approach for synthesizing polyglycolic acid copolymers from C1 feedstocks and fatty ester epoxides Yusuf Reyhanoglu†, Ertugrul Sahmetlioglu‡,§, Ersen Gokturk†*

†Department

of Chemistry, Hatay Mustafa Kemal University, 31001, Hatay, Turkey

‡Department

of Chemistry, M. Çıkrıkçıoğlu Vocational College, Erciyes University, 38039 Kayseri, Turkey

§Nanotechnology

Research Center (ERNAM), Erciyes University, 38039, Kayseri, Turkey

Mailing address: Hatay Mustafa Kemal University, Tayfur Sokmen Campus, Alahan, Antakya City, Hatay Province

†Corresponding

author: Ersen Gokturk ([email protected])

ACS Paragon Plus Environment

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Tel.: (+90) 3262213317 - 1144; fax: (+90) 3262455867 ABSTRACT: Over the past couple of years, replacement of petroleum-based products with biodegradable and biorenewable is an emerging topic in polymer science. Biodegradable polyglycolic acid (PGA), the simplest aliphatic linear polyester, can traditionally be synthesized through the ring opening polymerization of glycolide. Our previous studies revealed that PGA can alternatively be produced via one-step cationic polymerization of formaldehyde from trioxane and carbon monoxide (CO), which are potentially sustainable C1 feedstocks, under Brønsted acidic conditions. In this study, trioxane, CO and a minor amount of fatty ester epoxides are copolymerized to improve on the physical properties of PGA, such as solubility and appearance, under the same reaction conditions for PGA homopolymer synthesis (in DCM, at 800 psi CO, with triflic acid catalyst, reaction duration of 72 h). The results have shown that the addition of minor quantities of epoxide comonomers vastly improved the solubility and decreased the melting temperature of the PGA. The melting temperatures of the obtained copolymers decreased by increasing incorporation percentages of the epoxide


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comonomers and decreasing polymerization temperatures. The solubility of the copolymers increased with incorporation of the epoxides in the PGA backbone.

KEYWORDS: Polyglycolic acid, Formaldehyde, Carbon monoxide, Fatty acids, Epoxide, Cationic polymerization.

INTRODUCTION

Polymers from biorenewable resources have received growing attention in both scientific and industrial fields.1 Depletion of petroleum sources and poor degradation behaviors of fossil fuel based plastics inspired us finding more sustainable resources for the production of new generation polymers. Degradation of fossil fuel based polymers (such as polyethylene, polystyrene, etc.) is estimated to be thousands of years. Therefore, these incumbent materials constitute significant fractions of landfill waste and continuous global pollution.2 The production of sustainable and environmentally friendly biomass based plastics is necessary for the replacement of petroleum-based plastics.



Extensive research has been conducted on biodegradable polymers from bio-based raw materials such as plant oils, carbohydrates, etc.3,4 Biodegradable polymers have also gained considerable attention in the area of biomedical applications.5 Biodegradable polymers can mainly be used for the biomedical applications as drug delivery systems, tissue engineering, surgical sutures, etc.6,7 Especially, polyglycolic acid, polylactic acid, and their copolymers (PLGA) are particularly attractive and commonly used as synthetic biodegradable polymers. Their hydrolysis in physiological media gives lactic and glycolic acids, that are metabolized in the body as water and carbon dioxide.8 Currently, some medical implants for drug delivery, dental and orthopedic applications, such as screws, nails, etc., are mostly prepared from polyglycolic acid and its copolymers because of their biocompatibility and biodegradability.9 Polyglycolic acid (PGA, trade name is Kuredux)10 (Figure 1), a linear biodegradable poly(𝛼-hydroxy acid), is a rigid, very crystalline thermoplastic polymer (45-55 %)11 with a melting temperature (Tm) between 225 and 230 oC, and a glass transition temperature (Tg) around 35-40 oC.12 Because of its high crystallinity, it is not soluble in common


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solvents, except highly fluorinated solvents such as hexafluoroisopropanol up to a molar mass of 45,000 g/mol.13 PGA can be synthesized through the ring-opening polymerization of glycolide.14 Although this route is one of the best option for producing high yield and molecular weights, the expensive glycolide monomer limits industrial production of PGA.15 And, another issue is that the ring-opening polymerization of glycolide is mostly achieved using tin (II) octanoate/benzyl alcohol catalyst system.8 As tin compounds are known to be toxic, and it is not easy to remove them from the polymer product. The high cost of glycolide and toxicity of the catalyst make important to find alternative routes for synthesizing PGA.16

Figure 1.

