Miscibility of High Mw Poly(Lactic Acid) (PLA)

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BLENDS OF HIGH MOLECULAR WEIGHT POLY(LACTIC ACID) (PLA)

WITH COPOLYMERS OF 2-BROMO-3-HYDROXYPROPIONIC ACID AND

LACTIC ACID (PLB)

A Thesis

Presented to

The Graduate Faculty of The University of Akron

In Partial Fulfillment

of the Requirements for the Degree

Master of Science

Xia Lei

May, 2013

BLENDS OF HIGH MOLECULAR WEIGHT POLY(LACTIC ACID) (PLA)

WITH COPOLYMERS OF 2-BROMO-3-HYDROXYPROPIONIC ACID AND

LACTIC ACID (PLB)

Xia Lei

Thesis

Approved: Accepted:

______Advisor Dean of the College Dr. Coleen Pugh Dr. Stephen Cheng

______Faculty Reader Dean of the Graduate School Dr. Li Jia Dr. George Newkome

______Department Chair Date Dr. Coleen Pugh

ABSTRACT

Poly(lactic acid) (PLA) is considered to be one of the most promising biodegradable materials in the family of aliphatic polyesters. PLA and its copolymers, such as poly(lactic acid)-co-(glycolic acid), are widely used as biomedical materials or alternatives to petrochemical-based polymers. PLA has the advantage that it is produced commercially by an efficient method at relatively low cost. However, there are some disadvantages to PLA. It is brittle and difficult to functionalize. Blending is an extremely promising approach to improve the properties of polymers. Blends may exhibit the physical and chemical properties of both individual polymers. The miscibility of the two polymers can be evaluated by the glass transition temperature (Tg) method.

Different chemical properties, such as optimum hydrophilic/hydrophobic balance and the ability to act as a drug-carrier may be obtained by functionalization of our recently synthesized brominated PLA copolymers. Materials with good mechanical properties may be produced by blending functionalized PLA with high molecular weight commercialized PLA. This study investigates the miscibility of brominated PLA with high molecular weight PLA. The influence of different blends ratios, molecular weights of PLA and configurations of PLA on the miscibility is presented.

iii

ACKNOWLEDGEMENTS

I would like to thank my research advisor Dr. Coleen Pugh for providing me the opportunity and guidance for my research. I am very grateful for her patience and encouragement. I am also grateful to Dr. Li Jia to be my committee member.

I would like to thank Dr. Abhishek Banerjee to be my mentor at the beginning of my research. I would like to thank Dr. Robert Weiss and Dr. Allen Padwa for providing the chemical samples and suggestions for research. I would like to thank all of my group members, especially Gladys Montenegro and Cesar Lopez Gonzalez for their help of

GPC and DSC.

I would also like to thank all my family and friends.

TABLE OF CONTENTS Page

LIST OF TABLES ...... vii

LIST OF FIGURES ...... viii

LIST OF SCHEMES ...... x

CHAPTER

I INTRODUCTION ...... 1

II POLY(LACTIC ACID) ...... 3

2.1 Application ...... 3

2.2 Limitation ...... 4

III THEORIES OF POLYMER MIXTURES ...... 5

3.1 Flory-Huggins Theory ...... 5

3.2 Fox Equation ...... 6

3.3 Gordon-Taylor Equation ...... 7

IV MISCIBILITY OF PLA-CONTAINING BLENDS ...... 8

4.1 PLA blends with Poly(ethy1ene glycol) ...... 8

4.2 PLA Blends with Poly(ε-caprolactone) ...... 12

4.3 PLA Blends with Polyhydroxyalkanoates ...... 14

4.4 P(DL)LA Blends with Poly(methyl methacrylate) ...... 15 v

V EXPERIMENTAL ...... 17

5.1 Materials ...... 17

5.2 Instrument ...... 17

5.3 Synthesis of 2-Bromin-3-hydroxypropionic acid ...... 18

5.4 Copolymerization of LA and BrH ...... 20

5.5 Hydrolyze PLA ...... 21

5.6 Blending ...... 22

VI RESULTS AND DISCUSSION ...... 23

6.1 Study of different ratio of blends ...... 23

6.2 Study of different molecular weight PLA blends ...... 25

6.3 Study of different configuration of PLA ...... 29

6.4 Conclusions ...... 31

REFERENCES ...... 32

LIST OF TABLES

Table Page

1. Results from DSC analysis for the PLA/PEG Blends21 ...... 10

2. Results from DMA for the PLA/PEG Blends21 ...... 10

3. Mechanical Properties of PLA/PCL/TPP Blends24 ...... 12

4. Thermal Properties of P[(S)-LA]/ataPHB Blends26 ...... 14

5. Blend ratio of PLA and PL60B40 ...... 22

6. Summary of DSC analysis data ...... 23

7. GPC and DSC results of hydrolyzed PLA ...... 25

8. Summary of DSC analysis data ...... 26

9. Results of Tg calculated from Fox equation ...... 28

10. Results of Tg calculated from Gordon-Taylor equation ...... 28

11. Summary of DSC analysis data ...... 29

12. Results of Tg calculated from Fox equation ...... 30

13. Results of Tg calculated from Gordon-Taylor equation ...... 31

vii

LIST OF FIGURES

Figure Page

1. DSC thermograms of PEG/PLA blends ...... 8

2. Phase diagram of PLLA/PEO blends. The dotted line shows the proportional dependence of Tg with the blend composition22 ...... 11 3. （A）thermograms in the second heating runs for solution/precipitation DL-PLA/PMMA blends with compositions from 100/0 to 0/100 （B）thermograms in the second heating runs for solution-cast DL-PLA/PMMA blends with compositions from 100/0 to 0/100.27 ...... 16

