Amphiphilic fullerenes for biomedical and optoelectronical applications [Elektronische Ressource] / vorgelegt von Patrick Witte

Informations

• Publié par: friedrich-alexander-universitat_erlangen-nurnberg
• Publié le: 01 janvier 2009
• Nombre de lectures: 13
• Langue: English
• Poids de l'ouvrage: 8 Mo

Extrait

AMPHIPHILIC FULLERENES FOR
BIOMEDICAL AND OPTOELECTRONICAL
APPLICATIONS
Den Naturwissenschaftlichen Fakultäten
der Friedrich-Alexander-Universität Erlangen-Nürnberg
zur
Erlangung des Doktorgrades
vorgelegt von
Patrick Witte
aus NürnbergAls Dissertation genehmigt von den Naturwissenschaftlichen Fakultäten der
Universität Erlangen-Nürnberg
Tag der mündlichen Prüfung: 25.04.2008
Vorsitzender
der Prüfungskommission: Prof. Dr. Eberhard Bänsch
Erstberichterstatter: Prof. Dr. Andreas Hirsch
Zweitberichterstatter: Prof. Dr. Tim ClarkMeinem Doktorvater, Prof. Dr. A. Hirsch, gilt mein besonderer Dank für sein reges
Interesse am Fortgang dieser Arbeit sowie für seine Anregungen und die Diskussionen
mit ihm.
Die vorliegende Arbeit wurde in der Zeit zwischen Dezember 2003 bis Dezember
2007 am Institut für Organische Chemie der Friedrich-Alexander-Universität Erlangen-
Nürnberg durchgeführt.Dedication
For my Parents and Kati
- Science is facts;
just as houses are made of stones, so is science made of facts;
but a pile of stones is not a house and a collection of facts is not necessarily science
Henri Poincare (1854 - 1912)Index of Abbreviations
tBu . . . . . . . . . . . . . . . . . tert-Butyl
BAM . . . . . . . . . . . . . . . Brewster Angle Microscopy
Boc . . . . . . . . . . . . . . . . tert-Butoxycarbonyl
CV . . . . . . . . . . . . . . . . . Cyclic Voltammetry
DBU . . . . . . . . . . . . . . . 1,8-Diaza-bicyclo[5.4.0]undecen-7-en
DCE . . . . . . . . . . . . . . . 1,2-Dichloroethane
DCU . . . . . . . . . . . . . . . Dicyclohexylurea
DMA . . . . . . . . . . . . . . . 9,10-Dimethylanthracene
DMAP . . . . . . . . . . . . . . 4-Dimethylaminopyridine
DMSO . . . . . . . . . . . . . Dimethyl Sulfoxide
dpf . . . . . . . . . . . . . . . . . Days Post Fertilization
EA . . . . . . . . . . . . . . . . . Elemental Analysis
EDC . . . . . . . . . . . . . . . 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Hydrochloride
eq . . . . . . . . . . . . . . . . . . Equivalent
FAB . . . . . . . . . . . . . . . . Fast Atom Bombardment
FC . . . . . . . . . . . . . . . . . Flash Column Chromatography
HOBt . . . . . . . . . . . . . . . 1-Hydroxybenzotriazole
hpf . . . . . . . . . . . . . . . . . Hours Post Fertilization
HPLC . . . . . . . . . . . . . . High Performance Liquid Chromatography
IPR . . . . . . . . . . . . . . . . Isolated Pentagon Rule
IR . . . . . . . . . . . . . . . . . . Infrared Spectroscopy
LB . . . . . . . . . . . . . . . . . Langmuir-Blodgett
IMW . . . . . . . . . . . . . . . . Molecular Weight
NBA . . . . . . . . . . . . . . . 3-Nitrobenzylalcohol
NMR . . . . . . . . . . . . . . . Nuclear Magnetic Resonance
PBS . . . . . . . . . . . . . . . . Phosphate Buffered Saline
PCBM . . . . . . . . . . . . . . [6,6]-Phenyl-C Butyric Acid Methyl Ester61
pf . . . . . . . . . . . . . . . . . . Post Fertilization
ppm . . . . . . . . . . . . . . . . Parts per Million
ROS . . . . . . . . . . . . . . . Reactive Oxygen Species
RT . . . . . . . . . . . . . . . . . Room Temperature
STM . . . . . . . . . . . . . . . Scanning Tunneling Microscopy
SWCNT . . . . . . . . . . . . Single Walled Carbon Nanotube
TFA . . . . . . . . . . . . . . . . Trifluoroacetic Acid
THF . . . . . . . . . . . . . . . . Tetrahydrofuran
TLC . . . . . . . . . . . . . . . . Thin Layer Chromatography
UV/Vis . . . . . . . . . . . . . Ultraviolet-Visible Spectroscopy
XPS . . . . . . . . . . . . . . . . X-ray Photoelectron Spectroscopy
IITable of Contents
1 Introduction 1
1.1 Nanostructured Materials . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 The Discovery of Fullerenes . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.3 The Structure of Fullerenes . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.4 Physical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.4.1 Thermodynamic and Kinetic Stability of C . . . . . . . . . . . . 760
1.4.2 Solubility of C . . . . . . . . . . . . . . . . . . . . . . . . . . . . 760
1.5 Spectroscopic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . 9
1.5.1 UV/Vis-Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . 9
1.5.2 Mass Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . 10
1.5.3 NMR Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . 11
3 11.5.3.1 He and H Spectroscopy . . . . . . . . . . . . . . . . . 11
131.5.3.2 C Spectroscopy . . . . . . . . . . . . . . . . . . . . . 13