We previously reported a new method for the production of PGA from the cationic polymerization of formaldehyde (from trioxane) and carbon monoxide (CO) in a solvent with Brønsted acidic conditions (Figure 2). PGA was successfully obtained with high yields (up to 92%) from one step cationic polymerization of trioxane (formaldehyde



source) and carbon monoxide in the presence of triflic acid (TfOH) in dichloromethane at 170 oC in a pressured vessel at 800 psi in 72h. 18,19 This procedure has the benefits of using inexpensive C1 monomers formaldehyde and CO potentially made from methanol, which has been a sustainable/green monomer for a long time. Methanol was produced through the distillation of wood by heating to around 500 oC. Therefore, the common name of methanol is known as wood alcohol.17 Besides methanol, CO is also a readily available C1 building block produced from agricultural waste, natural gas or coal.20

Figure 2.

The brown or beige color displayed by PGA diminishes its use in many packaging applications. In order to utilize PGA in other marketing materials such as packaging, the polymer should be specifically engineered to improve the physical properties by a copolymerization strategy by utilizing appropriate comonomers. Our approach for the copolymerization strategy consists of incorporation of alkyl branches into the PGA


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backbone. Incorporation of well-defined alkyl branches into the PGA backbone breaks its crystallinity. The influence of the side chains of epoxides on the breaking crystallinity of polyesters obtained from alternating copolymerization of epoxides and carbon monoxide was reported in the literature.21 Introduction of side chains on epoxide comonomer results in a decrease of the crystallinity, decreases the melting temperature and the glass transition temperatures of the obtained polyester. In addition to that, Miller and coworkers reported that linear low-density polyoxymethylene (LLDPOM) could be synthesized through the cationic ring opening polymerization of trioxane and epoxides with

long

alkyl

branches.

Branching

strategy

disrupts

the

crystallinity

of

polyoxymethylene and allows for the preparation of LLDPOM with tunable thermomechanical properties.22 Using the same approach, the physical properties of PGA could be modulated by copolymerization

of

formaldehyde

and

CO

with

long

chain

epoxides.

The

copolymerization of PGA with fatty ester epoxides allows for lowering polymerization temperatures and disrupting crystallinity of PGA.23 This approach also helps to increase the solubility of PGA-based copolymers in common organic solvents and improve some



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of their physical properties (appearance, thermal property, etc.). These new attributes provide important polymer structure/property relationship and differentiate the utility of the comonomers for modulating the physical properties of PGA. EXPERIMENTAL

Chemicals and Reagents. Dichloromethane (DCM) was purified by stirring over calcium hydride for 24 hours and then vacuum transfer into an oven dried Straus flask. Palmitic acid (Acros organics, catalog # 129700010), Lauric acid (Acros organics, catalog # 167285000), Stearic acid (Merck, catalog # 8006731000), Oleic acid (SigmaAldrich, catalog # 27728), 10-undecenoic acid (Sigma-Aldrich, catalog # 124672), Sodium hydroxide (Merck, catalog # 1064981000), Dichloromethane (Sigma-Aldrich, catalog # 24233), meta-chloroperbenzoic acid (m-CPBA, Acros organics, catalog # 255791000),

Glycidol

(Acros

organics,

catalog

#

120051000),

1,1,1,3,3,3-

Hexafluoroisopropanol (HFIP, Acros organics, catalog # 147540250), Triflic acid (TfOH, Sigma-Aldrich, catalog # 158534), Trioxane (Acros organics, catalog # 140295000), Diethyl ether (Merck, catalog # 1009215000), Hexane (Merck, catalog # 1043682511),


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Chloroform (Merck, catalog # 1024452500), Silicagel (Sigma-Aldrich, catalog # 717185), N,N`-dimethylamino pyridine (DMAP, Acros Organics, catalog # 148271000), N,N`-dicyclohexylcarbodiimide

