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Doctoral Dissertations 1896 - February 2014
1-1-2008
Developing carborane-based functional polymeric architectures. Developing carborane-based functional polymeric architectures.
Yoan C. Simon University of Massachusetts Amherst
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DEVELOPING CARBORANE-BASED FUNCTIONAL POLYMERICARCHITECTURES
A Dissertation Presented
by
YOAN C. SIMON
Submitted to the Graduate School of the
University of Massachusetts Amherst in partial fulfillment
of the requirements for the degree of
DOCTOR OF PHILOSOPHY
September 2008
Department of Polymer Science and Engineering
UMI Number: 3336993
Copyright 2008 by
Simon, Yoan C.
All rights reserved
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DEVELOPING CARBORANE-BASED FUNCTIONAL POLYMERICARCHITECTURES
A Dissertation Presented
by
YOAN C. SIMON
Approved as to style and content by:
E. Bryan Coughlin, Chair
Todd S. Emrick, Member
Anthony D. Dinsmore, Member
Shaw-Ling Hsu, Head
Department of Polymer Science and Engineering
DEVELOPING CARBORANE-BASED FUNCTIONAL POLYMERICARCHITECTURES
A Dissertation Presented
by
YOAN C. SIMON
Approved as to style and content by:
Todd S. Emrick, Member
Anthony D. Dinsmore, Member
Shaw-Ling Hsu, Head
Department of Polymer Science and Engineering
DEDICATION
To my belovedfamily. .
.
ACKNOWLEDGMENTS
First of all, I would like to express my gratitude and appreciation to my advisor.
Prof. E. Bryan Coughlin. Through his encouragement and constant optimism, Bryan has
always found a way to motivate me even in the darkest hours and has helped me
overcome the different hurdles of my PhD. His guidance and excitement for research
have been very inspiring and have encouraged me to pursue a career in academia. I
would also like to acknowledge Prof. Todd Emrick and Prof Anthony Dinsmore for
serving on my committee. 1 have learned a lot through their insightful comments and
constructive criticism. I hope to make good use of their scientific advice in my future
endeavors. Additionally, Todd has been a great mentor, a great basketball teammate and
a knowledgeable wine connoisseur. I would like to thank Tony for his kindness and
willingness to support me in my various scholarship applications. Generally speaking, I
am extremely grateful to all three of my committee members for all their help and
availability. They have been truly instrumental in my search for a postdoctoral position
and I am truly indebted to them.
All faculty members in the PSE department have had a major impact on my
vision of science but I would like to specifically express my gratitude to Prof Harry
Bermudez for his invaluable advice on career and his help in the various aspects of my
relocation to Switzerland. We have collaborated with Prof. Ken Carter on a number of
different projects and I want to emphasize how pleasant it has been working with him.
Also, 1 might have never come to UMass if it was not for Prof Jacques Penelle's help
and I need to thank him warmly for his contribution to my education.
Special thanks go to Dr. Charles Dickinson and Dr. Weiguo Hu for teaching me
about NMR and making my czar duties much easier. Dr. Stephen Eyles, Dr. Greg
Dabkowski and Dr. Sekar Dhanasekaran have all played a very important role in
keeping the facilities up and running, and I am truly appreciative of their work,
knowledge and pleasant conversation. I also need to pay tribute to the administrative
staff for their fantastic, and too often overlooked, job.
Before I go into thanking profusely the members of the Coughlin group who
have been outstanding professionals and amazing friends, I would like to acknowledge
the kindness and compentency of my fellow students and postdocs in the department. I
would particularly like to express my appreciation to all of the people on the sixth floor
who have helped me scientifically, and cheered up my days in our conversations in the
hallway. Same goes for all of my classmates. Additionally, I would like to express my
gratitude to the members of the Carter group who have been an extended branch of my
research group, my "home away from home". Notably, I want to thank Joe and Isaac for
our fruitful collaborations and for their friendship.
All of the Coughlin group members, past and present, have played an
instrumental role in my stay in Western Massachusetts. Firat, Push, Greg, Ramon,
Jeanette, Nui have been among the first to welcome me and help me settle in the group.
I have inherited Raji's space but I have gotten much more from her. Her kindness and
sagacious career advice have been very important to me. Brad has been a great
basketball teammate and a great pal who taught me many things about American pop
culture and sports. It has been a privilege to work alongside Bon-Cheol, Tarik, Chris
and Liz, and to collaborate with three great students from Mainz: Christian, Melanie
vi
and Christine. More generally, I want to thank all ofmy group members for coping with
my questions about how to say this or that in a foreign language, particularly, Shilpi,
Ying and Makoto-san who had to deal with my fascination for eastern languages. Ranga
also helped me in these endeavors. He has been a true inspiration as a very skilled
chemist, a great cook and an awesome friend. It has been a real treat to join the group at
the same time as Rich who has been a role model for me, and with whom I shared great
moments in B666. Whether it was about column chromatography, music, or le Tour de
France, he has always been a very fun person to talk to. I also made three genuine
friends during my stay in the group. I will really miss my endless conversations with
Sergio and Gunjan about science. 1 will also miss their opinionated views about politics,
life and culture, or whatever subject they felt like talking about that day. I already miss
talking to my fellow French compatriot, Gregoire, who has left for warmer horizons. He
has been a piece of France in Western Mass, a real guide for me, a veritable friend.
These tliree muskateers will stay dear to my heart.
I must also thank all of the microbiology crew Dave, Dmitry, Jeff, Kimmie and
Cathy for their support and friendship. My stay here would never have been the same
without them. I want to thank my friends from the dorms and from Europe, and I have a
particular thought for my friend Lionel, who left us too quickly. I also need to express
my attachment to my roommates: Wei, Bing and Bemabe. They were my surrogate
family for one year and I truly cherish the times that we had together.
I want to express my gratitude and affection to all the members of my family
who have always been very supportive and have provided me with the love that I
needed (even when they did not understand why 1 was staying in school for so long). I
vii
want to share this accompHshment with them, as it is also the fruit of their labors in my
upbringing. In spite of the distance, my parents, Lionel and Annie, and my brother
Yannick have always been there for me, and I can never stress how appreciative I am.
Nicky has been more than just a sibling all these years; he has been my accomplice and
my friend. His wit, kindness and brotherhood have empowered me. I would have never
become a researcher if it was not for my father's affection, inspirational curiosity and
his incredible attention to detail. His openmindedness for other people's culture is the
very reason why I came to the United States. I could have never become a researcher,
had I not been nurtured my mother's perseverance and patience. Her love and
encouragement could help me overcome anything.
Finally, I need to reserve an entire paragraph for my love, Emily. Em, it has
been a true honor to share my life with you for the past four years, and I am looking
forward to the many years to come. Meeting you was the best thing that could happen to
me. You have been my best friend and my confident. From delicious meals you
prepared to the mundane tasks of life, you have brightened up every minute of my stay
here. I can never thank you enough for your support, your patience and your love.
viii
ABSTRACT
DEVELOPING CARBORANE-BASED FUNCTIONAL POLYMERICARCHITECTURES
SEPTEMBER 2008
YOAN C. SIMON,
DIPLOME DTNGENIEUR, ECOLE NATIONALE SUPERIEURE DE CHIMIE DEMONTPELLIER, FRANCE
Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST
Directed by: Professor E. Bryan Coughlin
The research presented in this thesis focuses on the development of novel
functional hybrid organic-inorganic architectures containing chemically-tethered
icosohedral carboranes. The motivation behind this work was to understand and
overcome the challenges associated with the incorporation of inorganic boron clusters
into a variety of well-defined polymeric architectures. This task was critical for the
advancement of scientific understanding, as well as the improvement and
implementation of novel hybrid materials towards technological applications. Chapter 1
illustrates some of these potential target applications, and highlights the advantages
associated with the utilization of hybrid materials, in particular those containing boron.
The synthesis of a novel silyl-protected oxanorbomene imide carborane
(SONIC) monomer as well as its copolymerization by ring-opening metathesis
polymerization (ROMP) to obtain amphiphilic diblock copolymers is described in
Chapter 2. The subsequent ftinctionalization and labeling of the polymers, and their
solution behavior have been investigated. Initial biological studies have shown the
ix
incorporation of the carborane-containing polymers in carcinoma cells. These findings
pave the way for future investigations of these polymeric architectures as delivery
agents for boron neutron capture therapy in cancer treatment.
The random copolymerization of SONIC and cyclooctene is reported in Chapter
3. Polymers with varying compositions have been obtained and hydrogenated to afford
polyethylene-like materials. The structural and thermal properties of these materials
have been evaluated and compared to model compounds.
Carboranes have also been introduced into conjugated polyaromatic structures
as side chains. The synthesis of a polyfluorene monomer having two pendant
silylcarborane groups is reported in Chapter 4. The homopolymerization of this
monomer, and its copolymerization with 2,7-dibromo-9,9-di-/7-hexylfluorene by
microwave-assisted nickel(0)-mediated coupling was investigated. The advantage
offered by the presence of bulky silylcarborane groups is described.
Finally, the versatility of carborane-containing polymers is demonstrated
through their utilization as resists for nanoimprint lithography (NIL). A novel
silylcarborane-containing aerylate has been synthesized as described in Chapter 5. The
utilization of only 1 0 wt% of the carborane-containing resist lead to a two-fold decrease
in etch rate. Excellent image transfer was also observed, allowing for the fabrication of
gold interdigitated electrodes. This work provides a new set of tools for the efficacious
implementation of NIL.
X
TABLE OF CONTENTS
Page
ACKNOWLEDGMENTS v
ABSTRACT ix
LIST OF TABLES xiv
LIST OF FIGURES xv
LIST OF SCHEMES xviii
LIST OF ABBREVIATIONS xix
CHAPTER
1 INTRODUCTION 1
1.1 Hybrid Organic-Inorganic Materials: How to Tailor Architectures to
Benefit from Both Counterparts 2
L 1 . 1 Relevance and Synthetic Strategies 2
L 1 .2 Applications of Hybrid Nanocomposites 6
1.1.3 Opportunities for Research 7
1.2 Introduction to Boron, Boron Clusters and Their Applications 8
1.2.1 Carboranes and Boron Clusters 8
1 .2.2 A Brief Overview of Possible Applications 1
4
1 .2.3 A Review of Previous Literature on Carborane Polymers 1
9
1 .3 Outline of the Dissertation 22
1.4 References 23
2 AMPHIPHILIC BLOCK COPOLYMERS FOR BORON NEUTRONCAPTURE THERAPY 28
2.1 Introduction 28
2.2 Route A: Polymerization Using a Protected Amine, Deprotection and
Subsequent Functionalizations 29
2.2.1 Experimental Section 29
2.2.2 Results and Discussion 38
xi
2.3 Route B: Using PEGylated Norbomene Esters 47
2.3.1 Experimental Section 47
2.3.2 Results and Discussion 49
2.4 Conclusions 50
2.5 References 51
3 RING-OPENING METATHESIS COPOLYMERIZATION OFCYCLOOCTENE AND A CARBORANE-CONTAININGOXANORBORNENE 54
3.1 Introduction 54
3 .2 Experimental 55
3.2.1 Materials 55
3.2.2 Instrumentation 56
3.2.3 Synthesis and Spectral Data 57
3.3 Results and Discussion 59
3.3.1 Copolymerization 59
3.3.2 Hydrogenation 62
3.3.3 Thermogravimetric Analysis 64
3.3.4 Wide-Angle X-ray Scattering (WAXS) 66
3.4 Conclusions 70
3.5 References 70
4 SYNTHESIS OF POLYFLUORENES WITH PENDANTSILYLCARBORANES 72
4.1 Introduction 72
4.2 Experimental Section 74
4.2.1 Materials 74
4.2.2 Instrumentation 75
4.2.3 Synthesis and Spectral Data 75
4.3 Results and Discussion 79
4.4 Conclusions 84
4.5 References 85
5 DEVELOPMENT OF SILYLCARBORANE MONOMERS FORLITHOGRAPHY 87
xii
5.1 Introduction 87
5.2 Experimental Section 90
5.2.1 Materials 90
5.2.2 Instrumentation 91
5.2.3 Synthesis and Spectral Data 93
5.3 Results and Discussion 95
5.4 Conclusion 101
5.5 References 102
6 CONCLUSIONS AND RECOMMENDATIONS 1 04
6.1 Dissertation Summary 104
6.2 Future work 107
6.2. 1 Materials for BNCT 1 07
6.2.2 Influence of the silyl-protecting group and utilization in
radiation shielding applications 1 09
6.2.3 Polyfluorenes with carboranes in the backbone 1 1
3
6.2.4 Novel high-boron content resists for EUV lithography and
nanoimprint lithography 115
6.3 Final word 1 1
7
6.4 References 118
APPPENDICES
A BORON NEUTRON CAPTURE THERAPY AND ENHANCEDPERMEABILITY AND RETENTION 1 19
B RADIATION SHIELDING 1 26
BIBLIOGRAPHY 132
xiii
LIST OF TABLES
Table Page
2.1 Tabulated data for the homopolymerization of SONIC 39
2.2 Tabulated data for the copolymerization of SONIC 4 and BONIA by
ROMP 40
3.1 Conditions and results for the polymerization of monomers 4 and COE 62
3.2 Hydrogenation results for the polymers 5 and 12 synthesized in
dichloromethane 64
3.3 Thermogravimetric analysis and differential scanning calorimetry results of
12, H-12, Hand H-14 66
5.1 Imprint and etch profilometry results 98
xiv
LIST OF FIGURES
Figure Page
1.1 Examples of hybrid materials in nature: (a) Diatom: eurkaryotic algae with a
silicate wall (image from Ref. [2]), (b) Enamel and dentin in teeth (image
from Ref. [9]), (c) Seashell nacre (image from Ref [10]) 3
1.2 Design of hybrid organic-inorganic materials from various nanobuilding
blocks (image from Ref. [2]) 4
1.3 Examples of self-assembly from micellar and polymeric structures (image
from Ref [13]) 6
1.4 Examples of metallacarboranes (image from Ref. [25]) 10
1 .5 Synthesis of o-carborane by coupling of acetylene with decaborane 11
1 .6 The three isomers: o-, m-, p-carboranes 12
1.7 Size analogy between carboranes and phenyl rings (image from Ref [25]) 13
1.8 Examples of carriers 14
1.9 Research towards ion exchange membranes radioactive 15
1.10 Representations of unsubstituted [12]mercuracarborand-4 (left) and
[9]mercuracarborand-3 (right) 16
1.11 Illustration of the non-coordinating properties of the monocarbaborane,
formation of a silver complex (image from Ref. [68]) 16
1.12 Hafnium catalyst for alkyne hydrogenation 1
7
1.13 Liquid crystals and self-assembly. An example of possible liquid-crystalline
structure (top), clusters self-assembly (bottom, image from Ref. [69]) 18
1.14 Cycles and rods. Macrocycles containing carboranes (top). B) Illustration of
the staggered morphology observed by transmission electron microscopy
(bottom, image from Ref [71]) 19
1.15 Examples of polymers with carboranes in the backbone 20
1.16 Examples of polymers containing carboranes as pendant groups 21
1.17 Reported examples of quasi-living polymerizations for the design of
macromolecular architectures embedding boron clusters by ATRP 22
XV
2.1 Synthesis of the SONIC monomer 3. TBDMS: /erbutyldimethylsilyl. DIAD:
diisopropylazodicarboxylate 35
2.2 Ring-opening metathesis polymerization and subsequent amine deprotection
syntheses. TBDMS: /er/-Butyldimethylsilyl, TFA: Trifluoroacetic acid 37
2.3 Post-polymerization modifications 38
2.4 GPC chromatograms in THF of poly(SONIC) (solid line, PDI = 1.08, Mn =
37 kg/mol) and poly(SONIC-^-BONIA) (dashed line, Entry 6v, PDI =
1.11 Mn = 65 kg/mol) 41
2.5 Illustration of the appearance of the ammonium peak at 8 ppm 42
2.6 Distribution of sizes measured by dynamic light scattering (left) and atomic
force microscope image (right) of micellar aggregates (Entry 6v) .....43
2.7 'H NMR experiment illustrating the solvents of different polarities 44
2.8 Confocal microscopy image of HEp-2 carcinoma cells after a 22h incubation
period 47
2.9Triblock copolymer formation and labeling 49
2.10 RI (left) and UV (right) GPC chromatograms of 10 and 11 50
3.1 Ring-Opening Metathesis copolymerization of 1 and COE 59
3.2 Illustration of the differences in alternation depending on solvent polarity 60
3.3 Conditions for the hydrogenation of polymer 12 63
3.4 Proton NMR spectrum of H-12(25)-D 63
3.5 Synthesis of model polymers 14 and H-14 to evaluate the influence of the
silylcarborane cage on thermal properties 65
3.6 Wide angle X-ray scattering results for the series of polymers 3 68
3.7 Wide angle X-ray scattering results for the series of polymers H-12 69
4.1 Synthesis strategies to attain monomer 17. i. CH2CI2, TsCl,
pyridine(dropwise); ii. CH2CI2, 0 °C, CBr4, PPha; iii. THF, tBuOK, 2,7-
dibromofluorene; iv. PhH/Et20 (2:1 V:V), tBuOK, 2,7-dibromofluorene 74
4.2 'HNMR ofhomopolymer 18(100) 79
4.3 ^HNMR ofhomopolymer 18(50) ..79
xvi
4.4 Microwave assisted polymerization of 17: (a) homo and (b) copolymerizations
with 2,7dibromo-dihexylfluorene 81
4.5 Gel permeation chromatograms for polymers 18(100) and 18(50) 82
4.6 UV absorption (left) and emission spectra (right) for polymers 18 83
5.1 Synthesis of the silylcarborane aerylate 19 95
5.2 Components of the photopolymer solution (Formulation A) 96
5.3 Determination of etch rates of the control formulation (A) and the modified
(B) resists 97
5.4 Bar chart for visual aid of depth amplification from etch resists A and B 98
5.5 Imprinted and etched device features. On the left are features patterned into
unmodified formulation A (i) and (iii), on the right are the same features
patterned into formulation B, (ii) and (iv) 99
5.6 Patterned gold features, (i) Unresolved interdigitated electrodes using
formulation A as an imprint layer (top) and (ii) using the B resist resolved
patterns are observed (bottom) 100
6.1 Synthetic strategy towards biodegradable BNCT agents 109
6.2 Deprotection of the hydrogenated polySONIC H- 12(1 00). Schematic(top)
and GPC chromatograms (bottom) Ill
6.3 'H NMR spectrum of H-2 1 .* Solvent impurity 112
6.4 Alternative route to obtain deprotected carborane polymers 1 13
6.5 'H NMR spectrum of monomer 20 113
6.6 Synthesis of monomers incorporating carboranes along the backbone.
Sonigashira conditions: (Ph3P)2PdCl2, Cul, EtiNH 114
6.7 'H NMR spectrum of intermediate 22 116
6.8 'H NMR spectrum of intermediate 22 117
A.l Schematic of the elimination of diseased tissues using BNCT 121
A.2 Schematic of the principles of the EPR effect (image from Ref. [8]) 123
B. l Efficiency of blends of '^B and polyethylene and other materials for neutron
shielding (image from Ref [10]) 130
xvii
LIST OF SCHEMES
Scheme Page
3.1 The perfectly alternating structure of polymer 12(50) 60
5.1 Illustration of the use of an etch-resistant imprint layer for pattern
amplification in metallization processes 90
5.2 Comparative schematic illustrating the mechanism by which the patterns are
obtained. The brown layer represents the silicon wafer, the gray layer is
the imprint layer and the top layers are the two respective types of
formulations 101
xviii
LIST OF ABBREVIATIONS
AFM Atomic force microscopy
AIBN Azobisisobutyronitrile
ATRP Atom transfer radical polymerization
BNCT Boron neutron capture therapy
Boc Butoxycarbonyl
BONIA Boc-protected oxanorbomene imide amine
COD Cyclooctadiene
COE Cyclooctene
DAPI 4',6-Diamidino-2-phenylindole
DCM Dichloromethane
DIAD Diisopropylazodicarboxylate
DLS Dynamic light scattering
DMF Dimethylformamide
DMSO Dimethylsulfoxide
DPn Average degree of polymerization
EPR Enhanced permeability and retention
EUV Extreme ultra-violet
FBS Fetal bovine serum
OCR Galactic cosmic rays
GUI Grubbs' third generation catalyst
GPC Gel permeation chromatography
HEMA Hydroxyethylmethacrylate
HEp Human epithelial
ICP Inductively Coupled Plasma
ISS International space station
Mn Number average molecular weight
NBB Nanobuilding blocks
NBD Nitroxybenzoxydiazole
NHC N-heterocyclic carbene
NHS N-hydroxysuccinimide
NMR Nuclear magnetic resonance
PDI Polydispersity index
PEG Polyethylene glycol
PF Polyfluorene
PGMEA Propylene glycol methyl ether acetate
PHEMA Poly(hydroxyethylmethacrylate)
PLED Polymer light emitting diode
PMDS Pentamethyldisilyl
POSS Polyhedral oligomeric silsesquioxane
ppm Parts per million
PVDF Poly(vinyldifluorine)
RBE Radiobiological effectiveness
RIE Reactive ion etching
ROMP Ring-opening metathesis polymerization
XX
SEP Solar energetic particles
SONIC Silylprotected oxanorbomene imide carborane, monomer 4
TBAF Tetra «-butylammonium fluoride
TBDMS Tert-butyldimethylsilyl
TFA Trifluoroacetic acid
TsCl Tosyl chloride
UV I Iltra-violpt
WAXS Wide-angle X-ray scattering
wt% Weight percent
xxi
CHAPTER 1
INTRODUCTION
Materials have always had a pivotal role in the evolution of civilizations. They are
actually so vital for the sake of societies that some of them have been used to classify
certain prehistoric periods, namely the Stone Age, the Bronze Age, and the Iron Age. If
one was, however, to name this modern day era for a type of material, it would certainly
be polymers. Since the term macromolecule was first coined by Staudinger in the early
1920s,[l] the success of commodity plastics and specialty products derived from polymer
chemisty has been staggering. From the car industry to home appliances, polymeric
materials have revolutionized our lifestyles.
That is why, at a time when an increasing number of functional materials are
needed to address the worldwide energy crisis, water decontamination or the challenges
associated with the advent of the communication era, it is only natural to believe that
some of these answers will come from the field of soft-matter chemistry. Nevertheless, it
would be pretentious to think that these challenges can be solved single-handedly by
seeking immediate results. This quest for new functional materials needs to be global and
thorough efforts to explore novel materials, sometimes, simply for the sake of acquiring
new scientific knowledge upon which major advances could be built. This foreword is
meant to illustrate the approach that was taken here, where novel hybrid inorganic-
organic materials were designed with a fundamental perspective but whose potential field
of applications is remarkably wide. The present chapter describes the properties and
1
advantages of hybrid inorganic-organic materials as well as some of the particular
characteristic of boron and boron clusters.