27 4. Tg versus compositions in solution-cast P(DL)LA/PMMA blends ...... 16

5. 1H NMR spectrum of 300 MHz 1H NMR spectrum of 2-bromo-3-hydroxypropionic acid ...... 20

1 6. H NMR spectrum of PL60B40...... 21

7. Normalized DSC thermograms in second-heating runs of L-PLA/PL60B40 blends different L-PLA/ PL60B40 ratio (9/1, 8/2, 6/4, 5/5); L-PLA (Nature Works 5 3 PLA6202, 2% D-isomer) Mn = 1.16×10 , PL60B40 Mn = 8.69×10 ...... 23

8. Tg of L-PLA and PL60B40 blends with different weight ratios of L-PLA ...... 24

9. L-PLA molecular weight and Tg as a function of hydrolysis time at 60 ℃ in 100% relative humidity...... 26

10. Normalized DSC thermograms in second-heating runs of 6/4 L-PLA / PL60B40 blends with different molecular weight L-PLA prepared by hydrolysis (time in hours) of high molecular weight L-PLA (0 h, Nature Works PLA6202, 2% 3 D-isomer); PL60B40 Mn = 8.69×10 ...... 27

11. Normalized DSC thermograms in second-heating runs of 6/4 D-PLA/ PL60B40 Blends with different molecular weight DL-PLA prepared by hydrolysis (time in viii

12. hours) of high molecular weight DL-PLA (0 h, Nature Works PLA4060, 10% 3 D-isomer); PL60B40 Mn = 8.69 x 10 ...... 30

LIST OF SCHEMES

Scheme Page

1. Polymerization route to poly(lactic acid) ...... 4

2. Structure of PEO and PEG ...... 8

3. Structure of PCL ...... 12

4. Structure of PHB and PHBV ...... 13

5. Structure of PMMA ...... 15

CHAPTER I

INTRODUCTION

Poly(lactic acid) (PLA) is an important aliphatic polyester that can be obtained by condensation polymerization of lactic acid or ring-opening polymerization of lactide. It is biodegradable and sustainable. PLA and its copolymers, such as poly(lactic acid)-co-(glycolic acid) (PLGA), are widely used as alternatives to petrochemical-based polymers. They have been used as biomedical materials, such as surgical suture,1 drug delivery systems2 and tissue engineering3 because of their biodegradability and non-toxicity. However, there are some disadvantages to PLA. It is brittle and difficult to functionalize.

Blending of polymers is an effective method to modify polymer properties. Blends may exhibit the physical and chemical properties of both individual polymers. The mechanical properties, such as modulus, of high molecular weight PLA are better than those of the low molecular polymers, which are brittle. This thesis investigates the miscibility of brominated PLA with high molecular weight PLA, which is produced in a

factory by an efficient method at relatively low cost. Our recently synthesized PLA and its co-polymers with molecular weight ≤ 3 × 104 can be relatively easily functionalized to achieve different chemical properties, such as a range of hydrophilicities and hydrophobicities, and the ability to carry drugs.

The miscibility of blends of PLA and their copolymers can be tested by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA).

CHAPTER II

POLY(LACTIC ACID)

2.1 Application

Poly(lactic acid) (PLA) is considered one of the most promising biodegradable materials in the family of aliphatic polyesters. It can be obtained by condensation polymerization of lactic acid and by ring-opening polymerization of lactide. Cargill

Nature Works LLC has a patented, low-cost continuous process for the production of lactic acid based polymers.4

Scheme 1 shows the polymerization routes to PLA. It is an environmentally friendly material5 that may provide an alternative to petro-based materials. It is also used for medical and ecological applications.6 Its use in surgical suture,1 drug delivery systems2 and tissue engineering3 applications are reported.

Scheme 1. Polymerization route to poly(lactic acid)

2.2 Limitation

PLA is a thermoplastic material with a glass transition (Tg) at 50-60 ℃.7 Poly(L-lactic acid) (PLLA) is crystalline and poly(D,L-lactic acid) (P(DL)LA) is amorphous. They can be processed by different methods, including injection molding and melt spinning.7 PLA has good physical properties, such as high strength, thermoplasticity and fabricability.

However, the transition from ductile to brittle failure in tension due to physical aging8 has limited the applications of PLA. Its crystallinity is also not ideal for many usages.

CHAPTER III

THEORIES OF POLYMER MIXTURES

Blending is an extremely promising approach to improve the properties of polymers. It is efficient and easy. The benefits of two components can produce blends with unique superiority. The miscibility of the two components can be evaluated by the Tg method.9 A single glass transition indicates that the blend is miscible, while two glass transitions indicate that the blend is a 2-phase system. The temperatures of the two Tgs depend on the composition in partially miscible polymers, whereas the two Tgs are independent of composition with totally immiscible polymers.

3.1 Flory-Huggins Theory Flory10 and Huggins11 made the first attempt to describe the thermodynamic properties of polymer solutions. The “configurational” entropy of mixing term (∆푆푚푖푥푖푛푔) due to the length and volume of the polymer in solution is shown in eq 1,

∆푆푚푖푥푖푛푔 = −푘[푁1푙푛푣1 + 푁2푙푛푣2] eq 1 where 푁푖 is the number of molecules i, 푣푖 is the volume fraction of component i, and k

is Boltzmann’s constant.