(DCC,

Sigma-Aldrich,

catalog

#

D80002)

and

commercial PGA (Sigma Aldrich, catalog # 46746) were purchased and used as received. Synthesized comonomers were stored under nitrogen and in a refrigerator. pH 3.0 citrate buffer (from 0.1 M (7 mL) sodium citrate and 0.1 M (93 mL) citric acid), pH 5.0 acetate buffer (prepared from 0.1 M (70.5 mL) sodium acetate and 0.1 M (29.5 mL) acetic acid), pH 7.0 phosphate buffer (from 0.1 M (100 mL) potassiumdihydrogen phosphate and 0.1 M (58.2 mL) NaOH) and pH 9.0 Borate buffer (prepared from 0.618 g boric acid, 0.13 g NaOH and 100 mL water) were prepared and used for degradation experiments. Instrumentation. A Parr 300-mL high-pressure reactor (PARR/USA 4766HT, titanium, max pressure 2000 psi and max temperature 316 oC) was used for the experiments. Proton nuclear magnetic resonance (1H NMR) spectra were recorded using a BrukerInstruments-NMR Spectrometer (DPX-400). NMR sample preparation: about 0.5 g of sample was dissolved in DMSO-d6. Chemical shifts are reported in parts per million



(ppm) downfield relative to tetramethylsilane (TMS, 0.0 ppm) or residual protons in the specified solvent. The FT-IR spectra were recorded on Shimadzu IRAffinity-1S spectrometer by using ATR probe in the region of 4000-400 cm-1 and 64 scans/sample. Differential scanning calorimetry thermograms were obtained with a Mettler-Toledo DSC 1 Star system instrument. About 5-10 mg of each sample was weighed and sealed in a pan. Thermal history was established by a heat/cool cycle at 10 oC/min from -50 oC to 250 oC. Thermogravimetric analyses were performed under nitrogen with Mettler-Toledo TGA/DSC 1 Star system and Perkin Elmer Diamond Thermogravimetric and Differential Thermal Analysis Instruments. About 5-10 mg of each sample was heated at 10 oC/min from RT to 500 oC. Gel permeation chromatography (GPC) was performed at 40 oC using a Shimadzu LC-20AD Instrument with an internal differential refractive index detector, and an Agilent PLgel mixed-B column using HPLC grade N,N`Dimethylformamide (DMF) as the mobile phase at a flow rate of 1 mL/min. Calibration was performed with narrow polydispersity polystyrene (PS) standards. Gel permeation chromatography (GPC) for degradation experiments was performed at 40 oC using a Perkin Elmer Series 200 Instrument with an internal differential refractive index detector,


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and two TSK gel AM SEC GEL columns using HPLC grade N,N`-Dimethylformamide (DMF) as the mobile phase at a flow rate of 0.5 mL/min. Calibration was performed with narrow polydispersity polystyrene (PS) standards. Representative Copolymerization Procedure. Under nitrogen atmosphere, a mixture of trioxane, an epoxide compound, and TfOH catalyst in DCM was placed in a 300-mL high-pressure reactor, charged with 800 psi CO, and heated to the desired reaction temperature. The reaction was stirred under CO pressure for 72 h at the same reaction temperature. After cooling to room temperature, the pressure was released, and the mixture was poured into cold basic methanol. The product was isolated by filtration, and washed with methanol and DCM, and dried under vacuum. RESULTS AND DISCUSSION

On the basis of our previous work on the synthesis of PGA from the alternating copolymerization of formaldehyde and CO in BrØnsted acidic conditions,18,19 we have focused on the synthesis of PGA-based copolymers with a variety of epoxides obtained from long alkyl chain fatty acids to explore their effects on the physical properties of



PGA (Figure 3). Fatty acids are important sustainable sources due to their abundances, low toxicities, and ease of functionalization.24 Since methanol (wood alcohol), CO and fatty acids are potentially sustainable, synthesis of PGA copolymers from the copolymerization of trioxane, CO and fatty ester epoxides is also efficient, inexpensive, and sustainable.

Figure 3.

