© 2013 Xiaochen Li All Rights Reserved

XIAOCHEN LI

HYDROPHILIC [60]FULLERENE END-CAPPED

POLYSTYRENE-BLOCK-POLY (ETHYLENE OXIDE) COPOLYMERS: SYNTHESIS

AND SELF-ASSEMBLY IN SOLUTION

A Thesis

Presented to

The Graduate Faculty of The University of Akron

In Partial Fulfillment

of the Requirements for the Degree

Master of Science

Xiaochen Li

May, 2013

HYDROPHILIC [60]FULLERENE END-CAPPED

POLYSTYRENE-BLOCK-POLY (ETHYLENE OXIDE) COPOLYMERS: SYNTHESIS

AND SELF-ASSEMBLY IN SOLUTION

Xiaochen Li

Thesis

Approved: Accepted:

Advisor Dean of the College Dr. Stephen Z.D. Cheng Dr. Stephen Z.D. Cheng

Faculty Reader Dean of the Graduate School Dr. Matthew L. Becker Dr. George R. Newkome

Department Chair Date Dr. Coleen Pugh

ABSTRACT

Recently, “shape amphiphiles” has attracted great attention. “Shape amphiphiles” usually refer to molecules possessing differences in the shape of the molecular moieties.

It is found that these shape amphiphiles can self-assemble into diverse structure in solution, which is similar as small molecule surfactant and block copolymer, but has distinct molecular designs and topologies. Shape and interactions are two crucial factors to detect the self-assembly of these models. The previous research in our group has revealed that the giant molecular shape amphiphiles based on polystyrene-hydrophilic

[60]Fullerene (AC60) conjugates can self-assemble into various structure.

In this thesis, a comprehensive study on the synthesis and self-assembly behaviors in solution of a new giant molecular shape amphiphile, namely, the hydrophilic

[60]Fullerene (AC60) tethered with polystyrene-b-poly(ethylene oxide) block copolymer

(PEO-b-PS-AC60) has been investigated.

The synthesis highlighted the Bingel-Hirsch cyclopropanation reaction for C60 surface functionalization and the Huisgen 1,3-dipolar cycloaddition of azide−alkyne,

which is also well-known as “click” reaction, between alkyne functionalized AC60 and

iii

azide functionalized diblock copolymer PEO-b-PS to give rise to shape amphiphiles with precisely defined surface chemistry and molecular topology. For the block copolymer, the

molecular weight of PEO was fixed at 2K/mol, a series of block copolymer PEO45-b-PSn with different chain length of PS and narrow molecular weight distribution were synthesized by Atom Transfer Radical Polymerization (ATRP). The chemical structure of all intermediate and final products were fully confirmed and characterized by proton nuclear magnetic resonance(1H-NMR), carbon nuclear magnetic resonance (13C-NMR),

Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass, Fourier transform infrared spectroscopy (FTIR) and size-exclusion chromatography (SEC).

The self-assembling behaviors of shape amphiphiles as-prepared in solution was investigated by using 1,4-dioxane/DMF mixture as the common solvent and water as the selective solvent. As revealed by transmission electron microscopy (TEM), these shape amphiphilies exhibit versatile self-assembled micellar morphophogies, which can be tuning by changing initial molecular concentration or chain length of PS.

Finally, the critical water concentration (CWC) of all shape amphiphiles as-prepared was determined by static light scattering (SLS) experiments. The results indicate that the value of (CWC) is dependent on the chain length of PS.

DEDICATION

This thesis is dedicated to my parents.

ACKNOWLEDGEMENTS

I would like to express my deepest gratitude to my advisor, Dr. Stephen Z.D. Cheng, for his continuous guidance, support and encouragement through the course of my research.

He is a great mentor with enthusiasm to science.

I would like to thank my faculty reader Matthew L. Becker who graciously gave his time to evaluate my work and provided helpful suggestions.

I would like to thank all my former and current group members for their discussion and friendships. Special thanks are given to Mr. Xinfei Yu, Mr. Zhiwei Lin for their assistance in constructing many experimental setups.

Last but not least, I would like to express my appreciation and love to my parents, my friends. They always stood by me and encouraged me to achieve my dream.