1.1 Hybrid Organic-Inorganic Materials: How to Tailor Architectures to Benefit
from Both Counterparts.
1.1.1 Relevance and Synthetic Strategies
From bones to seashells to teeth, nature displays a multitude of examples of
hybrid materials in which an organic and an inorganic part are synergistically united to
assume a specific function. Consequently, synthetic hybrid materials containing an
organic and an inorganic component have been contemplated as potential candidates for
fiinctional materials. [2] The possibility to benefit from the advantageous conjunction of
both counterparts is not foreign to the development of this class of materials.
Traditionally, the organic part provides the modularity and the flexibility to these
materials, whereas the inorganic part confers the robustness. However, the inorganic part
offers much more than mere reinforcement. It offers the possibility to explore areas such
as magnetism, optical quantization effects or electroactivity.[3-7]
In order to put the present study in context and understand its implications, it is
important to define the different types of hybrid materials and to highlight the diverse
approaches to obtain these. Sanchez et a/. [2,8] have reviewed the design of organic-
inorganic nanocomposites from various nanobuilding blocks (Figure 1 .2). There, hybrids
are classified into two categories Class I and Class II, that can be obtained via four types
of synthetic strategies, paths A through D.
2
Figure 1.1 Examples of hybrid materials in nature: (a) Diatom: eurkaryotic algae
with a silicate wall (image from Ref. [2]), (b) Enamel and dentin in teeth (image
from Ref. [9]), (c) Seashell nacre (image from Ref [10])
Class I illustrates a category of materials where neither covalent bond nor iono-
covalent bond (highly polarized bond that has intermediate properties between a classical
covalent bond and a pure ionic bond) exist between the two entities forming the
composite. In these hybrids, the different components of the material are held together by
weak interactions such as dipole-dipole interactions or Van der Waals forces. Class II
refers to covalently or iono-covalently attached amalgamates, the main focus of this
study.
Path A encompasses soft chemistry methodologies such as sol-gel chemistry or
the utilization of multifunctional precursors and hydrothermal synthesis. These
methodologies, while very interesting for their low cost and ease of implementation, offer
relatively limited control in terms of directed assembly. Path B relies on the utilization of
nanobuiliding blocks (NBB). As indicated by their name, NBB are inorganic clusters
upon which bigger architectures can be built. They can be used in assembly techniques as
nanometric bricks, in which case the organic component can be viewed as the mortar
keeping the inorganic components together, or in dispersive routes where they are
distributed in an organic matrix. Path C is the so-called self-assembly or bottom up
approach, which combines elements of the two previous routes, but whose main objective
3
resides in the controlled assembly of the different parts via the use of templates
(surfactants, block copolymers, etc.) and/or specific interactions. Finally, Path D is an
integrative approach which combines these nanometer-scale directed assemblies with
micron-scale shape control (colloidal masks, interfacial assembly) to obtain hierarchical
structures.
Figure 1.2 Design of hybrid organic-inorganic materials from various nanobuilding
blocks (image from Ref.[2]).
The necessity to investigate self-assembled structures, i.e. structures obtained
from the bottom-up approach, becomes apparent when observing natural systems. Rather
than utilizing extremely complex functionalities, nature has opted for a much more
elegant route,[l 1] wherein a limited number of building blocks are used and assembled in
particular conformations. Therefore, the specific functionality does not arise from the
4
intricacy of tiie building blocks themselves, but rather from the complexity of their
arrangement. The use of inorganic NBB in an organic matrix to direct self-assembly
results from a simple observation. Reproducing, with high fidelity, controlled structures
over several orders of magnitude lengthwise when the only tool at hand is the organic C-
C bond (~ 1.5 A) is no easy task. For that very reason, embedding, within an organic
matrix, well-defmed inorganic structures of larger size than the C-C linkage is an
appealing tactic. Conversely, it is extremely hard to gain control over monolithic
inorganic architectures. Their fabrication process (crystallization, condensation, etc) does
not allow an accurate rendition over vast domains. That is why an intermediate strategy
involving nanobuilding blocks comprising a reactive organic end bound to an inorganic
core of uniform size is highly valued. Other work has demonstrated the use of organic
scaffolds (block copolymers, vesicles, liposomes) to direct the assembly of inorganic
materials. [12]
5
I.aAM
Figure 1.3 Examples of self-assembly from micellar and polymeric structures (image
from Ref. [131).
1.1.2 Applications of Hybrid Nanocomposites
The utilization of hybrid materials is not a novel idea; the paint and polymer
industries have used them for decades in the form of pigments and fillers. [8] However,
with the growing desire to impart functionalities in novel materials, the interest in
nanocomposites has grown unabated. Aside for the evident advantage of benefiting from
the inorganic and organic components, the success of nanocomposites is a direct result of
their geometry. By decreasing the size of the inorganic part, the surface to volume ratio
increases. In doing so, the amount of interface between the two constituents is increased
dramatically leading to novel properties. The best example of this success of this
miniaturization effect is quantum dots. By reducing the size of the inorganic nanocrystals,
the energy levels become discretize, leading to unique electronic and optical properties
directly correlated to the size of the inorganic component. [14] However, in order for
quantum dots to have a practical application, they need to benefit from the dispersing
6
power of organic ligands. In particular, there has been a lot of interest in the utilization of
polymers, by grafting from or grafting to approaches, to achieve this goal. [15]
The second and maybe more obvious application of hybrid materials is
mechanical reinforcement. A variety of nanoscale inorganic fillers have been utilized to
toughen polymers from nanoparticles, to nanoclay or metal-oxide nanoclusters.[3]
Additionally, the modes of incorporation of these inorganic fillers has been incredibly
varied from very conventional mixing and methods to exfoliation methods to the use of
supercritical carbon dioxide to infuse polymeric matrices. Recent work by Gauckler et al.
has illustrated the possibility of mimicking biomaterials to obtain tough yet ductile
polymeric hybrids. [16] This work exemplifies the power of utilizing hybrid
nanocomposites to master the mechanical properties of materials.
The functions presented in this section are by no means an exhaustive inventory.
In fact, the list of applications already on the market is impressive: high-performance
coatings, biomaterials, electo- and optically-active materials, high-temperature seals, etc.
These examples illustrate the advantage of hybrid systems and the necessity for further
fundamental studies.
1.1.3 Opportunities for Research
Hybrid materials are clearly interesting and warrant further investigation. The
previous two subsections (1.1.1. and 1.1.2.) have highlighted the various pathways to
obtain organic-inorganic nanocomposites and the applied motivations. However, rather
than focusing on a specific application and constraining one's horizons, identifying a type
of inorganic material that has great potential, but whose utilization in hybrid polymeric
7
systems has been thus far very limited, promises to be far more interesting. To facihtate
this investigation, it is essential to have systems that are easily characterized.
Consequently, path B (Figure 1.2.) is a very attractive tactic, in that it offers the
possibility to utilize well-defined NBB with no distribution of size and with limited
reactivity. Additionally, the best way to control the incorporation of these NBB is
through their covalent attachment to a reactive handle {class IT). The strategy adopted
here revolves around the covalent tethering of boron hydride clusters to polymerizable
units with the view to acquire new functional polymeric architectures.
1.2 Introduction to Boron, Boron Clusters and Their Applications
1.2.1 Carboranes and Boron Clusters
1.2.1.1 Boron
Boron is a fascinating element that owes its name to the first ore discovered:
borax from the Arabic buraq, meaning white. Having many interesting features, it is
surprisingly one of the simplest elements in the periodic table. Its atomic number is 5
leading to the electron shell configuration Is 2s 2p. It has a standard atomic mass of
10.81 1 g.mol"' due to the presence of two isotopes "B (80.22%) and '^B (19.78%). It is
part of the second period and belongs to Group III of Mendeleyev's classification. The
only non-metal of its group, boron is part of the metalloid category along with Si, Ge, As,
Sb, Te and Po.
Borax ore, also referred to as fincal, (Na2B407- IOH2O) coexists with other types
of boron minerals like kemite, ulexite or colemanite.[17] All of the above are hydrated
versions of boric acid originating from former volcanic activity. The main extraction sites
8
are located in California, Nevada, Turkey, Argentina and Russia. The abundance of boron
in the earth crust is estimated at approximately 1 0 ppm.
The discovery of the element is attributed to Sir Humphry Davy (UK), Joseph-
Louis Gay-Lussac (Fr) and Louis Jacques Thenard (Fr) in 1808, and its subsequent
purification to Henri Moissan (Fr) in 1892. Boron appears under different forms as a
"pure'' material (P-rhombohedral, a-tetragonal, etc), as borates (tincal, rasorite, etc),
borides (B4C, Mg2B, etc), boron halides (BF3, BCI4") and boranes. In this study, boron
clusters, boron hydrides and boranes will be used interchangeably.
1.2.L2 Nomenclature of Boranes and Carboranes.
Based on the initial work by Alfred Stock et <3/.[18] in the early 1910's, the
chemistry of boron hydrides (BpHm) has spread remarkably and has become a science of
its ovm, at the border between organic and inorganic chemistry. Given its success and
uniqueness, boron cluster chemistry soon established its own philosophy and
nomenclature. This revolutionary remodeling led to the award of the Nobel Prize to
William N. Lipscomb in 1976 for the "studies of boranes which have illuminated
problems of chemical bonding". [19]
The borane continuum (BnHm) can be classified in 5 general subcategories: [17,20]
• c/o5o-boranes (from the Greek cage) comprise a series of fully closed
polyhedra formed of deltahedral faces.
• «/Jo-boranes (from the Latin nest) designate non-closed structures
resulting from the removal of one vertex from a corresponding closo
architecture.
9
• arachno-borams (from Greek spider's web) emanate from the withdrawal
of one of the vertices contiguous to the open face in a nido structure.
• hypho-horanQS (from Greek net) characterize clusters with the greatest
aperture proceeding from the same iterative vertex removal process.
• conjuncto-boranes (from Latin joining) results from any condensation of
the abovementioned entities.
These geometries can be typically predicted by Wade-Mingos's rule,[21,22] an
extension of molecular orbital theory. Carboranes, metallaboranes and metallocarboranes
are spin-offs of boron hydride chemistry. [23,24]
• C.CH •BH. B R=We. &S)*»
cr
M = Ta.Nb f.f = Fe.C5c
Figure 1.4 Examples of metallacarboranes (image from Ref. [25]).
1.2.1.3 Properties of Closo-Carboranes
In addition to their proximity in the periodic table, carbon and boron share many
common features. [26] For instance, boron hydrides or boranes are the analogs of
10
hydrocarbons or alkanes. Certainly, because of its ubiquity in living organisms and the
simplicity of its bonding patterns, carbon has overshadowed its "next-case" neighbor.
Beyond the intrinsic capacity of boron to self-catenate, carboranes (discovered in
1959 by R.E. Williams and CD. Good)[27,28] illustrate this remarkable asset of boron to
covalently bind to carbon. This feature allows carboranes to be integrated into virtually
any organic systems allowing the two chemistries to merge. Carboranes have a
nomenclature akin to their parent boranes. Consequently, several categories and sizes
coexist. In the present survey, only the dicarba-c/o5o-dodecaboranes (C2B10H12) will be
of interest and discussed. Therefore, any allusion to carboranes will be restricted to this
framework unless mentioned otherwise.
Among the 12-vertex carboranes, there are three types of isomers: ortho, o or 1,2;
meta, m. or 1,7; para, p or 1,12. All three present an icosohedral geometry that is shown
Figure 1.6. The synthesis of o-carborane (Figure 1.5), first reported in 1963 by two
groups, [29-32] results from the condensation of acetylene with decaborane in the
presence of ligands (generally acetonitrile, tertiary amine or thioether).[33-35]
2CH3CN + H = H ^ ^ ^ CH3CN + H2
oBH• CH
Figure 1.5 Synthesis of o-carborane by coupling of acetylene with decaborane
11
Figure 1.6 The three isomers: o-, m-, p-carboranes.
Functionalized acetylenes can be used during the synthesis so long as the groups
are not nucleophile. The m- and p-carborane are obtained successive high temperature
isomerizations whose mechanism was explored by Lipscomb and then refined by
Parisini. [36-39] These isomerizations occur under inert atmosphere between 400 and
500°C for the meta and 600-700°C for the para derivative (Figure 1.6). [40]
Even if chemists have crafted numerous ways to functionalize them, [4 1-54]
closo-carboranes display a relative chemical inertness in addition to a phenomenal
resistance to high temperatures. This sturdiness emerges from the nature of its core
component: boron. With more valence orbitals (3) than valence electrons (4), boron is
present in conventional 2e-2c bonds (e: electrons, c: centers) and non-classic 2e-3c
bonds.
In the latter systems, three atoms each provide one orbital to produce one bonding
and two non-bonding molecular orbitals. Only two electrons are therefore shared between
the three centers.[55-57] This particularity gives rise to the deltahedral (triangular)
geometry, characteristic of borane chemistry. This thought-provoking binding pattern
allows for the unique superaromaticity of carboranes. [58-60] that makes them the 3-D
equivalents of benzene. Their size (5.25A for the diameter of a carborane vs 4.72A for
benzene) and reactivity (electrophilic substitutions) are surprisingly similar. [61] As
12
illustrated by their electron withdrawing character (ortho » meta >para),[62] carboranes
have relatively low pKa at the C positions {pKa{ortho) = 22.0, pKa{mefa) = 25.6,
pKaipara) = 26.8)[59] that enable functionalization through deprotonation by organo
alkali reagents.
Figure 1.7 Size analogy between carboranes and phenyl rings (image from Ref. [25])
Their melting point ranges between 294-296°C for the ortho form. The meta form
is the intermediately thermally stable since its m.p. is around 272-273°C and the para
form, despite its being the thermodynamic isomer, has the lowest fusion temperature 259-
26rC.[63]
In order to understand how carboranes are going to behave in a polymeric matrix,
it is important to understand how carboranes assemble. Density is a property that reflects
this packing. The density of crystalline carborane is 0.999 g/cm at 25°C.[63] Like other
globular structures, carborane are classified as plastically crystalline. [64] This
denomination signifies that they are similar to crystals in the sense that their center of
mass organizes in a crystalline fashion. However, there is a temperature above which the
molecules can revolve about this barycenter, the glass transition temperature (by analogy
with plastics). Carlorimetric studies show that o-carborane undergoes a first order
transition at 273.6 K and a second order transition at 160 K. More importantly, o-
carborane presents a glass transition temperature situated at 120 K which underlines a
13
certain useful plasticity at low temperatures. These features will most definitely be useful
as we study the possible crystallization behavior of carborane in our polymers.
1.2.2 A Brief Overview of Possible Applications
Carboranes find applications in a multitude of fields. [25,65-66] For the sake of
brevity, the following is a non-exhaustive itemized list of applications. References are
provided should the reader desire to learn more about a particular item:
• Boron clusters in medicine
Boron clusters have been used in boron neutron capture therapy of cancer (see
Chapter 2). The following examples illustrate two of the many systems that have been
envisioned for the delivery of boron agents to tumor cells. [25]
X = NMe3.Se
Figure 1.8 Examples of carriers
• Metal ion extraction
The example below illustrate a possible utilization of cobalt dicarboUide for
nuclear waste treatment. The highly stable cobalt dicarbollide ion allows for the exchange
of sodium ions with radioactive cesium ions. This separation is of high importance in
14
terms of waste treatment. In a spent fuel rod used to power a nuclear plant, the waste is
chiefly composed of uranium and plutonium (over 95%) and the latter can be isolated
from the other radioactive elements, mostly '^^Cs and ^*^Sr, by acid treatment. However,
storage still represents an issue that has yet to be addressed. On the other hand having a
method that permits the recovery of cesium in a suitable form can serve in applications
such as medical supplies and food sterilization. [65]
Figure 1.9 Research towards ion exchange membranes radioactive
• Anti-crown reagent
Much like crown ethers are known for their ability to specifically separate cations.
Hawthorne et al. have developed a variety of mercury bridged compounds susceptible of
separating anions and particularly halogen atoms according to their size. [25,67]
15
Figure 1.10 Representations of unsubstituted [12]mercuracarborand-4 (left) and
[9]mercuracarborand-3 (right)
• "Almost" non coordinating ions[68]
Due to their extremes stability, carborane anions (here the monocarbaborane)
display amazing non coordinating properties that are particularly useful in the synthesis
of superacids and various organometallic architectures.
« f
Figure 1.11 Illustration of the non-coordinating properties of the monocarbaborane,
formation of a silver complex (image from Ref. [68])
• Homogeneous catalysis
A wide variety of catalysts have been developed using boron cluster chemistry
including rhodium, hafnium, titanium or zirconium catalysts for hydrogenation,
hydrosilation, hydroformylation and olefin polymerization. [25]
16
Figure 1.12 Hafnium catalyst for alkyne hydrogenation
• Liquid crystals and self assembly
Liquid crystalline materials have been developed using carboranes with the view
of diversifying the core molecules that chemists could use as well as benefiting from the
extreme stability of carboranes. Various studies have shown the utilization of boron
clusters for self-assembly processes. Whether it is through the particularities of the B-H
bonding or just using molecular interactions, carborane systems exhibit astounding self-
assembly properties that could, coupled with polymers, yield compelling
structures. [25,69-70]
17
• c
O BH
Figure 1.13 Liquid crystals and self-assembly. An example of possible liquid-
crystalline structure (top), clusters self-assembly (bottom, image from Ref. [69])
• Chains/Rings/Rods
A vast array of molecular rods, cycles and other morphologies have been
synthesized using the various possibilities offered by the different isomers (ortho, meta
and para). In addition, transmission electron microscopy studies of carboranes confined
inside the walls of carbon nanotubes have revealed an interesting staggered
morphology . [25,7 1]
18
Figure 1.14 Cycles and rods. Macrocycles containing carboranes (top). B)
Illustration of the staggered morphology observed by transmission electron
microscopy (bottom, image from Ref. [71])
1.2.3 A Review of Previous Literature on Carborane Polymers.
Due to their very good thermal stability, carboranes have been mostly used to
enhance thermomechanical behaviors of polymers. Though they have been incorporated
as plain fillers, most of the attention revolves around their utilization in applications
where they are covalently bound to a monomeric unit either in the backbone or as a side-
group. [52,65,66,73-86] Consequently, the present survey will only include examples of
main-chain and pendant group carborane polymers.
Examples of carborane polymers and their formulae are shown below (Figure
1.14 and 1.15). They are classified according to the position of the carborane (backbone
or side-group). We acknowledge that this list is far from being complete, but it illustrates
the most relevant polymers in respect to this work.
19
Figure 1.15 Examples of polymers with carboranes in the backbone
Main-chain carborane polymers have drawn the attention of polymer scientists
due to initial results showing that thermal resistance was somewhat greater than their
side-chain counterparts. As a consequence, they represent the greater part of the work in
this field. However, with this route, one has to resign to using step-growth polymerization
techniques. The latter does not offer as much control of architectures as chain
polymerization. In actuality, both methods can and have been employed for pendant-
carborane polymers. In our search for tailored architectures, we will mostly focus on
chain polymerization techniques except in Chapter 4.
20
Figure 1.16 Examples of polymers containing carboranes as pendant groups.
At the time when this study begun, there had been only two reports of well-
defined macromolecular architectures incorporating carboranes in the literature. Adronov
et al. had reported their incorporation in dendritic structures as well as the polymerization
of an acrylate carborane monomer by atom-transfer radical polymerization
(ATRP). [52,87] This work is also pivotal in that it is one of the first examples of the
utilization of carboranes for properties other than mere thermomechanical reinforcement.
Unpublished work from the doctoral thesis by Man had also emphasized the versatility of
carborane-based polymers, by using them as ion exchange membranes. [65] During the
course of this work, the number of studies dealing with the incorporation of carboranes in
controlled architectures for advanced applications has increased dramatically. These
recent advances will be discussed in the following chapters, alongside the findings of the
present work.
21
Figure 1.17 Reported examples of quasi-living polymerizations for the design of
macromolecular architectures embedding boron clusters by ATRP.
1.3 Outline of the Dissertation
In this introductory chapter, we have reviewed the basic philosophy of hybrid
polymers and particularly, the incorporation of inorganic structures in polymeric
materials, and we have discussed carborane chemistry from its core component to its
applications and incorporation in macromolecules. Based on this knowledge, this thesis
will focus on the incorporation of carborane clusters so as to obtain carborane-based
functional polymeric architectures. In chapter 2, the possibility to design novel
amphiphilic diblock copolymers containing carboranes via ring-opening metathesis
polymerization is explored. There, the synthesis and polymerization of a novel
oxanorbornene is described as well as some data about solution behavior and cytotoxicity
of the polymer. Chapter 3 reports the copolymerization of that oxanorbornene polymer
with cyclooctene and dicusses some of the structural and morphological properties of the
obtained polymers. Dibromofluorenes with pendant silylcarborane moieties are
synthesized in chapter 4. Their homo- and copolymerization with dihexylfluorene using
nickel-mediated polymerization is investigated. Chapter 5 highlights the possibility to
utilize well-defined boron clusters for applications in lithographic applications.
Particularly, their utilization in nanoimprint lithography is depicted. Finally, chapter 6
22
illustrates potential research avenues based on some of the preliminary findings of this
work.
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[79] D. A. Brown, H. M. Colquhoun, J. A. Daniels, J. A. H. Macbride, I. R.
Stephenson, K. Wade, Journal ofMaterials Chemistry 1992, 2, 793.
[80] S. Packirisamy, D. Schwam, M. H. Litt, Journal of Materials Science 1995, 30,
308.
[81] H. M. Colquhoun, P. L. Herbertson, K. Wade, I. Baxter, D. J. Williams,
Macromolecules 1998, 31, 1694.
[82] M. A. Fox, K. Wade, Journal ofMaterials Chemistry 2002, 12, 1301.
[83] R. Ma, Y. Bando, Chemical Physics Letters 2002, 364, 314.
[84] M. K. Kolel-Veetil, H. W. Beckham, T. M. Keller, Chemistry ofMaterials 2004,
76,3162.
[85] M. Patel, A. Swain, J. L. Cunningham, J. J. Murphy, R. S. Maxwell, S. C. Chinn,
Abstracts of Papers, 230th ACS National Meeting, Washington, DC, United
States, Aug. 28-Sept. 1, 2005 2005, MSE.