1.6 Electronic Structure and Reactivity of Fullerenes . . . . . . . . . . . . . 14
1.7 Spherical Aromaticity of C . . . . . . . . . . . . . . . . . . . . . . . . . 1560
1.8 Chemistry of C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1660
2 Proposal 20
3 Results and Discussion 22
3.1 Water-soluble Amphiphilic Fullerene-Monoadducts . . . . . . . . . . . . 22
3.1.1 Synthesis of Anionic Amphiphilic Monoadducts . . . . . . . . . . 24
IIITable of Contents
3.1.2 Synthesis of an Anionic Amphiphilic Monoadduct Carrying an
Unsaturated Fatty Acid . . . . . . . . . . . . . . . . . . . . . . . . 33
3.1.3 Synthesis of a Cationic Amphiphilic Monoadduct . . . . . . . . . 39
3.1.4 Amphiphilic Fullerenes as Potential Drug Candidates . . . . . . . 44
3.1.4.1 Introduction and Background . . . . . . . . . . . . . . . 44
3.1.4.2 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . 47
3.1.4.3 Cytochrome C Binding . . . . . . . . . . . . . . . . . . 52
3.1.4.4 In vivo Studies of the Amphiphilic Fullerenes using Ze-
brafish (Danio Rerio) Embryos as Model System . . . . 57
3.1.5 Mechanistic Aspects of the Reaction of Fullerenes with Superoxide 69
3.1.5.1 Cyclic Voltammetry Measurements of Amphiphilic Mono-
adducts . . . . . . . . . . . . . . . . . . . . . . . . . . . 70
3.1.5.2 Kinetic Measurements of Amphiphilic Monoadducts . . 73
3.1.6 Amphiphilic Fullerenes in Material Science Applications . . . . . 77
3.1.6.1 Formation of LANGMUIR-Films with Amphiphilic Fullerene-
Monoadducts . . . . . . . . . . . . . . . . . . . . . . . . 79
3.1.6.2 Incorporation of the Amphiphilic Fullerene-Monoadducts
in Organic Solar Cell Devices . . . . . . . . . . . . . . . 85
3.2 Triazole Dendrimers Based Fullerenes via "Click Chemistry" . . . . . . . 89
3.2.1 Synthesis of Novel Dendritic Triazol-Fullerenes . . . . . . . . . . 92
3.3 Synthesis of Novel Fullerene-SWCNT Hybrids . . . . . . . . . . . . . . 102
3.3.1 Covalent Sidewall Functionalization of SWCNT’s with a Fullerene-
Monocarboxylic Acid Derivative . . . . . . . . . . . . . . . . . . . 103
3.3.2 Non-Covalent Functionalization of SWCNT’s with a Fullerene-
Pyrene Dyad . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 106
3.4 Supramolecular Approach for the Formation of C -Bisadducts . . . . . 11660
3.4.1 Metallomacrocycles as Tethers for Regioselective Cyclopropana-
tion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
3.4.2 Hydrogen-bonded Dimers as Tethers for Regioselective Cyclo-
propanation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
IVTable of Contents
3.5 Synthesis of Novel Multiple Fullerene Arrays Consisting of Mixed C -60
Hexakisadduct Units . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
3.5.1 Synthesis of Bisfunctionalized Janus-Type Fullerene-Dimers . . 127
3.5.2 Synthesis of a Fullerene-Rich Nanocluster . . . . . . . . . . . . . 137
4 Summary 142
4 Zusammenfassung 146
5 Experimental Part 151
5.1 Chemicals and Instrumentation . . . . . . . . . . . . . . . . . . . . . . . 151
5.2 Synthetic Procedures and Spectroscopic Data . . . . . . . . . . . . . . 154
Appendices 224
A Materials and Methods for the Determination of Biological Activity in vivo 224
B Materials and Methods for the Preparation and Examination of SWCNT-
Fullerene-Hybrid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229
References 231
VCHAPTER 1
1 Introduction
1.1 Nanostructured Materials
Although the idea of carrying on manipulations at smaller and smaller scales has been
around for quite some time the birth of nanotechnology, at least on an ideological level,
is usually traced back to a speech by RICHARD FEYNMAN at the December 1959 meet-
ing of the American Physical Society. In his speech, he challenged his fellow scientists
to find ways by which to create manufacturing, storage, and retrieval systems that are
as efficient as DNA and to contain such systems in a submicroscopic, self-contained
unit with the size of a cell. It would be over two decades before the first recognized
[1]paper on molecular nanotechnology was published.
The challenge in nanoscience is to understand how materials behave when sample
sizes are close to atomic dimensions. Figure 1.1 for example shows an overview of
artificial nanostructures, being of the same size as biological entities, which allows
them to interact with biomolecules on the surface of the cell and inside it. When the
characteristic length scale of the structure is in the 1- 100 nm range, it becomes com-
parable with the critical length scales of physical phenomena, resulting in the so-called
"size and shape effects". This leads to unique properties and the opportunity to use
1