TABLE OF CONTENTS

Page

LIST OF TABLES……………………………………………………………………….xii

LIST OF FIGURES…………………………………………………………………...... xiii

LIST OF SCHEMES…………………………………………………………………...... xv

CHAPTER

I. INTRODUCTION ...... 1

II. BACKGROUND ...... 4

2.1 Fullerene ...... 4

2.1.1 Fullerene: Introduction ...... 4

2.1.2 Fullerene: Molecular Allotropes of Carbon ...... 5

2.1.3 Fullerene: Application ...... 6

2.1.4 Principles of Fullerene Chemistry ...... 6

2.1.5 Water Soluble Fullerene ...... 9

2.2 Methods of Controlled/Living Radical Polymerization ...... 9

2.2.1 Introduction to Controlled/Living Radical Polymerization methods ...... 9

2.2.2 Atom Transfer Radical Polymerization ...... 11

vii

2.3 Click Chemistry ...... 12

2.3.1 The Concept of Click Chemistry ...... 12

2.3.2 Cu-catalyzed Acetylene Azide [3+2] Cycloaddition ...... 13

2.4 Amphiphilic Block Copolymers ...... 15

2.4.1 Introduction of Block Copolymers ...... 15

2.4.2 Introduction of Amphiphilic Block Copolymers ...... 17

2.4.3 Self-assembly of Amphiphilic Block Copolymers in Solution ...... 18

2.5 Shape Amphiphiles ...... 21

2.5.1 Introduction of Shape Amphiphiles ...... 21

2.5.2 Polymer-tethered Nanoparticles ...... 22

2.5.3 Molecular Nanoparticles ...... 23

2.5.4 Giant Molecular Amphiphile...... 23

III. EXPERIMENTAL ...... 26

3.1 Materials and Instrumentals ...... 26

3.2 Sample Synthesis ...... 27

3.2.1 The Synthesis of Malonate 1 ...... 28

3.2.2 The Synthesis of Methanofullerene 2 ...... 29

3.2.3 The Synthesis of Malonate 3 ...... 29

3.2.4 The Synthesis of [5:1]-Hexakisadducts 4 and 5 ...... 30

viii

3.2.5 The Synthesis of PEO-Br ...... 30

3.2.6 The Synthesis of PEO-b-PS ...... 31

3.2.7 The Synthesis of PEO-b-PS-N3 ...... 31

3.2.8 The Synthesis of PEO-b-PS-tC60 (6) and PEO-b-PS-AC60 (7) ...... 32

3.3 Micelle Preparation ...... 32

3.4 Transmission Electron Microscopy ...... 33

3.5 Static Light Scattering Experiments ...... 33

IV. RESULTS AND DISCUSSION ...... 34

4.1 The Characterization of Malonate 1...... 34

4.1.1 Synthetic Scheme of Malonate 1 ...... 34

4.1.2 NMR Characterization of Malonate 1 ...... 34

4.2 The Characterization of Methanofullerene 2 ...... 36

4.2.1 Synthetic Scheme of Methanofullerene 2 ...... 36

4.2.2 NMR Characterization of Methanofullerene 2 ...... 36

4.2.3 MALDI-TOF Characterization of Methanofullerene 2 ...... 37

4.3 The Characterization of Malonate 3...... 38

4.3.1 Synthetic Scheme of Malonate 3 ...... 38

4.3.2 NMR Characterization of Malonate 3 ...... 39

4.4 The Characterization of [5:1]-Hexakisadducts 4 and 5...... 40

4.4.1 Synthetic Scheme of [5:1]-Hexakisadducts 4 and 5 ...... 40

4.4.2 NMR Characterization of [5:1]-Hexakisadducts 4 and 5 ...... 41

4.5 The Characterization of PEO-Br...... 44

4.5.1 Synthetic Scheme of PEO-Br ...... 44

4.5.2 MALDI-TOF Characterization of PEO-Br ...... 44

4.6 The Characterization of PEO-b-PS ...... 45

4.6.1 Synthetic Scheme of PEO-b-PS ...... 45

4.6.2 NMR Characterization of PEO-b-PS ...... 46

4.7 The Characterization of PEO-b-PS-N3...... 47

4.7.1 Synthetic Scheme of PEO-b-PS-N3 ...... 47

4.7.2 FT-IR Characterization of PEO-b-PS-N3 ...... 48

4.8 The Characterization of PEO-b-PS-tC60 and PEO-b-PS-AC60 ...... 49

4.8.1 Synthetic Scheme of PEO-b-PS-tC60 and PEO-b-PS-AC60 ...... 49

4.8.2 NMR Characterization of PEO-b-PS-tC60 and PEO-b-PS-AC60...... 50

4.8.3 FT-IR Characterization of PEO-b-PS-tC60 ...... 51

4.8.4 SEC Characterization of PEO-b-PS-tC60 ...... 52

4.9 Micellization of Shape Amphphiles at Different Molecular Concentration ...... 53

4.9.1 Self-assembled Micellar Morphologies of PEO45-b-PS75-AC60 ...... 53

4.9.2 Self-assembly Morphologies of PEO45-b-PSn-AC60 at C = 0.25(wt)% .. 55

4.9.3 The Critical Water Concentrations in Forming Micelles...... 57

V. SUMMARY ...... 59

REFERENCES ...... 61

LIST OF TABLES

Table Page

2.1 Typical features of [60]fullerene...... 6

3.1 Instrumentals...... 26

3.2 Materials ...... 27

4.1 Molecular Weight Characterization of PEO-b-PS...... 46

4.2 Summary of Molecular Characterizations PEO-b-PS-AC60 ...... 53

4.3 CCWC (%) of PEO45 -b-PSn-AC60 ...... 58

xii

LIST OF FIGURES

Figure Page

2.1 Schematic representations of C60. (A) ball and stick model, (B) space filling model, (C) VB formula...... 5

2.2 C60 addition reactions: (A) Bingel-Hirsch cyclopropanation, (B) Azide addition, (C) Diels-Alder reaction ...... 7

2.3 Mechanism of ATRP polymerization ...... 12

2.4 The mechanism of Huisgen 1,3-dipolar cycloadditions ...... 14

2.5 Schematic illustrations of different copolymer architectures: (A) random copolymer, (B) diblock copolymer, (C) triblock copolymer, (D) graft copolymer, and (E) star copolymer...... 16

4.1 1H NMR and 13C NMR spectra of Malonate 1 ...... 35

4.2 1H NMR spectra of Methanofullerene 2 ...... 37

4.3 MALDI-TOF mass spectra of Methanofullerene 2 ...... 38

4.4 1H NMR and 13C NMR spectra of Malonate 3 ...... 40

4.5 MALDI-TOF mass spectra for [5:1]-Hexakisadducts 5...... 42

4.6 1H NMR and 13C NMR spectra of [5:1]-Hexakisadducts 4 and 5 ...... 43

4.7 MALDI-TOF mass spectra for PEO-Br ...... 45

4.8 1H NMR spectra of PEO-b-PS ...... 47

xiii

4.9 FT-IR spectrum of PEO-b-PS-N3 ...... 48

1 4.10 H NMR spectra of (a) PEO-b-PS-tC60 and (b) PEO-b-PS-AC60 ...... 50

4.11 FT-IR spectrum of PEO-b-PS-tC60 and PEO-b-PS-N3 ...... 51

4.12 SEC overlay of PEO-Br (Black), PEO-b-PS-Br (Red) and PEO-b-PS-tC60 (Blue) ...... 52

4.13 TEM images of self-assembly morphologies of PEO45-b-PS75-AC60 with different initial molecular concentrations in the 1,4-dioxane/DMF/water system ...... 54

4.14 TEM images of self-assembly morphologies of PEO45-b-PSn-AC60 with initial molecular concentrations at 0.25(wt)% in the 1,4-dioxane/DMF/water system ... 55

4.15 PEO45-b-PS182-AC60 light scattering intensity versus water content in the 1,4-dioxane/DMF/water system ...... 57

xiv

LIST OF SCHEMES

Scheme Page

2.1 Huisgen 1,3-dipolar cycloadditions of azides and alkynes ...... 14

3.1 Full synthetic route of the sample PEO-b-PS-AC60 ...... 28

4.1 The synthesis of Malonate 1 ...... 34

4.2 The synthesis of Methanofullerene 2 ...... 36

4.3 The synthesis of Malonate 3 ...... 38

4.4 The synthesis of [5:1]-Hexakisadducts 4 and 5 ...... 41

4.5 The synthesis of PEO-Br ...... 44

4.6 The synthesis of PEO-b-PS ...... 45

4.7 The synthesis of PEO-b-PS-N3 ...... 47

4.8 The synthesis of PEO-b-PS-tC60 and PEO-b-PS-AC60...... 49

CHAPTER I

INTRODUCTION

Recently, “shape amphiphiles” has received considerable attention depending on their interesting properties about self-assembly and phase separation, which is usually consisted of the molecular segments with different shapes. Depending on interactions and the constraints imposed by the rigid shape of the molecular segments, the self-assembled shape amphiphiles can also show various and intriguing hierarchical structures and phase behaviors, such as spheres, vesicles, and cylinders. And the self-assembly morphology and phase separation size of shape amphiphiles can be well controlled via adjusting the molecular structure and the solvent performance, which is similar as small molecular surfactants and amphiphilic block copolymers. Meanwhile, small-molecular amphiphiles

(surfactants and lipids) and amphiphilic block copolymers are also well-known to aggregate the various micellar morphologies in selective solvents. For shape amphiphiles, however, the design of molecular structure and topologies are different from them.

There is a kind of giant molecular shape amphiphiles, namely, hydrophilic

[60]Fullerene (AC60) tethered with one or two PS chains at one junction point, which can

form the self-assembly morphologies in 1,4-dioxane/DMF/water system with different initial molecular concentration and molecular chain lengths of PS blocks. In this thesis, we aim to further explore this kind of giant molecular shape amphiphiles by one step, where the hydrophilic chains of poly(ethylene oxide) (PEO) was induced at the end of PS

chains, namely, the hydrophilic [60]Fullerene (AC60) tethered with

polystyrene-b-poly(ethylene oxide) block copolymer (PEO-b-PS-AC60). And the design, synthesis, and self-assembly of them were systematically investigated.

For the studies on the self-assembling behaviors of shape amphiphiles

PEO-b-PS-AC60 in different solutions, 1,4-dioxane/DMF mixture and water were employed as the common solvent and selective solvent, respectively. For the tail segments, the PEO blocks were well defined with polymerization degree at 45, and the

PS blocks were designed with variational polymerization degrees at 48, 75, 115, 144, and

182, respectively. Through transmission electron microscopy (TEM) and static light scattering (SLS) techniques, morphological investigation of these shape amphiphiles was carried out, indicating that the versatile self-assembled micellar morphologies can be controlled by changing the initial molecular concentration and/or molecular chain length of PS blocks.

The outline of the present studies will be described as follows. This thesis consists of five chapters. 2

In chapter I, the general introduction of this thesis was shown.

In chapter II, the historical background and the development of fullerene chemistry, the click chemistry, shape amphiphile and block copolymer micelle were introduced.

In chapter III, the methods for the synthesis of the new giant molecular shape

amphiphile PEO-b-PS-AC60 and those for the preparation of micelle were systematically described.

In chapter IV, present studies were adequately analyzed, and the self-assembly

behaviors of as-prepared PEO-b-PS-AC60 solution in 1,4-dioxane/DMF/water system were discussed.

In chapter V, conclusion of the studies in this thesis was summarized.

CHAPTER II

BACKGROUND

2.1 Fullerene

2.1.1 Fullerene: Introduction

[60]fullerene was discovered in 1985 by Kroto, Smalley, and Curl.1 It was named after Richard Buckminster Fuller (1895-1985) which had the shape of a truncated icosahedron.

C60 (buckminsterfullerene) and C70 (falmarene) are accessible on which many studies have been carried out. Following access to fullerenes in macroscopic amounts, versatile functionalization methods of fullerene were developed and a great variety of organic reactions have been carried out with this molecule, e.g. arylation, halogenation, hydroxylation, alkoxylation.2,3 The multifunctionality of fullerene shows the possibility for versatile two-dimensional and three-dimensional exohedral modification. They have become of increasing interest to polymer chemists as building blocks for the construction of novel materials with particular properties.

2.1.2 Fullerene: Molecular Allotropes of Carbon

Fullerenes are built up of pentagons and hexagons. Each molecule of the fullerene

family (Cn) is consisted of 12 pentagons and m number of hexagons, referring to the relation m = (n-20) 2-1 (Euler's theorem). 4 The most abundant fullerene is the

5 Ih-symmetrical C60 (Figure 2.1) with a soccer ball shape, which is composed of 32 faces:

20 hexagons and 12 pentagons. The carbon atoms of C60 are arranged at the 60 vertices of a

truncated icosahedron formed as an Ih-symmetry. There are only one type of carbon atom and two types of C–C bonds as [5, 6] bond and [6, 6] band. Moreover, some of the

6 features of C60 are summarized in Table 2.1.

Figure 2.1 Schematic representations of C60. (A) ball and stick model, (B) space filling model, (C) VB formula.

