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3rd International Summer School
“Supramolecular Systems in Chemistry and Biology”
Lviv (Ukraine), 6 - 10 September 2010
_________________________________________
SUPRAMOLECULARITY
OF CARBON NANOTUBES
Mykola T. Kartel
Chuiko Institute of Surface Chemistry, NAS of Ukraine
17 General Naumov Street, Kiev, Ukraine
INTRODUCTION
Supramolecular chemistry – chemistry of molecular ensembles
and intermolecular bonds (J.-M. Lehn, 1978)
Other definitions:
- Chemistry outside of a molecule;
- Chemistry of non-covalent bonds
Supramolecule is a complex molecule, usually big (host), bonded
other molecule (guest)
Supramolecular interactions (on energy of bond):
- Interaction ion-ionic (100-350 kJ/mol), are close to covalent bond
- Ion-dipole interaction (50-200 kJ/mol)
- Dipole-dipole interaction (5-50 kJ/mol)
- Hydrogen bond (4-120 kJ/mol)
- Cation-π-interaction (50-80 kJ/mol)
- π-π - Steking-interaction (0-50 kJ/mol)
- Van-der-Vaals forces (< 5 kJ/mol)
Supramolecular phenomena are the interdisciplinary area: supra
systems are considered in chemistry, biology, biochemistry, life sciences
and materials science.
Objects of consideration of supramolecular chemistry can be high
disperse and high porous materials possessing a considerable specific
surface area.
High disperse (nanodisperse) materials with the size of particles ~ 1
nm have an external surface area >100 m2/g.
High porous (nanoporous) materials with the size of holes ~ 1 nm
have an internal surface area >1000 m2/g.
Already the morphology (texture, structure, supramolecular
structure) of such materials has character of supramolecularity
(interaction of elements of a skeleton – chains, tetrahedrons, planes,
globules, etc.)
Atoms or the molecules adjoining a surface energetically are not
compensated. It is the reason of many superficial phenomena:
adsorption, heterogeneous catalysis, double electric layer, adhesion and
cohesion, wetting, corrosion, capillary phenomena, flotation, surfactant
action, number of biological processes.
For example, system “adsorbent / adsorbate” can be considered and
discussed in terms "host / guest".
“Classical” objects of supramolecular chemistry are
carbon ones: graphite and fullerenes.
For “macroobiect” graphite it is known the intercalation
phenomenon by acids, salts and metals with reception of
numerous inclusion compounds, thermoexfoliated graphite
and also extreme display – crystal rupture on separate layers
(graphene-like structures).
For nanoobjects fullerenes it is known an ability to act as the
guest (inclusion compounds with macrocycles of calixarenes,
cyclodextrin, hydroquinon), or the host (metalorganic
complexes, metallic and bimetallic complexes with properties
of a superconductor).
SOME sp2-CARBON FORMS
Graphene
Graphite
Nanotubes
(CNT) S. Iijima. Helical microtubules of
graphitic carbon. -Nature, 1991, - V.354. P.56-58
(SWCNT) М. Endo et al. Carbon, 1975
(MWCNT) L.V.Radushkevich, V.M.Lukjanovich.
About structure of the carbon formed at
thermal decomposition of carbon oxide on iron
contact. –Russian J.Phys.Chem., 1952, -V.26,
N1. - P.88-95
Fullerene
H.W. Kroto et al. C60Buckminster-fullerene. Nature, 1985, -V.318. P.162-163
VERSIONS OF CNT
SWCNT
MWCNT
CNT are cylindrical structures with a diameter from
one to several tens nm and length from several nm to
several μm.
They consist of one or several graphite layers with
hexagonal organization of carbon atoms. Tubes come
to an end with the hemispherical head formed from
half fullerene.
Unlike fullerenes, which represent the molecular form
of carbon, CNT combine properties nanoclusters and a
massive firm body that causes occurrence special, at
times unexpected properties. CNT are characterized
absolutely new mechanical, adsorption, optical,
electric, magnetic, etc. properties.