[86] D. T. Welna, J. D. Bender, X. Wei, L. G. Sneddon, H. R. Allcock, Advanced
Materials (Weinheim, Germany) 2005, 17, 859.
[87] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Journal of the
American Chemical Society 2005, 727, 12081.
27
CHAPTER 2
AMPHIPHILIC BLOCK COPOLYMERS FOR BORON NEUTRON CAPTURE
THERAPY
2.1 Introduction
As pointed out in the previous chapter, there has been a growing interest in
incorporating carboranes into tailored macromolecular structures by means of Hving or
quasi-Hving polymerizations. [1-3] This regain of interest stems from the rising awareness
that carborane-based macromolecules can span a gamut of applications, for example:
non-linear optical materials, [4-9] precursors for ceramics,[10-13] boron neutron capture
therapy of cancer (BNCT),[14,15] etc. The work reported in this chapter is particularly
relevant to the latter application and a brief explanation of the principles governing
BNCT and some basics about polymer drug delivery can be found in Appendix A.
Adronov was the first to report the direct incorporation of carborane moieties in well-
defined macromolecules (PDI < 1.2) by controlled radical polymerization, and by
sequential dendrimer synthesis. [2, 16- 18] In their controlled radical experiment, they have
demonstrated the possibility of incorporating carboranes in polymers of narrow
polydispersity. However, loss of control upon attempted formation of the second block
hampered the formation of well-defined amphiphilic structures. [2, 16] Seminal work by
Sneddon and coworkers on precursors for boron-containing ceramics have highlighted
the use of ring-opening metathesis polymerization (ROMP) to obtain high-boron content
polymers that can undergo pyrolysis to form a boron carbide/carbon network. [1,1 9-22]
Building upon this work, Malenfant et al. have recently shown how ROMP can be used
28
for the synthesis of boron-containing diblock copolymers and their subsequent
transformation into nano-ordered ceramics. [3]
In the following chapter, the synthesis of a boron-containing monomer based on
an oxonorbomene functionalized o-carborane and its subsequent ring-opening metathesis
polymerization to obtain low-polydispersity (PDI < 1.1) high-molecular weight
carborane-based polymers is described. The formation of amphiphilic block copolymers
is demonstrated via sequential monomer addition, followed by deprotection of the second
block to generate the amphiphilic copolymers. Initial solution behavior studies by
dynamic light scattering (DLS) and atomic force microscopy (AFM) are also discussed.
Once the diblock was characterized, post-polymerization modifications on the pendant
amine are explored and subsequent cell studies are reported. Additionally, an alternative
route using norbornene esters with polyethylene glycol (PEG) chains is also investigated.
These copolymers are unique examples of a narrow polydispersity amphiphilic
architectures incorporating carboranes that paves the way for the exploration of potential
applications ranging from nanoscopic templates in thin film applications, [23] to boron
neutron capture therapy for the treatment of cancer. [14,24]
2.2 Route A: Polymerization Using a Protected Amine, Deprotection and
Subsequent Functionalizations
2.2.1 Experimental Section
2.2.1.1 Materials.
All organic reactants and reagents were purchased from Aldrich Chemical Co.
and used as received unless specified otherwise. Anhydrous benzene and diethyl ether
29
were dried over sodium with benzophenone as an indicator. Dichloromethane (DCM)
was obtained through Fisher, distilled over calcium hydride and degassed with freeze-
pump-thaw cycles. 0-carborane was supplied by KatChem.[25] Grubbs' third generation
catalyst was synthesized according to the literature procedure and stored under nitrogen
atmosphere. [26]
2.2.1.2 Instrumentation.
Gel permeation chromatography (GPC) measurements for the homopolymers 4
were performed in tetrahydrofuran (THF) at 1.0 mL/min using a Knauer K-501 Pump
with a K-2301 refractive index detector and a K-2600 UV detector, and a column bank
consisting of two Polymer Labs PLGel Mixed D columns at 40°C. All other
measurements were performed using a similar system with a column banks consisiting of
three Polymer Labs PLGel Mixed D columns at 40°C. Molecular weights are reported
relative to polystyrene standards.
NMR, "B NMR and '^C NMR were recorded at 300 MHz, 128 MHz and 100
MHz respectively on a Bruker NMR spectrometer at room temperature in deuterated
chloroform. The individual NMR spectral assignments do not list the carborane B-H
resonances. Due to the quadrupolar nature of boron, the resonances for the 10 B-H are
observed as broad multiplets (6 (ppm) = 3.20-1.01). The integration of these multiplets
accounts for 10 H. Melting points were measured with a melting point apparatus
Electrochemical Mel-Temp in a capillary tube.
Dynamic Light Scattering (DLS) was performed in 1 8 mQ water. The sample was
prepared as followed; 30 mg of deprotected polymer were first dissolved in dimethyl
30
sulfoxide DMSO (30mL). To this solution, 30 mL of 18 mQ water were added using a
syringe pump at a rate of 1 5 mL/h. The solution was then transferred into a dialysis bag
and dialyzed against 2 L of 18 mQ. water for 2 days, renewing the water three times along
the process. All experiments were performed at room temperature using an ALV unit
equipped with an ALV/SP-125 precision goniometer (ALV-Laser Vertriebsgessellschaft
m.b.h.), an Innova 70 argon laser (Xq = 514.5 nm, max. power 3 W. Coherent Inc.)
operated at 300 mW, and a photomultiplier detector (Thorn EMI Electron Tubes). Signal
from the detector was processed by an ALV 5000 Multiple Tau Digital Correlator board
and associated software. The solutions were prefiltered through PVDF filters of 0.25-mm
pore size. The experiment was performed using a polymer (PDI = 1.10, Mn = 30.500
g/mol with complete deprotection as monitored by 'H NMR, molar ratio
(S0NlC/B0NlA)-2/l).
The investigation of the shape and topography of the micelles was performed
using Atomic forceMicroscopy (Digital Instrument, Dimension TM 3100) using
Nanoscope ® Ilia, version5.12r3 software, in tapping mode.
For the cell studies, monolayers of HEp-2 human laryngeal carcinoma cells were
grown to approximately 80% confluency in 10% fetal bovine serum (FBS, Atlanta,
Biologicals, Lawrenceville, GA) and imemzo (Richter's improved MEM insulin, Irvino
Scientific, Santa, Ana CA). The media was then removed and 195 |j.L of the dialyzed
solution of polymer was added to 250 \xL 10% FBS/Cyclohexamide (Cyclohexamide
overlay medium base, Cambrex, Walkersville, MD) and put on cells. [27] The cells were
incubated for about 22 h and were then washed three times with sterile phosphate buffer
31
solution. The washed cells were then mounted with DAPI mounting medium. The
viability of the cells was measured using a Trypan blue exclusion test.
2.2.1.3 Synthesis and Spectral Data
Preparation of the l-(tert-butyl-dimethylsilanyl)-l,2-dicarba-closo-
dodecaborane(12) 2. Compound 2 was prepared using a slight modification of a
Hawthorne procedure. [28] In a round-bottom 500 mL Schlenk flask capped with a rubber
septum and equipped with a magnetic stir bar. Under a nitrogen atmosphere, sublimed o-
carborane 1 (15 g, 104 mmol, 1 eq) in a 2:1 mixture of benzene/ether (40 mL/20 mL)
was deprotonated using n-butyl-lithium (78 mL, nBuLi 1.6 M, 125 mmol, 1.2 eq) at 0 °C
dropwise. After 45 min, t-butyldimethylsilyl (TBDMS) chloride (TBDMS-Cl, 20.4 g,
135 mmol, 1.3 eq) in 30 mL of a benzene/ether (2:1 V:V) solution was added. After the
addition of the silyl compound, the stopcock was closed and the septum removed. A
rubber septum-capped condenser was fitted on top of the reaction flask with a nitrogen
overpressure. The stopcock was then opened and the solution was brought to reflux. After
refluxing overnight, the solution was quenched with a few drops of methanol to prevent
exothermic reaction upon addition of 40 mL of water. The layers were separated in a
separatory funnel and the aqueous solution was extracted with additional Et20 (2 x 40
mL). The combined extracts were dried over MgS04 and concentrated in vacuo to give a
slightly yellowish solid that was then distilled (85 °C, 20 mTorrs) to yield 24.7 g of a
white powder, silyl-o-carborane 2 (92% yield). Also, there was no trace of remaining o-
carborane. To verify the absence of any starting material in the final product, a careful
sweep of temperatures, from 20°C up to 85 °C, at constant pressure (10 mTorrs) was
32
performed with no apparent condensation of any solid prior to the final temperature.
Conversely, keeping a constant temperature (85 °C) and carefully decreasing the pressure
in the system, from 1 atm down to 10 mTorrs, no remaining o-carborane condensation
was noted. High Resolution MS (EI+): m/z calcd 258.2758, found 258.4915; 'H NMR
(CDCI3): 6 (ppm) = 3.46 (s, IH, CH), 1.03 (s, 9H, CCH3), 0.26 (s, 6H, SiCHs); '^C NMR
(CDCI3): 5 (ppm) = 66.02, 60.25, 26.98, 19.32, -4.56 ; "B {'H} NMR (CDCI3): 6 (ppm)
= 0.28 (IB), -1.80 (IB), -7.03 (2B), -10.75 (2B), -13.28 (2B); mp = 61°C.
Preparation of the [2-(tert-butyl-dimethyl-silanyl)-l,2-dicarba-closo-
dodecaboran(12)-l-yl]-propan-l-ol 3. Compound 3 was prepared using a slight
modification of a Hawthorne procedure in a setup comparable to the one used for 2. [28]
Under a nitrogen atmosphere, compound 1 (15 g, 58 mmol, 1 eq) in benzene/ether (2:1
V:V) was deprotonated using dropwise addition of nBuLi (43.5 mL of a 1.6 M solution,
69.6 mmol, 1.2 eq) at 0°C. Trimethylene oxide (4.9 mL, 75.4 mmol, 1.3 eq) was added
after 45 min and the solution turned light yellow. The solution was refluxed overnight
and turned orange. The reaction was quenched with a few drops of methanol and 40 mL
of water. The layers were separated in a separatory funnel and the aqueous solution was
extracted with additional Et20 (2 x 40 mL). The combined extracts were dried over
MgS04 and concentrated in vacuo to give a sticky solid. The paste was then
recrystallized from boiling hexanes followed by cooling at -4 °C. The thin fibrous white
crystals were then filtered over sintered glass to obtain 15.6 g of carboranylpropanol 3
(85% yield). High Resolution MS (EI+): m/z calcd 315.3160, found 315.3155; 'H NMR
(CDCI3): 5 (ppm) = 3.69 (q, 2H, C//2OH), 2.34 (qu, 2H, C//2CH2OH), 1.78 (t, 2H, CH2-
Cage), 1.06 (s, 9H, CCH3), 0.31 (s, 6H, SiCH3); ); ^^C NMR (CDCI3): 5 (ppm) == 81.28,
33
76.47, 61.55, 35.51, 34.68, 27.80, 20.35, -2.48; "B {'H} NMR (CDCI3): 6 (ppm) = 0.21
(IB), -3.95 (IB), -7.33 (2B), -10.31 (6B); mp = 83°C.
Preparation of (lR,2R,6S,7S)-4-{3-[2-(tert-Butyl-dimethylsilanyl)-l,2-clicarba-
closo-dodecaboran( 1 2)- 1 -yl]propy 1 } - 1 0-oxa-4-aza-tricyclo[5.2.1.0^-^]dec-8-ene-3,5-dione
referred to as Silyl-protected OxoNorbornene Imide Carborane (SONIC) 4. In a dry 500
mL flask, exo-7-oxonorbomene imide (7.6 g, 46 mmol, 1 eq), [2-(tert-butyl-dimethyl-
silanyl)-l,2-dicarba-closo-dodecaboran(12)-l-yl]-propan-l-ol 3 (16 g, 51 mmol. 1.1 eq)
and triphenylphosphine (13.3 g, 51 mmol, 1.1 eq) were dissolved upon stirring in 300 mL
of freshly distilled dry tetrahydrofuran (THF). The flask was kept under nitrogen pressure
and cooled down to 0°C with an ice bath. After 5 minutes, diisopropylazodicarboxylate
(DIAD) (3.2 mL, 16.26 mmol, 1.1 eq) was added and the solution turned yellow. The
reaction was allowed to react overnight (16 h) affording a deep-yellow solution. The
crude mixture was then concentrated in vacuo to obtain a sticky yellow paste. The paste
was then redissolved in minimum amount of THF and precipitated by dropwise addition
into hexanes (800 mL). The precipitate was a white powder with a slight reddish tint. The
powder was then redissolved and precipitated a second time. The precipitate was then
recrystallized from boiling methanol followed by cooling at -4°C, affording 18.6 g of flat
square white crystals (87% yield). High Resolution MS (FAB-): m/z calcd 463.3505,
found 463.3560; 'H NMR (CDCI3): 6 (ppm) = 6.52 (s, 2H, CH=CH), 5.24 (s, 2H,
bridgeheads), 3.46 (t, 2H, NCH2), 2.85 (s, 2H, NC(O)CH), 2.09 (m, 2H, NCH2CH2), 1.82
(m, 2H, NCH2CH2CH2), 1.06 (s, 9H, CCH3) 0.32 (s, 6H, SiCHs); '^C NMR (CDCI3): 5
(ppm) = 176.13, 136.53, 80.96, 80.37, 75.92, 47.43, 37.97, 34.98, 28.31, 27.51, 20.39, -
34
2.60; "B {'H} NMR (CDCI3): 5 (ppm) = 0.31 (IB), -3.85 (IB), -7.49 (2B), -10.25 (6B);
mp= 136°C.
.Si
a) nBuLi, 0"C
b) TBDMS-CI, 40°C
c) MeOH/H20
Benzene/Et20
Benzene/
Et20
oMitsunobu Coupling
THF, DIAD, PPh3
a) nBuLi, 0"C
b) Oxetane, 40°C
c) MeOH/H20
4 3
Figure 2.1 Synthesis of the SONIC monomer 3. TBDMS: /^rbutyldimethylsilyl.
DIAD: diisopropylazodicarboxylate.
Homopolymerization of SONIC 5. The procedure was the same for every
homopolymerization. Here is a standard procedure for the reactions carried out in septum
vials, under constant agitation and under nitrogen atmosphere. To a 1 mL of solution of
the desired amount of GUI, 200 mg of monomer 4 (4.31mmol) in 10 mL of
dichloromethane were introduced rapidly and stirred for 6 minutes. After that time, the
reaction was quenched with an excess of ethylvinylether and precipitated dropwise in
cold methanol (150 mL) to afford a white powder. Table 1.1 shows the resuhs obtained
for different monomer to catalyst ratios. 'H NMR (CDCI3): 6 (ppm) = 6.09 (br s, 0.84H,
olefin trans), 5.82 (br s, 1.1 6H, olefin cis), 5.02 (br t, 1.16, CHO, cis), 4.46 (br s, 0.84H,
CHO, trans), 3.6-3.2 (m, 4H, N-CH2, CH-C(O)), 3.0-1.3 (br, 14H, BH, CH2CH2), 1.08 (s.
35
9H, CCH3), 0.34 (s, 6H, SiCHs); '^C NMR (CDCI3): 5 (ppm) = 175.31, 131.10, 80.96,
80.18, 76.24, 52.37, 38.07, 35.13, 28.46, 27.54, 20.40, -2.47.
Diblock copolymer synthesis 6. In a screw cap vial under nitrogen atmosphere and
constant agitation, the desired amount of SONIC was dissolved in 5mL of DCM and the
catalyst was introduced as a 10 mM solution in DCM. After 5 min. {2-[(lR,2R,6S,7S)-
3,5-Dioxo-10-oxa-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl]-ethyl}-carbamic acid tert-
butyl ester referred to as Boc-protected OxoNorbomene Imide Amine (BONIA),[29]
dissolved in 5 mL of DCM, was introduced into the reaction media using a syringe. The
reaction was quenched after lOmin by addition of excess ethyl vinylether. The solution
was then precipitated into 50 mL of hexanes and filtered over sintered glass as a white
solid.
Deprotection; Synthesis of an amphiphilic diblock copolymer 7. In a 35 mL
round-bottom flask, the polymer (150 mg) was dissolved in 4 mL of DCM and 15 mL of
trifluoroacetic acid and allowed to react overnight. The polymer salt was then
precipitated in diethyl ether and filtered over sintered glass.
36
c) <^0^6 7
Figure 2.2 Ring-opening metathesis polymerization and subsequent amine
deprotection syntheses. TBDMS: /^r/-Butyldimethylsilyl, TFA: Trifluoroacetic acid.
Post-polymerization PEGylation 8a. In a 50 mL round-bottom flask, polymer 7 (1
equiv.) was dissolved in dimethylsulfoxide (20 mL). Triethylamine (2 equiv.) were added
and the reaction was allowed to stir for 20 min. PEG-acrylate (10 equiv.) was then added
to the mixture and the mixture was allowed to react for 2 days. To obtain 8b, the same
procedure was utilized except that the reaction temperature was increased to 60 °C and
some of the polymer solution was dialyzed against THF after reaction. In both cases, the
yields were extremely low (below 10%) and just enough was recovered for 'H NMR.
Attachment ofRhodamine-B 9. In a 25 mL round-bottom flask, polymer 7 (Ig, 1
equiv.) was dissolved in DMSO (15 mL) and rhodamine B isothiocyanate (40 mg, 0.1
equiv.) was added to the mixture. A drop of triethylamine was then added and the
mixture was allowed to react in the dark for 1 day. The mixture was then precipitated in
cold diethyl ether to yield 850 mg of a pink powder (Yield 85%).
37
X"
Figure 2.3 Post-polymerization modifications
2.2.2 Results and Discussion
Gomez et al. had previously reported a protocol to synthesize the 3-[2-(ferNbutyl-
dimethylsilanyl)-l,2-dicarba-c/o50-dodecaboran(12)-yl)propan-l-ol 3 (Figure 2.1). [28]
The synthesis of this entity was key to the elaboration of the targeted monomer 4.
However, while reproducing their experiments, slight modifications were introduced. The
distillation of o-(C2BioHii)SiMe2/Bu 2 occurred at higher pressure and lower
temperatures than previously reported.
The oxanorbomene derivative 4 was synthesized via Mitsunobu coupling of exo-
7-oxonorbomene imide and 3. [30,31] A previous study in our group had demonstrated
the difference in polymerization rates between exo and endo carborane-containing
38
norbomene derivatives, [3 2] corroborating findings by Grubbs and coworkers. [3 3] In
order to maximize the polymerization rates, an isomerically pure exo compound was
needed. Furthermore, to avoid the problems of head-to head and head-to-tail additions, a
symmetric monomer was desirable. To address these issues, we undertook the synthesis
of SONIC (Silyl-protected OxaNorbomene Imide Carborane), whose symmetry and
stereochemistry were specifically designed for faster and more controlled polymerization
kinetics. This control permits the exploration of well-defined architectures, such as
blocky structures.
Table 2.1Tabulated data for the homopolymerization of SONIC
Target
DPn
TargetPDf Yield
5i 54 25,000 22,000 1.07 83%5ii 108 50,000 58,600 1.09 82%5iii 162 75,000 79,100 1.05 87%5iv 216 100,000 97,600 1.03 89%
^ g.mor'. As measured by GPC vs polystyrene standards.
The homopolymerization of SONIC afforded polySONIC 5 in good yields (>
82%)) and very narrow polydispersity (PDI < 1.1). To achieve this task, advantage was
taken of the versatility and efficacy of ROMP catalysts, that not only give a living
character to the polymerization, but also display a greater tolerance to diverse chemical
functionalities. [26] The reaction happens indeed within minutes and offers good control
over molecular weight and molecular weight distribution, with no apparent broadening
even for the highest Mn.
39
Table 2.2 Tabulated data for the copolymerization of SONIC 4 and BONIA by
ROMP.
EntryMolar Ratios
SONIC BONIADPn(S) DPn(B)
Target
6i 4 5 22 28 18,835 17,300
6ii 2 1 50 25 30,894 32,990
6iii 8 5 54 34 35,523 33,800
6iv 4 5 54 68 46,006 45,500
6v 4 5 86 108 73,178 65,100
PDl"
g.mol"'. As measured by GPC vs polystyrene standards.
The diblock copolymers were obtained by sequential addition of SONIC and
BONIA (Boc-protected OxoNorbomene Imide Amine) (Figure 2.2). These copolymers
were obtained in good yields (> 80%) and with molecular weights ranging from 17 to 65
kg/mol. Also, the favorable comparison, between estimated and measured molecular
weights, suggests that the polymers obtained behave like random coils in tetrahydrofuran.
Even at high molecular weights, the polydispersity remains very narrow (Figure 2.4;
Table 2.2, Entry 6v). The gel permeation chromatogram illustrates the increase in
molecular weight upon addition of the second block (Figure 2.4). In addition, the molar
feed and incorporation ratios are within 5% of one another as determined by 'H-NMR
spectroscopy.
40
18 20 22
ButionTinrBfmn'i
Figure 2.4 GPC chromatograms in THF of poly(SONIC) (solid line, PDI = 1.08, M„= 37 kg/mol) and poly(SONIC-A-BONIA) (dashed line. Entry 6v, PDI = 1.11 M„ = 65
kg/mol).
Homopolymers of BONIA had previously been reported by our group as potential
antibacterial polymers. [29] Their low toxicity to red blood cells opens the prospects of
medical applications for the synthesized diblock copolymers. The amphiphilicity,
necessary for the formation of micelles that can be used as boron neutron capture therapy
agents, [14] was achieved through a post polymerization cleavage of the ?Boc protecting
group in the second block. In so doing, the copolymers obtained are a unique example of
a well-defined (PDI < 1.15) amphiphilic copolymer containing carborane. The
deprotection can be monitored by the disappearance of the characteristic N-H carbamate
peak at 6 = 6.89 ppm integrating for IH and the disappearance of the 9H from the tert-
butyl protons at 5 = 1.35 ppm. At the same time, the appearance of the ammonium peak
41
at 5 = 8.01 ppm integrating for 3H is observed. As observed by 'H NMR spectroscopy,
the cleavage is quantitative.
50 0.0
ppm(fl)
Figure 2.5 Illustration of the appearance of the ammonium peak at 8 ppm.