The forming principle of the fullerenes is influenced by the Euler theorem, which means that 12 pentagons are required for the closure of each spherical network of n hexagons, with n = 1 exception. 5

Table 2.1 Typical features of [60]fullerene6

Pentagons 12 Hexagons 20 Faces 32

Symmetry Ih Hybridization sp2 -Bonds (bent) 30 C-C distance (pm) 146 C=C distance (pm) 138.3 Diameter (nm) 0.7 Van der Waals diameter (nm) 1.1 Rotation (in solid) (rotations s-1) 109 Decomposition temperature ( ) 650±700 Hydrophobic, contact angle (deg) 100 Color of benzene solution Deep magenta

2.1.3 Fullerene: Application

Fullerenes show the vital applications in the chemical and material science, such as microscopic engineering, semiconductors, and polymer, 7 , 8 also in biomedical field, including antibiotic, antiviral and anti-cancerous activities, enzyme inhibition, DNA cleavage, cell signaling, and nuclear medicine.9-111011

2.1.4 Principles of Fullerene Chemistry

Many studies concerning on the chemical reactions with C60 have been reported since it

was discovered. It is proved that C60 can participate in many kinds of chemical reactions such as nucleophilic additions, radical additions, cycloadditions, hydrogenation, 6

halogenation, and redox processes. And these chemical modifications give the different

derivatives of C60. Three kinds of fullerene chemical reactions were well investigated and widely employed for the practical modification of fullerene, which are Bingel-Hirsch cyclopropanation reaction, azide addition, Diels-Alder reaction, respectively, as summarized in Figure 2.2.

Figure 2.2 C60 addition reactions: (A) Bingel-Hirsch cyclopropanation, (B) Azide addition, (C) Diels-Alder reaction

(a) Bingel-Hirsch cyclopropanation reaction:

The Bingel-Hirsch cyclopropanation reaction was first developed by Bingel12 in the year 1993 by using NaH and bromomalonate, which was subsequently improved by

13 Hirsch in 1997 via the direct reaction of malonate with the presence of CBr4 (or I2) and diazabicyclo[5.4.0]undec-7-ene. Based on the addition-elimination mechanism, this

reaction is one of the most versatile and efficient methodologies to functionalize C60 with 7

good yields (in the range 30–60%),12, 14 which can also afford the simple and stable methanofullerene products. This reaction proceeds via an addition-elimination mechanism.12

(b) Azide addition reaction:

The azide addition reaction was first discovered by Wudlet et al.15,16 There are two possible reaction mechanisms for this reaction as follows: (1) a sequential [3+2] cycloaddition reaction, 17 generates a [6,6] triazoline intermediate which is further converted to [5,6]-open azafulleroids (2) nitrene addition,18 attacks the [6,6] bond to afford [6,6]-closed aziridines. The azide addition reaction generally leads to a sufficient yield, and the preparation of azides is easy. Therefore, this reaction further widens the range of fullerene chemistry.

The Diels-Alder reaction is a kind of cycloaddition in fullerene chemistry, and the

[6,6] bonds of fullerenes are considered as dienophiles in cycloadditions process. The

4-membered rings can be obtained by [2+2]cycloadditions with benzyne. This reaction creates the stable cyclohexene structures, which can be further converted to the other functionalities.19 As reported by Rubin et al,20,21 this reaction was applied to addition at

[6, 6] bonds with functional dienes.

2.1.5 Water Soluble Fullerene

Even though fullerenes are entirely water-insoluble, some suitable functionalizations can the structure of their surface, and in turn realize the solubility of fullerenes. Via the studies on water-soluble fullerenes, the interactions of fullerenes with proteins, DNA, and living cells were discovered as reported in 1993, indicating that the biological activity of fullerenes is due to their radical quenching, photochemistry, and hydrophobicity by forming supramolecular from one-dimensional structure to three-dimensional one.22 It is found that the functionalized fullerenes with three-dimensional structure behave as the unique electronic properties, which show the great potential application as the extremely promising nanostructures for the new advanced materials or biologically active molecules.23-312425262728293031

2.2 Methods of Controlled/Living Radical Polymerization

2.2.1 Introduction to Controlled/Living Radical Polymerization methods

Free-radical polymerization is a widely applied process for polymer synthesis during industrial production. There are many advantages for this technique, such as easy performance, good tolerance to many functional groups, products with high molecular weight. However, the main drawback of radical polymerization is the lack of control over molecular weight, molecular weight distribution, and macromolecular architecture, which 9

is attributed to the fast radical-radical terminations. Therefore, the investigation of CRP was widely carried out with the aim to obtain the polymer with well-defined structure. In

1982, the term iniferter32,33 known as initiator transfer agent terminator was proposed for the following scheme:

nM A-B A• + B• A-Mn-B

In this scheme, A• is a reactive radical that participates in initiation and then propagation, and B• is a less reactive radical that enters into primary radical termination.

This iniferter concept constitutes the first attempt to establish a controlled/living radical polymerization (CRP). Based on a large number of investigations on CRP in the past decade, the limitations of free radical polymerization have been well overcome and many novel materials with well-defined molecular structure can be synthesized. 34 The as-synthesized novel materials include not only precisely controlled macromolecules but also many new hybrids in which precisely defined organic polymers are covalently attached to inorganic materials.35-41363738394041

CRP42 is referred as polymerization techniques that combine the versatility of free radical polymerization with the control of anionic polymerization basing on two principles: reversible termination reaction and reversible chain transfer reaction. In both case, macromolecular radicals undergo reversible deactivation, such as activation-deactivation cycles. At the deactivation state, the molecular chains are end-functionalized by a specific 10

group, which can be lose and active the molecular chain for the further chain growth. The dynamic activation-deactivation equilibrium leads to chain building up and growth simultaneously during the whole polymerization process. And CRP methods enable the synthesis of polymers with low polydispersity, predetermined molar mass, and precisely-defined end groups. The major advantage of CRP methods is for the synthesis of block copolymers which cannot be prepared by existing living techniques.

Nowadays, CRP methods mainly include nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP) and polymerization by reversible addition fragmentation chain transfer (RAFT). In this thesis, in order to obtain the shape amphiphiles with amphiphilic block copolymer tails, ATRP technique was employed for the synthesis of PEO-b-PS diblock copolymers.

2.2.2 Atom Transfer Radical Polymerization

In 1995, ATRP 43 was introduced independently by Sawamoto 44 and

Matyjaszewski.45,46 And now, ATRP can be successfully applied to a broad variety of monomers. ATRP is based on the reversible transfer of a halogen atom between a dormant alkyl halide and a transition metal catalyst using redox chemistry. The general mechanism for ATRP is shown in the Figure 2.3. Radical generation in ATRP undergoes a reversible redox process involving an organic halide catalyzed by a transition metal 11

compound such as cuprous halide.47 As shown in the figure, L is a ligand that helps to

solubilize the cuprous salt in the organic reaction system. ka and kd are rate constants for

 activation and deactivation of the halide initiator, respectively, with K = ka/kd. R is the reactive radical that initiates polymerization. In the most case, the Cu(I) species are employed as the activator, corresponding the Cu(II) species as deactivator. And if the initiation step starts from Cu(I), the process is called as direct ATRP with an alkyl halide initiator. In opposite, if the initiation step starts from Cu(II), the process is called as reverse ATRP with classical initiator. For the synthesis of PEO-b-PS amphiphilic block copolymer, the direct ATRP technique was employed and PEO-Br was used as initiator.

Figure 2.3 Mechanism of ATRP polymerization47

2.3 Click Chemistry

2.3.1 The Concept of Click Chemistry

Different from the specific reaction, click chemistry is a new reaction concept, which generates substances by joining small modular units. In the year 2001, the Nobel

Laureate, Professor K. B. Sharpless, proposed the concept of “click” chemistry as a “set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new 12

compounds and combinatorial libraries”.48 This perfect chemical reaction was soon accepted by many researchers and showed great contribution for many fields, such as pharmic synthesis and molecular biology. Over the last several years, since these initial publications, the area of click chemistry has turned into a highly creative research area with exponential growth.

Click chemistry is a synthetic approach for modular units, which can result in the high yields of only one product, and the by-products can also be easily removed. Such

−1 reaction has a very high thermodynamic driving force (> 20 kcalmol ), which is typically associated with the formation of carbon–heteroatom bonds. Actually, click chemistry is not limited to a single specific reaction, which is a synthetic philosophy that comprises of a range of reactions with common reaction features.

2.3.2 Cu-catalyzed Acetylene Azide [3+2] Cycloaddition

In this section, one of the typical “click” reaction employed in this thesis is briefly introduced, which is Cu-catalyzed acetylene azide [3+2] cycloaddition (CuAAC) as represented in Scheme 2.1.49 The Huisgen 1,3-dipolar cycloaddition of azide-alkyne has been well-known as one of the most popular reactions within “click” chemistry, using a

Cu catalyst at room temperature,48 which was first defined as the Huisgen reaction,49 and further improved and developed with highly efficiency by two different research groups 13

in 2002.50,51 Now, it has been found that azide-alkyne Huisgen cycloaddition is a powerful method to design the precisely-defined structures with high fullerene functionality, and hence, it has been widely applied in fullerene chemistry field.52,53

Scheme 2.1 Huisgen 1,3-dipolar cycloadditions of azides and alkynes

The mechanism of azide-alkyne Huisgen 1,3-dipolar cycloaddition is shown in Figure

2.4. This reaction is therefore a [3+2] cycloaddition similar to the Diels-Alder Reaction.

The condition for this reaction is similar to the theory of the interacting HOMO and

LUMO orbital which depends on the relative orbital energies. Diazomethane is an electron-rich dipolar compound and thus can react with electron-poor alkenes. Without appropriate catalyst, this reaction is generally slow. In the presence of Cu(I), however, copper binds to terminal alkynes to form intermediate copper acetylides, and this cycloaddition reaction is dramatically accelerated.