The Flory-Huggins theory (F-H) is extremely versatile and convenient. The expression

12 for the Gibbs free energy (∆Gm) of mixing of two polymers derived by Scott is presented in eq 2,

푅푇푉 휑1 휑2 ∆퐺푚 = ( ) ln휑1 + ln휑2 + 휒12휑1휑2 eq 2 푉푅 푋1 푋2 where V is the total mixture volume, 푉푅 is the reference volume, 휑1 and 휑2 are the volume fractions, 푋1 and 푋2 are the polymer chain lengths and 휒12 is the polymer-polymer interaction parameter. The parts containing 휑푖 are entropic and go to zero as 휑푖 increases. The entropy of polymer blends at high molecular weight goes to zero. Therefore, ∆Gm can only be negative when the 휒12 is negative.

The existence of an upper critical solution temperature (UCST) can be demonstrated by calculations based on Flory-Huggins theory. The F-H theory was extended by Prigogine13 and Flory14 to include free volume. McMaster15 applied the

Prigogine-Flory theory to polymer-polymer systems. The existence of a lower critical solution temperature (LCST) was predicted. The thermal expansion coefficient proved to be the most important parameter for polymer blend systems.

3.2 Fox Equation

The glass transition temperature of blends can be predicted by the Fox equation,16

which is shown in eq 3. 푇푔 is the glass transition temperature of the blend, while 푇푔,1 and 푇푔,2 are the glass transition temperatures of the individual components. The terms

휔1 and 휔2 are the weight fraction of components 1 and 2. 6

1 휔 휔 = 1 + 2 + ⋯ eq 3 푇푔 푇푔,1 푇푔,2

This equation can be rearranged to eq 4. and eq 5. to determine the composition of the partially miscible phases.

휔1 = 푇푔,1(푇푔,2 − 푇푔)/[푇푔(푇푔,2 − 푇푔,1)] eq 4

휔2 = 푇푔,2(푇푔 − 푇푔,1)/[푇푔(푇푔,2 − 푇푔,1)] eq 5

3.3 Gordon-Taylor Equation

The Gordon-Taylor equation17 shown in eq 6. is used to predict the relationship between Tg and composition for ideal systems that are miscible and amorphous over the whole composition range.

푘푤2(T푔2−T푔1) T푔 = T푔1 + eq 6 푤1+푘푤2

T푔 is the glass transition temperature of the blend, T푔1 and T푔2 are glass transition temperatures of the individual components, 푤1 and 푤2 are the weight fractions of components 1 and 2, and 푘 is an adjustable parameter that may be related to the interaction strength between the components in the blend.

CHAPTER IV

MISCIBILITY OF PLA-CONTAINING BLENDS

There are many reports of blends containing PLA. In some cases, the other component is biodegradable, while in others it is not. The miscibility of PLA blends with biodegradable poly(ethylene glycol), poly(ε-caprolactone), and polyhydroxyalkanoates were studied. Blends of PLA with non-biodegradable poly(methyl methacrylate) are also reported.

4.1 PLA blends with Poly(ethy1ene glycol)

Scheme 2. Structure of PEO and PEG

Poly(ethy1ene glycol) (PEG) is a type of poly(ethylene oxide)s (PEO) with hydroxyl end groups. Scheme 2 shows the structure of PEO and PEG. PEG usually has molecular weights of 20,000 or below. PEG is nontoxic and cleared by the U.S. Food and Drug

Administration for internal use in the human body.18

Younes and Daniel19 studied the phase separation of different molecular weight PEGs

(Mv =1500, 3400, 6000, 35,000 from Aldrich and Fluka) and PLA (Mv = 28,000) blends made by solution casting. The melting endotherm is used to infer the miscibility of blends.

If the melting endotherm depends on the composition of the blend, this indicates that the components of the blend are miscible. A constant melting temperature (Tm) occurs when the components of the blend are immiscible and fully phase-separated; each crystallizable component of the mixture will exhibit the Tm of the pure homopolymer. The difference between the solubility parameters (δ) of the components of the blend is related to the morphology of blends; the values of δ of PEG and PLA are both in the 9.5-9.8 range,20 showing a tendency for their phases to mix.

4 Figure 1. (A) presents DSC thermograms of PEG (Mv = 3.5×10 )/PLA blends (Mv=28,000). (a) 10 wt% PEG. (b) 20 wt% PEG. (c) 30 wt% PEG. (d) 70 wt% PEG. (e) 3 80 wt% PEG. (B) presents DSC thermograms of PEG (Mv = 3.4×10 )/PLA blends. (a) 10 wt% PEG. (b) 20 wt% PEG. (c) 30 wt% PEG. (d) 70 wt% PEG. (e) 80 wt% PEG.19 4 4 Figure 1 shows the DSC traces of PEG (Mv = 3.4×10 and 3.5×10 ) and PLA blends; the melting temperatures of these PEGs and PLA are 55-68 oC and 172 oC, respectively.

When each component is more than 20 wt%, the blends are able to crystallize into two semi-miscible crystalline phases that are dispersed in an amorphous matrix; the

PEG-dominated phase melts immediately after the glass transition of the amorphous matrix. For other ratios, only the major component is able to crystallize. These results indicate that the blends are semi-miscible, exhibiting some chain interpenetration. With regards to the effect of molecular weight of the PEG component, the higher molecular weight PEG produces blends with higher crystallizability of blends.