In addition, solution studies in water, using DLS, show the propensity of these
polymers to aggregate. This phenomenon can be imputed to the formation of micelles
were the charged hydrophilic block constitute the corona and the carborane containing
block the core. These aggregates have an average hydrodynamic radius (Rh) of 41rmi
(Figure 2.6).
42
Atomic force microscopy was utilized to confirm the presence of aggregates and
evaluate their shape. Figure 2.6 shows the presence of circular objects on a silica surface.
These objects are found to have a radius of approximately 87 nm. This number is much
larger than the hydrodynamic radius found in solution by DLS. However, the micelles are
expected to flatten out as the positively charged ammoniums interact with the negatively
charged silanols of the silica surface, leading to an apparent increase in size. This
interaction is confirmed when looking at the profile of these cylindrical objects, as they
are measured to be only 10 nm tall. A back of the envelope calculation allows us to
calculate both the volume of a sphere with a 40 nm radius and a 1 0 nm-tall cylinder with
a radius of 90 nm to be approximately 250 nm . Therefore, there seems to be a
conservation of volume and these results lead us to believe that the value obtained by
DLS is probably more accurate. Nevertheless, AFM provides some valuable insight into
the shape of the micellar objects. Additionaly, the size might appear bigger because of the
finite curvature of the AFM tip.
Figure 2.6 Distribution of sizes measured by dynamic light scattering (left) and
atomic force microscope image (right) of micellar aggregates (Entry 6v).
43
8 0 7 0 6.0 5 0 4 0 3 0 2 0 1 0
ppm (f1)
Figure 2.7 'H NMR experiment illustrating the solvents of different polarities
As illustrated by Figure 2.3, the deprotected amine provides us with a number of
different post-polymerization possibilities. In particular, the PEGylation of the amine via
a Michael addition of PEG-acrylate has been investigated at different temperatures. In
both cases, the disappearance of the ammonium peak at 5 = 8.0 ppm was observed as
well as the appearance of the characteristic PEG signal at 3.5 ppm. The synthesis of 8b
was attempted as a way to accelerate the kinetics of the reaction by increasing the
reaction temperature. However, after taking an aliquot after 1 day, it was observed that
the signals corresponding to the silyl group at 5 = 1.06 and 0.33 ppm had disappeared,
while a new signal at 5.1 ppm had appeared (Figure 2.5). The latter signal is the
characteristic resonance of the C-H bond of carborane. Although the mechanism still
44
remains unclear, it seems that the presence of triethylamine at high temperature is directly
correlated with cleavage of the TBDMS group. A similar observation has been made
when trying to hydrogenate polymer 5 in the presence of tri-«-propylamine, as will be
discussed in chapter 3.
The introduction of PEG side chains is particularly important for the utilization of
polymers in intravenous systemic delivery. Firstly, the PEG chains act as a hydrated
cushion that prevents the adhesion of opsonizing proteins. [34] By making the polymer
"stealthy" to the immune system, the PEG chains increase the blood circulation half-time
of the polymer which results in better accumulation at the desired location. [35] Secondly,
the bottle-brush architecture is believed to limit renal excretion by hampering the
reptation of the macromolecules in the kidney. [36] Again, this phenomenon also prolongs
the circulation of the drug, rendering it more efficacious.
For topical applications, the presence of PEG chains is not quite as relevant as the
risks of opsonization are greatly reduced. Therefore, it is very interesting to study the
interaction of the charged polymer with carcinoma cells. In order to study this interplay
in vitro, the attachment of a rhodamine B isocyanate was also undertaken (Figure 2.3).
The yields were increased in comparison to those of the PEGylation reaction, as the
solubility of the PEG groups complicates the precipitation step. Nevertheless, it was still
difficult to quantify the level of attachment. In particular, the ionic nature of the polymer
was a limiting factor for its injection in a GPC apparatus, to monitor the dye attachment
to the polymer by UV detection. During the dialysis process of polymer 9 against water,
a light pink coloration appeared outside of the dialysis bag. This phenomenon indicates
that there is still some unattached dye that was not removed by the precipitation in diethyl
45
ether. However, the coloration gradually faded upon continuous changing of the dialysis
water. After 3 days, virtually no color change was observed. The presence of a dark pink
color inside the bag suggests that the majority of the water-soluble dye had, in fact,
coupled with the amine. The polymer was dialyzed for another 2.5 weeks to ensure that
no residual dye would be present.
Confocal microscopy was utilized to evaluate the use of polymer 9 as potential
agent for BNCT. Figure 2.8 illustrates the results obtained upon incubation of HEp-2
carcinoma cells with a solution of dialyzed polymer. Three very important observations
have to be made. First of all, the internalization of labeled polymer 9 is apparent as
illustrated by the z-sections taken on the cells. Secondly, the majority of the internalized
polymer appears to be preferentially located around the nucleus of the cells. This
observation is important as it has been cited that BNCT is more efficient when the
delivery agent releases its cytotoxic payload closer to the nucleus of the cancerous cell.
Finally, it is important to remark that without the presence of any neutron source,
polymer 9 showed no cytotoxic effect after 22 h of incubation on cells in culture. The
viability of cells was determined by a Trypan blue exclusion test. The principle of this
test is that live, hardy cells possess an undamaged cell membrane that will exclude
certain dyes such as Trypan blue. Upon adding the dye, the number of cells in the
microscope field that had internalized the dye was comparable between the experimental
and control groups (~ 3 to 5%).
46
Figure 2.8 Confocal microscopy image of HEp-2 carcinoma cells after a 22h
incubation period.
While the synthesis of 8a, 8b and 9 showed the versatiHty of the chemistry that
can be performed on the deprotected amine, it proved difficuk to characterize the
compounds. Therefore, the very nature of these post-polymerization routes complicates
their implementation on a larger scale. Consequently, a possible alternative to the
synthetic routes described in part 2.2 was investigated using a PEG-norbornene ester.
2.3 Route B: Using PEGylated Norbornene Esters
2.3.1 Experimental Section
The PEG-functionalized norbornene, the NHS-norbomene ester and the tBoc-
protected dye were kindly provided by Dr. Alfred Sterling and Dr. Ahmad Madkour. Gel
permeation chromatography was performed with RI and UV detection with an excitation
at 460 nm.
Synthesis of triblock copolymers 10. In a 20 mL screw-cap vial, compound 4 (200
mg, 0.428 mmol) was dissolved in DMF (3 mL) and a 1 mL solution containing 10 mg of
47
Grubbs third generation catalyst (0.011 mmol) was added. After 5 min, the PEG
norbomene ester (200 mg, 0.167 mmol) in 3 mL of DMF was added and the mixture was
allowed to react for 30 min. The NHS activated norbomene ester (6 mg, 0.22 rrmiol) was
then introduced and the reaction was quenched after 3 min by addition of an excess of
ethyl vinyl ether.The polymer was then precipitated in cold diethyl ether (cooled with
liquid nitrogen) and filtered to yield 357 mg of a grey powder (88%).
Labelling of the triblock copolymer 11. In a 25 mL round-bottom flask, tBoc-
protected nitrobenzoxydiaxole (NBD) (13 mg, 4 equiv.) was dissolved in THF (8 mL)
and TFA was added (5 mL). After 4 h, the reaction mixture was syringed into another
round-bottom flask containing polymer 10(100 mg, 1 equiv.) in 10 mL of dry DMF. The
reaction was allowed to stir overnight.
48
N02
Figure 2.9Triblock copolymer formation and labeling.
2.3.2 Results and Discussion
The alternative route described here presents the advantage of circumventing the
post-polymerization PEGylation used in Route A by utilizing a PEG-functionalized
monomer. While no solution studies have been performed on these materials, they are
expected to lead to the formation of micellar assemblies comparable to that of Route A.
The triblock copolymers were obtained by sequential additions of the monomers (Figure
2.9). The control obtained for the obtained polymer is remarkable as the PDIs are below
1.15. The number average molecular weight (22,500 g/mol) is however much inferior to
the expected molecular weight (36,100 g/mol). This discrepancy can be accounted for by
49
the fact that comb architecture display a lower apparent molecular weight by GPC.[37]
The attachment of the dye was monitored by GPC using UV detection. The GPC
chromatograms (Figure 2.10) clearly show the detection of a refractive index change
upon elution of the unlabeled polymer 10 and the NBD-labeled polymer 11. However, by
UV detection, the unlabelled polymer is not detected which indicates the attachment of
the dye onto the polymer.
14 16 18 20 22 24 26 14 16 18 20 22 24 26
Figure 2.10 RI (left) and UV (right) GPC chromatograms of 10 and 11.
2.4 Conclusions
We have successfully developed a new monomer, SONIC, that enabled us to
synthesize amphiphilic diblock copolymers containing carborane with low PDI (< 1.15)
by two methods. The newly synthesized monomer was homopolymerized using ROMP
yielding materials with low PDI (< 1.1). The solution behavior of the copolymers
obtained by the polymerization-deprotection strategy (Route A) was characterized by
DLS and AFM. It was shown that spherical micelles can be obtained. Post-
Elution Time (min) Elution Time (min)
50
polymerization modifications were successfially undertaken to attach PEG-acrylate via
Michael addition and Rhodamine B isothiocyanate by nucleophilic substitituion.
Additionally, preliminary cell studies showed the incorporation of the labeled-polymers
inside carcinoma cells by confocal microscopy. An alternate method (Route B) was also
investigated where the carborane-containing oxanorbomene was polymerized with a
PEG-functionalized norbomene and an NHS activated norbomene ester. The NHS group
allowed for facile labeling of the triblock copolymer as monitored by GPC. The obtained
polymers by both routes are expected to provide a solid base for further exploration of
amphiphilic carborane-based copolymers in BNCT applications.
2.5 References
[1] X. L. Wei, P. J. Carroll, L. G. Sneddon, Chemistry ofMaterials 2006, 75, 1 113.
[2] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Macromolecular
Symposia 2003, 196, 201.
[3] P. R. L. Malenfant, J. Wan, S. T. Taylor, M. Manoharan, Nature Nanotechnology
2007, 2, 43.
[4] N. Tsuboya, M. Lamrani, R. Hamasaki, M. Ito, M. Mitsuishi, T. Miyashita, Y.
Yamamoto, Journal ofMaterials Chemistry 2002, 72, 2701
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[5] J. Taylor, J. Caruso, A. Newlon, U. Englich, K. Ruhlandt-Senge, J. T. Spencer,
Inorganic Chemistry 2001, -/O, 3381
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[6] R. Hamasaki, M. Ito, M. Lamrani, M. Mitsuishi, T. Miyashita, Y. Yamamoto,
Journal ofMaterials Chemistry 2003, 7i, 21.
[7] C. D. Entwistle, T. B. Marder, Angewandte Chemie, International Edition in
English 2002, 41, 2927.
[8] D. G. AUis, J. T. Spencer, Inorganic Chemistry 2001, 40, 3373.
[9] D. G. Allis, J. T. Spencer, Journal ofOrganometallic Chemistry 2000, 614, 309.
[10] R. K. Zalavutdinov, A. E. Gorodetsky, A. P. Zakharov. Mikrochimica Acta 1994,
77-7-775, 533.
51
[11] V. L. Solozhenko, N. A. Dubrovinskaia, L. S. Dubrovinsky, Applied Physics
Letters 2004, 85, 1508.
[12] L. G. Sneddon, K. Su, P. J. Fazen, A. T. Lynch, E. E. Remsen, J. S. Beck, lUPACMacromolecular Symposium Inorganic and Organometalic Oligomers and
Polymers, Pure and Applied Chemistry 1991, 33, 199.
[13] S. Y. Rybakov, V. M. Sharapov, L. E. Gavrilov, Journal de Physique IV 1995, 5,
921.
[14] M. F. Hawthorne, Angew. Chem. Int. Ed. Engl. 1993, 950.
[15] R. N. Grimes, Journal ofChemical Education 2004, 81, 657.
[16] S. E. A. Gratton, M. C. Parrott, A. Adronov, Journal of Inorganic and
Organometallic Polymers and Materials 2005, 75, 469.
[17] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Journal of the
American Chemical Society 2005, 127, 12081.
[18] S. R. Benhabbour, M. C. Parrott, S. E. A. Gratton, A. Adronov, Macromolecules
2007. 40, 5678.
[19] X. L. Wei, P. J. Carroll, L. G. Sneddon, Organometallics 2006, 25, 609.
[20] X. L. Wei, P. J. Carroll, L. G. Sneddon, Organometallics 2004, 23, 163.
[21] M. J. Pender, K. M. Forsthoefel, L. G. Sneddon, Pure and Applied Chemistry
2003, 75, 1287.
[22] M. J. Pender, P. J. Carroll, L. G. Sneddon, Journal of the American Chemical
Society 200\, 123, 12222.
[23] T. Thum-Albrecht, R. Steiner, J. DeRouchey, C. M. Stafford, E. Huang, M. Bal,
M. Tuominen, C. J. Hawker, T. Russell, Advanced Materials (Weinheim, Federal
Republic ofGermany) 2000, 12, 787.
[24] R. F. Barth, J. A. Coderre, M. G. H. Vicente, T. E. Blue, Clinical Cancer
Research 2005, 11, 3987.
[25] L. Zheng, R. J. Farris. E. B. Coughlin, Journal of Polymer Science, Part A:
Polymer Chemistry 2001, 39, 2920.
[26] J. A. Love, J. P. Morgan, T. M. Tmka, R. H. Grubbs, Angewandte Chemie,
International Edition in English 2002, 41, 4035.
[27] L. B. Luo. J. Tarn, D. Maysinger, A. Eisenberg, Bioconjugate Chemistry 2002,
13, 1259.
52
[28] F. A. Gomez, S. E. Johnson, M. F. Hawthorne, Journal ofthe American Chemical
Society \99\J1 3. 59\5.
[29] M. F. Ilker, K. Nuesslein, G. N. Tew, E. B. Coughlin, Journal of the American
Chemical Society im^, 126, 15870.
[30] S. Messaoudi, F. Anizon, B. Pfeiffer, M. Prudhomme, Tetrahedron 2005, 67,
7304.
[31] Y. Wang, J. Cai, H. Rauscher, R. J. Behm, W. A. Goedel, Chemistry—A European
Journal 2005. 77,3968.
[32] Y. C. Simon, E. B. Coughlin, Polymer Preprints (American Chemical Society,
Division ofPolymer Chemistry) 2005, 46, 111.
[33] R. H. Grubbs, Handbook ofMetathesis, Vol. 3, Wiley, John & Sons, Incorporated,
2003.
[34] D. E. Owens, N. A. Peppas, International Journal of Pharmaceutics 2006, 307,
93.
[35] R. Duncan, Nature Reviews Drug Discovery 2003, 2, 347.
[36] E. R. Gillies. J. M. J. Frechet, Journal of the American Chemical Society 2002,
124, 14137.
[37] Y. Nakamura, Y. Wan, J. W. Mays, H. latrou, N. Hadjichristidis, Macromolecules
2000, 33, 8323.
53
CHAPTER 3
RING-OPENING METATHESIS COPOLYMERIZATION OF CYCLOOCTENE
AND A CARBORANE-CONTAINING OXANORBORNENE
3.1 Introduction
As reported in the previous chapter, we have synthesized a novel carborane-
containing monomer 4 (silyl-protected oxanorbomene imide carborane: SONIC). Its
subsequent incorporation in homopolymers and amphiphilic diblock copolymers by ring-
opening metathesis polymerization has been successful.[l] Here, we wish to report the
incorporation of 4 in polyethylene-like materials by copolymerization with cyclooctene
(COE) followed by hydrogenation in the presence of/>-toluenesulfonylhydrazide (TSH).
The possibility to control the composition of the copolymer based on the feed ratio is
demonstrated and the optimization of the hydrogenation conditions are also discussed.
Preliminary results of the investigations of the morphological and thermal properties of
the copolymers, and the evaluation of the influence of molecular weight, hydrogenation
and composition upon these properties is reported. A model compound was also
synthesized and homopolymerized to determine the influence of the silyl-functionalized
carborane clusters on the physical properties of the polymer. Ultimately, these polymers
have elemental compositions making them suitable candidates for utilization in radiation
shielding materials.
54
3.2 Experimental
3.2.1 Materials.
All organic reactants and reagents were purchased from Aldrich Chemical Co and
used as received unless specified otherwise. Toluene was dried over sodium with
benzophenone as an indicator. Dichloromethane was obtained through Fisher, distilled
over calcium hydride and degassed with freeze-pump-thaw cycles. 0-carborane was
supplied by KatChem. Grubbs 1^' generation was purchased from Strem Chemicals.
Grubbs 3'^'' generation catalyst was synthesized according to the literature and stored
under nitrogen atmosphere. [2] Monomer 4 was synthesized as previously described in the
literature, the polymerization of this monomer by ROMP has also been described.[l] o-
Xylene was passed through an activated alumina column prior to use. p-
Toluenesulfonylhydrazide was purchased from Aldrich Chemical Co. and recrystallized
from benzene.
The nomenclature for the different compounds is as follow. Copolymers of 4 and
COE were named 12(XX)-T or 12(XX)-D. where T,and D, indicate the reaction solvents
toluene or dichloromethane respectively, and XX represents the molar percentage of
monomer 1 in the feed. For example, a polymer with a targeted composition of 75% of 4,
synthesized in toluene, is designated as 12(75)-T. Subsequent hydrogenation of the
materials will be indicated by an H in front of the descriptor. Therefore, the result of the
hydrogenation of a polymer with 50% SONIC originally synthesized in dichloromethane
will be noted: H-12(50)-D. Even though homopolymers of 4 were reported in the
previous chapter as 5, they will be reported as 12(100) in the present chapter to simplify
the discussion.
55
3.2.2 Instrumentation.
Gel permeation chromatography (GPC) measurements for the polymers were
performed in tetrahydrofuran (THF) at 1.0 mL/min using a Knauer K-501 Pump with a
K-2301 refractive index detector and a K-2600 UV detector, and a column bank
consisting of two Polymer Labs PLGel Mixed D columns at 40°C. All other
measurements were performed using a similar system with a column banks consisiting of
three Polymer Labs PLGel Mixed D columns at 40°C. Molecular weights are reported
relative to polystyrene standards. The 'H NMR and '^C NMR were recorded at 300 MHz
and 100 MHz respectively on a Bruker NMR spectrometer at room temperature in
deuterated chloroform. For 'h NMR, the protons attached directly to the boron atoms of
the carborane cage integrate for 10 protons as broad multiplets due to couplings with
boron nuclei (5 (ppm) = 3.20-1.01 (br, lOH, BH)). Thermogravimetric analyses (TGA)
were performed on a TA-Instruments 2950 with a heating rate of 10°C per minute,
sweeping temperatures ranging from 25°C to 700°C under inert atmosphere. Differential
Scanning Calorimetry (DSC) measurements were performed on a Mettler-Toledo DSC
822e and a DuPont Instrument 2910 with a heating rate of 10°C per minute from 25°C to
250°C for the homopolymers (12(100)-D, H-12(100)-D, 14 and H-14), and from -50 °C
for the copolymers (12(XX) and H-12(XX), with XX < 100). Wide-angle X-ray
scattering (WAXS) patterns were recorded using a Paranalytical X-pert X-ray
diffractometer for angles ranging between 1 and 30 degrees. All samples were fine
powders and were pressed to obtain a smooth surface.
56
3.2.3 Synthesis and Spectral Data
Synthesis of 12(XX). The polymerization of copolymers with different feed ratios
was run alternatively in toluene or dichloromethane as follows. In a round bottom flask
purged with nitrogen and equipped with a stir bar, the desired amount of 4 (463.70 g/mol)
was dissolved in the reaction solvent so as to obtained a 0.2 mol/L solution. Using a
syringe, the desired amount of COE was added. A solution of Grubbs 1^' generation
catalyst was then introduced such that the final concentration of catalyst would be 1000
times less than that of the combined monomers. The reaction was allowed to proceed for
24 h and was stopped by addition of an excess of ethyl vinyl ether. The polymer was then
precipitated in cold methanol and filtered over sintered glass. The stringy solid was then
dried in a vacuum oven for 12 h at 40 °C. For NMR characterization see the discussion
section.
Hydrogenation ofthe polymers. The following is a typical experimental procedure
performed on the samples obtained in dichloromethane. In a 50 mL round-bottom flask
mounted with a condenser, the polymer (110 mg) and TSH (330 mg) were dissolved in
25 mL of o-xylene and the mixture was brought to reflux (130°C) under constant
agitation and with the slight nitrogen purge. After 2h the reaction was allowed to cool to
50°C and was then precipitated in methanol. The following is the NMR for 12(100)-D:
'H NMR (CDCI3): 5 (ppm) = 3.79 (br s, 2H), 3.41 (br s, 2H), 3.11 (br s, 2H), 1.07 (s,
9H), 1.33 (s, 6H); '^C NMR (CDCI3): 5 (ppm) = 175.88, 81.15, 80.16, 76.20, 52.22,
37.80, 35.16, 31.10, 28.45, 27.55, 20.40, -2.47.
Synthesis of exo-N-propyl-7-oxabicyclo[2,2,l]hept-5-ene-2J-dicarboximide 13.
In a dry 500 mL flask, exo-7-oxonorbomene imide (7.6 g, 46 mmol, 1 equiv.), propan-1-
57
ol (3.8 mL, 51 mmol, 1.1 eq) and triphenylphosphine (13.3 g, 51 mmol, 1.1 equiv.) were
dissolved upon stirring in 300 mL of freshly distilled dry tetrahydrofuran (THF). The
flask was kept under nitrogen pressure and cooled down to 0°C with an ice bath. After 5
minutes, diisopropylazodicarboxylate (DIAD) (3.2 mL, 16.26 mmol, 1.1 equiv.) was
added and the solution turned yellow. The reaction was allowed to react overnight ( 1 6 h)
affording a deep-yellow solution. The crude mixture was then concentrated in vacuo to
obtain a sticky yellow paste. The paste was then redissolved in a minimum amount of
THF and precipitated by dropwise addition into hexanes (800 mL). The precipitate was a
white powder with a slight reddish tint. The powder was then redissolved and precipitated
a second time. The precipitate was then recrystallized from boiling methanol followed by
cooling at -4°C, affording 9.5 g of white powder (78 % yield). 'H NMR (CDCI3): 5
(ppm) = 6.51 (s, 2H, CH=CH), 5.27 (s, 2H, CHO), 3.45 (t, 2H, J = 7.2 MHz, NCH2), 2.83
(s, 2H, CH-C=0), 1.60 (qt, 2H, J = 7.5 MHz, J = 7.2 MHz, CH2CH2CH3), 0.88 (t, 3H, J =
7.5 MHz, CH3); '^C NMR (CDCI3) 5 (ppm) = 176.37, 136.54, 80.91, 47.37, 40.53, 20.96,
11.15.