SPECIFIC PROPERTIES OF CNT
1. Mechanical properties: strength and flexibility (hardening of
metals and polymers, polymeric composites, additives to lubricants
and oils, etc.);
2. Electronic properties: semi- and/or metallic conductivity,
magnetoresistance, cold emission of electrons (electronic
devices of the molecular size, information recording, diodes, field
transistors, cold cathodes, materials for displays, quantum dots and
wires, cathodes for X-ray radiation, electric probes, etc.);
3. Optical properties: resonant absorption of IR-radiation (lightemitting diodes, optoelectronic devices, thermal nanobombs);
4. Physical and chemical properties: developed surface and
variable surface chemistry, programmed reactivity and carrier
for active chemical and biological objects (sorbents, catalysts,
chemical sensors, electrode materials, chemical batteries, fuel
elements and supercondensers);
5. Biological properties: biocompatibility and toxicity!!!,
penetration ability into biological cell!!! (preparations, medical
nanoinstruments, biosensors, prosthetics, means of gene
engineering).
SCALE OF NANOSIZED OBJECTS
1 nm
1000 nm
METHODS OF RECEPTION OF CNT
(1) Voltaic arc dispersion of graphite;
electrolytic synthesis
(2) Laser evaporation (ablation) of
graphite; carbon epitaxy
(3) Catalytic decomposition of
hydrocarbons and carbon monoxide
(CVD-technology)
MECHANISM OF CNT GROWTH
The metal drop acts a catalyst role at formation carbon
nanotube and defines its size
(drawing from a site http://students.chem.tue.nl/).
AGGREGATES OF NANOTUBES AND NANOFIBERS
The ordered and chaotic growth on substrates
Kinds of nanofibers in a light microscope
«Hair of water-nymph»
(Moscow State University
Department of Chemistry)
PURIFYING AND ENRICHING CNT
 Demineralization by strong acids and alkalis;
 Thermoprogrammed annealing of amorphous carbon;
 Thermoprogrammed wall-by-wall annealing of multi-walled
tubes (enriching by single-walled tubes);
 Electrolytic annealing of conducted tubes (enriching by
semi-conductor tubes);
 Chemical updating (increase of solubility of tubes);
 Dispersion by means of ultrasound and surfactants,
sedimentation separation (ultracentrifugation) individual
tubes from aggregates.
SEPARATION OF NANOTUBES (SURFACTANTS,
ULTRASOUND, ULTRACENTRIFUGE)
Variants of "wrapping" of nanotubes by surfactants.
AUTOMATED ANALYSIS OF CNT
(analysis of data received by TEM, SEM and АFМ methods)
 Analysis of diameters of nanotubes
 Analysis of thickness and orientation of
nanofibers
 Definition of length, thickness, curvature and
size distribution of nanotubes
 Analysis of structure of multiwalled
nanotubes
 Analysis of impurities in nanotubes
COST OF CNT
PRODUCTION AND PRICES
№
Product name
Price, USD per
gr.
60
1
SWNT (single wall CNT), as produced from cellular zone, 40-50%
2
SWNT, purified 80%
380
3
SWNT, purified 90 %
Expected
4
SWNT-COOH, purified (70-80%) with 2-5% of –COOH groups
380
5
SWNT-NH2, purified (70-80%) with 2-5% of - NH2 groups
600
6
SWNT-CONH-C18H37, purified (70-80%) with 2-5% of -CONH-C18H37 groups
600
7
SWNT-COO-R-OH (2-5% groups)
600
8
SWNT shorted, purity 90%, length 200-500 nm, 5-10% of –COOH groups
1200
9
SWNT shorted, purity 90%, length 200-500 nm, 5-10% of –NH2 groups
1600
11
SWNT-COO-R-OH shorted (200-500 nm), (5-10% groups)
1600
12
Solutions of functionalized SWNT in different solvents
+150
13
Substituted pyrrolidinofullerene derivatives
2000
14
Lower bulk density SWNT-COOH, purified (70-80%) with 2-5% of –COOH groups
460
15
DWNT (double wall CNT), 20-30% purity
250
16
DWNT (double wall CNT), 90% purity
17
SWNT with attached building blocks from MedChemLabs Inc., collection
1500
Discussed
COST OF CNT
PRODUCT
DISCRIPTION
CARBONACEOUS
PURITY*
METAL CONTENT
PRICE**
MINIMUM
ORDER
wt % from TGA in air
AP-SWNT
As prepared
40-60%
30
$50/g
2g
P2-SWNT
Purified, low
functionality
70-90%
7-10
$400/g
0.5 g
P3-SWNT
Purified, high
functionality
80-90%
5-10
$400/g
0.1 g
P5-SWNT
Organic
soluble
(functionalized
with ODA)
80-90% (50%
SWNT loading)
4
$150/
100 mg
0.1 g
P7-SWNT
Water soluble
(functionalized
with PEG)
80-90% (70%
SWNT loading)
6
$150/
100 mg
0.1 g
P8-SWNT
Water soluble
(functionalized
with PABS)
80-90% (30%
SWNT loading)
3
$150/
100 mg
0.1 g
P9-SWNT
Amide
functionalized
SWNTs
80-90%
6-8
$150/
100 mg
0.1 g
Pilot manufacture of MW CNT
on OAS “ARTEMOV TAMBOV’ ENTERPRISE “KOMSOMOLETS”
Tambov, Russia
Productivity 2-2.5 t/year
Dynamics of world production of
CNT (t/year)
Pilot manufacture of MW CNT on experimental section of
CHUIKO INSTITUTE OF SURFACE CHEMISTRY and
ENTERPRISE "ТМ-SPETSMASH“-LTD
Kiev, Ukraine
Installation of synthesis
multiwalled CNT and CNF by
CVD-method (catalytic pyrolysis
of hydrocarbons).