Sheth et al.21 studied melt-blended PLA/PEG films in different weight ratios (100/0,

90/10, 70/30, 50/50, and 30/70). The DSC and DMA results in Tables 1 and 2 indicate that the PLA and PEG form miscible blends when the content of PLA is less than 50%.

PEG plasticizes the PLA when the blends contain 50% PEG; these blends have higher elongations and lower modulus values. With >50% PEG, the crystallinity of PEG increases. As a result, the modulus increases and the elongation of the blends at break decreases. With increasing PEG content, the tensile strength decreases in a linear manner.

Table 1. Results from DSC analysis of PLA/PEG Blends21

Table 2. Results from DMA of PLA/PEG Blends21

Nijenhuis et al.22 studied the miscibility of blends of high molecular weight P(L)LA

5 6 (Mv=8 × 10 ) with high molecular weight PEO (Mv=4 × 10 ) by DSC. A solution/precipitate method was used to prepare the blends. Dichloromethane was used as the solvent. Figure 2 shows the phase diagram of PLLA/PEO blends.

5 Figure 2. Phase diagram of PLLA/PEO blends; P(L)LA Mv = 8 x 10 , PEO Mv = 4 x 106. The dotted line shows the proportional dependence of Tg on the blend composition22 The blends containing up to 50 wt% PEO showed a single glass transition. The melting temperature of PLLA in these blends decreased slightly as the fraction of PEO increased.

With 10 wt% to 20 wt% PEO, the blends became flexible. The elongation at break was 11

more than 500% for a blend with 20% PEO. In addition, the blends swelled with absorbed water as a result of the increased hydrophilicity.

4.2 PLA Blends with Poly(ε-caprolactone)

Scheme 3. Structure of PCL Poly(ε-caprolactone) (PCL) is an important biodegradable plasticizer with a Tg of

-60 ℃. Scheme 3 shows the structure of PCL. PCL can be blended with PLA to regulate

PLA’s degradation and drug release behavior.23 PCL is immiscible with PLA.

Table 3. Mechanical Properties of PLA/PCL/TPP Blends24

-4 Blend Tensile Elongation Elastic Mn x10 PDI composition Strength at (%) modulus PLA/PCL/TPP break (psi) (104) 100/0/0 7000 3 33.0 9.5 2.69 80/20/0 6410 28 8.48 7.8 2.99 80/20/2 4800 127 14.7 4.2 5.23

24 4 Wang et al. prepared two blends of PCL (Mn=8 × 10 ) with PLA (Mn =

9.5 × 104) ether in the presence or absence of a catalyst, which was used as a coupling or branching agent. Triphenyl phosphite (TPP) was the most effective catalyst. As

summarized in Table 3, the elongation at break of pure PLA is only 3%. The elongation at break of PLA/PCL (80/20) blends increases from 28% for unreacted PLA/PCL (80/20) blend to over 127% for reacted blend. The components of the reacted blend have decreased molecular weight, presumably due to ‘back-biting’ and intramolecular transesterification catalyzed by TPP.

4.3 PLA Blends with Polyhydroxyalkanoates

Scheme 4. Structure of PHB and PHBV Polyhydroxyalkanoates (PHAs) are microbial products that are formed as naturally occurring storage polyesters. Their biodegradable and biocompatible properties are suitable for applications in the biomedical field. Poly(3-hydroxybutyrate) (PHB) and its copolymers with 3-hydroxyvalerate (PHBV) are the best known polymers in the PHA family. Scheme 4 shows the structure of PHB and PHBV.

The miscibility of different molecular weight P[(S)-LA] (Mw = 9900-530,000) with

5 poly[(R)3-hydroxybutyric acid] (P[(R)-3HB]) (Mn=3 × 10 , PDI=2.2) blends were reported by Koyama and Doi.25 P[(S)-LA] is known as PLLA also. The Blends were

4 made in the melt at up to 200℃. Low molecular weight P[(S)-LA] (Mw≤1.8×10 ) is

4 miscible with P[(R)-3HB]. High molecular weight P[(S)-LA] (Mw≥2×10 ) forms blends with two separate Tgs. The authors estimated that the solubility parameters δ1 and δ2 in the

3 1/2 Flory-Huggins equation would differ by 0.34 (J/cm ) .

The miscibility and solid-state structures of blends of P[(S)-LA] with atactic PHB were reported by Ohkoshi et al.26 The blends were also prepared in the melt at up to 200 ℃.

The DSC results summarized in Table 4 indicate that the blends of P[(S)-LA]

5 (Mw=6.8×10 , PDI=2.3) are miscible with up to 50 wt% low molecular weight ataPHB

3 (Mw=9.4 × 10 , PDI=1.6). Blends of PLA with high molecular weight ataPHB

5 (Mw=1.4×10 , PDI=1.5) showed two glass transitions. Polarized optical microscopy images demonstrated that a small amount of ataPHB promotes the crystallization of

P[(S)-LA].

Table 4. Thermal Properties of P[(S)-LA]/ataPHB Blends26

Sample Composition(w/w) 푇푔 (℃) 푇 (℃)

100/0 59 138 95/5 53 119 5 P[(S)-LA] (Mw=6.8×10 , 85/15 41 91 PDI=2.3)/ataPHB 75/25 29 84 3 (Mw=9.4× 10 , PDI=1.6) 50/50 10 77 40/60 -2,10 74 0/100 -16 100.0 59 138 95/5 5, 58 131 P[(S)-LA] (M =6.8×105, w 85/15 0, 56 123 PDI=2.3)/ataPHB(M =1.4×105, w 75/25 1, 56 115 PDI=1.5) 50/50 1, 54 113 0/100 0

4.4 P(DL)LA Blends with Poly(methyl methacrylate)

Scheme 5. Structure of PMMA Poly(methyl methacrylate) (PMMA) is an important polymer that does not biodegrade.