Polymerization of the model monomer 13 to afford polymer 14. The
polymerization of 13 was performed following the procedure employed for the synthesis
of 12(100)-D. 'H NMR (CDCI3): 5 (ppm) = 6.23 (bs, 0.95 H, CH=CH trans), 5.58 (bs,
1.05 H, CH=CH cis), 5.02 (bm, 1.05 H, CHO cis), 4.46 (bm, 0.95 H, CHO trans), 3.43
(bs, 2H, NCH2), 3.35 (s, 2H, CH-C=0), 1.72 (bs, 2H, CH2CH2CH3), 0.89 (bs, 3H, CH3);
'^C NMR (CDCI3) 6 (ppm) = 175.72, 131.91, 81.10, 52.38, 40.52, 31.01, 1 1.27; GPC (PS
std) : Mn = 91,600 g/mol, PDI = 1.07.
58
Hydrogenation ofthe model polymer-H-14. The hydrogenation procedure was the
same as that utilized for the obtention of H-5 and H-12 'H NMR (CDCI3): 5 (ppm) = 3.82
(bs, 2H, CHO), 3.42 (bs, 2H, CH2N), 3.11 (bs, 2H, CHC=0), 1.96 (bs, 4H, CH2
backbone), 1.57 (bs, 2H, CH2CH2CH3), 0.88 (bs, 3H, CH3), GPC (PS std) : Mp = 88.500
g/mol, PDl = 1.13.
rtv p
Figure 3.1 Ring-Opening Metathesis copolymerization of 1 and COE.
3.3 Results and Discussion
3.3.1 Copolymerization.
Since the homopolymerization of 4 has previously been described elsewhere, the
present discussion will focus on the statistical copolymerization of monomer 4 and COE
(Figure 3.1). Previous work in our laboratory has pointed out the possibility to obtain
strictly alternating structures by copolymerization of COE with oxanorbomene
monomers. [3] Other laboratories have reported similar observations. [4] In the present
investigations, it would be expected that consumption of the exo monomer 4, would
occur much more rapidly than that of COE leading to the formation of a tapered block
copolymer. This is clearly the case when the polymerization is carried out in
dichloromethane, as illustrated by the presence of the two strong signals at 5 = 5.3 (a
tram) and 6.1 ppm (d) characteristic of homopolymer sequences (Figure 3.2). It is
59
observed, however, for the copolymerization of 4 and COE conducted in toluene, that the
result is a much more randomized structures where alternation, although not strict
(Scheme 3.1), seems to prevail (Figure 3.2). Another way to evaluate the amount of
alternation consists in comparing the ratios of signals b cis/trans and b' cis/trans (Figure
3.2). As can be observed for 12(50)-T, and unlike 12(50)-D, the signal of b' is much
greater than the b counterpart which further illustrates the tendency towards alternation
obtained in the case of toluene as a solvent.
Scheme 3.1 The perfectly alternating structure of polymer 12(50).
1i
1
1
1
i
\ 11
•
\ 1 1
i
I
I r r
I
I i \ \
6.00 5.50 5 00 4 50
ppm(ll)
Figure 3.2 Illustration of the differences in alternation depending on solvent
polarity.
60
This notable difference can be accounted for by the difference in polymerization
rate upon changing the solvent. An initiation rate increase of 30% has been observed in
the literature upon altering the dielectric constant of the reaction medium when switching
from toluene (e = 2. 38) to dichloromethane (e = 8.9). [5] This phenomenon is attributed
to the stabilization of the products of the dissociation of the phosphine ligand from the
ruthenium complex. This displacement of the equilibrium towards the dissociated species
favors the homopolymerization of COE with respect to alternation by accelerating the
homopolymerization rate. Conversely, in the presence of a less polar solvent such as
toluene, the metal alkylidene is much more tightly bound to the phosphine and remains in
the active form for shorter times. This phenomenon contributes to a selectivity decrease
and favors the alternation of monomers 4 and COE. Since the catalyst spends a longer
time in its "dormanf state, it becomes less selective and has the tendency to coordinate to
whichever of the two monomers enters its sphere of coordination.
As far as incorporation ratios are concerned, it can be observed that they are
consistent with the feed ratios (Table 3.1). Also, it is to be noticed that in the case of the
copolymerizations in toluene, at ratios of SONIC:COE of 1:3 and 3:1 (Table 3.1, entries
12(75)-T and 12(25)-T), there are virtually no homopolymer sequences of the limiting
monomer as indicated by the absence of characteristic resonance in the NMR spectra. In
the case of dichloromethane as a reaction solvent, similar observations can be made. The
polymerizations in toluene seem to lead to the formation of much shorter chains. Again,
this could be explained by the fact that the polymerization rate is accelerated in
dichloromethane. Additionally, unlike ruthenium alkylidenes bearing a N-heterocyclic
carbene (NHC), complexes with two phosphines are much more prone to phosphine
61
recoordination as they do not benefit from the donor effect of the NHC. If recoordination
is disfavored by use a more polar solvent, it is expected that the molecular weights
attained should be greater (Table 3.1). Also, since the catalyst spends much less time in a
dormant state, the polymerization is less well-controlled leading to globally higher
polydispersity indices.
Table 3.1 Conditions and results for the polymerization of monomers 4 and COE.
Entry M„ (g/mol)' PDl' Molar Ratios^
SONIC COE
12(100)-D 58,600 1.09 100 0
12(75)-D 544,500 1.63 74 26
12(50)-D 135,900 4.32 49 51
12(25)-D 42,900 2.4 25 75
12(75)-T 55,300 1.15 77 23
12(50)-T 24,800 2 51 49
12(25)-T 25,800 2.61 23 77
As measured by GPC vs. polystyrene standards. ^ As measured by *H NMRspectroscopy by comparing the integrations of the oleflnic region with the
silylmethyl peak at 5 = 0.33 ppm.
3.3.2 Hydrogenation.
Previous studies in our group have demonstrated the possibility of using
arylsulfonyl hydrazide at high temperatures to hydrogenate polyoligomeric
silsesquioxane-containing polymers. [6] Several hydrogenation conditions were attempted
on different polymers, changing solvent (toluene vs xylenes), duration (from 1 to 16 h)
and the additive (tri-«-propylamine). Although Hahn reported the necessity of employing
a high-boiling amine to prevent any side reaction, in particular the protonation of olefmic
sites upon formation of p-toluenesufinic acid, it was observed that the amine actually
contributed to a sharp decrease of molecular weight upon hydrogenation. [7] This
62
observation is believed to be a result of the degradation of the polymer. Although the
mechanism is still unclear and is currently being investigated, it is suspected that the
amine interacts with the silyl group which leads in turn to the alteration of the periphery
of the carborane cluster. [8]
Figure 3.3 Conditions for the hydrogenation of polymer 12.
b
c,d
c,d
1r— T 1 1—I
1—I1 1
^i
1 1
'
\
1 1'
1
1 1—T1
1
' 1
1—I
\
—I
1—I1
\ r
7.0 6.0 5 0 4 0 3 0 2 0 1 0 0 0
ChemicalShift (ppm)
Figure 3.4 Proton NMR spectrum of H-12(25)-D.
After several optimization steps, the most advantageous conditions were found
(Figure 3.3 and 3.4). Reaction temperatures and reaction times proved to have a key role
on the outcome of the reaction. The results for the hydrogenation are reported in Table
3.2. The hydrogenated product can be obtained in reasonably high yield with virtually no
63
remaining unsaturation as monitored by H NMR spectroscopy. Furthermore, no
significant increase in polydispersity can be recorded. Also, despite the net increase in
molecular weight by addition of hydrogen onto the C-C double bonds, the apparent
molecular weights of the hydrogenated materials are overall lower than their unsaturated
counterparts. This phenomenon can be accounted for by the fact that the chain becomes
more flexible as the double bonds are removed due to the free rotation about the newly
formed carbon-carbon single bonds. This increase in the degree of freedom allows for the
chain to adopt a much more compact conformation and therefore, an apparently smaller
hydrodynamic radius.
Table 3.2 Hydrogenation results for the polymers 5 and 12 synthesized in
dichloromethane.
EntryMn
(g/mol)^PDI' Yield
H-12(100)-D 43,900 1.05 88%H-12(75)-D 416,300 1.65 99%H-12(50)-D 115,000 3.92 98%H-12(25)-D 37,600 3.6 95%
Measured by GPC against polystyrene standards.
3.3.3 Thermogravimetric Analysis.
In this section, we describe the influence of molecular weight, unsaturations, and
the composition (copolymer and presence of carborane) on the thermograms. We also
synthesized model polymers 14 and H-14 in order to evaluate the influence of the cage
on thermal properties (Figure 3.5). To evaluate the influence of unsaturation and
molecular weight, two series of polymers were considered (12 and H-12). Thermal
64
decomposition for both series does not seem to be molecular weight dependent, as the
thermograms are superimposable. This superimposition stems from the fact that the
polymers are above the critical molecular weight for which the chain length would play a
role. As expected, the unsaturated polymer 12 shows a lower onset of decomposition
temperature than H-12, as the presence of allylic protons undermines the thermal stability
of the polymer (Table 3.3). Nevertheless, the double bonds favor the formation of char
through crosslinking, resuhing in higher char yields. Also, not surprisingly, when
comparing with the model compound 14, the hydrogenated version, H-14, with the
carborane cage leads to increased char formation upon pyrolysis for 12(100)-D, resp. H-
12(100)-D (Table 3.3). However, if the weight percent of the carborane cage matches the
increase in char for the unsaturated versions (12(100)-D v^. 14), it does not appear to be
so for the hydrogenated analogs (H-12(100)-D vs. H-14). Additionally, and as expected,
it can be noted that the char yield increases with the increase in carborane content.
14 H-14
Figure 3.5 Synthesis of model polymers 14 and H-14 to evaluate the influence of the
silylcarborane cage on thermal properties.
65
Table 3.3 Thermogravimetric analysis and differential scanning calorimetry results
of 12, H-12, Hand H-14.
EntryTo Td Char
EntryTo Td Char
(^C) (^C) Yield Co ("C) Yield
12(100)-D 153 370 31.6% H-12(100)-D 145 423 15.5%
12(75)-D 99 310 14.6% H-12(75)-D 88 410 1 1 .0%
12(50)-D 78 300 13.2% H-12(50)-D 91 407 10.2%
12(25)-D 32 241 9.0% H-12(25)-D 32 393 6.7%
12(0)-Db b
H-12(0)-Db b b
14 131 396 9.8% H-14 103 411 3.2%
According to reference [4]. Not measured.
3.3.3.1 DSC Analysis.
DSC analysis was used to study the effect of the new polymer structures and
molecular weights on the observed thermal transition (glass transition temperature (Tg),
melting temperature (Tm)). As observed for the TGA experiments, the molecular weights
do not seem to affect the Tg (data not shown here). However, a decrease by nearly 10 °C
was observed for the hydrogenated version H-12 with respect to their unsaturated
counterparts 12. This decrease can be explained by fact the free volume generated upon
hydrogenation. The latter confers flexibility to the backbone as it allows for the rotation
about the C-C single bond, thereby generating more free volume in the polymeric
structure. This phenomenon is also observed in the case of the model compound. Also,
the influence of the silyl protecting group on the aggregation of the carboranes in the
polymeric matrix is being evaluated.
3.3.4 Wide-Angle X-ray Scattering (WAXS).
The crystalline nature of 4 encouraged us to investigate the morphological
behavior of the homo- and copolymers containing carborane cages. We have previously
66
demonstrated in our laboratory, the possibility to drive self-assembly of inorganic-
organic hybrid copolymers through the crystallization of inorganic nano-building blocks
based on polyhedral oligomeric silsesquioxane (POSS) cages. [6,9] The aggregation of
POSS has been demonstrated to be the driving force for the formation of raft-like
structures and can lead to the formation of elastomers with physical crosslinks. [10]
However, despite the crystallinity of 4, no crystallization was observed in the case of
homopolymers, i.e. the highest loading possible (Figure 3.6 and 3.7). This dispersion can
be explained by the weakness of the intermolecular interactions between the boron
clusters. The aggregation of POSS depends chiefly on its periphery and is stronger in the
case of cyclopentenyl and phenyl peripheries.[ll] The presence of interlocked organic
side chains contributes greatly to the stability of the crystals made by these silicon oxide
clusters. Conversely, carboranes do not possess peripheral groups favoring
crystallization. Carborane clusters are known to be plastically crystalline, i.e. above a
certain temperature (approx. 120 K),[12] only their center of mass is located on a regular
lattice, which diminishes the likelihood of the clusters crystallizing within a polymeric
matrix.
67
-55-
>.
inc(D
wMiiiWKtHiij.^
10 20 30
29 (deg)
Figure 3.6 Wide angle X-ray scattering results for the series of polymers 3.
One could have thought that the crystalHzation of the boron clusters would have
been favored by the presence of more flexible segments of COE as well as by the
hydrogenation of the said chains. However, neither alternative to make the backbone
more flexible seemed to induce carborane crystallinity in these copolymer. We are
currently investigating what role the silyl group has on influencing this crystallinity, or
lack thereof. [8]
68
H-12(100)-D
H-12(75)D
H-12(50)D
H-12(25)D
2e (deg)
Figure 3.7 Wide angle X-ray scattering results for the series of polymers H-12.
The fact that the boron clusters do not aggregate could actually be advantageous.
In particular, their utilization as radiation shielding materials is envisaged (Appendix B).
Simulation studies by Singleterry et al. have highlighted the potential of '°B loaded
polyethylene as space survivable materials. [13] Additionally, Wilson et al. have pointed
out that polymeric materials are excellent candidates for space exploration because they
combine light weight, good and adjustable thermomechanical properties and are
relatively inexpensive to process. [14, 15] We believe that the present synthetic approaches
described here offer a level of control that could allow for tailoring of properties.
Furthermore, the elemental compositions allows for the thermalization of neutrons
through inelastic collisions with the hydrogens along the poly-ethylene like backbone as
well as neutron capture due to the high cross capture area of '*^B.[13,16]
69
3.4 Conclusions
We have reported the copolymerization of 4 and COE to obtain polyethylene-Hke
materials which incorporate carborane pendant groups. The reaction conditions for the
hydrogenation subsequent to the ROMP of the two monomers have been optimized. The
possibility to control the composition of the copolymer has been highlighted as well as
the influence of solvent polarity on the statistical polymerization. Thermogravimetric
analysis has shown enhanced thermal properties upon increasing the fraction of monomer
4 in the feed. Both differential scanning calorimetry and X-ray diffraction analyses
indicated the absence of crystallization of the boron clusters. Contrary to what could have
been expected, the hydrogenation and composition have no influence on the
crystallization behavior of the polymer.
3.5 References
[1] Y. C. Simon, C. Ohm, M. J. Zimny, E. B. Coughlin, Macromolecules 2007, 40,
5628.
[2] J. A. Love, J. P. Morgan, T. M. Tmka, R. H. Grubbs, Angewandte Chemie,
International Edition in English 2002, 41, 4035.
[3] M. F. Ilker, E. B. Coughlin, Macromolecules 2002, 35, 54.
[4] L. Morbelli, E. Eder, P. Preishuber-Pflugl, F. Stelzer, Journal of Molecular
Catalysis a-Chemical 2000, 160, 45.
[5] M. S. Sanford, J. A. Love, R. H. Grubbs, Journal of the American Chemical
Society 2001, 123, 6543.
[6] L. Zheng, R. J. Farris, E. B. Coughlin, Journal of Polymer Science, Part A:
Polymer Chemistry 2001, 39, 2920.
[7] S. F. Hahn, Journal of Polymer Science, Part A: Polymer Chemistry 1992, 30,
397.
[8] Y, C. Simon, E. B. Coughlin, Submitted.
70
L. Zheng, S. Hong, G. Cardoen, E. Burgaz, S. P. Gido, E. B. Coughlin,
Macromolecules 2004, 37, 8606.
B. Seurer, E. B. Coughlin, Macromolecular Chemistry and Physics 2008, 209,
1198.
A. J. Waddon, E. B. Coughlin, Chemistry ofMaterials 2003, 75, 4555.
R. H. Baughman, Journal ofChemical Physics 1970, 53, 3781.
R. C. J. Singleterry, S. A. Thibeault, LaRC NASA, 2000.
J. W. Wilson, F. A. Cucinotta, M. H. Y. Kim, S. W., in 1st International
Workshop on Space Radiation Research and 11th Annual NASA Space Radiation
Health Investigators' Workshop, 2001.
J. W. Wilson, M. S. Clowdsley, F. A. Cucinotta, T. R.K., J. E. Nealy, G. DeAngelis, 2002.
B. W. Robertson, S. Adenwalla, A. Harken, P. Welsch, J. I. Brand, P. A. Dowben,
J. P. Claassen, Applied Physics Letters 2002, 80, 3644.
71
CHAPTER 4
SYNTHESIS OF POLYFLUORENES WITH PENDANT SILYLCARBORANES
4.1 Introduction
For a little over 30 years, conjugated polymers have stimulated the imagination of
chemists, physicists and material scientists alike, and the desire to tailor properties
through careful design has continued unabated. [1,2] Aside from the mere scientific
curiosity, this desire has been fueled by the multitude of applications for which these
compounds are used: antistatic coatings, electrochromic pannels, polymer light-emitting
diodes (PLEDs), photovoltaic devices, e/c.[3] However, one of the highly sought-after
features of these materials, i.e. extended conjugation through aromatic moieties, is also
one of their pitfalls. The rod-like nature of these systems contributes to the tendency of
conjugated systems to bundle and jc-stack. These phenomena are detrimental to the
processability of such systems and pose subsequent problems in terms of their utilization
in optoelectronic devices. [4,5] To circumvent these issues, chemists have devised
synthetic strategies to confer solubility and stability to conjugated polymers while
preserving their remarkable properties.
Notably, 9,9-disubstituted polyfluorenes (PFs) have emerged as a unique class of
blue-emitting materials for PLEDs. [3,4] The planarization of the structure by the carbon
bridge and the possibility for facile property tuning and solubility via functionalization at
the 9 position as well as their remarkable quantum efficiency have made PFs a
noticeable candidate in the field of optoelectronics. [6] Despite the presence of these
solubilizing groups, commonly alkyl groups, it has been observed that upon applying a
72
current or upon annealing, the chains have the tendency to aggregate and various groups
have explored methodologies to efficiently thwart this phenomenon. [5,7] Notably, Miller
et al. have successfully illustrated the possibility to use fourth generation dendrons via
end-capping as a means to efficiently contravene stacking. Additionally, Mullen et al.
have demonstrated the utilization of polyaromatic dendrons as a successful strategy to
address this unwanted behavior. [5]
The utilization of boron in conjugated systems often stems from its Lewis acidic
character, which makes the resulting compounds particularly attractive for sensor
applications, and recently, copolymers of dibenzoborole and fluorene have been utilized
as a route to detect anionic contaminants. [8] Another strategy to introduce boron in
conjugated systems revolves around the utilization of carboranes. Several groups have
utilized these inorganic clusters, both in the main chain or as side groups, to provide these
systems with electrochemical stability and novel electronic properties, whether in small
molecules or in polymers. [9- 12] Particularly, seminal work by Vicente et al. on pyrroles
and thiophene has underlined the advantage of introducing carboranes as a way to
reinforce the thermo oxidative resistance of electronic materials. [13,14]
In the present document, we report the synthesis of a novel fluorene monomer 17
disubstituted with bulky silylcarborane clusters. The homopolymerization of 17 using
microwave-assisted Yamamoto coupling, as well as its copolymerization with 2,7-
dibromo-9,9-dihexylfluorene 18 are described hereafter. Finally, the spectral properties of
the homo- and copolymers are investigated and practical applications are discussed.
73
TBDMS3 ^OH
17
Figure 4.1 Synthesis strategies to attain monomer 17. i. CH2CI2, TsCl,
pyridine(dropwise); ii. CH2CI2, 0 °C, CBr4, PPhj; iii. THF, tBuOK, 2,7-
dibromofluorene; iv. PhH/Et20 (2:1 V:V), tBuOK, 2,7-dibromofluorene.
4.2 Experimental Section
4.2.1 Materials.
All organic reactants and reagents were purchased from Aldrich Chemical Co and
used as received unless specified otherwise. Anhydrous benzene and diethyl ether were
dried over sodium with benzophenone as an indicator. Dichloromethane (DCM) was
obtained through Fisher, distilled over calcium hydride and degassed with freeze-pump-
thaw cycles. 0-carborane was supplied by KatChem.
74
4.2.2 Instrumentation.
Gel permeation chromatography (GPC) measurements for the polymers were
performed in tetrahydrofuran (THF) at 1.0 mL/min using a Knauer K-501 Pump with a
K-2301 refractive index detector and a K-2600 UV detector, and a column bank
consisting of two Polymer Labs PLGel Mixed D columns at 40°C. All other
measurements were performed using a similar system with a column banks consisiting of
three Polymer Labs PLGel Mixed D columns at 40°C. Molecular weights are reported
relative to polystyrene standards.
'H NMR, "B NMR and '^C NMR were recorded at 300 MHz, 128 MHz and 100
MHz respectively on a Bruker NMR spectrometer at room temperature in deuterated
chloroform. The individual NMR spectral assignments do not list the carborane B-H
resonances. Due to the quadrupolar nature of boron, the resonances for the 10 B-H are
observed as broad multiplets (6 = 3.20-1.01 ppm). The integration of these multiplets
accounts for 10 H. Mehing points were measured with a mehing point apparatus
Electrochemical Mel-Temp in a capillary tube. For polymers 18, the number in
parenthesis represents the percentage of monomer 17 in the feed ratio.
4.2.3 Synthesis and Spectral Data
Preparation of 3-[2-(tert-butyl-dimethylsilanyl)-l,2-dicarha-closo-
dodecaboran(12)-l-yl]-propan-l-p-toluenesulphonate 15. [2-(/err-butyl-
dimethylsilanyl)-l,2-dicarba-c/o5o-dodecaboran(12)-l-yl]-propan-l-ol 1 (0.500 g, 1.5
mmol, 1 equiv.) was placed into a 50 mL two neck round bottom flask and flushed with
nitrogen. DCM (1.5 mL, freshly distilled from CaHi) was added and the solution was
75
cooled to 0°C. /7-Toluenesulfonylchloride (0.451 g, 2.3 mmol, 1.5 equiv.) was added
during a slight nitrogen overpressure, pyridine (0.25 mL, 0.248 g, 3.6 mmol, 2 equiv.)
was subsequently added. The reaction mixture was stirred at 0 °C for 4 h and the course
of reaction was followed by TLC (hexane/ethyl acetate, 3:1). After completion of the
reaction, ether (40 mL) were added, and the organic layer was washed with 40 mL of
each water, IM HCl and a 5% NaHCOs solution. The ether phase was then dried over
MgS04 and concentrated in vacuo to give 0.504 g of a white powder (71 % yield).