Productivity of 1-1,5 kg/day
(> 0.5 t/year)
TEM of CNT
CARBON NANOTUBES.
Specifications
TU U 24.1-03291669-009:2008
TOXICOLOGY OF CNT
RESPONSE OF ORGANISM, BODY OR TISSUE TO ACTION OF
NANOPARTICLE AS DAMAGING AGENT
THE FACTORS ARE CAPABLE TO LEAD TO DAMAGES IN TISSUES, BODY
OR ORGANISM AS A WHOLE:
 High indicator of a specific surface (i.e. the relation of the area
of a particle to its weight) provides the big area of contact to
cellular membranes and causes effective adsorption of substances
and influences on their transport
 High indicator of keeping time (low mobility in tissues, long time
of deducing from an organism): more contact time - more
damages
 High index of reactivity: reactionary ability is interconnected
with an indicator of a specific surface, heterogeneity (deficiency) of
a material, and also its chemical cleanliness (for example, presence
of nanoparticles of toxic metals)
WAYS OF PENETRATION OF CNT TO THE
HUMAN BODY AND ANIMALS
 At inhalation (contact to a mucous and
pulmonary tissue)
 Contact with skin covering
 Food intake and water drinking
 Intended introduction under skin, in
GIТ and in blood
Following action on cellular level !
WAYS OF CNT PENETRATION INTO CELL
 PUNCTURE
 PERMEATION
 ENDOCYTOSIS
CYTOTOXICITY OF CNT
Authors
Material
Type of cell
Result
Shvedova et
al, 2003
SW CNT, Fe-catalyst
Keratinocytes of human (НаСаТ) – put in
solution with 0.06-0.24 mg/ml CNT,
contact 8 h
Accelerated oxidative stress (growth of
quantity of free radicals and peroxides, an
exhaustion of the general antioxidant reserves;
losses in viability of cells and morphological
changes
MonteiroRiviere et al,
2005
MW CNT, (CVDmethod), purified
Keratinocytes of human (НЕК) – put in
solution with 0.1-0.4 mg/ml CNT, contact
till 48 h
Production preinflammatory cytokinin (IL);
reduction of viability of cells depending on
time and a dose
Tamura et al,
2004
CNT, purified
Human blood neutrophils – contact with
solution CNT during 1 h
Production increase superoxide anion-radicals
and inflammatory cytokine (TNF-α); decrease
in viability of cells
Cherukuri et
al, 2004
SW CNT, purified
Phagocytic cells of mice (J774.1)
Catching ~50% of nanotubes, no cytotoxic
effect
Shvedova et
al, 2005
SW CNT, Fe-catalysts
Macrophagic murine cells (RAW264.7)
Pro-fibrotic mediator TGF-1 was increased;
no oxidative burst, nitric oxide production or
apoptosis was observed
Muller et al,
2005
MW CNT, purified
Peritoneal and alveolar macrophages –
incubation in solution with 20, 50 и 100
mg/ml CNT, contact 24 h
Emission of lactate dehydrogenase and
inflammatory cytokinin (мRNA squirrel TNF-α)
Jia et al, 2005
SW and MW CNT
(arc, CVD), purified
Alveolar macrophages – solution of CNT,
modified dose regime of contact, conc.