Scheme 5 shows the structure of PMMA. Blends of P(DL)LA and PMMA prepared by both solution-casting and solution/precipitation were studied by Zhang et al.27 The DSC results in Figure 3 show one Tg for the blends prepared by solution/precipitation, while two Tgs are observed for the same ratio of P(DL)LA /PMMA blends prepared by solution-casting. Figure 4 shows the Tg versus composition in solution-cast

P(DL)LA/PMMA blends. The P(DL)LA/PMMA was indicated to be miscible by solution/precipitation method and partially miscible by solution-casting method.

The Tg relationship for P(DL)LA/PMMA miscible systems follow the Gordon–Taylor

17 equation : Tg = Tg1 + kω2(Tg 2 − Tg1) /(ω1 + kω2), where ω푖 is the weight fraction for component i. P(DL)LA also has no more tendency to form miscible blends with

PMMA than PLLA when the crystalline phase of PLLA is melted to the amorphous state.

High temperature allows two components mixing together.

Figure 3. DSC second heating thermograms of DL-PLA/PMMA blends with compositions from 100/0 to 0/100: （A）blends prepared by solution/precipitation;（B） blends prepared by solution-casting.27

Figure 4. Tg versus composition in solution-cast P(DL)LA/PMMA blends. Lines A and B correspond to the PMMA-rich and P(DL)LA-rich phases, respectively.27

CHAPTER V

EXPERIMENTAL

5.1 Materials Diphenyl ether (DPE, Sigma-Aldrich, 99%), D,L-lactic acid (LA, Acros, 85%),

D,L-Serine (Sigma-Aldrich, 98%), DL-PLA (PLA4060, Nature Works 10% D-isomer), hydrogen bromide (HBr, Acros, 58% solution in water), L-PLA (PLA6202, Nature Works,

2% D-isomer), methanol, ethyl aetate (Fisher, 99%), methylene choloride (CH2Cl2, Fisher,

99%), p-toluene sulfonic acid (p-TSA, Fisher, laboratory grade), potassium bromide (KBr,

Acros, 98%), sodium nitrite (NaNO2, Aqua Solutions, laboratory grade), anhydrous magnesium sulfate (MgSO4, Fisher, 97%) were used as received.

5.2 Techniques

All reactions (under N2 atmosphere) and polymerizations (under vacuum) were conducted on a Schlenk line unless noted otherwise. 1H NMR (300 MHz) spectra were recorded with a Varian Mercury 300 spectrometer. Unless noted otherwise, all spectra were recorded in CDCl3, and the resonances were measured relative to residual solvent resonances and referenced to tetramethylsilane (0.00 ppm). Number-average (Mn) and

weight-average molecular weights (Mw) and polydispersities (PDI=Mw/Mn) were determined by gel permeation chromatography (GPC) relative to linear polystyrene from calibration curves of log Mn vs. elution volume at 35 ºC using THF as solvent (1.0 mL/min), a set of 50, 100, 500, 104 Å, and linear (50-104 Å) Styragel 5 m columns, a

Waters 410 differential refractometer, and Millenium Empower software. All samples

(~1.0 g/L) were dissolved in THF and filtered through a 0.45 µm PTFE filter.

A Perkin-Elmer Pyris 1 differential scanning calorimeter was used to determine the thermal transitions, which were read as the maximum or minimum of the endothermic or exothermic peaks, respectively. Glass transition temperatures (Tg) were determined as the middle of the change in heat capacity. Transition temperatures were calibrated using indium and tin standards; enthalpy was calibrated using an indium standard. The samples were heated from 0 to 200 °C and annealed at 200 °C for one minute to erase the thermal history. Then the samples were cooled down to 0 °C and maintained for 1 minute followed by a second heating to 200 °C at a rate of 10 °C/min. Some of the samples were cooled a second time and heated a third time using the same conditions.

5.3 Synthesis of 2-Bromin-3-hydroxypropionic acid

2-Bromo-3-hydroxypropionic acid (BrH) was prepared using the method reported by our lab.29 D,L-serine (20 g, 0.20 mol), KBr (80 g, 0.66 mol), and HBr (52 mL, 0.46

mol) were dissolved in H2O (300 mL) in a 3-neck round bottom flask (3-N RBF). NaNO2

(24 g, 0.34 mol) was dissolved in H2O (100 mL) and transferred to an addition funnel.

The 3-N RBF was cooled in a salt-water bath with dry ice to reach the temperature below

-10℃. The NaNO2 aqua solution was added dropwise over 2 h to the 3-N RBF. The solution became brown during the NaNO2 addition, and a brown gas was evolved. After the NaNO2 was added, the solution became a clear green color. The reaction mixture was stirred at room temperature for an additional 24 h. The solution became clear and colorless.