Main focus in this study was to improve the physical properties of PGA by copolymerization with epoxides derived from long chain fatty acids. Table 1 presents the results of different epoxide incorporations in the PGA backbone. Epoxide comonomers in Table 1 were successfully synthesized and purified as described in ESI. Initially, incorporation of oxirane-2-ylmethyl laurate (OML) as renewable fatty ester epoxide in the PGA backbone was investigated by using the same reaction conditions for PGA homopolymer synthesis in our previous studies (polymerization of trioxane and 800 psi CO with triflic acid catalyst in DCM at different temperatures in 72 h). Different


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epoxide feed ratios and reaction temperatures were also employed to optimize polymerization conditions. Reaction temperature and epoxide feed ratio had profound impacts on the physical properties of the obtained copolymers. The influence of CO pressure was reported in our previous work,18,19 and optimum CO pressure had been found to be 800 psi. The polymerization yield was lower for below 800 psi CO pressure, and did not change above 800 psi CO pressure. We also seeked to understand how the increasing feed ratio of epoxide comonomers changes the physical properties of PGA copolymers by altering trioxane/epoxide feed ratios from 95/5 to 90/10. Optimization results showed that the polymerization yield decreased with increasing trioxane/epoxide feed ratio. The obtained copolymers with higher epoxide contents provided more soluble behaviors in common organic solvents and lower melting temperatures. The incorporation percentages of the epoxides in the polymer

backbone

increased


by

increasing

ACS Sustainable Chemistry & Engineering 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

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Table 1. Trioxane, CO and epoxide comonomer copolymerization resultsa Feed ratio

Tp

Yield

Inc. (mol %)

T90

T50

(mol %)

(oC)

(%)

by 1H-NMR

(oC)

(oC)

95/5

100

55

1.4

256

307

95/5

110

89

1.1

225

95/5

120

83

0.9

4

90/10

110

78

5b

95/5

110

6

95/5

Tpeak

Tg

Tm

(oC)

(oC)

317

32

179

292

319

30

190

240

327

353

37

202

13.0

295

342

356

31

93

12.3

307

361

376

100

55

3.8

240

290

95/5

110

78

1.4

230

95/5

120

77

1.6

9

90/10

110

14

10b

95/5

110

11

95/5

Mn (g/mol)

Đ

40700

1.69

6800

1.08

49800

1.28

8600

1.17

129900

1.17

12000

1.28

194

71500

1.48

31

194

131800

1.13

306

34

178

44000

1.60

6800

1.11

298

312

31

186

68200

1.06

14700

1.10

232

325

341

30

194

95700

1.28

14300

1.08

9.9

286

336

344

12

172

65000

1.59

86

9.1

293

328

333

21

178

125900

1.15

100

38

1.6

265

305

306

17

179

27500

1.27

7500

1.10

95/5

110

78

0.8

208

290

302

35

189

66400

1.15

20400

1.08

95/5

120

74

1.1

286

330

342

34

195

100200

1.11

26100

1.08

14

90/10

110

22

4.5

284

341

352

16

174

73300

1.44

15b

95/5

110

82

2.3

279

319

324

34

195

93900

1.25

95/5

100

50

4.3

254

327

348

19

181

48000

1.67

5900

1.13

Entry

Comonomer

Copolymer

1

(oC) DTG

O O

C11H23

2 3

O

Oxirane-2ylmethyl laurate (OML)

O O

C15H31

7 8

O

Oxirane-2ylmethyl palmitate (OMP)

O O

C17H35

12 13

O

Oxirane-2ylmethyl stearate (OMS)

O

16

O

O 8


Page 15 of 48 Ethyl 9-(oxiran-

17

50100

1.28

8300

1.11

117200

1.19

11600

1.24

177

64100

1.45

24

190

93700

1.22

288

40

140

44000

1.60

6800

1.11

302

325

28

180

16400

1.25

222

284

306

42

187

38700

1.45

-

-

-

-

-

-

-

-

2.7

254

318

337

18

186

49400

1.61

95/5

110

51

4.5

224

329

350

23

188

18

95/5

120

37

2.9

239

310

338

21

192

19

90/10

110

20

6.3

231

313

349

8

20b

95/5

110

65

4.5

269

327

341

95/5

100

7

1.6

208

272

95/5

110

20

1.6

235

95/5

120

16

0.4

90/10

110

0

95/5

110

29

2-yl) nonanoate (EON)

O

21 7

22

O 7

OEt

O

R' O

Ethyl 8-(3-octyl oxiran-2-yl)