Recrystallization from acetonitrile afforded 0.41 1 g of pure product 15. (68% yield) High
Resolution MS (FAB-): m/z calcd 47L3296, found 471.3257; NMR (CDCI3): 6 (ppm)
= 7.76 (d, J= 8.35, 2H), 7.36 (d, J= 7.36, 2H), 3.99 (t, J,= 5.63, 2H, CH2OTS), 2.29 (m,
2H, CH2CH2OTS), 1.85 (m, 2H, CHs-Cage), 1.03 (s, 9H, CCH3), 0.31 (s, 6H, SiCHa); '^C
NMR (CDCI3): 5 (ppm) = 145.25, 132.63, 130.06, 127.85, 80.07, 77.47, 76.54, 68.80,
34.14, 29.37, 27.51, 2L67, 20.32, -2.52; m.p: 101 °C.
Preparation of l-bromo-3-[2-(tertbutyl-dimethylsilanyl)-L2-dicarba-closo-
dodecaboran(l 2)-1-yl]propane 16. [2-(^er/-butyl-dimethylsilanyl)-l,2-dicarba-c/o5o-
dodecaboran(12)-l-yl]-propan-l-ol 1 (500 mg, 1.58 mmol, 1 equiv.) and
carbontetrabromide CBr4 ( 785 mg, 2.37 mmol, 1.5 equiv.) were placed into a 50 mL
two-neck round-bottom flask and flushed with nitrogen. DCM (6 mL) was added and
after cooling the mixture to 0°C, triphenylphosphine (621 mg, 2.37 mmol, 1.1 equiv.)
was added to the solution with an slight nitrogen overpressure. After 3 hours of stirring,
the reaction solution was concentrated in vacuo and EtOH was added in order to
crystallize. After filtration, 474 mg of a white powder were obtained. (Yield 80%) High
Resolution MS (FAB-): m/z calcd 379.2374, found 379.2380; 'H NMR (CDCI3): 5 (ppm)
76
= 3.38 (t, 2H, CHzBr, J = 6 Hz), 2.39 (m, 2H, CH2CH2CH2), 2.08 (m, 2H, CHz-Cage),
1.10 (s, 9H, CH3C), 0.36 (s, 6H, CHsSi), '^C NMR (CDCI3): 5 (ppm) = 80.31, 76.36,
36.90, 32.54, 32.43, 27.78, 20.55, -2.23; m.p.: 91 °C.
Preparation of 2,7-dibromo-9,9-di[15]fluorene 17a. In a 50 mL round-bottom
flask flushed with nitrogen, 2,7-dibromofluorene (0.137 g, 0.425 mmol, 1 equiv.) and [2-
(?er/-buty1-dimethyIsilany1)- 1 ,2-dicarba-c/o50-dodecaboran( 1 2)- 1 -yl]-propan- 1 -p -
toluenesulphonate (0.5 g, 1.062 mmol, 2.5 equiv.) were dissolved in freshly distilled THF
and cooled to 0 °C. t-BuOK (1.3 mL of IM solution in THF, 3 eq ) was introduced
dropwise with a syringe over a period of 30 min. The solution was then heated to 40 °C
and the solution turned purple. After 1 day, the reaction was stopped by adding water (20
mL) and the product was extracted with 3 x 20 mL of DCM. The organic phases were
gathered and dried in vacuo to afford a sticky yellow solid which was recrystallized in
methanol (Yield 30%). For Characterization see 17b.
Preparation of 2, 7-dibromo-9,9-di{3-[2-(tertbutyl-dimethylsilanyl)-l,2-dicarba-
closo-dodecaboran(12)-l-yl]propane}fluorene from compound 17b. In a 25 mL 2-neck
round-bottom flask, 2,7-dibormofluorene (0.5g, 1.54 mmol, 1 equiv.) and tBuOK (415
mg, 3.70 mmol, 2.4 equiv.) were dissolved in 15 mL of a 4:1 mixture (V:V) of benzene
and diethylether. Upon addition of the solvent mixture, the solution turned deep purple.
To the solution, 3 (1.46 g, 3.86mmol, 2.5 equiv.) was added. The mixture was allowed to
react overnight and turned dark orange. To terminate the reaction, ethyl acetate (10 mL)
and water (20 mL) were added to the reaction. A slurry formed and was filtered. The
filtrate was washed with additional water (10 mL) and the solid was set aside. The
organic phase was dried over magnesium sulfate and concentrated in vacuo to afford a
77
yellow solid. The solid was rinsed with methanol to remove any remaining bromide. The
solid resulting from the filtration of the slurry was dissolved in dichloromethane (5 mL)
and methanol (20 mL) and the solution was concentrated in vacuo to give a yellow solid.
Both solids were combined and identified as monomer 17b (Yield = 65%). High
Resolufion MS (FAB-): m/z calcd 921.5210, found 920.5282; NMR (CDCI3): 5 (ppm)
= 7.6 (d, 2H, Jortho = 8.1 Hz), 7.53 (dd, 2H, Jonho = 8.1 Hz, J^eta = 1-5 Hz), 7.33 (d, 2H,
Jmeta = 1-5 Hz), 1.91 (t, 4H, J = 8.4 Hz), 1.82 (t, 4H, 7.8 Hz), 1.00 (s, 18H, CCH3), 0.80
(bm, 4H, CH2CH2CH2), 0.17 (s, 12H, SiCHj), '^C NMR (CDCI3): 5 (ppm) = 150.28,
139.09, 131.41, 125.93, 122.13, 122.04, 81.18, 76.12, 54.86, 39.30, 37.69, 37.60, 24.42,
20.44, -2.65;; m.p. = 235 °C.
Microwave-assisted of homo and copolymerization 18. In a microwave tube
equipped with a stir bar, the monomer (1 equiv.) was introduced as well as bipyridine
(2.2 eq). The tube was then pumped into a glove box and Ni(COD)2 (2.3 equiv.) was
added. The tube was sealed and taken out of the glove box. Additional COD (2.7 equiv.)
was added and the reagents were dissolved in 4 mL of a toluene:DMF (4:1) mixture. The
tube was quickly degassed and filled with nitrogen twice. The tube was then introduced
in a microwave apparatus and the solution was allowed to react for 20 min at 130 °C. The
solution was then filtered using a syringe mounted with filter paper as well as a 0.2 nm
anodisc filter and precipitated in 20 mL of a solution of acidified methanol (0.5M HCl).
A yellowish solid was recovered and identified as the desired polymer by 'H NMR
(Figures 4.2 and 4.3).
78
Results and Discussion
79
In order to synthesize monomer 17, a monofunctional silylcarborane moiety had
to be obtained. In chapter 2, a reliable method to obtain [2-(^err-butyl-dimethyl-silanyl)-
l,2-dicarba-c/o5'o-dodecaboran(12)-l-yl]-propan-l-ol 3 is reported. [ 1 6] The conventional
approach to obtain 9,9-disubstituted fluorenes involves deprotonating the benzylic bridge
using two equivalents of a base, and subsequently adding in excess of an electrophile,
usually an alkylbromide.[17] To emulate this strategy, the connectivity of 3 had to be
reversed so as to obtain an electrophilic moiety and this has been done using two routes
(Figure 4.1). First, using p-toluenesulfonyl chloride, the alcohol was tosylated affording
compound 15. [18] Alternatively, the connectivity reversal was undertaken by means of
an Appel reaction in the presence of triphenyl phosphine and carbon tetrabromide to
obtain compound 16. [19]
The next step was the coupling of 2,7-dibromofluorene with 2 or 3 to synthesize
the desired monomer 4 (Figure 4.1). After several optimization steps, the solvent was
chosen to be a 2:1 (V:V) mixture of benzene and diethylether. Remarkably, in spite of the
steric hindrance of the silylcarborane, no monosubstituted fluorene was observed or
recovered. Once the monomer was fully characterized, its polymerization was
undertaken. In order to homo- and copolymerize 4, microwave-assisted Yamamoto
coupling was performed (Figure 4.4). This nickel-mediated coupling usually proceeds
under mild conditions in excellent yields. [20] However, several groups have highlighted
the interest of utilizing microwave-assisted aryl-aryl couplings to accelerate the screening
process for novel polymeric semiconductors. [21] Additionally, through a significant
reduction of the formation of side products, the yields of the reaction are often increased
80
making microwave heating an ideal candidate for the laboratory synthesis of libraries of
optoelectronic materials. [22]
18(50)
Figure 4.4 Microwave assisted polymerization of 17: (a) homo and (b)
copolymerizations witii 2,7dibromo-dihexylfluorene.
For the Yamamoto protocol, the reaction sequence is reported to proceed through
an oxidative addition followed by disproportionation, and finally reductive elimination to
obtain the diaryl moiety. The last step is essential so as to understand some of the
limitations that one can face while using sterically hindered molecules. Under the current
conditions, the presence of bipyridine which binds to two adjacent coordination sites
facilitates the elimination of the aryl to form the covalent C-C bond. While this step is
crucial for the polymerization of 17, one can easily understand that, as the polymer starts
to grow, it becomes harder and harder for the aryl chains to approach each other, as the
81
silylcarborane groups contribute to steric crowding of the chains. This phenomenon
makes the hkelihood of two aryl moieties being in two adjacent coordination sites less
likely, as molecular weight increases, leading to an eventual plateau of molecular weight.
This trend has been observed for the synthesis of 18(100). The reaction temperature was
varied from 100 °C to 150 °C without any observable increase of molecular weight. The
number average molecular weight was found to plateau at approximately 7,000 g/mol
which, if the end of the polymers were to be brominated, corresponds to a degree of
polymerization, DPn = 8-9. This number is obviously a crude approximation since the Mn
are measured vs polystyrene standards and do not take into account the rigid nature of
18(100), but they allow us to get a sense how efficient the reaction was.
6 5
Mn = 1 3.000 gimol Mn = 7^0C>
POI = 2.15 POP =1.73
Elution Time (mrn}
Figure 4.5 Gel permeation chromatograms for polymers 18(100) and 18(50).
In the case of copolymerization, polymer 18(50) was found to attain higher
molecular weights, which can be explained by the diminution of steric hindrance with the
introduction of linear «-hexyl side groups. This increase in molecular weight is
corroborated by the red shift in the emission spectrum of 18(50) with respect to 18(100)
82
(Figure 4.6B). This displacement towards the high wavenumbers is consistent with the
molecular weight of 18(100) being below the threshold (~ 10 units) after which
conjugation length is no longer affected by the DPn.[4] Additionally, the fluorescence
emission and UV absorption sharpen with higher MW, consistent with studies of other
oligomeric polyfluorenes.[15]
260 280 300 320 340 360 380 400 420 440 460 480 500-v.^^ : 1
.,
• 1 .1
. 1 .
Wavelength (nm) 300 350 400 450 500 550
Wavelength (nm)
Figure 4.6 UV absorption (left) and emission spectra (right) for polymers 18.
Similarly to the work by Shim, Wei and Tang where polyhedral oligomeric
silsesquioxane cages were added as a way to enhance thin film stability of PFs,[7,23,24]
the present work is thought to provide an elegant alternative to provide enhanced
resitance to thermal treatment. The behavior of the thin films is currently being
investigated so as to determine to what extent silylcarboranes contribute to stabilizing
PFs structures upon annealing. More importantly, polymers 18 are thought to be
interesting materials for neutron detection. [25] The high boron content coupled with the
83
high neutron capture area of '^B could potentially lead to a pathway for the detection of
fissile materials.
Several routes could contribute to the detection of neutrons. First, the ionizing
particles emitted upon capture of a thermal neutron can cause ionization of the
conjugated backbone leading to changes in its emission. Alternatively, one could utilize
the secondary gamma radiation to detect the presence of a neutron. Pei et al. have
demonstrated the use of PFs blends with dyes and gamma sensitizers for the detection of
gamma rays. [26] Inspired by this methodology, the utilization of carborane-containing
PFs could offer an interesting alternative to costly gas chamber detectors. Finally, studies
to introduce the carborane in the backbone are underway. This last approach is thought to
be even more promising for neutron detection, in that the conjugation of the polymer
would be directly modified by the loss of a-aromaticity upon neutron capture. Moreover,
the electronics of the subsequent polymers might lead to electrochemically stable PFs
with unique emission spectra.
4.4 Conclusions
We have successfully developed a new monomer, 17, that allowed for the
synthesis of polyfluorenes with bulky silylcarborane side chains. It was observed that the
molecular weights of the homopolymers was constrained by steric limitations and that its
fluorescence maximum was blue-shifted with respect to conventional fluorenes. To
remediate this phenomenon, copolymerization with 2,7-dibromo-9,9-dihexylfluorene was
undertaken leading to a significant increase in molecular weight. Both homo- and
copolymerizations studies were performed using microwave-assisted Yamamoto
84
couplings. Finally, we have alluded to some of the potential applications of such
materials, including stabilization upon annealing as well as utilization in neutron
detection, and alternative strategies incorporating carboranes in the main chain have been
depicted and are currently being investigated.
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C. H. Chou, S. L. Hsu, K. Dinakaran, M. Y. Chiu, K. H. Wei, Macromolecules
2005, 38, 745.
A. J. Peurrung, Nuclear Instruments & Methods in Physics Research Section a-
Accelerators Spectrometers Detectors and Associated Equipment 2000, 443, 400.
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10, 1848.
86
CHAPTER 5
DEVELOPMENT OF SILYLCARBORANE MONOMERS FOR LITHOGRAPHY
5.1 Introduction
Carboranes, and more specifically icosohedral carbaboranes, have been utilized in
various areas of research, including boron neutron capture therapy,[l-3] non-linear
optical materials and super-acid chemistry. [4,5] Recently, carborane-containing polymers
have shown promising results in a variety of nanotechnological applications, [6] and more
specifically in lithographic systems. [7-9] For instance, Ober has synthesized boron-
containing polymeric resists for EUV lithography starting with poly(styrene-Z)- 1,2-
butadiene) copolymers followed by a post-polymerization functionalization approach
employing the pendant olefins and a hydroboration/hydroxylation procedure to attach
pendant carborane cages. [7] The advantage of tethering inorganic clusters to a polymeric
matrix is that both the processability of polymers and the etch resistance of inorganics are
combined within a single material. The resistance of inorganic clusters stems from the
potential of forming non-volatile oxides upon treatment with an oxygen plasma. Boron
clusters are particularly interesting from the standpoint of generating novel of resists
because of their transparency to UV, and particularly extreme UV.[10]
With applications ranging from microelectronics to protein nanoarrays,[l 1,12]
nanoimprint lithography (NIL) is a very useful technique whose domain of utilization is
continuously expanding thanks to its ease of implementation and high-throughput
capability. [13] Nanoimprint lithography is intriguing from a cost perspective since
imprint systems do not require the sophisticated optics of conventional steppers. Rather,
87
imprint lithography uses polymers that harden while conforming to a physical template
upon exposure to ultraviolet light or upon a thermal actuation. In particular, UV
nanoimprint lithography (UV-NIL) limits pattern distortion and accelerates the
patterning process. [14] It is therefore a particularly attractive nanopatteming method. As
UV-NIL grows into a widespread patterning technique, the composition of UV-
crosslinkable resists becomes accordingly more and more diversified and sophisticated.
One can draw similarities among the formulations used in conventional photoresists.[15]
These comprise a series of monomers, for polymerization (monofunctional), crosslinking
and etch resistance, as well as a UV-sensitive free radical initiator. All of these
components are dissolved in a suitable solvent to allow for spin-casting. Additionally, the
viscosity of the ensemble is controlled to permit low-temperature embossing.
One of the most critical material components in the imprint lithographic process is
the photopolymerized resist layer; sometimes this resist layer is called the etch barrier or
imaging layer. The resist polymer chemistry needs to be designed so that it provides
higher etch resistance (selectivity) than the underlying layer which allows for pattern
transfer. While NIL resists that contain no inorganic additives have been used to make
patterned magnetic media with features as small as 35 nm, performance is limited by the
innate material properties of the resist layer. [16] Several advances have been made to
improve the properties of resists for NIL. One of the challenges associated with the
fabrication of metalized features at the nanoscale resides in the fabrication of overhang
structures that are convenient for the lift-off step. Matsui et al. have elegantly addressed
the issue of lift-off by utilizing water-soluble poly(vinyl alcohol) as the replicated
material. [17] This method is all the more interesting as it opens new perspectives in terms
88
of "green chemistry". However, such a technique requires the use of thermal NIL which
could eventually pose problems for the replication of small features in addition to the
associated costs. Willson et al. have shown more recently a method whereby the
imprinted resist could be un-crosslinked to allow for facile stripping of the copolymer
network, constituting the resist.[15] Carter has demonstrated an improved nanoimprint
lithographic process involving the pre-curing using a commercial polyurethane resist
which was used to make transistor devices after lift-off. [16]
Introduction of inorganic materials into resists has been a common route for
increasing oxygen plasma etch resistance. For example, the Willson group embraces the
use of siloxane-containing aerylate monomers in their NIL resist formulations. [14]
Carter recently reported the use of phosphazene-containing monomers in UV-NIL
formulations leading to excellent etch resistance properties. [18]
Lift-off is a particular concern when the mask features are shallow.[19] In order to
obtain a homogeneous pattern across a silicon wafer regardless of its roughness, it is
preferable to obtain features with high aspect ratio. That is why one must design and
formulate resists that will provide sufficient etch resistance to allow for pattern
amplification (Scheme 5.1). This property will facilitate pattern transfer as it eases the
lift-off step, by allowing the solvents to penetrate below the metalated features. This is
critical for the broader implementation ofNIL.
89
Scheme 5.1 Illustration of the use of an etch-resistant imprint layer for pattern
amplification in metallization processes.
Unamplified features Amplified features
Metallation
Lift-off
Partial lift-off
Unresolved pattern
In this report, the synthesis of a well-defined acrylate monomer containing both
boron and silicon and its incorporation into a UV-NIL resists is described. The resistance
to oxygen plasma etching is compared to a conventional resist formulation. We then take
advantage of the etch resistance of silyl-fiinctionalized carboranes to enable the
fabrication of high aspect ratio features. Microscopy combined with profilometry was
utilized to demonstrate pattern amplification. The patterns were subsequently metalized,
and the lift-off step was shown to be improved by the presence of boron and silicon in the
resist formulation.
5.2 Experimental Section
5.2.1 Materials.
All solvents and reagents were obtained from Aldrich and VWR and were used
without further purification unless specified otherwise. Single sided polished mechanical
grade 1.5" silicon wafers were purchased from University Wafer. Ethoxylated bisphenol
A dimethacrylate from Sartomer, methanol and chlorodimethyloctylsilane 97%, from
Fisher, 2-ethyl-2-(hydroxymethyl)- 1,3 -propanediol triacrylate, 2,2-dimethoxy-2-
90
phenylacetophenone, 2-hydroxyethyl methacrylate (HEMA) 98%, «,«'-
azoisobutyronitrile (AIBN) 98%, 1 -dodecanethiol 98%, 3-(trimethoxysilyl)propyl
methacrylate 98%, propylene glycol methyl ether acetate (PGMEA), from Sigma-
Aldrich, Gold 99.999% (Kurt J. Lesker), chromium (R. D. Mathis), were used as
received. The silylcarboranylpropanol 3 was prepared as previously described.[20,21]
Patterned silicon wafers containing test patterns and transistor structures were fabricated
by known photolithographic processes.
5.2.2 Instrumentation.
'H NMR and '^C NMR were recorded at 300 MHz and 100 MHz respectively on
a Bruker NMR spectrometer at room temperature in deuterated chloroform. The
individual NMR spectral assignments do not list the carborane B-H resonances. Due to
the quadrupolar nature of boron, the resonances for the 10 B-H are observed as broad
multiplets (5 (ppm) = 3.20-1.01) . The integration of these multiplets accounts for 10
hydrogens. Gel permeation chromatography (GPC) measurements for the lift-off layer
polymer were performed in tetrahydrofuran (DMF) at 1.0 mL/min using a Knauer K-501
Pump with a K-2301 refractive index detector and a K-2600 UV detector, and a column
bank consisting of two Polymer Labs PLGel Mixed D columns at 40°C. All other
measurements were performed using a similar system with a column banks consisiting of
three Polymer Labs PLGel Mixed D columns at 40°C. Molecular weights are reported
relative to polystyrene standards.
Photopolymer Mold Preparation. Glass cover slips of #2 thickness from Fisher
were rinsed with acetone, isopropanol and dried under a stream of N2. The surface of the
91
glass was then activated by exposure to 100 millitorr oxygen plasma at 30 W for 7 min.
Immediately after activation the glass pieces were immersed in a dry, N2 purged toluene
solution containing 3-methacryloxypropyl trimethoxysilane (1% v/v) and heated at 80°C
for 12 hrs to assemble an adhesion monolayer. Patterned Si masters were cleaned by
exposure to O2 plasma for 3 min, coated with chlorodimethyloctylsilane, and heated to
130 °C for 20 min to create a protective alkyl release layer to ensure proper separation of
the cured photopolymer mold. Polymeric relief structures were formed on the treated
glass by placing a small drop (~ 50 |il) of a photocurable acrylate resin (Formulation A)
containing ethoxylated bisphenol A dimethacrylate 76.5 wt %, 2-ethyl-2-
(hydroxymethyl)-l,3-propanediol triacrylate 23.2 wt %, and 2,2-dimethoxy-2-
phenylacetophenone 2.5 wt % as initiator on the silicon master and carefully laying a
piece of treated glass over the drop allowing capillary forces to spread the resin between
the two surfaces. The two pieces were then exposed to 365 nm UV light to cure the resin.
Careful separation of the two surfaces yielded nano-pattemed features bonded to the glass
slide. A release layer was applied over the cured polymer features to aid separation
during the contact molding process.
Contact Molding with Etch Resist. Si substrates were cleaned by rinsing with
THF, acetone, and isopropanol, and blown dry with a stream of N2.