Figure 2.4 The mechanism of Huisgen 1,3-dipolar cycloadditions

2.4 Amphiphilic Block Copolymers

2.4.1 Introduction of Block Copolymers

Polymers have been widely employed as functional materials due to their various properties. With the increasing requirements on the performance of the materials, the homopolymers may not be able to meet the needs of practical applications. More and more researches are currently focusing on copolymers and polymer blends. Generally speaking, copolymerization is an effective way to combine the various kinds of properties of macromolecules to build into one polymer via making up of different polymerized monomers. Depending on polymerization procedures, copolymers can be synthesized with different molecular architectures, such as random copolymer, diblock and triblock copolymers, graft copolymer, and star copolymer, and their sketches are briefly shown in

Figure 2.5. Among them, block copolymers have been widely investigated by both academia and industry during the recent decade, which are interesting due to their self-assembly behaviors in solution and at bulk state. The various morphologies of block copolymers show the great potential for the application as functional polymer in some special condition.

Figure 2.5 Schematic illustrations of different copolymer architectures: (A) random copolymer, (B) diblock copolymer, (C) triblock copolymer, (D) graft copolymer, and (E) star copolymer.54

Block copolymers are polymers which are comprised of two or more homo-polymeric subunits or blocks linked by covalent bonds, which can be classified by the number of blocks and how the blocks are connected. Block copolymers can be successfully synthesized by different polymerization methods, such as step-growth polymerization controlled radical polymerization (CRP), and living ionic polymerization.55 Macroscopic properties of block copolymers can be tuned by changing block monomers, which can behave as the different solubilities in solvents such as hydrophilic-hydrophilic copolymers56 and amphiphilic block copolymers. For the amphiphilic block copolymer, poly(ethylene oxide) (PEO) has been greatly reported as the hydrophilic blocks in many literature.57,58

For the synthesis of block copolymers, CRP technique has been remarkably developed in the past three decades, depending on the concept of reversible chain 16

termination pioneered by Otsu and Yoshita. 59 During CRP process, the inducing of dormant agent can reversibly transform the active free radical into the dormant chain.

Based on the balance of reaction between active free radical and dormant chain, thermodynamic equilibrium of the transition between active polymer chain and dormant polymer chain can be reached, so as that the polymer chains synchronously grow with the conversion. By using CRP technique, well-defined copolymers with pre-determined molecular weights, narrow molecular weight distributions, pre-designed composition profiles and complex macromolecular architectures may be achieved.

2.4.2 Introduction of Amphiphilic Block Copolymers

Amphiphilic property is a special attribute, which means "loving both" or "having an affinity for both". Amphiphilic molecules are consisted of both hydrophilic and hydrophobic groups, and these groups are chemically bonded together. Meanwhile, the hydrophobic/hydrophilic interactions can drive amphiphilic molecules to phase separate in water, and surfactants are the typical amphiphilic molecules. Amphiphilic block copolymer is one of the examples of amphiphilic molecules, which can be obtained by chemically link blocks of two dissimilar polymers. The simplest case is that a hydrophobic block and a hydrophilic block are linked together. For example, polystyrene-block-poly

(ethylene oxide) (PS-b-PEO) is a common block copolymer, where PS segment is the 17

hydrophobic block and PEO segment is the hydrophilic one. In this thesis, PS-b-PEO copolymers were employed tails to explore the self-assembly properties of end-capped

C60.

2.4.3 Self-assembly of Amphiphilic Block Copolymers in Solution

When amphiphilic block copolymers are dissolved in a selective solvent, due to different solubilities of each block in the solvent, they may associate to form micelles or aggregates with various morphologies.60 And whether the amphiphilic block copolymers associate into star-like micelles or crew-cut ones is determined by both molecular architecture and solvent property. Star-like micelles can be obtained directly by dissolving a highly asymmetric block copolymer in a selective solvent with good solubility for the long blocks, in which the corona is much thicker than the core.72 In the opposite, crew-cut micelles are formed by a bulky core and a relatively thin corona.

Different from star-like micelles, crew-cut ones are prepared by first dissolve a highly asymmetric block copolymer in a common solvent with good solubility for both blocks and then added a selective solvent with good solubility only for the short blocks, so as to induce the aggregation of the long blocks.

During the formation process of micelle, the attractive force between the insoluble blocks leads to aggregation and the repulsive force between the soluble blocks prevents 18

infinitely growth of the micelle into macroscopic phase. Furthermore, the interaction between the soluble blocks and the solvent can stabilize the micelles in the solution.

It is well-known that amphiphilic block copolymers can form nano-scale morphology in solutions via self-assembly. 61 When the concentration of an amphiphilic block copolymers is above their critical micelle concentration (CMC) in a selected solvent, the amphiphilic block copolymers can self-assemble into micelle.62 If the amphiphilic block copolymers containing water-soluble blocks, the micelles with various nano-scale morphologies can be obtained as in aqueous solution such as sphere, cylinder, and vesicle.63,64 Meanwhile, the morphologies of amphiphilic block copolymer induced by self-assembly can also be effectively controlled by volume fractions of the hydrophilic and/or hydrophobic blocks and total solid concentrations of molecules.

For polar solvents, water shows a singular cohesive energy due to the hydrogen bridging network. Therefore, the self-assembly behaviors of amphiphilic block copolymers in aqueous solutions have been widely investigated. For the investigation of micellization process of amphiphilic block copolymers in solution, the critical water content (CWC) is an important value, which is defined as the amount of added water when the micelles start to form. This parameter depends on both copolymer concentration and molecular weight. 65 Compared with small molecular surfactant, amphiphilic block copolymer chains exhibit various conformations during micellization process via 19

self-assembly, which is due to the random-coil-like flexibility of macromolecular chains.

And hence, this in turn affects their entropy and free energy, so as to finally change their aggregation behavior.

Among amphiphilic block copolymers, one of the most extensively studied hydrophilic blocks is poly (ethylene oxide) (PEO), which is attached to various apolar moieties. The hydrophilic PEO block is soluble in water, depending on its strong hydration, which is attributed to a notable favorable fitting of the ethylene oxide unit with water molecule’s structure. Moreover, the hydration of the ethylene oxide unit is strongly temperature-dependent, resulting in an upper critical solution temperature (UCST). It is expected that aqueous solubility of PEO and the block copolymer with PEO blocks may be tuned by changing temperature, which further provides an alternative way to alter their self-assemble behaviors.

Micellization of PS-b-PEO diblock copolymers in a selective solvent has been investigated for several decades.66 In the solution of PS-b-PEO copolymers, PEO blocks are hydrophilic and serve as coronas. They are especially attractive due to their biocompatibility. Recently, the micellization and the morphological transition of a asymmetric PS-b-PEO copolymers in binary solvent systems of N,N-dimethylformamide

(DMF)/water and DMF/acetonitrile have been systematically studied,67 concluding that the variation of temperature can effectively drive the micellization performance of 20

PS-b-PEO diblock copolymers in DMF/water binary solvent. And the morphological transition of PS-b-PEO diblock copolymers in DMF/water binary solvent system indicates that the increasing temperature leads to the change of micellar morphology from vesicles to worm-like cylinders and then to spheres.

It is accepted that the PS-b-PEO block copolymers are available for the application as encapsulation of hydrophobic materials in an aqueous suspension due to its hydrophilic property. Moreover, PEO is a kind of synthetically inert polymers, which is expected to cause that the amphiphilic blocks may have potential applications in drug delivery systems.68 Therefore, PS-b-PEO is a kind of important block copolymer, and the further investigation of it is absolutely significant for the application of block copolymers. And hence, in this thesis, PS-b-PEO was employed as the amphiphilic block copolymer for research.

2.5 Shape Amphiphiles

2.5.1 Introduction of Shape Amphiphiles

Recently, a new class of amphiphiles named “shape amphiphiles” has emerged. Shape amphiphiles usually refer to molecules possessing differences in the shape of the molecular moieties.69 It is found that these shape amphiphiles can self-assemble into diverse structures in solution which is similar to small molecule surfactants and block 21

copolymers, but the molecular design and topologies are completely distinct. Several models about shape amphiphiles have been reported, such as polymer-tethered nanoparticles, molecular nanoparticles, and giant molecular amphiphile. Shape and interactions are two crucial factors to detect the self-assembly of these models.