24

octanoate

25b

(EOO)

aReactions

R O a) R= -CH2(CH2)6-C-O-CH2CH3, R'= -CH2(CH2)6CH3 O

=

23

O

=

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


b) R= -CH2(CH2)6CH3, R'= -CH2(CH2)6-C-O-CH2CH3

conducted with 1 mol % TfOH as initiator, dichloromethane as solvent, under 800 psi CO pressure and a reaction time of 72 hours. breaction conducted with the

condition of a, but the reaction was first stirred at 40 oC for 24 hours, then temperature was raised to 110 oC and stirred for 72 hours at that temperature. Tp= polymerization temperature, T90= the temperature at 90% residue, T50= the temperature at 50% residue, Tg= glass transition temperature, Tm= melting temperature, Mn= the number average molecular weight, Đ = polydispersity index. Tpeak (oC) DTG: the first derivative of the TGA curves.



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epoxide feed ratio, but on the other hand the polymerization yield was dramatically decreased with increasing epoxide feed ratio (for example, Table 1 entries 2 and 4). Increasing epoxide feed ratio to 90/10 decreased the copolymerization yield, while epoxide incorporation in the polymer backbone increased (Table 1, entry 4). After trying several reaction temperatures, the optimum polymerization temperature for the highest yield was found to be 110 oC. In contrast to the PGA homopolymer synthesis, the copolymerization temperatures were lower than that of PGA synthesis. The yield decreased at lower or higher temperatures than 110 oC. At lower reaction temperatures, epoxide incorporations in the copolymer backbone were also increased (Figure 4) as the effect of reaction temperature on the cationic ring opening polymerization of epoxides is of prime importance. Even though increasing reaction temperature increased the rate of the ring opening polymerization of epoxides, it could also decrease the yield and the molecular weight of the obtained polyether due to the increased chain transfer and termination reactions compared to the propagation steps.25 Copolymerization reactions in this study were performed at relatively high reaction temperatures such as 100 oC. Therefore, incorporation of epoxides in the polymer


16

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backbone was predicted to be low at reaction temperatures above 100 oC. These results are also consistent with the synthesis of POM based copolymers that was obtained from trioxane and epoxides at room temperature in the literature.21 According to this report, trioxane and epoxides with long side chains could be cationically copolymerized

to

produce

Linear

Low-density

Polyoxymethylenes

(LLDPOM).

Incorporation of long chain epoxides in polyoxymethylene (POM) backbone was expected to disrupt the crystallinity of POM, and the melting temperatures of the obtained copolymers were anticipated to decrease compared to POM homopolymer.21

Figure 4.

The maximum yield (89%) for the OML incorporation experiments was obtained at entry 2 in Table 1. The incorporation percentage of OML in the polymer backbone was 1.1 mol% according to the 1H NMR result. We next, focused on further improving the polymerization yields and epoxide incorporations in the polymer backbone by performing the reactions under first room temperature conditions to obtain POM based


17


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copolymer. Then, the reaction temperature was increased to 110 oC to obtain PGAbased copolymers (Figure 5). According to the obtained results in Table 1 (entries 5, 10, 15, 20 and 25), the polymerizations carried out in that condition were achieved with the highest yields and molecular weights. Epoxide incorporation percentages in the PGA backbone were also relatively high.

Figure 5.

The promising results obtained using OML epoxide incorporated copolymer synthesis prompted us to consider other epoxide comonomers including OMP, OMS, EON and EOO shown in Table 1. After optimization of feed ratio and polymerization temperature parameters from OML incorporation experiments, Table 1 entry 5 was decided to be the optimized copolymerization condition and used for other epoxide incorporations (OMP, OMS, EON and EOO). As shown in Table 1, copolymers were successfully synthesized in very good yields between 65-93 %, except the polymerization carried out with EOO comonomer from oleic acid. Among epoxide comonomers used in the study, the EOO


18

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comonomer obtained from oleic acid showed relatively low polymerization tendency (Table 1, entries 21, 22, 23, 24 and 25). Since the epoxide ring of the EOO comonomer is not a terminal epoxide, it contains two different vicinal groups with long hydrocarbons (alkyl and ester) and these groups constitute a significant steric barrier for the epoxide ring. Thus, the nucleophilic attack on this epoxide ring is not easy. Therefore, copolymerization yields carried out with EOO comonomer were quite low and varied between 7% and 29%. In addition to that, no product could be observed in the polymerization (Table 1 entry 24) where EOO feed ratio was at 10 mol%.

