Medicinal Chemistry and Pharmacological Potential of Fullerenes and Carbon Nanotubes

410 Pages·2008·6.209 MB·English

by  Tatiana Da Ros (auth.), Dr. Prof. Franco Cataldo, Dr. Tatiana Da Ros (eds.)

Medicinal Chemistry and Pharmacological
Potential of Fullerenes and Carbon Nanotubes
CARBON MATERIALS: CHEMISTRY AND PHYSICS
A comprehensive book series which encompasses the complete coverage of carbon materials
and carbon-rich molecules from elemental carbon dust in the interstellar medium to the most
specialized industrial applications of elemental carbon and its derivatives. A great emphasis
is placed on the most advanced and promising a pplications ranging from electronics to
medicinal chemistry. The aim is to offer the reader a book series which not only consists of
self-sufficient reference works, but one which stimulates further research and enthusiasm.
Series Editors
Dr. Prof. Franco Cataldo Professor Paolo Milani
Director of Lupi Chemical Research Institute University of Milan
Via Casilina 1626/A Department of Physics
00133 Rome, Via Celoria, 26
Italy 20133, Milan, Italy
Volume 1:
Medicinal Chemistry and Pharmacological Potential
of Fullerenes and Carbon Nanotubes
Volume Editors
Dr. Prof. Franco Cataldo Dr. Tatiana Da Ros
Director of Lupi Chemical Research Dipartimento di Scienze
Institute Farmaceutiche
Via Casilina 1626/A, University of Trieste
00133 Rome, Piazzale Europe,
Italy I-34127 Trieste, Italy
Franco Cataldo • Tatiana Da Ros
Editors
Medicinal Chemistry and
Pharmacological Potential
of Fullerenes and Carbon
Nanotubes
Editors
Dr. Franco Cataldo Dr. Tatiana Da Ros
Lupi Chemical Research Institute University of Trieste
Rome, Italy Trieste, Italy
ISBN 978-1-4020-6844-7 e-ISBN 978-1-4020-6845-4
Library of Congress Control Number: 2008930078
© 2008 Springer Science + Business Media B.V.
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Preface
The emerging field of nanotechnology is affirming its increasing importance day
by day. In this context fullerenes and carbon nanotubes (CNTs) play an important
role. These new allotropic forms of carbon have been discovered in the last two
decades, and, since then, they have stimulated the curiosity and interest of physicists
and chemists.
This book is the first of a new series entitled “Carbon Materials:
Chemistry and Physics”, the purpose of which is to analyze the new frontiers of
carbon.
This volume summarizes the more recent advances on fullerenes and carbon
nanotubes facing the biological-medical horizon, an important and interesting area
to the scientific community.
We will present general overviews of fullerenes and CNTs that are state-of-
the-art in biomedical applications, deepening their principal and more promising
exploitations.
In particular for fullerenes, antioxidant properties and photodynamic activity are
presented in detail, together with the analysis of gadolinium endohedrals as mag-
netic resonance imaging (MRI) contrast agents. Moreover, drug delivery based on
carbon nanomaterials has been illustrated.
Few chapters are dedicated to toxicity and to the use of nanomaterials as pollut-
ant probes. The debate on fullerene and CNT toxicity is open and reports different
results, which are not always able to abolish the concern about pollution related to
the industrial production and their impact on the environment. However, it is possi-
ble to state that positive evidence for their favorable applications in medicine has
emerged.
Theoretical calculation potentialities have been examined in few chapters,
giving new instruments to predict fullerene solubility in different solvents, such
as fatty acid esters. Visualization approaches necessary to study unusual compounds
such as CNT are herein presented. Despite the structural novelty of CNT, its
resemblance to cellular structures is highlighted, launching or confirming the
hypothesis of using CNTs as communication devices between cells.
Considering the specificity of the field, this book is mainly addressed to
researchers who have delved, or who want to delve, into carbon nanoworld, but at
v
vi Preface
the same time, it presents a general and accurate view of carbon nanotechnology
accessible to researchers intrigued by this topic, but not yet experts in the field.
April 2008 Tatiana Da Ros
Franco Cataldo
Contents
Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
1 Twenty Years of Promises: Fullerene in Medicinal Chemistry. . . . . . 1
Tatiana Da Ros
2 Biomedical Applications of Functionalised Carbon Nanotubes . . . . . 23
Alberto Bianco, Raquel Sainz, Shouping Li,
Hélène Dumortier, Lara Lacerda, Kostas Kostarelos,
Silvia Giordani, and Maurizio Prato
3 Antioxidant Properties of Water-Soluble Fullerene Derivatives. . . . . 51
Florian Beuerle, Russell Lebovitz, and Andreas Hirsch
4 Fullerenes as Photosensitizers in Photodynamic Therapy. . . . . . . . . . 79
Pawel Mroz, George P. Tegos, Hariprasad Gali,
Timothy Wharton, Tadeusz Sarna, and Michael R. Hamblin
5 Photodynamic Inactivation of Enveloped
Viruses by Fullerene: Study of Effi cacy and Safety. . . . . . . . . . . . . . . 107
Vladimir V. Zarubaev, Inna Belousova, Vladimir Rylkov,
Alexander Slita, Alexey Sirotkin,
Pavel Anfimov, Tatyana Muraviova,
and Andrey Starodubtsev
6 Effects of Photoexcited Fullerene C -Composites in Normal
60
and Transformed Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
S.V. Prylutska, I.I. Grynyuk, O.P. Matyshevska, A.A. Golub,
A.P. Burlaka, Yu.I. Prylutskyy, U. Ritter, and P. Scharff
7 Biological Effects in Cell Cultures of Fullerene C :
60
Dependence on Aggregation State . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Levon B. Piotrovsky, Mikhail Yu. Eropkin,
Elena M. Eropkina, Marina A. Dumpis, and Oleg I. Kiselev
vii
viii Contents
8 Gadolinium Endohedral Metallofullerene-Based
MRI Contrast Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Robert D. Bolskar
9 Biomolecules Functionalized Carbon Nanotubes and
Their Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Daxiang Cui
10 Applications of Carbon-Based Nanomaterials for
Drug Delivery in Oncology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Nicole H. Levi-Polyachenko, David L. Carroll,
and John H. Stewart, IV
11 Visualization of Carbon Nanoparticles Within Cells and
Implications for Toxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 267
Alexandra Porter and Mhairi Gass
12 Pharmacological Applications of Biocompatible
Carbon Nanotubes and Their Emerging Toxicology Issues . . . . . . . . 283
Tae-Joon Park, Jeffrey G. Martin, and Robert J. Linhardt
13 Solubility of Fullerenes in Fatty Acids Esters:
A New Way to Deliver In Vivo Fullerenes.
Theoretical Calculations and Experimental Results . . . . . . . . . . . . . . 317
Franco Cataldo
14 New Approach to QSPR Modeling of Fullerene C
60
Solubility in Organic Solvents: An Application
of SMILES-Based Optimal Descriptors . . . . . . . . . . . . . . . . . . . . . . . . 337
A.A. Toropov, B.F. Rasulev, D. Leszczynska,
and J. Leszczynski
15 Functionalized Nanomaterials to Sense Toxins/Pollutant
Gases Using Perturbed Microwave Resonant Cavities . . . . . . . . . . . . 351
Aman Anand, J.A. Roberts, and J.N. Dahiya
16 Cellular Nanotubes: Membrane Channels for
Intercellular Communication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Raquel Negrão Carvalho and Hans-Hermann Gerdes
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Color Plates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
Chapter 1
Twenty Years of Promises: Fullerene
in Medicinal Chemistry
Tatiana Da Ros
Abstract Many biological activities have been envisioned for fullerenes and some