2.5.2 Polymer-tethered Nanoparticles

Polymer-tethered nanoparticles are a new class of shape amphiphiles, which are usually consisted of a nano-sized polar or macroionic head-group and one or more hydrophobic polymer chains as the tails at various geological locations.70 Several kinds of polymer-tethered nanoparticles have been reported, such as polymer-tethered gold particles, 71 , 72 quantum dots, 73 , 74 globular protein, 75 , 76 and molecular nanoparticles

77,78 (MNPs). And for the case of MNPs, [60]fullerene (C60) and polyhedral oligomeric silsesquioxane (POSS)79,80 have been reported as the template. It is found that MNPs are advantageous in providing a precisely defined and readily tunable nano-sized structural scaffold. Therefore, it is the current research focus for the study of polymer-tethered nanoparticles. Recently, many literatures about the investigation of polymer-tethered nanoparticles have been published. Song et al.81 synthesized the PEO tethered fullerenes

and studied the effect of miscibility and C60 concentration on the aggregation behavior of 22

the polymer-tethered nanoparticles. However, systematical exploration in the structure of these polymer-tethered nanoparticles is still limited.

2.5.3 Molecular Nanoparticles

Among those MNPs, fullerene (C60) shows a perfectly spherical shape with a

truncated icosahedral (Ih) symmetry and a diameter of 1 nm, and hence it is an ideal structural motif for the study of MNPs’ self-assembly. Amphiphilic fullerenes have been designed and synthesized via fullerene chemistry which provides a specific way to

functionalize C60. Meanwhile, the self-assembly morphology of these amphiphilic fullerenes is stable, and it is hard to be tuned via changing the physical parameters.

2.5.4 Giant Molecular Amphiphile

Giant molecular amphiphile refers to molecule with molecular nanoparticle head and polymeric tail. Recently, our group has concentrated on the study of “giant surfactants”

82 based on POSS and C60 with various surface functionalities. It is interesting to investigate “giant surfactants” which have molecular sizes comparable to amphiphilic diblock copolymers, a similar molecular shape as small-molecule amphiphiles, and a polar head with a rigid conformation.

One of such giant surfactants, carboxylic-acid-functionalized polyhedral oligomeric silsesquioxane end-capped with PS tails (APOSS-PS) can self-assemble into the various micelles (spheres, cylinders, and vesicles). PS tails are found to be highly stretched, which is similar to those observed in small molecule surfactant assemblies.83 This is due to the strong APOSS-APOSS interactions in PS-APOSS micelles and the conformational rigidity of the APOSS head groups, which force the PS tails to stretch so as to minimize their overall free energy.

Other self-assembly examples of such giant surfactants are two model series of

molecular shape amphiphiles and hydrophilic [60]fullerene (AC60) tethered with one or

84 two polystyrene (PS) chain(s) at one junction point (PSn−AC60 and 2PSn−AC60). The concentration-sensitive phase behavior of these molecular shape amphiphiles is unique, compared with the traditional surfactants and the block copolymer systems. The stretching

ratio (defined as S) of the PS tails in the spherical micelles of the series of PSn-AC60 exhibits a structure-dependent property, which is that S decreases with the increasing length of PS tail, indicating the variational micellar behavior from the small molecular surfactant-like type to an amphiphilic block copolymer-like type. As the molecular

concentration higher than 0.25 wt%, the series of PSn−AC60 micelles form the various morphologies of spheres, cylinders, and vesicles, which are determined by the initial

molecular concentration and the length of PS tail. However, for the series of 2PSn−AC60, 24

the micellar morphology remains at the state of bilayer vesicles in the same concentration range.

Based on the previous interesting results, the topological variation in giant molecular shape amphiphiles was further explored by one step in this thesis, in which the amphiphilic

diblock copolymer PS-b-PEO and AC60 were employed as the tail of polymer chains and polar head, respectively.

CHAPTER III

EXPERIMENTAL

3.1 Materials and Instrumentals

The instruments employed for the characterization of specimen are listed in Table 3.1, and the materials using in this study are listed in Table 3.2.

Table 3.1 Instrumentals2

Instrumentals Type Company 1H-NMR Varian Mercury 300 Spectra 13C-NMR Varian Mercury 500 Spectra MALDI-TOF Bruker Daltonics, Billerica, MA TEM JSM-123 JEOL FT-IR Excalibur Series FT-IR Spectra Digilab, Randolph, MA SEC Waters 150-C Plus instrument/ three HR-Styragel columns/ double detector system SLS Laser Light Scattering System

Table 3.2 Materials3

Name Abbreviation Purity Source

[60]Fullerene C60 99.5% MTR Ltd Toluene 99.5% Aldrich Malonic acid 99.9% Aldrich tert-butyl bromoacetate 98% Aldrich Triethylamine TEA 99.9% Aldrich Ethyl acetate EA 99.9% Aldrich

Iodine I2 99.8% Aldrich 1,8-diazabicyclo[5.4.0]undec-7-en DBU 99% Aldrich e

Trifluoroacetic acid TFA(CF3COOH) 99% Aldrich

Dichloromethane DCM(CH2Cl2) Anhydrous Acros Ortho dichlorobenzene ODCB 99% Aldrich N,N’,N’,N’’,N’’-pentamethyldieth PMDETA 99% Aldrich ylenetriamine Copper(I) bromide CuBr 98% Aldrich Styrene 99% Aldrich Methyl malonyl chloride 97% Aldrich 5-trimethylsilyl-4-pentyn-1-ol 96% Aldrich Pyridine 99.8% Aldrich Hexanes 99% Aldrich Ethyl ether 99% Aldrich

3.2 Sample Synthesis

The synthetic route of PEO-b-PS-AC60 is briefly sketched in Scheme 3.1, which was carried out by the several steps as described following.

Scheme 3.1 Full synthetic route of the sample PEO-b-PS-AC602

3.2.1 The Synthesis of Malonate 1

Methyl malonyl chloride (0.89 mL, 8.3 mmol) was added into a solution of

5-trimethylsilyl-4-pentyn-1-ol (1.5 mL, 8.3 mmol) and pyridine (0.67 mL, 8.3 mmol) in

o CH2Cl2 (70 mL) at 0 C. After 2 h, the mixture was warmed up to room temperature and then stirred overnight. Subsequently, the mixture was filtered and washed with brine, and finally dried by using anhydrous sodium sulfate. Upon removal of the solvent, the residue

was purified by column chromatography on silica gel with a mobile phase of hexanes/ethyl acetate (v/v = 5/1). The product Malonate 1 (1.9 g, 90%) was colorless oil.

3.2.2 The Synthesis of Methanofullerene 2

DBU (0.43 mL, 2.8 mmol) was added into a stirred solution of C60 (1.00 g, 1.4 mmol),

I2 (0.38 g, 1.5 mmol), and Malonate 1 (0.37 g, 1.45 mmol) in toluene (1.2 L) under argon at room temperature. The mixture was stirred for 7 h, and then filtered through a short silica column with toluene as the eluent to remove the salt. Upon removal of the solvent, the residue was purified by column chromatography on silica gel with toluene/hexanes (v/v =

2/1) as the eluent. The product was Methanofullerene 2 (0.78g, 57%).

3.2.3 The Synthesis of Malonate 3

5.56 mL of TEA (2.59 g, 26 mmol) and tert-butyl bromoacetate (5.00 g, 26 mmol) was added into a stirred solution of malonic acid (1.33 g, 13 mmol) in 50 mL ethyl acetate.

After the stirring for 2 days, the mixture was filtered and washed with brine, and then dried over anhydrous sodium sulfate. Upon removal of the solvent, the residue was purified by column chromatography on silica gel with hexanes/ethyl acetate (v/v = 4/1) as the eluent. The product Malonate 3 (4.7 g, 75%) was obtained at colorless oil state.

3.2.4 The Synthesis of [5:1]-Hexakisadducts 4 and 5

DBU (0.64 mL, 4.24 mmol) was added into a stirred solution of Methanofullerene 2

(0.2 g, 0.21 mmol), I2 (0.55 g, 2.1 mmol), and Malonate 3 (0.68 g, 2.1 mmol) in ODCB (40 mL) under argon at room temperature. The mixture was stirred for 18 h, and then filtered through a short silica column with toluene/ethyl acetate (v/v = 2/1) as the eluent to remove the salt. Upon removal of the solvent, the residue was purified by column chromatography on silica gel with toluene/ethyl acetate (v/v = 8/1) as the eluent. The product was

[5:1]-Hexakisadducts 4 (0.25 g, 46%).

TBAF (0.19 mL, 1M in THF) was added into [5:1]-Hexakisadducts 4 (0.25 g, 0.095 mmol) in THF solution (5.0 mL) and stirred for 3 h. The mixture was then filtered through a short silica column with toluene/ethyl acetate (v/v = 2/1) as the eluent. The product was

[5:1]-Hexakisadducts 5 (0.23 g, 95%).