According to the NMR results (see ESI), epoxides were randomly copolymerized with the glycolic acid repeating units to produce polyester/ether structures. In order to obtain more detailed structural information, the HMBC (heteronuclear multiple bond coherence) NMR spectrum of entry 4 in Table 1 was taken to provide multiple bond connectivities within the copolymer backbone (Figure 6). The HMBC NMR spectrum provided information related to the three-bond couplings between epoxide carbons and neighboring protons. In the HMBC spectrum, multiple cross peaks appeared at

13C


19


Page 20 of 48

resonances of opened epoxide carbons around 60 and 52 ppm. These cross-peaks were assigned to the interactions of opened epoxide carbons with the adjoining monomer which was either methylene protons of glycolic acid repeat unit, or another opened epoxide repeat unit protons. The multiple peaks around 50 and 62 ppm were therefore, considered to be related to the monomer sequence randomization during the polymerization proving the formation of random copolymers.

Figure 6.

The possible polymerization mechanism of epoxide incorporation in the PGA backbone is depicted in Figure 7. The polymerization reaction of trioxane, an epoxide and CO in acidic conditions has an entropic driving force.25a The trioxane ring can be opened by removal of two moles of formaldehyde. Then, the formation of protonated formaldehyde allows for the nucleophilic addition of CO to form a new acylium ion intermediate. A formaldehyde or an epoxide compound can attack to the acylium ion to generate a new oxonium ion intermediate; and polymerization propagates (Figure 7).


20

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Obtained copolymers are soluble in DMF and DMSO, and slightly soluble in THF and acetone. The copolymers showed lighter colors than commercial PGA. Some of the obtained copolymers are off-white colored. GPC analyses were performed to show molecular weights of the obtained copolymers. Some of the copolymers exhibited bimodal molecular weight distributions and narrow polydispersity index, using polystyrene standards in DMF. The observation of the bimodal molecular weight distribution was attributed to the termination of some active chains by either impurities or chain transfer reactions by hydrogen abstraction to the comonomer (formaldehyde or epoxide). Some of the copolymers showed very high molecular weights. The reason of obtaining high molecular weights could be due to the aggregation of the obtained copolymers in DMF and that could be another reason for the observation of bimodal molecular weight distribution. The observation of low PDI’s are probably related to leaving low molecular weight materials in solution during the work-up procedure, in which the reactions were cooled down to room temperature, CO was released, and products were precipitated with cold basic methanol, and washed with DCM.


21


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Figure 7.

To inquire the thermal stabilities of the copolymers, thermogravimetric analysis was performed. The thermal properties of these copolymers were summarized in Table 1. Thermogravimetric analysis (TGA and DTG) curves of the copolymers and PGA homopolymer were also shown in Figure 8. Weight loss curves of the copolymers and PGA homopolymer were shown as solid lines, and their respective derivatives were displayed as dashed lines (Figure 8). DTG curves of the all copolymers also show only one step decomposition from 200 oC to 380 oC under nitrogen atmosphere. The first derivative curves indicate the inflection points which the highest weight losses occurred at those temperatures. DTG curve of the PGA homopolymer shows maximum weight loss at 319 oC. However, the obtained copolymers exhibit maximum weight losses around 324 to 376 oC with above 94 % of degradations. Small amount of residue remained at those temperatures.

Figure 8.


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The thermal properties of the obtained copolymers can also be correlated directly to the epoxide incorporation percentage and polymerization temperatures. As shown in Table 1, the increasing epoxide incorporation percentages of the OML comonomer strongly affect the melting temperatures of the obtained copolymers (Figure 9a). The melting temperatures of the obtained copolymers were also less than that of the commercial PGA (226 oC). The observation of lower melting temperatures is a result of the epoxide incorporation of PGA backbone. The similar observation was also reported for random P(LLA-GA) copolymers synthesized from L-lactic acid (LLA) and glycolic acid (GA) by Tsuji et al.26 They reported that the melting temperature and the crystalline size of the P(LLA-GA) copolymer decreased with increasing LLA content. Incorporation of large-sized LLA unit in glycolic acid units strongly induces the structural strain or disorder in the crystalline lattices of the obtained copolymer. Melting temperatures of the copolymers also increases with increasing reaction temperature (Figure 9b). While the copolymers obtained at 100 oC present low melting temperatures, the copolymers obtained at 120

oC

show much higher melting

temperatures in Table 1. The relationship between the epoxide incorporation


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percentages and polymerization temperatures on the copolymer melting temperatures are shown in Figure 9.