Poly(hydroxyethylmethacrylate) (PHEMA) (6.5 wt% in methanol) was applied to the
substrate and spun at 3000 rpm for 10 sec followed by baking at 130 °C for 30 sec
forming a 180 nm thick PHEMA film. An adhesion promoter, 3-(trimethoxysilyl)propyl
methacrylate, as was then applied and spun at 3000 rpm for 5 sec and the sample was
baked at 130 °C for 1 min. Excess adhesion promoter was washed off by spinning under
92
a pure stream of PGMEA for 15 sec at 3000 rpm followed by drying with N2.
Photopolymer by itself or loaded with 10 wt% carborane-acrylate, diluted in PGMEA to
10 wt% overall, and filtered through a 0.45 ^im syringe filter, was then applied and spun
at 3000 rpm for 1 5 sec.
Immediately after spin coating, a mold was placed directly on the photopolymer
film and the setup was inserted into the NX-2000 imprinter. After pressurizing to 75 psi
the photopolymer was cured by 365 nm UV light for 30 sec. Release of the sample from
the mold yielded patterned substrates.
Etching, metal deposit, and lift-off step. Patterned films were etched in a Trion
Technologies Phantom III inductively couple plasma (ICP) reactive ion etcher (RIE)
under 250 milliTorr of O2 pressure at a flow rate of 49 seems, with ICP and RIE power of
500 W and 25 W, respectively, until the underlying silicon wafer was exposed in the
recessed regions throughout the imprint (-80 sec for photopolymer and -105 sec for
photopolymer/carborane acrylate). Etched wafers were coated with approximately 2 nm
of chromium followed by 10 nm of gold by vacuum evaporation. Lift-off was achieved
by sonication in warm methanol for 5 to 10 min followed by a methanol rinse.
5.2.3 Synthesis and Spectral Data.
Synthesis of silylcarborane acrylate 19. In a dry round-bottom flask,
silylcarboranylpropanol (1 equiv.) was dissolved in freshly distilled ether. The solution
was placed under a nitrogen flow with constant agitation, and triethylamine (1.5 equiv.)
was added dropwise with a syringe. The mixture was cooled to 0 °C and acryloyl
chloride (1.3 equiv.) was added dropwise to the solution. Upon addition, a white
93
precipitate formed indicating of the formation of the triethylammonium salt. The mixture
was then allowed to warm up to room temperature and stirred for one hour. A solution of
saturated brine was then added and the organic phase and aqueous phase were separated
in a separatory funnel flask. The aqueous phase was further extracted with 2 x 50mL of
diethyl ether. The organic phases were combined and dried over MgS04 and concentrated
in vacuo to afford a yellowish powder. The powder was then dissolved in boiling hexanes
and recrystallized at -4 °C (Yield = 73%). 'H NMR (CDCI3, 400MHz): 5 (ppm) = 6.40
(q, IH, Jtrans= 16Hz, Jgem = 1 .6Hz), 6.07 (q, IH, Jcs = 9.2Hz, Jtrans= 1 6Hz), 5.85 (q, IH,
Jgem = 1.6Hz, Jcs = 9.2Hz), 4.14 (t, 2H, CH2O), 3.20-1.01 (br, lOH, BH, CH2, CH2CB),
1.05 (s, 9H, SiCH3), 0.26 (s, 6H, CCH3); '^C NMR (CDCI3): 165.93, 131.35, 127.96,
80.51, 76.25, 63.13, 34.73, 29.38, 27.59, 20.35, -2.49.
Synthesis of poly(hydroxyethylmethacrylate) (PHEMA). Ethanol (7.5 mL) was
charged in a 25 ml round bottom flask and nitrogen was bubbled for 5 minutes. AlBN
(0.07 g, 0.43 mmol), HEMA (5.37 g, 5 mL, and 41.31 mmol) and dodecane thiol (0.43 g,
0.5 mL) were dissolved in the ethanol, the flask was sealed with a rubber stopper, and the
solution was heated under N2 at 60°C for 4 hours with stirring. The solution was cooled
and precipitated dropwise into hexanes. The polymer was filtered, washed with hexanes
and dried to obtain polyhydroxyethylmethacrylate (PHEMA) (4.5 g, 84%) as a white
solid. GPC data (in DMF): Mn=32,000 g/mol, PDI = 1.37.
94
OH
a) Dry EtjO, NEtg
b) 0"C,
5.3 Results and Discussion
We focused on developing a novel type of etch resistant monomer to facilitate the
lift-off process in the case of shallow patterns allowing for the fabrication of cleaner
metalated structures by NIL. The synthesis of silylcarborane acrylate 19 is depicted in
Figure 5.1. The optimized preparation of 3 that was based on a previous synthesis
published by Hawthorne is described in Chapter 2.[21] The incorporation of a silyl group
on the carborane serves a dual purpose. In the first case the steric demands of this group
ensures monosubstitution of ortho carborane allowing for the high yield preparation of 3.
Additionally, the presence of silicon will contribute to reinforcing the overall etch
resistance of the material by adding one more element capable of forming a stable non-
volatile oxide upon oxygen plasma treatment. The slow dropwise addition of acryloyl
chloride to a cooled solution of 3 in dry diethyl ether, in the presence of a slight excess of
a base scavenger (NEts), results in the formation of silylcarborane acrylate 19 and the
concomintant production of triethylammonium chloride. Following standard liquid-
liquid extraction procedure and recrystallization from hexanes 19 was obtained in good
yield as a colorless solid.
95
Figure 5.2 Components of the photopolymer solution (Formulation A)
To evaluate the etch resistance enhancement provided by the incorporation of the
silylcarborane acrylate monomer 19, two solutions were spun-cast from propylene glycol
methyl ethyl acetate (PGMEA) onto silicon wafers, cured under a UV lamp and etched
using oxygen plasma. The first formulation (A) was a conventional resist used for
nanoimprint lithography and served as a control (Figure 5.2). The second formulation
(B) was prepared by taking Formulation A and adding 10% by weight of 19. Figure 5.3
illustrates the difference in etch rate between the control formulation A, and the
carborane-containing counterpart formulation B. Assuming that both UV cured materials
are homogeneous along the direction perpendicular to the wafer and that the etch rates of
both materials are linear with respect to etching time, etch rates of approximately 268
nm/min for A and 163 nm/min for B were obtained. These results were obtained by
averaging the thicknesses measured by spectral reflectance of ten spots per cured sample.
96
600-
550-
500
450
400
350
300
250
200
150
100
50-1
0
Formulation AFormulation B (10% Carborane)
T ' I ' r00 02 04 06 08 1 0 1 2 1,4 1 6 1 8 20 2,2
Etch Time (min)
Figure 5.3 Determination of etch rates of the control formulation (A) and the
modified (B) resists.
Once the enhanced etch resistance was estabHshed, imprints were performed with
the two formulations. Table 5.1 combines the results obtained by profilometry in both
cases. Given that the same mask was utilized for A and B, it was expected to find similar
imprint depths and this finding suggests that the incorporation of the silylcarborane
acrylate does not dramatically affect the template filling dynamics of the resist precursor.
However, the drastic difference in feature depth after etching, here referred to as etch
depth, confirms the possibility to amplify features by means of incorporation of 19. The
amplification factor can better be appreciated by plotting the imprint depth and etch depth
in a bar chart (Figure 5.4).
97
Table 5.1 Imprint and etch profilometry results
Sample A Bimprint depth 55.41 56.91
etch depth 63.64 130.97
height change 8.23 74.06
(nm)
Amp Factor 1.15 2.30
% change 14.85% 130.14%
Depth Amplification
150.00
— 130.00
c
£ 110.00Q.<X)
T5
2i 90.00
^ 70.00
50.00
Figure 5.4 Bar chart for visual aid of depth ampliflcation from etch resists A and B.
Two patterns, small and large interdigitated electrodes, were imprinted onto the
resists to demonstrate visually the difference in depth amplification. The patterns were
imprinted and etched using an oxygen plasma reactive ion etch (RIE). Micrometric
features were chosen so as to facilitate the characterization of the imprints and all images
are taken at the point of break-through to the underlying wafer during RIE. In the case of
imprints realized with the conventional formulation A (Figure 5.5, i and iii), a brown film
can be observed indicating that the film covering the surface is relatively thin. In contrast,
a blue color can be observed when 19 is introduced (Figure 4, ii and iv). The blue color is
attributed to spectral reflectance due to constructive interference between the beams of
light reflecting from the surface of the film and the substrate. This coloration is an
98
imprint depth
cLch depth
A
additional qualitative confirmation of the efficacy of 19 to act as an etch resistant
additive.
Figure 5.5 Imprinted and etched device features. On the left are features patterned
into unmodified formulation A (i) and (iii), on the right are the same features
patterned into formulation B, (ii) and (iv).
This difference in resist thickness at break-through is critical as far as allowing
the patterns to be used successfully in a lithographic process. The patterns were coated
with gold by vacuum evaporation and a lift-off step was performed using methanol. After
metallization and lift-off, it can be clearly seen that the thickness of the features prepared
using formulation A were not tall enough to allow easy diffusion of the lift-off solvent
99
under the interdigitated features (Figure 5.6 and Scheme 5.2). However, in the case of
the ampHfied features prepared by means of incoprorating the carborane-modified resist
B, the lift-off easily resolves the interdigited lines.
Figure 5.6 Patterned gold features, (i) Unresolved interdigitated electrodes using
formulation A as an imprint layer (top) and (ii) using the B resist resolved patterns
are observed (bottom).
The difference in thickness at breakthrough actually originates from the difference
in etch resistance between the imprint layer and the lift-off layer. In the case of the
conventional formulation (A), both the imprint layer and the lift-off layer have
comparable etch resistance which translates into virtually no amplification of the patterns.
In contrast, the carborane containing formulation (B) is resistant enough to RIE to afford
an amplification of the interdigitated electrode pattern (Scheme 5.2).
100
Scheme 5.2 Comparative schematic illustrating the mechanism by which the
patterns are obtained. The brown layer represents the silicon wafer, the gray layer
is the imprint layer and the top layers are the two respective types of formulations.
Silylcarborane-containingConventional resist
resist
Unresolved
interdigitated
electrodes
Pattern
Amplification
Resolved
interdigitated
electrodes
5.4 Conclusion
A novel acrylate monomer 19 containing an inorganic boron cluster that is further
fiinctionalized with a silicon-containing group has been synthesized. Incorporation of
10% by weight of the silylcarborane acrylate 19 in formulation for UV-NIL showed a
significant improvement in the etch resistance of the imprint layer. Additionally, the etch
rates measured using an oxygen plasma were considerably decreased relative to a control
sample lacking both boron and silicon and lead to an amplification improvement of a
101
factor of two. The latter contributed to facilitating the lift-off step after metallization of
interdigitated electrode patterns. The utilization of inorganic cluster additives in resist
technology is a novel approach to the appliflcation of features in UV-NIL and we are
currently investigating the possibility to expand this methodology to other types of
inorganic cluster additives.
5.5 References
[I] M. F. Hawthorne, Angewandte Chemie, International Edition in English 1993,
950.
[2] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Journal of the
American Chemical Society 2005, 727, 12081.
[3] J. F. Valliant, K. J. Guenther, A. S. King, P. Morel, P. Schaffer, O. O. Sogbein, K.
A. Stephenson, Coordination Chemistry Reviews 2002, 232, 173.
[4] D. M. Murphy, D. M. P. Mingos, J. M. Forward, Journal ofMaterials Chemistry
1993, 5, 67.
[5] C. A. Reed, Chemical Communications 2005, 1669.
[6] P. R. L. Malenfant, J. Wan, S. T. Taylor, M. Manoharan, Nature Nanotechnology
2007, 2, 43.
[7] J. Dai, C. K. Ober, Proceedings of SPIE-The International Society for Optical
Engineering 2003, 5039, 1 1 64.
[8] J. Dai, C. K. Ober, Proceedings of SPIE-The International Society for Optical
Engineering 2004, 5376, 508.
[9] J. Dai, C. K. Ober, L. Wang, F. Cerrina, P. Nealey, Proceedings of SPIE-The
International Societyfor Optical Engineering 2002, 4690, 1 193.
[10] D. Bratton, D. Yang, J. Y. Dai, C. K. Ober, Polymers for Advanced Technologies
2006, 17, 94.
[II] B. D. Gates, Q. B. Xu, M. Stewart, D. Ryan, C. G. Willson, G. M. Whitesides,
Chemical Reviews 2005, 705, 1 1 71
.
[12] L. J. Guo, Journal ofPhysics D-Applied Physics 2004, i7, R123.
102
[13] P. R. Krauss, S. Y. Chou, Applied Physics Letters 1997, 77, 3 1 74.
[14] M. D. Stewart, C. G. Willson, Mrs Bulletin 2005, 30, 947.
[15] F. Palmieri, J. Adams, B. Long, W. Heath, P. Tsiartas, C. G. Willson, ACS Nano2007, /, 307.
[16] I. W. Moran, A. L. Briseno, L. S., K. R. Carter, Chemistry of Materials 2008, 20.
[17] K. Nakamatsu, K. Tone, S. Matsui, Japanese Journal ofApplied Physics Part l-
Regular Papers BriefCommunications & Review Papers 2005, 44, 8186.
[18] E. C. Hagberg, M. W. Hart, L. H. Cong, C. W. Allen, K. R. Carter, Journal ofInorganic and Organometallic Polymers and Materials 2007, 17, 377.
[19] L. J. Guo, Advanced Materials 2007, 19, 495.
[20] F. A. Gomez, M. F. Hawthorne, Journal ofOrganic Chemistry 1992, 57, 1384.
[21] Y. C. Simon, C. Ohm, M. J. Zimny, E. B. Coughlin, Macromolecules 2007, 40,
5628.
103
CHAPTER 6
CONCLUSIONS AND RECOMMENDATIONS
This final Chapter comprises two parts. The first section provides an overview of
the work described in Chapters 2 through 5. In the second part, each Chapter is revisited
individually, providing an outline of future directions for the projects and suggesting
some possible project extensions based on preliminary data.
6.1 Dissertation Summary
The main goal of this work was to understand and overcome the challenges
associated with the incorporation of carboranes in polymeric architectures. In order to
realize the versatility of carborane-based inorganic-organic hybrid materials, novel
synthetic strategies have been developed allowing for the creation of unique functional
materials. This dissertation illustrates how the utilization of well-defined inorganic
clusters tethered to a polymerizable handle leads to novel hybrid materials that are easily
characterized and whose range of application is immense. Rather than focusing on one
particular application, the approach taken here was meant to open up new areas of studies
in the field of hybrid materials in general, and in the realm of carborane-containing
polymers in particular. This strategy has proven to be fruitful as it allowed for the
development of four distinct projects described in Chapters 2-5.
The present work complements previous studies on the incorporation of silicon
oxide frameworks in polymeric architectures.[l] The key to all chapters was the synthesis
of monofunctional carborane alcohol and its subsequent modifications to yield a
polymerizable moiety. This synthesis was achieved using silicon protecting groups by
104
improving the reliability of previously published protocols. [2] Although this was not the
emphasis of the present work, the presence of /erZ-butyldimethylsilyl protecting group
imparted some very important characteristics to the polymers. As will be discussed in
section 6.2.2, the presence of the silyl group seems to have an unforeseen role in the
ROMP of monomer 4 present in both Chapters 2 and 3. The presence of the bulky silyl
group was a very important part in the addition of sterically hindered side-chains
disrupting molecular packing (Chapter 4). In Chapter 5, the presence of a silyl group
contributed to the incorporation of etch resistant silicon in the resist formulation.
In Chapter 2, the first examples of amphiphilic diblock copolymers have been
described. In order to achieve this goal, a new oxanorbornene monomer was developed
and ROMP was chosen as a versatile method of polymerization. It is important to observe
that the reported work is only the second type of controlled blocky architectures
containing carboranes.. Two different approaches were utilized. The first route is based
on polycationic species obtained after acidic cleavage of a ?erf-butoxycarbonyl group.
The resulting ammonium provided the necessary water solubility to the second block and
offered a latent reactive site for the coupling of a rhodamine-B isothiocyanate dye and
attachment of PEG-groups by means of a Michael addition. Confocal microscopy
revealed the internalization of the labeled polymer inside the cells. Additionally, the
solution behavior of these polymer was monitored by dynamic light scattering and atomic
force microscopy and it was found that these polymers aggregate as spherical micelles in
aqueous solution.
The second approach (Chapter 2) is a somewhat more direct approach to the
introduction of PEG side chains into the polymer using a PEG norbomene ester. The
105
sequential addition of three monomers afforded a block copolymer that was further
labeled using nitrobenzoxadiazole. Both routes allowed for the synthesis of blocky
architectures with excellent control over the polydispersity of the resulting copolymers.
Chapter 3 is a direct extension of the polymerization studies done in Chapter 2.
The carborane-based oxanorbomene was copolymerized with cyclooctene to yield
polyethylene-like materials. Remarkable structural changes were observed as the polarity
of the reaction solvent was modified. Despite the crystallinity of monomer 4 and contrary
to what has been found in the case of silicon oxide nanoclusters, no crystallization was
observed, even when introducing flexibility into the chain by means of hydrogenation or
by increasing the loading of cyclooctene. As observed for other hybrid materials, the
thermal properties were improved by increasing the carborane loading.
While studying the crystallization behavior of SONIC-COE copolymers, the
potential to incorporate bulky silylcarborane pendant groups to give particular properties
to polyaromatic structures became apparent. In Chapter 4, the development of
silylcarborane-containing fluorene was achieved based on the reversal of connectivity of
alcohol 3 in two ways: a tosylation and a bromination using an Appel reaction. The latter
proved to be more efficient as the yields were significantly improved to obtain a
dibromofluorene with two bulky silylcarborane side chains. Using microwave-assisted
Yamamoto-coupling, it was observed that the molecular weights of homopolymers was
limited due to steric hindrance. Copolymers of dihexylfluorene and carborane-containing
monomer 17 were performed to circumvent this limitation. As anticipated, the
introduction of a monomer with less steric hindrance led to higher molecular weight
106
polymers. This finding was corroborated by the red-shift observed in solution indicating a
longer conjugation length.
Finally, in Chapter 5, a new silylcarborane acrylate has been synthesized and
incorporated in formulations for imprint lithography. With as little as 10% incorporation,
the modified resists showed significant improvement in etch resistance upon plasma
treatment, with amplification factors above two for the imprinted layers. The modified
formulation allowed for facile lift-off after metallization of interdigitated electrode
patterns.
As of 2003, only one published record of boron clusters in controlled polymeric
architectures existed. Since then, a strong push for carborane-containing polymers has
been witnessed, highlighting the relevance of the work described in this manuscript. [3 -8]
This dissertation opens up unique avenues for research in the field of carborane-based
polymeric architectures. The following section highlights some of the possible
continuations of the present work, some of which are already well underway. Due to the
different nature of each subject developed in Chapter 2-5, the recommendations made
here will follow the arrangement of the dissertation.
6.2 Future work
6.2.1 Materials for BNCT
In Chapter 2, novel carborane-based amphiphilic architectures have been
developed. One obvious extension of this work is evaluating the potential of these
materials as BNCT agents. Initial in vitro studies have shown the internalization of the
charged amphiphilic structures into human epithelial carcinoma cells. In order to identify
107
whether these types of architectures are viable alternatives to the current delivery
methods used in BNCT,[9] more thorough in vitro testing is needed. In particular, it will
be critical to find a way to assess the quantity of boron internalized by the diseased cells,
to investigate the chances of success for this approach. Another critical point that needs
to be addressed is the efficacy of these materials in intravenous deliveries. PEG chains
along the backbone of the polymers were specifically incorporated so as to improve the
pharmacokinetics of the polymeric drug. [10] The success of this strategy can only be
monitored by the use of animal models to evaluate the stealth nature of these systems.
The advantage of utilizing polymers in drug delivery stems from the possibility of
introducing a whole array of functionalities, such as markers or site-specific tags. In
particular, seminal work by Kiessling et al. has demonstrated the possibility to
polymerize gadolinium chelating norbomene moieties to serve as magnetic resonance
imaging contrast agents. [11] The copolymerization by ROMP of these markers with the
monomer designed in Chapter 2 will facilitate the implementation of in vivo testing of the
presented architectures. Additionally, one can also think of adding cancer-specific tags
such as cholesterol or folic acid, to specifically target the malignant tissues. [12, 13]
Finally, aUhough the utility of ROMP to synthesize controlled architectures for
drug delivery has been demonstrated, some questions still remain unanswered in terms of
the biocompatibility of these macromolecules. Another very interesting approach consists
in utilizing polyesters and click chemistry. The fact that polyesters can be easily
hydrolyzed in the body by enzymatic reactions makes them attractive biodegradable
delivery vehicles. Emrick et al. have demonstrated the usefulness of such strategies for
attachment of cationic polypeptides for gene delivery by click chemistry. [14] Based on
108
that work. Figure 6.1 illustrates a possible synthetic strategy to obtain water soluble
carborane-based polyesters.
b) NaNg
V
Figure 6.1 Synthetic strategy towards biodegradable BNCT agents
6.2.2 Influence of the silyl-protecting group and utilization in radiation shielding
applications
As discussed in Appendix B, the copolymers of cyclooctene and monomer 4 offer
numerous advantages in terms of composition which could make them excellent
candidates for radiation shielding applications. Therefore, initial simulation work needs
to be done to evaluate the shielding potential of these materials. In parallel, these
polymerization reactions need to be scaled up to evaluate the thermomechanical behavior
of the obtained structures. Mechanical integrity will play a major role in the use of
109
polymers as radiation protection. Although the chemistry shown here presents some
undeniable advantages in terms of multifunctionality, it is naive to believe that they will
solve all problems and an integrative engineering approach will probably be necessary to
incorporate these materials into functional radiation protection systems, such as space
suits or rovers.
Aside from these very practical considerations, the work presented here raises a
number of more fundamental questions, which are maybe even more interesting. In
particular, the observation that in the presence of amines at elevated temperatures the
silyl group has a tendency to cleave off the carborane cage might be an alternative
strategy for the synthesis of heterodifunctional carboranes. It is important to notice that in
both cases there is an available source of hydrogen in the reaction media: residual acid
from the ammonium in Chapter 2, /?t7ra-toluenesulfonylhydrazide in Chapter 3. Further
studies will have to determine whether this proton source plays a role in the cleavage of
the silyl protecting group. This information will in turn allow for the development of
novel protection-deprotection strategies that can be important in carborane chemistry.