Salt (NaCl) was added into the 3-N RBF until it was saturated. The solution was extracted 3 times with ethyl acetate (EA; 100 mL). The organic extracts were washed 3 times with saturated aqueous NaCl (50 mL), and dried over MgSO4. After filtration and removing the solvent by rotary evaporation, the resulting solid was recrystallized from

CH2Cl2; i.e. the BrH was dissolved in small amount of CH2Cl2 (15 mL) at 35 ℃, and crystallized overnight in the freezer at -5 ℃. The crystals were collected in a fritted glass funnel, washed with CH2Cl2, and dried in vacuo overnight, to yield 17.6 g (54.8%) of a white solid.

1 Figure 5 presents the H NMR spectrum of BrH in CDCl3 (7.27 ppm) with one drop

of DMSO (2.5 ppm). The methine (CH) (t, 4.12 ppm), methylene (CH2) (dd, 3.83 ppm

and dd, 3.73 ppm), and hydroxy (OH) (6.8 ppm) are consistent with published29 data.

Jan042012-Xia-BrH

7.27 4.14 4.12 4.10 3.87 3.84 3.83 3.80 3.74 3.72 3.70

2.41 1.00 2.26

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 Chemical Shift (ppm)

Figure 5. 300 MHz 1H NMR spectrum of 2-bromo-3-hydroxypropionic acid

5.4 Copolymerization of D,L-Lactic Acid and 2-Bromo-3-hydroxypropionic acid

Poly(lactic acid)-co-(2-bromo-3-hydroxypropionic acid) (PLxBy) was synthesized in a 100 mL RBF. LA (0.52g, 5.8mmol), BrH (0.56g, 3.3mmol), p-TSA( 0.05g) and

DPE (1mL) were added in to the RBF immersed in an oil bath and heated to 95℃ in vacuo for 48 hours. The solution was then cooled down to room temperature and was kepted the refrigerator overnight with 50ml CH2Cl2 added. Then the copolymer solution was filtered to remove DPE.

The solvent was removed by rotary evaporation and an oil was collected. The polymer was precipitated by adding the oil dropwise into cold methanol (150 mL), followed by a small amount CH2Cl2 used to wash the wall of the flask. The precipitate was collected in a fritted glass funnel. The polymer was dried under vacuum overnight to

obtain a white powder. The yield is about 56-58%; Mn =9.17 × 10 , PDI = 2.40.

1 Figure 6 presents the H NMR spectrum of PL60B40. The methyl and methine protons of LA resonate at 1.58 ppm and 5.18 ppm, respectively. The methine and methylene protons of the BrH units both resonate at ~4.57 ppm. The copolymer composition can be calculated from the relative integrals of the LA and BrH units:

푥 1. = { . . For example, x equals 60.2 and y equals 39.8 for PL60B40. 푥 + 푦 = 100

Feb022912-Xia-PLB64

7.27 5.31 5.31 5.19 5.16 4.59 4.52 1.64 1.61 1.58 1.55

1.55 3.00 5.25

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 Chemical Shift (ppm) 1 Figure 6. 300 MHz H NMR spectrum of PL60B40.

5.5 Synthesis of Lower Molecular Weight PLAs by Hydrolysis Lower molecular weight PLA was prepared by hydrolysis of commercial samples in

100% relative humidity (RH) at 60 ℃. For each experiment, a separate sample of PLA

(2 g, 28 mmol repeat unit) was placed in a 4 mL vial with distilled water (0.04 g, 2 mmol), and all open vials were placed in a wide-mouth jar with an additional open 4 mL vial containing H2O (3 mL). The wide-mouth jar was sealed with a cap and placed in an oven at 60 ℃ to achieve 100% RH. The PLA samples were heated for different times to produce PLA samples with different molecular weights. All of the samples were

dried at room temperature under vacuum for 60 h on Schlenk line.

5.6 Blending

The two components, PLA and PLB, were dissolved in a small amount of CHCl3, and then precipitated with MeOH. Solvent was removed by rotary evaporation, followed by drying in vacuo on a Schlenk line more than 24 h. Table 6 summarizes the blends the components and composition of the blends that were prepared.

Table 5. Blend ratio of PLA and PL60B40 Name Weight ratio of PLA(%) Weight ratio of PL60B40 (%) L-PLA/PL60B40 (90/10) 90 10 L-PLA/PL60B40 (80/20) 80 20 L-PLA/PL60B40 (60/40) 60 40 L-PLA/PL60B40 (50/50) 50 50 L-PLA_2h/PL60B40 (60/40) 60 40 L-PLA_2h/PL60B40 (60/40) 60 40 L-PLA_2h/PL60B40 (60/40) 60 40 L-PLA_2h/PL60B40 (60/40) 60 40 DL-PLA/PL60B40 (60/40) 60 40 DL-PLA_2h/PL60B40 (60/40) 60 40 DL-PLA_24h/PL60B40 (60/40) 60 40

CHAPTER VI

RESULTS AND DISCUSSION

6.1 Study of different ratio of blends

Figure 7. Normalized DSC thermograms in second-heating runs of L-PLA/PL60B40 blends different L-PLA/ PL60B40 ratio (9/1, 8/2, 6/4, 5/5); L-PLA (Nature Works 5 3 PLA6202, 2% D-isomer) Mn = 1.16×10 , PL60B40 Mn = 8.69×10 .

Figure 7 presents the DSC thermograms from the second-heating runs of L-PLA and

PL60B40 and their blends with compositions of 9/1, 8/2, 6/4, and 5/5. Table 6 summarizes the thermal behavior of the blends and their components as determined by DSC analysis.

The blends were prepared by the solution/precipitation method.