Figure 9.

Biodegradation of PGA homopolymer requires either aqueous conditions or aqueous conditions including enzymes, such as esterase, to accelerate the hydrolysis rate of PGA. Degradation behavior of PGA in different physiologic and pathologic conditions is very important since it is commonly used as surgical sutures and needs to retain enough strength under different pH conditions (for example, pH in the stomach is around 1.0, and pH of the pancreatic fluids is around 7.5-8.0).27 In the literature, 70 % of PGA in pH 6.8 (distilled water) condition degrades within 90 days.28 Similarly, degradation of PGA in pH 7.4 buffer (phosphate buffered saline) was reported as 20 weeks.29 It was reported that PGA exhibited better strength in the acidic buffers than in alkaline conditions.27 In order to understand the effect of different pH conditions on the hydrolytic degradations of the obtained copolymers, OML incorporated copolymer (entry


24

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5 in Table 1) was chosen as a representative product since all copolymers have similar functional groups and contain ester and ether functionalities. Hydrolytic degradation of OML incorporated copolymer in four different pH buffers (pH: 3.0, 5.0, 7.0 and 9.0) were carried out at 25 oC in order to determine degradation duration of the obtained copolymers and degradation duration was compared in terms of the mass percent of the copolymer residue. According to the degradation experiments for OML incorporated copolymer at different pHs, the copolymer underwent a rapid degradation (hydrolysis) under slightly basic and neutral conditions (see ESI for degradation experiments, and obtained results). Both weight loss and decrease in molecular weight of the copolymer occur at a faster rate. The effects of the degradation rates of sequenced and random copolymers for poly(lactic-co-glycolic acid) (PLGA) in pH 7.4 phosphate buffer at 37 oC was reported to be significantly dependent on the monomer sequence on the copolymer.30 According to the report, degradation rate could be altered by controlling monomer sequences on the copolymer. Sequenced PLGA degrades much slow at more constant rate compared to the random PLGA. The degradation rate of the synthesized OML incorporated copolymer was therefore expected to be fast since it is a random


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Page 26 of 48

copolymer. The degradation duration of the copolymer at pH 9.0 was found to be approximately 30 days (Figure 10). Degradation of the copolymer in neutral (pH 7.0) and slightly acidic (pH 5.0) buffers was also as rapid as the pH 9.0 condition, and the degradation duration was found to be about 45 days (Figure 10). In the pH 3.0 buffer, 55% of the copolymer degraded at the end of the 60th day, while 45% of the polymer still remains. Decomposition of this copolymer in pH 3.0 buffer was predicted to be completed within 100 days according to the obtained results (Figure 10).

Figure 10.

CONCLUSION

In conclusion, a new family of polyglycolic acid anologues has been synthesized from inexpensive sources and characterized. The addition of minor quantities of epoxide comonomers vastly improves the appearance of the PGA and allows for the control of the polymeric properties, such as melting temperature and solubility. This method provides a cost-effective and efficient path for synthesizing PGA-based copolymers.


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The number of synthetic steps from simple feedstocks is greatly reduced and the starting materials are potentially sustainable from biomass and fatty acids. The results show that optimal polymerizations are obtained at temperatures lower than that of PGA synthesis. Higher reaction temperatures resulted in lower yields, but higher CO incorporation. Characterization of the copolymers show that the melting temperatures of the copolymers decreased with increasing incorporation percentages of the comonomer and decreasing polymerization temperatures. The solubility of the copolymers in organic solvents increased with incorporation of the epoxide in the PGA backbone and obtained copolymers were also lighter in color than the commercial PGA. Obtained copolymers also undergo rapid degradation (hydrolysis) under slightly basic and neutral conditions in degradation studies. ASSOCIATED CONTENT

The Supporting Information is available free of charge on the ACS Publications website at DOI:


27


1H

and

13C

Page 28 of 48

NMR spectra, DSC and TGA traces, FT-IR spectra and GPC

chromatograms are given in ESI.