of them seem to be very promising. The lack of solubility in biologically friendly
environments is the major obstacle in the development of this field. The possibility
of multiple fuctionalization can be exploited to get more soluble compounds but,
up to now, only a few polyadducts, presenting perfectly defined geometry, can be
selectively prepared avoiding long purification processes.
The toxicity of this third allotropic form of carbon is an aspect related to application
in medicine and biology, while the concern about the environmental impact is due
to the industrial production of fullerenes. Many studies are dedicated to both
aspects and, so far, it is not possible to have a definitive answer although the current
findings allow some optimistic vision.
In this chapter the main biological applications of fullerene and fullerene derivatives
will be reviewed, with special attention to the most recent advances in this field.
Antiviral and antibacterial activity, enzymatic inhibition, and DNA photocleavage are
some aspects considered herein, together with the use of these nanostructures as
possible vectors for drug and gene delivery. The most promising applications include
the use of endohedral fullerenes, filled by gadolinium, in magnetic resonance imaging
(MRI) and the antioxidant capacity exploitation of some tris-adducts and fullerols.
Keywords Antibacterial activity, anticancer activity, antioxidant properties, antiviral

activity, cell protection, contrast agent, drug delivery, photodynamic therapy, protein
interaction, radiotherapy, toxicity
1.1 Introduction
Fullerene reactivity and applications have been explored since being discovered in
1985. Nowadays, this chemistry has been intensely developed, although there is
still the possibility to find some new reactions, as recently underlined by Martín
University of Trieste, Italy
Email: [email protected]
F. Cataldo, T. Da Ros (eds.) Medicinal Chemistry and Pharmacological 1
Potential of Fullerenes and Carbon Nanotubes,
© Springer Science + Business Media B.V. 2008
2 T. Da Ros
...
... Enzyme Antioxidant
inhibition
MRI
Drug
contrast Biosensor
vector
agent
...
Antibacterial
Photodynamic
activity
therapy
Radioprotection
Fig. 1.1 Potential biological applications of fullerene
(2006). The main efforts are now devoted to broaden the applications of the fullerene
family and its derivates (Fig. 1.1). It is evident that the interest in C suffers from
60
the advent of carbon nanotubes (CNTs) and many researchers involved in fullerene
studies are moving toward CNT as a natural evolution of their research.
In this chapter we consider, above all, the most recent developments of biological
and toxicological aspects of fullerene and related compounds of the last few years,
considering that many reviews and books cover this topic up to 2006 (Jensen
et al., 1996; Nakamura et al., 1996; Da Ros and Prato, 1999; Tagmatarchis and
Shinohara, 2001; Bosi et al., 2003; Nakamura and Isobe, 2003; Sarova et al., 2006;
Bianco and Da Ros, 2007).
1.2 Cell Protection and Antioxidant Properties
The possibility to employ C as cytoprotective agents can be considered both one of
60
the most promising applications and one of the most studied since the publication
of the fundamental works of Dugan and coworkers, who analyzed fullerene capability
of scavenging reactive oxygen species (ROS) (Dugan et al., 1996, 1997, 2000;
Quick and Dugan, 2004; Ali et al., 2004).
The antioxidant properties of water-soluble fullerene derivatives, mainly
inspired to tris-malonic acid fullerene derivatives and dendrofullerene (Fig. 1.2),
have been studied in detail (Witte et al., 2007). A library has been created, containing
positively and negatively charged derivatives, which can be synthesized in an easy
scalable way, overcoming the main problems of polyadduct purification. In the
proposed series, dendrofullerenes are more active than polyadducts and, among
polyfunctionalized fullerenes, anionic compounds give higher protection than cationic