Table 6. Summary of DSC analysis data Name First Second Heating Cooling

Tg(℃) Tg1(℃) Tg2(℃) Tm(℃) L-PLA 62.3 60.6 - 164.8 L-PLA/PL60B40 (60/40) 57.6 58.2 45.8 165.6 L-PLA/PL60B40 (90/10) - 59.0 - 164.0 L-PLA/PL60B40 (80/20) 58.8 59.1 - 164.8 L-PLA/PL60B40 (50/50) 55.9 55.4 45.8 163.3 PL60B40 45.1 42.5 - -

Figure 8. Tg of L-PLA and PL60B40 blends with different weight ratios of L-PLA

From Figure 8, the blends with 90 and 80 wt% L-PLA show only one glass transition at a temperature slightly lower than that that of 100% L-PLA. The DSC instrument is not sensitive enough to detect the glass transition of the PL60B40 component when it makes up <20% of the blend. However, when the blend contains >40 wt% PL60B40, the blends exhibit two glass transitions at temperatures that 24

depend on the ratio of the two components, with the Tg of the PLB6040 shifting to higher temperature, and the Tg of the L-PLA component shifting to lower temperature.

Similarly, the melting temperature of the L-PLA component of the blends depressed relative to that of pure L-PLA. Therefore, high molecular weight L-PLA is partially

3 miscible with PL60B40 of Mn = 8.69×10 .

6.2 Study of blends with different molecular weight PLA

The miscibility of polymer blends generally decreases with increasing molecular weight. Therefore, PL60B40 may be more miscible with lower molecular weight L-PLAs.

We prepared lower molecular weight L-PLA samples by hydrolysis of L-PLA at 60 ℃ in 100% relative humidity (RH). As summarized by the data in Table 7 and Figure 9, the molecular weight and glass transition temperature of L-PLA decreases rapidly during the first two hours of hydrolysis, and then decrease only slightly at longer hydrolysis times. The molecular weight of these lower molecular weight L-PLAs varied from Mn =

1.61×104 to 4.25×104. Table 7 also includes data for two hydrolyzed samples of DL-PLA.

Table 7. GPC and DSC results of hydrolyzed PLA M M T Sample Hydrolysis time (h) n w PDI g × 10−4 × 10−4 （℃）

L-PLA 0 11.6 15.7 1.35 62 L-PLA_1h 1 4.25 9.19 2.16 61 L-PLA_2h 2 2.68 6.12 2.28 60 L-PLA_14h 14 2.08 4.75 2.29 56

L-PLA_24h 24 1.61 3.37 2.10 56 DL-PLA 0 - - - 58.3 DL-PLA_2h 2 - - - 58.5 DL-PLA_24h 24 - - - 57.7

Figure 9. L-PLA molecular weight and Tg as a function of hydrolysis time at 60 ℃ in 100% relative humidity.

Table 8. Summary of DSC analysis data Name First Second Heating Cooling

Tg(℃) Tg1(℃) Tg2(℃) Tm(℃) ∆ ( /g) L-PLA 62.3 60.6 - 164.8 11.4 L-PLA/PL60B40 (60/40) 57.6 58.2 45.8 165.6 35.4 L-PLA_1h 61.0 62.9 - 164.9 5.6 L-PLA_1h/PL60B40 (60/40) 60.3 58.3 - 164.3 24.2 L-PLA_2h 60.4 61.2 - 167.4 30.4 L-PLA_2h/PL60B40 (60/40) 58.0 57.6 - 163.9 35.2 L-PLA_14h 55.5 55.7 - 153.9 42.0 L-PLA_14h/PL60B40 (60/40) 51.1 56.1 - 162.0 29.8 L-PLA_24h 53.3 53.7 - 153.3 51.1 L-PLA_24h/PL60B40 (60/40) 52.9 54.8 - 161.6 39.5

PL60B40 45.1 42.5 - - -

Figure 10 compares the DSC thermograms (second heating) of 6/4 L-PLA/PL60B40 blends containing progressively lower molecular weight L-PLA with that of the original

5 high molecular weight L-PLA (Mn = 1.16×10 ).

Figure 10. Normalized DSC thermograms in second-heating runs of 6/4 L-PLA / PL60B40 blends with different molecular weight L-PLA prepared by hydrolysis (time in hours) of high molecular weight L-PLA (0 h, Nature Works PLA6202, 2% D-isomer); 3 PL60B40 Mn = 8.69×10 .

All the DSC results are summarized in Table 8. Like the high molecular weight

4 blend, the blend of the L-PLA generated after hydrolysis for 1 h (Mn = 4.25×10 ; Tg =

62.9 oC) exhibits two glass transitions that are shifted in temperature towards each other relative to the two components. This indicates that the 6/4 L-PLA_1h/PL60B40 blend is partially miscible. As the hydrolysis time increased and the molecular weight of the

L-PLA component decreases, the miscibility of the blends increases. Blends of the

L-PLAs hydrolyzed for two or more hours (L-PLA Mn < 26k), exhibit one Tg; i.e. PL60B40

3 of Mn = 8.69×10 is miscible with lower molecular weight L-PLAs with (Mn < 26k

L-PLA). In addition, the ability of the blend to crystallize seems to increase as the molecular weight of the L-PLA component decreases based on increased melting temperatures of higher enthalpy.

Table 9 compares the experimental Tgs of these blends to those calculated by the

Fox equation16,

1 휔 휔 = 1 + 2 eq 3 푇푔 푇푔,1 푇푔,2 where 푇푔,1 and 푇푔,2 are the glass transition temperatures of the L-PLA and PLB, respectively, and 휔1 and 휔2 are the weight fractions of components L-PLA and PLB.