3.2.5 The Synthesis of PEO-Br

TEA (0.303 g, 3.00 mmol) was added into a stirred solution of PEO-OH (Mn= 2.0 kg∙

-1 o mol , 4 g, 2.00 mmol) in 50 mL anhydrous CH2Cl2 at 0 C. The solution was subsequently added into the mixture of 2-bromoisobutyryl bromide (0.68 g, 3.00 mmol) in 5 mL of

anhydrous CH2Cl2 dropwise within 20 min. After the stirring for another 24 h at room temperature, the mixture was filtered and washed with brine, and then dried over 30

anhydrous sodium sulfate. After removal of the solvent, the residue was precipitated into excess cold ethyl ether and collected by filtration. PEO-Br (4.12 g, 88%) at white powder state was obtained by drying the product in vacuo for 24 h.

3.2.6 The Synthesis of PEO-b-PS

PMDETA (17.3 mg, 0.1 mmol) was added into a mixture of PEO-Br (Mn = 2.0 kg∙ mol-1, 0.2 g, 0.1 mmol), CuBr (14.4 mg, 0.1 mmol), styrene (3 mL) and 5 mL anhydrous toluene under argon at room temperature. After three extra freeze–vacuum–thaw cycles, the flask was immersed into a 110 oC oil bath. After reaction for 7h, the residue was then

filtered through a short silica column with CH2Cl2/CH3OH (v/v = 9/1) as the eluent to remove the salt. Then the polymer was recovered by precipitation in an excess mixture of cold ethyl ether and hexanes (v/v = 50/50), filtered, and dried ender vacuum for 24 h.

Finally, the PEO-b-PS block copolymers (0.93 g) at white powder state were obtained.

3.2.7 The Synthesis of PEO-b-PS-N3

-1 -1 A mixture of PEO-b-PS (Mn(PEO) = 2 kg∙mol , Mn(PS) = 9.0 kg∙mol , 0.8 g, 0.045 mmol) and sodium azide (29 mg, 0.45 mmol) was added into a stirred solvent of anhydrous

DMF (10 mL) at room temperature. After stirred for 24 h, the mixture was filtered and washed with brine, and then dried over anhydrous sodium sulfate. After removal of the 31

solvent, the polymer solution was added into an excess mixture of cold ethyl ether and

hexanes (v/v = 50/50). The product was dried in vacuo for 24 h to give PEO-b-PS-N3 (0.69 g)) as white powder.

3.2.8 The Synthesis of PEO-b-PS-tC60 (6) and PEO-b-PS-AC60 (7)

PMDETA (10μL) was added into a mixture of [5:1]-Hexakisadducts 5 (50 mg, 0.02

-1 mmol), PEO-b-PS-N3 (Mn = 2.4 kg∙mol , 60 mg, 0.025 mmol), CuBr (1 mg, 0.007 mmol) in degassed toluene (10 mL) under argon at room temperature. After stirring for 24 hours, the mixture was washed with brine and dried over anhydrous sodium sulfate. Upon removal of the solvent, the residue was purified by column chromatography on silica gel.

The column was eluted with toluene/ethyl acetate (v/v = 4/1) first to remove the excess tC60

and then with CH2Cl2/CH3OH (v/v = 9/1) to give a colored fraction PEO-b-PS-tC60 (6) (80

mg, 80%). Compound PEO-b-PS-tC60 (6) was dissolved in mixture of CH2Cl2 and

CF3COOH (v/v= 4/1) and stirred for 8 h. Removal of the solvent gave the product

PEO-b-PS-AC60 (7) (70 mg, > 95%).

3.3 Micelle Preparation

The PEO-b-PS-AC60 were first dissolved in a mixture of DMF and 1,4-dioxane (w/w

= 1/1) and stirred at room temperature to prepare a stock solution. The stock solution and 32

was then filtered through a filter of 0.22 μm pore size to remove dust. De-ionized water was also filtered through a filter of 0.22 μ pore size. Then de-ionized water was added into a vial containing 1.00g of the stock solution using a syringe pump until reach a final water content of 80 wt%. At this water content, PS was vitrified and there is no further morphological transformation.

3.4 Transmission Electron Microscopy

10 μL of the micelle solutions were deposited onto carbon coated copper grids. The excess solution was wicked away by a piece of filter paper. Then the sample was dried under ambient conditions. Bright filed images of transmission electron microscope (TEM) were recorded by using in a JEOL-1230 microscope with a voltage of 120 kV.

3.5 Static Light Scattering Experiments

In order to determine the critical micellization concentration (CMC), static light scattering experiments were conducted using a Brookhaven Instrument coupled with a

BI-9000AT correlator, BI-200SM goniometer, and an EMI-9863 photomultiplier tube for photon counting. A cylindrical glass scattering cell with diameter of 12 mm was placed in a thermostated bath (± 0.01oC) with decahydronaphthalene used for refractive index matching. 33

CHAPTER IV

RESULTS AND DISCUSSION

4.1 The Characterization of Malonate 1

4.1.1 Synthetic Scheme of Malonate 1

Scheme 4.1 The synthesis of Malonate 13

The synthesis of Malonate 1 was carried out via a chemical reaction of small molecules as sketched in Scheme 4.1. The reagents of methyl malonyl chloride and

5-trimethylsilyl-4-pentyn-1-ol malonic acid were reacted in pyridine in CH2Cl2 overnight.

The yield of Malonate 1 is 90%.

4.1.2 NMR Characterization of Malonate 1

The Malonate 1 was characterized by both 1H NMR and 13C NMR, and the results are shown in Figure 4.1, respectively. The detailed chemical shifts are listed below:

1 H NMR (CDCl3, 300 MHz, ppm, d): 4.24 (t, J = 6 Hz, 2H), 3.74 (s, 3H), 3.38 (s, 2H),

13 2.31 (t, J = 6 Hz, 2H), 1.86 (p, J = 6 Hz, 2H), 0.13 (s, 9H). C NMR (CDCl3, 75 MHz, ppm, d): 166.9, 166.3, 105.4, 85.4, 64.1, 52.6, 52.3, 41.2, 27.4, 16.3, 0.0.

Figure 4.1 1H NMR and 13C NMR spectra of Malonate 16

4.2 The Characterization of Methanofullerene 2

4.2.1 Synthetic Scheme of Methanofullerene 2

Scheme 4.2 The synthesis of Methanofullerene 2

As shown in Scheme 4.2, through the Bingel reaction mechanism, the modification

of C60 was carried out in a toluene solution, and the addition reaction occurred on only

one [6-6] bond of C60. The yield is 45%.

4.2.2 NMR Characterization of Methanofullerene 2

The Methanofullerene 2 was characterized by 1H NMR. The typical 1H NMR spectrum for the Methanofullerene 2 is shown in Figure 4.2.The detailed chemical shifts are listed below:

1 H NMR (CDCl3, 300 MHz, ppm, d): 4.61 (t, J = 6 Hz, 2H), 4.11 (s, 3H), 2.45 (t, J =

6Hz, 2H), 2.06 (p, J = 6 Hz, 2H), 0.18 (s, 9H).

Figure 4.2 1H NMR spectra of Methanofullerene 27

4.2.3 MALDI-TOF Characterization of Methanofullerene 2

Figure 4.3 shows the MALDI-TOF mass spectrum of Methanofullerene 2, and the theoretical one of Methanofullerene 2 is also displayed in Figure 4.3 (small part). It can be seen that only the single peak around 974.184 is obtained in Figure 4.3, confirming the cleanness of the reaction and the stability of the resulting fullerene products. Besides, good agreement between the obtained (974.184) and theoretical (974.2) mass spectra of is achieved, indicating the successful synthesis and good purity of Methanofullerene 2.

Figure 4.3 MALDI-TOF mass spectra of Methanofullerene 28

4.3 The Characterization of Malonate 3

4.3.1 Synthetic Scheme of Malonate 3

Scheme 4.3 The synthesis of Malonate 35

The synthesis of Malonate 3 was synthesized via a chemical reaction of malonic acid and tert-butyl bromoacetate as shown in Scheme 4.3. The reaction of them was carried out in ethyl acetate solution with the presence of TEA for two days. The product

Malonate 3 is the di-acid with carboxylic acid groups, which are protected by tert-butoxyl groups. The yield is 95%. 38

4.3.2 NMR Characterization of Malonate 3

The Malonate 3 was characterized by 1H NMR and 13C NMR. The results are shown in Figure 4.4, respectively. The detailed chemical shifts are listed below:

1 13 H NMR(CDCl3, 300 MHz, ppm, d):4.54 (s, 4H), 3.56 (s, 2H), 1.45 (s, 18H). C

NMR (CDCl3, 75 MHz, ppm, d): 166.0, 165.4, 82.6, 61.8, 40.4, 27.8. As the chemical shifts as well as the splits fit well with the design structure of the monomer, it can be confirmed the product is of the target structure.

After reaction, the 1H NMR spectra for Malonate 3 (Figure 4.4 (a) ) methyl protons

(-O-C-(CH3)3) can be clearly seen at  = 1.45 ppm, respectively. The chemical shift of the carboxylic proton was observed at  = 3.56 ppm. The integration ratio of 1 and 2 is 1: 2,

indicating a structure C=OCH2C=O.