AUTHOR INFORMATION

Corresponding Author *Ersen Gokturk. E-mail: [email protected].

Notes The authors declare no competing financial interest.

ACKNOWLEDGMENTS

This study was funded by The Scientific and Technological Research Council of Turkey (TUBITAK), 3501-Career Development Program via grant number 115Z482. Authors would also like to thank Dr. Basri Gülbakan and Dr. İlker Avan for their proofreading.

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Table of Contents Graphic


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Synopsis: Synthesizing polyglycolic acid copolymers from sustainable C1 monomers, formaldehyde and carbon monoxide potentially made from methanol, and fatty ester epoxides.

Tables

Table 1. Trioxane, CO and epoxide comonomer copolymerization resultsa

Figures

Figure 1. The structure of PGA.


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Figure 2. One step cationic polymerization of formaldehyde and CO, and synthesis of PGA.18,19

Figure 3. BrØnsted acid catalyzed cationic copolymerization of trioxane, CO and an epoxide.

Figure 4. Incorporation percentage of OML into the polymer backbone is inversely proportional to the polymerization temperature.

Figure 5. Synthesis of poly(acetal-ether) copolymers by polymerization of trioxane and epoxides from fatty acids at room temperature and addition of CO with increasing reaction temperature allows producing PGA based copolymers.

Figure 6. HMBC NMR spectrum of the copolymer entry 4 in Table 1.

Figure 7. The possible polymerization mechanism for epoxide incorporation in the PGA backbone.

Figure 8. TGA and DTG curves of the PGA homopolymer and synthesized copolymers (entries 5, 10, 15, 20 and 25 in Table 1).


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Figure 9. (a) The melting temperatures of the OML incorporated copolymers are inversely proportional to the OML incorporation percentage. (b) The melting temperatures of the copolymers are directly proportional to the polymerization temperature.

Figure 10. Hydrolysis/degradation studies of the copolymer (Table 1, entry 5) upon exposure to aqueous environments of pH 3.0, pH 5.0, pH 7.0 and pH 9.0.


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Figure 1. The structure of PGA. 20x15mm (300 x 300 DPI)



Figure 2. One step cationic polymerization of formaldehyde and CO, and synthesis of PGA.17,18 131x28mm (300 x 300 DPI)


Page 40 of 48

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Figure 3. BrØnsted acid catalyzed cationic copolymerization of trioxane, CO and an epoxide. 141x30mm (300 x 300 DPI)



Figure 4. Incorporation percentage of OML into the polymer backbone is inversely proportional to the polymerization temperature. 162x120mm (96 x 96 DPI)


Page 42 of 48

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Figure 5. Synthesis of poly(acetal-ether) copolymers by polymerization of trioxane and epoxides from fatty acids at room temperature and addition of CO with increasing reaction temperature allows producing PGA based copolymers. 216x27mm (300 x 300 DPI)



Figure 6. HMBC NMR spectrum of the copolymer entry 4 in Table 1. 187x118mm (150 x 150 DPI)


Page 44 of 48

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Figure 7. The possible polymerization mechanism for epoxide incorporation in the PGA backbone. 191x165mm (300 x 300 DPI)



Figure 8. TGA and DTG curves of the PGA homopolymer and synthesized copolymers (entries 5, 10, 15, 20 and 25 in Table 1). 793x398mm (96 x 96 DPI)


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Figure 9. (a) The melting temperatures of the OML incorporated copolymers are inversely proportional to the OML incorporation percentage. (b) The melting temperatures of the copolymers are directly proportional to the polymerization temperature. 321x87mm (96 x 96 DPI)



Figure 10. Hydrolysis/degradation studies of the copolymer (Table 1, entry 5) upon exposure to aqueous environments of pH 3.0, pH 5.0, pH 7.0 and pH 9.0. 127x93mm (96 x 96 DPI)


Page 48 of 48

An alternative approach for synthesizing polyglycolic acid copolymers

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