Conversely, the discovery of the possibility to cleave the silyl group in the
presence of amines raised some additional questions regarding the importance of the silyl
group on the morphology and thermomechanical properties of the polymer. Attempts to
deprotect the hydrogenated polymers H-12(100) with TBAF (Figure 6.2) resulted in an
apparent drastic decrease in molecular weights (from 58,000 g/mol to 19,000 g/mol) with
no increase in polydispersity (1.13 to 1.10). These findings are very puzzling and deserve
to be further investigated to determine whether this decrease is due to secondary
interactions or simply due to the loss of the bulky TBDMS groups. The disappearance of
110
the silyl peaks in the NMR and the appearance of a new signal at 5.1 ppm confirmed that
the deprotection was efficient (Figure 6.3).
-I—I—I—I—I—1—I—1—I—1—I—1—I—1—I—1—I—1—I—I—|-
15 16 17 18 19 20 21 22 23 24 25
Elution Time (min)
Figure 6.2 Deprotection of the hydrogenated polySONIC H-12(100). Scheinatic(top)
and GPC chromatograms (bottom)
111
lUnv *° ^° 2°
Figure 6.3 'H NMR spectrum of H-21. * Solvent impurity
Alternative pathways involving the preliminary deprotection of the monomer
prior to polymerization proved really promising (Figure 6.4). Despite the apparent loss of
control illustrated by the observation of multimodal chormatograms in GPC, it was
observed that the resulting polymers had some remarkable thermal properties with an
onset of decomposition temperature of 353 °C, a char yield of 46% and a Tg of 200 °C.
These polymers seem to have a bright future in uses for high temperature applications.
Also, unlike polyaromatic imides they are very soluble in most organic solvents which
makes them very attractive candidates for a variety of engineering applications.
As mentioned above, the polymers obtained by homopolymerization of 20 lead to
multimodal polymers. It would be therefore very interesting to evaluate how carboranes
interfere with the polymerization process for example with in situ NMR monitoring.
Finally, the changes in alternation upon solvent change lead us to believe that the
polymerization sequence can be controlled between polar and apolar monomers by
changing the polarity of the medium Simple experiments including the addition of
112
triphenylphosphine should give us an insight into the factors governing the order of
addition of the monomers.
21
Figure 6.4 Alternative route to obtain deprotected carborane polymers.
ppm (f1)7.0 6.0 5.0 4.0 3.0 2.0 1.0
Figure 6.5 H NMR spectrum of monomer 20.
6.2.3 Polyfluorenes with carboranes in the backbone
The possibiUty to incorporate carboranes as pendant group shows some promising
applications notably in terms of neutron detection or simply to prevent intermolecular
stacking upon annealing of the molecules. Therefore, the utilization of these materials for
113
these applications needs to be investigated. Additionally, efforts to incorporate
carboranes in conjugated polyfluorenes will be a great complement to initial studies by
Vicente et al. on polythiophenes.[12] Several possibilities can be envisioned including
the incorporation of paracarborane moieties in the backbone. Some of these strategies are
depicted below.[15]
Figure 6.6 Synthesis of monomers incorporating carboranes along the backbone.
Sonigashira conditions: (Ph3P)2PdCl2, Cul, Et2NH
114
6.2.4 Novel high-boron content resists for EUV lithography and nanoimprint
lithography
The synthesis of a carborane-containing aerylate 19 opened the opportunity to
investigate novel material for imprint lithography. Previous work by Ober et al. had
highlighted the advantages of using carborane-containing resists for EUV lithography.
The advantage of the silyl functionalization approach is the incorporation of silicon
which enhances etch resistance. It seems therefore like adding even more silicon into the
matrix will lead to better materials for lithography in general and potential unique resists
for EUV lithography. Figures 6.7, 6.8 and 6.9 illustrate some progress that has been
achieved towards that goal. By incorporating a pentamethyldisilyl (PMDS) protecting
group, the etch resistance of the material is expected to be improved. Additionally, the
absence of any oxygen in the monomer makes these polymers particularly suitable for
EUV radiations as boron, carbon, silicon and hydrogen are all transparent at these
wavelengths. The Si-Si bond of the PMDS group might limit the possibility to
polymerize 23 by radical techniques but should still be suitable for anionic
polymerization. This will however require a level of purity that has not been achieved
yet.
115
116
(0(0 0 (O (O
r T'-j"I
" ~\\ 1 [--1- !
I
1 1 1
i
11 1 1
i^
'
1 1 1
i
'
\ r—I"'" T"
-9.0 -10.0 -11.0 -12.0 -13.0 -14.0 -15.0 -16.0
ppm (f1)
Figure 6.8 *H NMR spectrum of intermediate 22
6.3 Final word
The opportunities for research presented in section 6.2 are direct continuations of
the work described in this thesis. Nevertheless, the field of functional-carborane
containing polymers is still young and is, by no means, limited to these extensions. The
possibilities to functionalize carboranes to obtain "camouflaged" structures with various
electronic compositions, the idea of attaching these compounds to non-cytotoxic gold
nanoparticles or even the possibility to create non-linear optical materials are just a few
examples that should motivate researchers in developing carborane-based functional
polymeric architectures.
117
6.4 References
[I] L. Zheng, A. J. Waddon, R. J. Farris, E. B. Coughlin, Macromolecules 2002, 35,
[2] F. A. Gomez, M. F. Hawthorne, Journal ofOrganic Chemistry 1992, 57, 1384.
[3] S. E. A. Gratton, M. C. Parrott, A. Adronov, Journal of Inorganic andOrganometallic Polymers and Materials 2005, 75, 469.
[4] P. R. L. Malenfant, J. Wan, S. T. Taylor, M. Manoharan, Nature Nanotechnology
2007,2,43.
[5] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Macromolecular
Symposia 2003, 196, 201.
[6] M. C. Parrott, E. B. Marchington, J. F. Valliant, A. Adronov, Journal of the
American Chemical Society 2005, 727, 12081.
[7] X. L. Wei, P. J. Carroll, L. G. Sneddon, Organometallics 2006, 25, 609.
[8] D. T. Welna, J. D. Bender, X. Wei, L. G. Sneddon, H. R. Allcock, Advanced
Materials (Weinheim, Federal Republic ofGermany) 2005, 77, 859.
[9] R. F. Barth, J. A. Coderre, M. G. H. Vicente, T. E. Blue, Clinical Cancer
Research 2005, 11, 3987.
[10] R. Duncan, Nature Reviews Drug Discovery 2003, 2, 347.
[II] M. J. Allen, R. T. Raines, L. L. Kiessling, Journal of the American Chemical
Society 2006, 725, 6534.
[12] E. Hao, B. Fabre, F. R. Fronczek, M. G. H. Vicente, Chemistry ofMaterials 2007,
79,6195.
[13] D. Pan, J. L. Turner, K. L. Wooley, Chemical Communications 2003, 2400.
[14] B. Parrish, R. B. Breitenkamp, T. Emrick, Journal of the American Chemical
Society 2005, 727, 7404.
[15] M. A. Fox, J. A. K. Howard, J. A. H. MacBride, A. Mackinnon, K. Wade, Journal
ofOrganometallic Chemistry 2003, 680, 155.
118
APPENDIX A
BORON NEUTRON CAPTURE THERAPY AND ENHANCED PERMEABILITY
AND RETENTION
A.l Principles of Boron Neutron Capture Therapy (BNCT)
The figures regarding cancer and cancer progression reported by the world heahh
organization are appalling.[l] By the year 2020, the cancer rate will have increased by 50
% and currently, in numerous countries, the disease is responsible for the death of a
quarter of the population. In spite of all the efforts by oncologists, an effective treatment
minimizing noxious effects has yet to be developed, particularly for the incurable
varieties of the disease. Ideally, one can dream of a method that eradicates exclusively the
diseased cells and leaves the healthy ones intact. BNCT is a process that provides a smart
solution to address this problem.
In 1936, based on Taylor's observation of the aftermaths of the capture of a
neutron by a "^B atom, Locher developed the principles of a radiation-based cure meant
to target specifically malignant cells, and thus BNCT was bom.[2,3] It consists of a two
step process. In the first step, a harmless boron containing species is accumulated in the
tumor cell. In the second step, upon neutron irradiation, the capture of a thermal neutron
by '^B engenders the formation of an unstable ["B] isotope that instantly decays. The
subsequent energetic reaction products, the lithium nucleus (''Li^^) and the a-particle
("^He^"^), will trigger ionizing events in the close vicinity, ~10 microns, of the malignant
cell. [4] The astuteness of this method lays in the fact that there is a huge difference
between the thermal neutron capture section of boron (3837 barns) and that of the
119
elements commonly found in the human body (C, H, N, O) (1.8 bams at best for N).
Furthermore, thermal neutrons present a dependable inertness with these elements. This
binary method offers thus great advantages in terms of efficiency and selectivity, leaving
virtually intact the cells in which no boron has been accumulated. The rate of linear
energy transfer (LET) of the lethal particles, produced by the "^B(«,a)^Li reaction, is
indeed so high that their energy is dissipated in minute volumes, ideally concentrating on
the affected cells.
If they are theoretically appealing, the application of these concepts is somewhat
difficult. In the following section, some of the limitations will be explained starting with
the accumulation problems, which is the very reason for this study. It has been
acknowledged that the efficiency of the treatment is highly dependent on the amount of
boron accumulated within the tumor tissues. It is important to maximize the amount of
boron with respect to the abundant quantities of nitrogen and hydrogen in particular. The
latter two can indeed react with thermal neutrons through the 'V(«,p)''*C and 'H(«,y)^H
reactions. A rough estimate for the minimum quantity of '^B that must be present for
adequate capture ranges from 10 to 30 ^g per g of tumor. This minimum is obviously
governed by the location of the boron containing entity with respect to the malignant cell.
The medical consequence of neutron capture events is measured by the relative biological
effectiveness (RBE). The latter represents the effective noxiousness of resulting particles
or y-radiation from neutron capture reactions. The RBE is defined as the quotient
between the energy dose of a reference radiation creating a certain biological effect and
the energy input necessary for the physical particle or radiation to have the same
120
biological impact. The RBE of the products of BNCT is commonly approximated around
2.5.
Figure A.l Schematic of the elimination of diseased tissues using BNCT
Another concern with BNCT lays with the development of appropriate sources of
neutron. BNCT relies on the encounter of a thermal neutron with a '^B.[5] The use of
thermal neutrons for treatment of deeply rooted glioma is unreasonable as a consequence
of scattering by hydrogen atoms that does not allow sufficient penetration. Scientists have
resorted to the use epithermal neutrons sources which, without harming the patient
through hydrogen recoil, will supply the tumor cell with a dependable source of thermal
neutrons upon declaration by inelastic collisions with H atoms.
A.2 Enhanced Permeability and Retention (EPR)
Selectivity is an ideal that oncologist pursue tenaciously. Yet, the human body
does not facilitate their task for the mechanisms governing affected and healthy cells are
very similar. Conventional molecular approach fails to deliver curing agent to only
malignant cells. The vectors of well-known chemotherapy display insufficient selectivity
and have the tendency to be distributed at random in the patient's body, undermining the
efficacy of such treatment. Nonetheless, the propensity of tumor tissues to amass
121
macromolecular assemblies, known as the EPR effect, fosters hope and augurs for the
uniting of polymer therapeutics and cancer treatment. [6]
This unique feature of malignant tissues is attributed to concomitant effect of
anatomical and physiological mutations, such as the augmentation of the vascular density
emerging from the formation of new blood vessels, the paucity of smooth muscle layer
therein and the alteration of the lymphatic system's ability to recover (lack of
drainage). [7] The escape of macromolecules into the diseased tissues is facilitated by the
production of substances facilitating the creation of blood vessels (vascular endothelial
growth or permeability factors VEGFA/^PF) and the massive release of mediators. The
buildup of bioactive macromolecules in the tumor surpasses largely their concentration in
plasma by up to a factor of ten. and possibly increasing the accumulation of drugs up to
70-fold.
Bearing these physiological considerations in mind, both intra- and extracellular
deliveries have been envisioned. [8] In the former, the polymer-drug or polymer-protein is
internalized in the tumor cell by endocytosis and the active agent is then released through
a pH response or an enzymatic treatment. On the contrary, extracellular delivery rests on
the delivery of a polymeric material in the interstitial tumor tissues. Two avenues have
been contemplated in regards to extracellular delivery. On the one hand, extracellular
systems involving membrane activity and recognition features have been designed. On
the other hand, the coupling of a macromolecular assembly containing a drug and a
polymer enzyme that would interact outside of the cell to release the drug has also been
examined. It is important to recall that no cytospecific recognition (antibody, cell
receptor/ligand binding) is needed for the EPR to happen.
122
Normal lieajB
TuTXMjr tissue
AngogQfiic lumojrvsssels ars dsorganzedand leaky
vasaNir into •, > ;Qi:|
nomal tKeu9' ^ij[ j . Norm* ^selB ^ave
a tight endotfteiiim
/.^i ritravenous injection
of poV^r therapeutic
Figure A.2 Schematic of the principles of the EPR effect (image from Ref. [8]).
Numerous systems (N-(2-hydroxypropyl) mathacrylamide-doxorubicin, styrene
maleic anhydride neocarzinostatin, etc.) and architecture (polymer-protein, micellar
entrapment, hyperbranched polymers) have been developed with encouraging results. [6-
8] A few conclusions have been drawn. Aside from the classical considerations
(hemolysis, cytotoxicity, etc), the macromolecular drug must be water-soluble and its
molecular weight must exceed 40 kDa to avoid renal excretion. Although polymeric
drugs can be neutral, it is commonly accepted that slightly charged systems show
stronger interactions with tumor tissues. Both negatively and positively charged have
their own advantages and thus, which is better is still a subject of debate. The former
123
offers longer plasma half-life and the beneficial absence of interaction with plasma
proteins. The latter facilitates the stabilization with the phosphate group of DNA
molecules as well as the interaction with the negatively charged membrane of tumor cells
for internalization. Further research is needed to determine which one is the most
efficient.
On another level, the release of the active agent as a whole poses a complicated
problem that is extremely hard to solve. Crafting linkages that are going to release the
drug at the right pH or upon action of a specific enzyme remains elusive. Therefore,
gaining control over the trigger is an integral component sought by researchers. To date,
they appear to have only looked at release methods where biological mechanisms are
involved.
In sum. researchers have had a hard time harnessing an effective trigger to release
active agents accumulated in tumor tissues by EPR. Conversely, they have not been able
to synthesize a carrier to efficiently bring boron containing molecules into the tumor
tissues for BNCT. Therefore, we propose to design a method in which biocompatible
carborane polymers will combine the natural accumulation of macromolecules described
as EPR effect and the ability of BNCT to produce cytotoxic particles in a controlled
fashion.
A.3 References
[1] World.Health.Organization, Vol. 2005, 2005.
[2] H. J. Taylor, Proceedings ofthe Physical Society, London 1935, 47, 873.
[3] G. L. Locher, American Journal ofRoentgenology. Radium Therapy 1936, 36, 1
.
[4] M. F. Hawthorne, Angew. Chem. Int. Ed Engl. 1993, 950.
124
[5] R. F. Barth, J. A. Coderre, M. G. H. Vicente, T. E. Blue, Clinical Cancer
Research 2005, 77,3987.
[6] Y. Matsumura, H. Maeda, Cancer Research 1986, 46. 6387.
[7] K. Greish, J. Fang, T. Inutsuka, A. Nagamitsu, H. Maeda, Clinical
Pharmacokinetics 2003, 42, 1089.
[8] R. Duncan, Nature Reviews Drug Discovery 2003, 2, 347.
125
APPENDIX B
RADIATION SHIELDING
B.l Introduction to the Requirements of Space-Resistant Materials
The increased necessity for more protective space-survivable materials emerged
from the newly resumed global endeavor to further space exploration.[l] The prospects
of Lunar inhabitation, the maintenance and development of the international space station
(ISS), and interplanetary travel (including manned missions to Mars), foretell many
challenges that will require breakthroughs in terms of material science to withstand the
hostile environment of space. [2,3] Such innovations will include the development of
successful shielding of crew-members, rovers and other spacecrafts from the damaging
effects of galactic cosmic rays (GCRs) and solar energetic particles (SEPs).[4] Currently,
to prevent the harmful consequences resulting from exposure to radiation, regulation is
performed through duration control and access restriction.
In the history of space travel, radiation shielding has not always been a major
concern. The duration of the voyages was short enough that the adverse effects on the
astronauts was negligible. Instead, the mechanical behavior of the chosen material was
the principal concern. However, as the space community is preparing to launch a journey
to Mars, protection from radiation and particularly GCRs has become a key factor. Given
the longer duration, the need for materials capable of encompassing new crew safety
issues (e.g. radiation protection) and maintaining the functional capabilities (e.g.
mechanical behavior) of the one formerly used is more apparent. Wilson et al. have
considered the implementation of multifunctionality in space mission and report,
126
"utilizing multifunctional materials ... will improve safety and lower mission costs". [5]
Furthermore, it has been emphasized that a multidisciplinary optimization is essential for
choosing the future components of spacecrafts. Consequently, concomitant work at the
frontier of material science, synthesis and radiation shielding will assure the successful
development of muhifunctional materials. [6]
Guidelines for materials research stipulate that polymeric materials are more
suitable for radiation shielding than metal alloys. An ideal shield "maximizes the number
of electrons per unit mass, maximizes the nuclear reaction cross section per unit mass and
minimizes the production of secondary particles". [5] High hydrogen-content materials
meet these requirements and show good efficacy. For example, polyethylene (PE) is
presently being tested as a shielding material in the ISS to ensure crew safety. However,
it offers limited versatility. Finding alternative solutions offering multifunctionality and
efficient radiation shielding has yet to be achieved.
Unlike unpredictable SEPs and local radiations trapped in belts, GCRs are a
continuous source of radiation, and thus understanding what their consequences could be
is crucial to the design of new shielding materials. When GCRs hit and penetrate matter,
nuclear reactions occur, yielding different particles (e.g. neutrons) and radiations. Fast
neutrons (E > 10 keV) are emitted through spallation processes[7] and prove to have
deleterious effects on organisms. Through collisions with living tissue, they are likely to
cause the ionization of hydrogen atoms (hydrogen recoil reaction), creating severe
damage to the living organism. Accordingly, research for an adequate shield will have to
take this fact into account.
127
B.2 Rationale for the use of carboranes in neutron shielding.
The great neutron-capture cross sectional area of has already been employed
in various laboratory neutron-shielding applications as well as for medical
processes. [8] [9] The nuclear reaction happening upon irradiation of a carborane cage is
namely '°B(«,a)^Li. The combination of PE, which slows down the neutrons, and boron-
containing materials, capturing the subsequent low-energy neutrons, thus appears to be a
savvy strategy. The neutrons will hit the numerous hydrogen atoms along the polymer
backbone and bring them to an energy range where '^B has a wide enough cross-sectional
area to harvest them via the '°B(«,a)^Li reaction. In order to safeguard the crew from
harmful exposures, incorporating boron-containing materials, such as hybrid carborane
polymers, is an innovative solution. Besides, the use of '^B enriched compounds might
increase the efficacy of our products. Looking carefully into those materials from the
standpoint of radiation shielding and tailoring an appropriate structure based on the use of
carboranes is an exciting challenge that should be undertaken.
While it is convenient from a structural point of view to describe the materials
discussed in Chapter 3 as polyethylene-like, it is important to also point out some of the
similarities and differences that could exist between them. In particular, it is important to
point out that the description of polyethylene-like materials seems only really valid in the
context of the materials containing the smallest amount of carboranes. As the fraction of
carborane oxanorbomene increases the materials lose all resemblance to polyethylene.
This phenomenon can be illustrated as one compares the neat increase in glass transition
temperature as one starts to incorporate more and more SONIC in the structure.
128
As was observed in Chapter 3, the copolymers of SONIC and COE do not
crystallize, which not only indicates that the carborane cage do not pack in a way that
leads to the formation of inorganic crystalline layers but also demonstrates that the linear
polyethylene-like segments are too short to favor nucleation. In that sense, the materials
that contain the least amount of carborane can be assimilated to low-density or very low-
density linear polyethylene. In particular, it is very interesting to assimilate the pendant
carborane to the short-chain a-olefms that are used in the process of making these
materials. More mechanical testing would most certainly enable a better comparison of
these SONIC-COE copolymers with polyethylene materials and permit to determine
whether or not they can be described as polyethylene-like from an engineering
perspective. Nevertheless, since the present manuscript was written from a more
chemistry oriented standpoint, the similarities in structure between low-density linear
polyethylene and the hydrogenated copolymers with low volume fraction of carborane
favor this association.
129
— Qocmi-IG poKeAi Ls
Figure B.l Efficiency of blends of '^B and polyethylene and other materials for
neutron shielding (image from Ref.[10])
The advantage of the copolymerization approach in comparison with a blending
approach is clearly a better control over the the density of carboranes. Another formal
advantage of borated polymers stands in the back-scattering of electrons. A conventional
PE reflects a lot of electrons which could prove to be ill-fated for extravehicular activity.
On the contrary, the capture of neutrons by boron mitigates the amount of neutrons back-
scattered. This feature will be very beneficial for long repairs on spacecrafts.
B.3 References
[1] President George W. Bush's Announcement, 2004.
[2] J. W. Wilson, M. S. Clowdsley, F. A. Cucinotta, T. R.K., J. E. Nealy, G. DeAngelis. 2002.
[3] C. Zeitlin, T. Cleghom, F. Cucinotta, P. Saganti, V. Andersen, K. Lee, L. Pinsky,
W. Atwell, R. Turner, G. Badhwar, Mercury, Mars and Saturn 2004, 33, 2204.
130
J. R. Letaw, R. Silberberg, C. H. Tsao, Nature 1987, 330, 709.
J. W. Wilson, F. A. Cucinotta, M. H. Y. Kim, S. W., in 1st International
Workshop on Space Radiation Research and 1 1th Annual NASA Space Radiation
Health Investigators' Workshop, 2001.
C. S. Allen, R. Burnett, J. Charles, F. A. Cucinotta, R. Fullerton, J. R. Goodman,
A. D. Griffith Sr, J. J. Kosmo, M. Perchonok, J. Railsback, S. Rajulu, D. Stilwell,
G. Thomas, T. Tri, J. Joshi, R. Wheeler, M. Rudisill, J. W. Wilson, A. Mueller, A.
Simmons, NASA, 2003, p. 102.
Jean Chemin, Personal Communication, 2004.
G. L. Locher, American Journal ofRoentgenology. Radium Therapy 1936, 36, 1.
B. W. Robertson, S. Adenwalla, A. Harken, P. Welsch, J. I. Brand, P. A. Dowben,
J. P. Claassen, Applied Physics Letters 2002, 80, 3644.
R. C. J. Singleterry, S. A. Thibeault, Langley Research Center NASA, 2000.
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