Table 9. Results of Tg calculated from Fox equation Name Tg (℃) Tg (℃) Tg(℃) Tg(℃) Error 1 2 (Experiment) (Theory)

L-PLA/PL60B40 42.1 62.3 44.4 55.6 52. 3

L-PLA_1h/PL60B40 42.1 61.0 49.3 59.6 51.8 L-PLA_2h/PL60B40 42.1 60.4 57.0 - 51.5 10% L-PLA_14h/PL60B40 42.1 55.5 55.3 - 49.2 11% L-PLA_24h/PL60B40 42.1 55.9 54.4 - 49.4 9%

Table 10 shows the results calculated from the Gordon-Taylor equation (eq 6) 17,

푘푤2(T푔2−T푔1) T푔 = T푔1 + eq 6 푤1+푘푤2 using the same nomenclature from the Fox equation; 푘 is an adjustable parameter that may be related to the interaction strength between the two components in the blend. A value of k = 0.56 provides the best fit of the glass transition temperature of these blends.

From the two calculated methods, the Tg received from DSC thermograms are relatively similar to the theoretical values. The error is about 10% for the Fox equation and less

than 5% for the Gordon-Taylor equation.

Table 10. Results of Tg calculated from Gordon-Taylor equation Name Tg1(℃) Tg2(℃) Tg(℃) Tg(℃) Error (Experiment) (Theory)

L-PLA/PL60B40 62.3 42.1 44.4 55.6 58.57

L-PLA_1h/PL60B40 61.0 42.1 49.3 59.6 57.51

L-PLA_2h/PL60B40 60.4 42.1 57.0 - 57.0 0%

L-PLA_14h/PL60B40 55.5 42.1 55.3 - 53.0 4%

L-PLA_24h/PL60B40 55.9 42.1 54.4 - 53.4 2%

6.3 Study of different stereopurities of PLA

The stereoregularity of PLA may also influence the miscibility of PLA with PL60B40.

We therefore investigated the miscibility of PL60B40 with D-PLA containing 10% D isomers (PLA4060, Nature Works), and two hydrolyzed samples (2 h; 24 h). Figure

11 compares the DSC thermograms (second heating) of 6/4 DL-PLA/PL60B40 blends containing progressively lower molecular weight L-PLA with that of the original high molecular weight DL-PLA. All three blends, including that containing the high molecular weight sample, exhibit only one glass transition at a temperature intermediate between that of the two components. Therefore, PL60B40 is miscible with DL-PLA of all molecular weights of studied.

Table 11. Summary of DSC analysis data Name First Cooling Second Heating

Tg(℃) Tg (℃) DL-PLA _24h 55.9 57.7 DL-PLA_24h/PL60B40 (60/40) 54.4 53.6 DL-PLA_2h 57.3 58.5 DL-PLA_2h/PL60B40 (60/40) 54.7 55.9 29

DL-PLA 56.9 58.3 DL-PLA /PL60B40 (60/40) 52.6 53.2

Figure 11. Normalized DSC thermograms in second-heating runs of 6/4 D-PLA/ PL60B40 Blends with different molecular weight DL-PLA prepared by hydrolysis (time in hours) of high molecular weight DL-PLA (0 h, Nature Works PLA4060, 10% D-isomer); 3 PL60B40 Mn = 8.69 x 10 .

The Tg values calculated from the Fox and Gordon-Taylor equations are shown in

Tables 11 and 12; k equals 0.34 in the Gordon-Taylor equation. The results from DSC analysis show less than 10% error for the Fox-equation and less than 3% for the

Gordon-Taylor equation.

Table 12. Results of Tg calculated from Fox equation Name Hydrolyzed Tg1 Tg2 Tg (℃) Tg (℃) Error Time(Hour) (℃) (℃) (Experiment) (Theory) DL-PLA/PL60B40 0 58.3 42.5 53.2 50.8 4% DL-PLA_2h/PL60B40 2 58.5 42.5 55.9 50.8 9% DL-PLA_24h/PL60B40 24 57.7 42.5 53.6 50.5 6%

Table 13. Results of Tg calculated from Gordon-Taylor equation Name Hydrolyzed Tg1 Tg2 Tg(℃) Tg(℃) Error Time(Hour) (℃) (℃) (Experiment) (Theory) DL-PLA/PL60B40 0 58.3 42.5 53.2 54.1 2% DL-PLA_2h/PL60B40 2 58.5 42.5 55.9 54.2 3% DL-PLA_24h/PL60B40 24 57.7 42.5 53.6 53.6 0% 6.4 Conclusions

Blends of PLA and our synthesized PLB were prepared by the solution/precipitation method, and their miscibility was determined by differential scanning calorimetry. High

5 molecular weight L-PLA (Mn = 1.16 x 10 ; 2% D isomer) is partially miscible with >40

3 wt% PL60B40 (Mn = 8.69 x 10 ). Lower molecular weight and less stereoregular PLAs are miscible with PL60B40. For example, L-PLAs (prepared by hydrolysis for at least 2

4 h at 60 ℃ in 100% relative humidity) with Mn < 2.68×10 are miscible with 40 wt%

PL60B40. DL-PLA containing 10% D-isomer is miscible with PL60B40. The glass transition temperatures of the miscible blends calculated from Fox and Gordon-Taylor equations are similar to the experimental results.

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