Figure 4.4 1H NMR and 13C NMR spectra of Malonate 3 9

4.4 The Characterization of [5:1]-Hexakisadducts 4 and 5

4.4.1 Synthetic Scheme of [5:1]-Hexakisadducts 4 and 5

As shown in Scheme 4.4, the modification of [5:1]-Hexakisadducts 4 was performed through a Bingel-Hirsch cyclopropanation reaction, and the addition reaction

occurred on five [6-6] bonds of C60 in the ODCB solution. The yield is 46%.

[5:1]-Hexakisadducts 5 is the deprotection of TMS and a high yield of 95%.

Scheme 4.4 The synthesis of [5:1]-Hexakisadducts 4 and 5 6

4.4.2 NMR Characterization of [5:1]-Hexakisadducts 4 and 5

The [5:1]-Hexakisadducts 4 and 5 was characterized by 1H NMR and 13C NMR. The results are shown in Figure 4.6 part a and b, respectively, in which the top one is due to

[5:1]-Hexakisadducts 4, and bottom one is due to [5:1]-Hexakisadducts 5. The detailed chemical shifts of 1H NMR and 13C NMR spectra are listed below:

1 [5:1]-Hexakisadducts 4: H NMR (CDCl3, 300 MHz, ppm, d): 4.67 (s, 20H), 4.36 (t,

J = 6 Hz, 2H), 3.87 (s, 3H), 2.33 (t, J = 6 Hz, 2H), 1.92 (br, 2H), 1.44 (s, 90H), 0.15 (s, 9H).

13 C NMR (CDCl3, 75 MHz, ppm, d): 165.5, 162.9, 145.9, 140.8, 105.3, 85.7, 82.5, 69.0,

68.7, 65.4, 63.0, 53.4, 44.7, 27.9, 16.4, 0.14.

1 [5:1]-Hexakisadducts 5: H NMR (CDCl3, 300 MHz, ppm, d): 4.67 (s, 20H), 4.36 (t,

J = 6 Hz, 2H), 3.88 (s, 3H), 2.32 (t, J = 6 Hz, 2H), 1.92 (br, 2H), 1.43 (s, 90H).

Figure 4.5 MALDI-TOF mass spectra for [5:1]-Hexakisadducts 5 10

The obtained (large part) and theoretically calculated (small part) MALDI-TOF mass spectra of [5:1]-Hexakisadducts 5 are shown in Figure 4.5. In the obtained mass spectra, only one single peak can be observed, confirming the cleanness of the reaction and the stability of the resulting fullerene product.

Figure 4.6 1H NMR and 13C NMR spectra of [5:1]-Hexakisadducts 4 and 5 11 43

4.5 The Characterization of PEO-Br

4.5.1 Synthetic Scheme of PEO-Br

Scheme 4.5 The synthesis of PEO-Br 7

-1 PEO-OH with the defined molecular weight (Mn = 2.0 kg∙mol ) was employed for the synthesis of PEO-Br. The resultant white powder was dried in vacuo for 24 hours to give PEO-Br, a yield of 88%.

4.5.2 MALDI-TOF Characterization of PEO-Br

The PEO-Br was characterized by MALDI-TOF mass spectrometry. The results were based on samples with PEO molecular weight of 2.0 kg∙mol-1 which shown in Figure 4.7, respectively. Only one single symmetric distribution of molecular weights is observed, where the monoisotopic mass of each peak matches well with the proposed structure (e.g., for [20mer·Na]+, found 2052.115 Da vs calcd. 2052.2 Da). The difference between neighboring peaks equals the mass of a PEO repeating unit (44.03 Da). The results unambiguously confirm the product of PEO-Br.

Figure 4.7 MALDI-TOF mass spectra for PEO-Br12

4.6 The Characterization of PEO-b-PS

4.6.1 Synthetic Scheme of PEO-b-PS

Scheme 4.6 The synthesis of PEO-b-PS 8

For the synthesis of PEO-b-PS diblock copolymers via ATRP polymerization, the

-1 -1 PEO blocks were controlled with Mn = 2.0 kg∙mol by using PEO-Br (Mn= 2.0 kg∙mol ).

And the PS blocks were designed as various molecular weighs as listed in Table 4.1. And the molecular weight control of PS blocks can be achieved by carrying out the synthetic 45

procedures with varational reaction time. Finally, the PEO-b-PS block copolymers were obtained after drying in vacuo for 24 h, and the yield was 88%. The PDI of as-synthesized

PEO-b-PS block copolymers was also listed in Table 4.1, which was around 1.08, indicating the well controlled polymerization of PS blocks.

Table 4.1 Molecular Weight Characterization of PEO-b-PS

-1 -1 Sample Mn(PEO)/ kg∙mol Mn(PS)/ kg∙mol PDI PEO-b-PS-5K 2.0 5.0 1.07 PEO-b-PS-7.8K 2.0 7.8 1.08 PEO-b-PS-12K 2.0 12 1.07 PEO-b-PS-15K 2.0 15 1.07 PEO-b-PS-19K 2.0 19 1.08

4.6.2 NMR Characterization of PEO-b-PS

The PEO-b-PS block copolymers were characterized by using 1H NMR. And a typical 1H NMR spectrum is shown in Figure 4.8. The detailed chemical shifts are listed

1 below: H NMR (CDCl3, 500MHz, ppm, d): 6.30-7.40 (br, 430H), 3.64 (br, 770H,

–CH2CH2O–), 1.67–2.15 (br, 87H), 1.20-1.67 (br, 174H), 1.20 (s, 9H), 0.93 (m, 6H).

Figure 4.8 1H NMR spectra of PEO-b-PS 13

4.7 The Characterization of PEO-b-PS-N3

4.7.1 Synthetic Scheme of PEO-b-PS-N3

Scheme 4.7 The synthesis of PEO-b-PS-N3 9

The as-synthesized PEO-b-PS block copolymers were further modified to introduce

the azide groups via chemical reaction as sketched in Scheme 4.7. And the PEO-b-PS-N3 was obtained in 87% yield (0.69 g) after drying under vacuum for 24 hours.

4.7.2 FT-IR Characterization of PEO-b-PS-N3

Figure 4.9 FT-IR spectrum of PEO-b-PS-N3 14

PEO-b-PS-N3 was characterized by FT-IR, and the spectrum is shown in Figure 4.9,

-1 respectively. FT-IR (cm ): 3082, 3060, 3027, 2920, 2869, 2098 (N3), 1943, 1884, 1807,

1730, 1641, 1601, 1493, 1452, 1349, 1300, 1249, 1110, 1029, 950, 844, 758, 699, 542.

In order to confirm the successful introducing azide groups to PEO-b-PS chains,

FTIR spectroscopy was employed, and the spectra of PEO-b-PS and as-synthesized

PEO-b-PS-N3 are displayed in Figure 4.9 part a and b, respectively. It can be clearly found that, compared with the spectrum of PEO-b-PS, a FTIR results confirmed the reaction as shown in Scheme 4.7.

4.8 The Characterization of PEO-b-PS-tC60 and PEO-b-PS-AC60

4.8.1 Synthetic Scheme of PEO-b-PS-tC60 and PEO-b-PS-AC60

The detailed synthetic protocol has been described in section 3.2.7, which is further sketched in Scheme 4.8.

Scheme 4.8 The synthesis of PEO-b-PS-tC60 and PEO-b-PS-AC60 10

4.8.2 NMR Characterization of PEO-b-PS-tC60 and PEO-b-PS-AC60

1 Figure 4.10 H NMR spectra of (a) PEO-b-PS-tC60 and (b) PEO-b-PS-AC6015

1 The H NMR spectra of PEO-b-PS-tC60 and PEO-b-PS-AC60 are shown in Figure

4.10 part (a) and (b), respectively. The detailed assignment of 1H NMR spectra of

PEO-b-PS-tC60 and PEO-b-PS-AC60 is listed below:

1 PEO-b-PS-tC60: H NMR (CDCl3, 300 MHz, ppm, d): 6.30-7.40 (br, 430H), 5.0-5.15

(br, 1H), 4.66 (s, 20H), 4.25 (s, 2H), 3.64 (br, 770H), 2.65 (s, 2H), 1.67-2.15 (br, 87H),

1.20-1.67 (br, 174H), 1.20 (s, 9H), 0.93 (m, 6H).

1 PEO-b-PS-AC60: H NMR (DMSO-d6, 300 MHz, ppm, d): 6.30-7.30 (br, m, 110H),

5.10-5.30 (br, 1H), 4.75 (s, 20H), 4.25 (s, 2H), 1.1-2.1 (br, 68H), 0.75-1.00 (br, 9H).

4.8.3 FT-IR Characterization of PEO-b-PS-tC60

Figure 4.11 FT-IR spectrum of PEO-b-PS-tC60 and PEO-b-PS-N3 16

Depending on the comparison of the FT-IR spectra of PEO-b-PS-tC60 and

PEO-b-PS-N3 as shown in Figure 4.11, it can be clearly found that the typical absorption

-1 band of azide (2100 cm ) for PEO-b-PS-tC60 disappears completely. This indicates that the successful of the “click” reaction.

4.8.4 SEC Characterization of PEO-b-PS-tC60

Figure 4.12 SEC overlay of PEO-Br (Black), PEO-b-PS-Br (Red) and PEO-b-PS-tC60 (Blue) 17

Figure 4.1.2 is a SEC trace overlay of PEO-Br macroinitiator, PEO-b-PS-Br block

copolymers, and the PEO-b-PS-tC60 chromatograms. The obvious increasing retention volume for PEO-b-PS-Br block copolymers can be seen, compared with that for PEO-Br, suggesting the increasing molecular weight of PEO-b-PS-Br block copolymers due to PS

blocks. Meanwhile, as indicated by the blue line of PEO-b-PS-tC60, the retention volume shows the slight higher shift than that of PEO-b-PS-Br block copolymers. Therefore, it

can be concluded that the PEO-b-PS was successfully connected with C60 molecules via

“click” reaction. 52

4.9 Micellization of Shape Amphphiles at Different Molecular Concentration

In Table 4.2 summarize the molecular characterizations of PEO-b-PS-AC60. Nps is the

1 degree of polymerization of the PS tail from SEC and H NMR measurements. Mn is the

molecular weight calculated from Mn(PEO) + Mn(PS) + Mn(AC60).

Table 4.2 Summary of Molecular Characterizations PEO-b-PS-AC605

Sample Nps Mn

PEO45-b-PS48-AC60 48 9.1K

PEO45-b-PS75-AC60 75 11.9K

PEO45-b-PS115-AC60 115 16.1K

PEO45-b-PS144-AC60 144 19.1K

PEO45-b-PS182-AC60 182 23.1K

4.9.1 Self-assembled Micellar Morphologies of PEO45-b-PS75-AC60

The TEM bright images of self-assembled micelles of PEO45-b-PS75-AC60

1,4-dioxane/DMF/water system with different initial molecular concentrations at 0.05, 0.1,

0.25, 1.0, and 2.0 (wt) % are displayed in Figure 4.13 part (a), (b), (c), (d), and (e),

respectively. It can be found that the morphology of PEO45-b-PS75-AC60 micelles in

1,4-dioxane/DMF/water system changes from spherical at an initial concentration of 0.05

(wt) %, to a worm-like cylinders at 0.1 (wt) %, to a worm-like cylinders network at 0.25

(wt) %, to a mixed morphology of cylinders and vesicles at 1.0 (wt) %, and finally to vesicles when the initial concentration reaches to 2.0 (wt) %.

Figure 4.13 TEM images of self-assembly morphologies of PEO45-b-PS75-AC60 with different initial molecular concentrations in the 1,4-dioxane/DMF/water system18

The effect of the initial copolymer concentration on the morphology of the aggregation can be explained by two factors. On the one hand, the aggregation number

(Nagg) is a function of the copolymer concentration. Nagg will increases as the water content

increases. Nagg also depends on the copolymer concentration (C), according to Nagg =

2(C/CMC)1/2, where C is the total copolymer concentration, CMC is the critical micelle concentration. On the other hand, the degree of ionization (α) of the carboxylic acid

groups will decreases with increasing the initial molecular concentration. α also depends

1/2 on the copolymer concentration (C), according to α (ka / C) , where C is the total

copolymer concentration, ka is the averaged dissociation constant of each carboxylic acid. 85 Thus micellar morphologies will favor larger aggregates with lower charge density in order to minimize the free energy of micelles. Therefore, changing the initial copolymer concentration can lead to the morphological variation of the aggregates.

4.9.2 Self-assembly Morphologies of PEO45-b-PSn-AC60 at C = 0.25(wt)%

Figure 4.14 TEM images of self-assembly morphologies of PEO45-b-PSn-AC60 with initial molecular concentrations at 0.25(wt)% in the 1,4-dioxane/DMF/water system 19

When the initial copolymer concentration is the same at 0.25 (wt)%, the morphology

of PEO45-b-PSn-AC60 changes with the increasing molecular chain length of the PS tail.

And the TEM images of PEO45-b-PSn-AC60 with n = 48, 75, 115, 144, and 182 are exhibited in Figure 4.14 part (a), (b), (c), (d), and (e), respectively. It is indicated that the

morphology of PEO45-b-PSn-AC60 changes from spherical micelles with n = 48, to

cylinders with n =75, and finally to vesicles with n =115, 114, and 182. The effect of the

PS tail length on the morphology of the aggregates can be explained by two factors. On the

one hand, since the PEO45-b-PSn-AC60 with a longer PS tail length results in the less stretching and thus the favor the morphological transitions for the entropic contribution.

On the other hand, the value of shape aspect ratio (P) can also explain these transitions.

The value of P can be estimated by the ratio between cross-section areas of the head and

tail (σhead/σtail), which was proposed by Israelachvili et al. to determine the self-assembled structures. Previous studies in our group indicated that the increasing molecular chain

length of PS tails leads to the increase of σPS and the decrease of P, which in turn drives the micellar morphological transitions.84 Therefore, variational PS tail length can affect

the morphology of PEO-b-PS-AC60 during aggregation process.

4.9.3 The Critical Water Concentrations in Forming Micelles

Morphological diagram for PEO45-b-PS182-AC60 in 1,4-dioxane/DMF/water system is shown in Figure 4.15. The results of morphological diagram reveals that the SLS

intensity changes with the water concentration for PEO45-b-PS182-AC60 at an initial molecular concentration of 0.1 (wt) %. The onset of the increase of scattering intensity

appears at CCWC, where the self-assembled micelles start to form. The position has been pointed by the arrow, where the slope occurs to suddenly increase as shown in Figure 4.15.

It is also found that the CCWC depends on the molecular weight of PEO-b-PS-AC60. For a

specific polymer concentration, the CCWC decreases with the increase of the PS block length.

Figure 4.15 PEO45-b-PS182-AC60 light scattering intensity versus water content in the 1,4-dioxane/DMF/water system 20

Table 4.3 CCWC (%) of PEO45 -b-PSn-AC60 6

Sample CCWC(%)

PEO45-b-PS48-AC60 11.6

PEO45-b-PS75-AC60 9.6

PEO45-b-PS115-AC60 9.2

PEO45-b-PS144-AC60 8.8

PEO45-b-PS182-AC60 6.9

In this thesis, the variation of CCWC for PEO-b-PSn-AC60 in 1,4-dioxane/DMF/water solution was also investigated by using static light scattering (SLS) technique. The results

are listed in Table 4.3. The observed value of CCWC for PEO45-b-PSn-AC60 decreases from

11.6 to 6.9 (wt) % with the increasing value of n from 48 to 182. It is noted that the the variation of SLS intensity becomes sharper with increasing the PS tail length due to the formation of larger size of aggregates.

CHAPTER V

SUMMARY

In this thesis, a comprehensive study on the synthesis and self-assembly behavior of

the giant molecular shape amphiphiles of end-capped hydrophilic [60]Fullerene (AC60) by

polystyrene-b-poly(ethylene oxide) (PEO-b-PS-AC60) in 1,4-dioxane/DMF solution has been investigated.

The PEO-b-PS block copolymers were synthesized via ARTP technique and the terminal groups of PEO-b-PS molecular chains were modified by using azide groups.

And the azide-terminated PEO-b-PS copolymers successfully synthesized with AC60 via

“click” reaction method, in which AC60 is located at the end of the PS block

(PEO-b-PS-AC60). The “click” reaction ensures a quantitative AC60 functionality at precise

locations of PEO-b-PS-AC60. The functionalized hydrophilic fullerene Hexakis-adducts of

C60 with carboxylic acid units (AC60) were synthesized via Bingel reaction.

The micellar morphologies of PEO-b-PS-AC60 have been systematically investigated in 1,4-dioxane/DMF/water system at room temperature. As revealed by TEM images, these shape amphiphiles exhibit versatile self-assembled micellar morphophogies, which

can be tuning by changing the initial molecular concentration in solution or the chain length of PS blocks. As the initial molecular concentration at 0.05, 0.1 and 1.0, and 2

(wt)%, PEO45-b-PS75-AC60 can self-assemble with the morphology of spheres, worm-like cylinders, mixture of cylinders and vesicles, and pure vesicles, respectively. As the initial concentration is constant at 0.25 (wt)%, the micellar morphologies transform from spheres, to cylinders, and finally to vesicles, with the increasing the molecular chain

length of PS blocks in the PEO45-b-PSn-AC60 molecules.

Finally, CWC of all the as-prepared shape amphiphiles was determined by SLS technique, and the results indicate that the value of CWC is dependent on the molecular

chain length of PS blocks in PEO45-b-PSn-AC60 molecules.

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