1.4-22.6 mg/cm2, 6 h
Reduction of viability of cells and easing of
their functional ability
Cui et al, 2005
SW CNT
Human embryonic kidney cells (НЕК 293)
– put in solution with 0.78-200 mg/ml
Induction of apoptosis and reduction of ability
to adhesion, reduction cellular proliferation
(on expression of corresponding genes)
The control of barrier function of membranes and activity
of mitochondria by EPR of spin probes
Intensity EPR
Nitroxyl radicals in research of oxidation-reduction
status of bioobjects
h+
h0
h_
t
h0/h_ – Parameter of
mobility of a probe, which
characterizes microdensity
Time, min
min
OH
EPR-spectra of a spin probe in erythrocyte cytosol of donor
blood after incubation 2 days at temperature 6 oC with CNT of
various concentrations: 1 – control; 2 – 10 μg/ml; 3 – 200
μg/ml.
CH3
CH3
CH3
N
O
CH3
.
100
80
I, %
60
40
20
1
2
3
4
5
Influence of donor blood erythrocytes incubation with
CNT of various concentrations on intensity of the
central component of EPR-spectrum of radicals:
1) – control; 2) – 10 μg/ml; 3) – 50 μg/ml; 4) – 100 μg/ml;
5) – 200 μg/ml.
Reduction of a spin probe in liver homogenate
after 4 hours incubation:
♦ - control; ∆ - about 200 μg/ml CNT.
5
2
4
ln I
1
3
2
Cl
0
5
10
15
20
25
30
35
t, min
N
HN
N
CH3
CH3
N
CH3
N
O
CH3
.
Cl
EPR spectra of lipophilic spin probe: in water solution; probe
and expander mixes; mixes of probe, expander and CNT; probe
in suspension of CNT.
INTERRACTION BETWEEN CNT AND NITROXYL RADICAL
(preliminary quantum chemical data)
BIOCOMPATIBILITY OF CNT (to cells)
Authors
Material
Type of cell
Result
Elias et al,
2002
CNT-containing
orthopedic materials
Osteoblasts – inoculation on material
Increase of osteoblast proliferation, growth
of alkaline phosphatase, absence of
cytotoxicity
Supronowicz et
al, 2002
PLA/CNT –
nanocomposites
Osteoblasts – contact with nanocomposites, action of current
Growth of proliferation of osteoblasts,
absence of cytotoxicity
Price et al, 2003
PU/CNTnanocomposites
Osteoblasts, chondrocytes, fibroblasts,
plain muscular cells – contact with
PU/CNT
Adhesion growth of osteoblasts, easing of
adhesion of other cells, absence of
cytotoxicity
Correa-Duarte
et al, 2004
MW CNT, oxidized
Fibroblasts of mice (L929) – inoculation
on CNT, observation - 7 days
Formation of the isolated cells, fusion after
7 days, absence of cytotoxicity
McKenzie et al,
2004
MW CNT, purified,
different diameter
Astrocytes ( cells which are responsible
for reduction of damages of nervous
tissue) – contact to CNT surface
Normal proliferation, adhesion and
functional activity on tubes, especially with
a diameter less than 100 nm.
Hu et al, 2004
PU/CNTnanocomposites
Astrocytes, aksons of rats – contact with
PU/CNT nanocomposites
Adhesion reduction of astrocytes, a growth
of inhibition of aksons. Cytotoxicity is
absent
Gabay et al,
2005
MW CNT, purified and
chemically modified
Neurons – inoculation on CNT,
observation - 4 days
Localization on CNT, proliferation of
aksons. Cytotoxicity is absent
McKnight et al,
2004
Vertically oriented
CNT with immobilized DNA
Cells of Chinese hamster ovary (CHO) –
centrifugation and pressing
Part of cells was lost, however cytotoxic
effect was not noted
Growth of colonies of yeast cells (control)
Growth of colonies of yeast cells at presence at a nutrient medium of suspension CNT
Kinetics of mobility (activity) of human spermatozoids
in the presence of CNT in various concentrations
POSSIBILITIES OF MEDICAL USE OF CNT
Nanocomposites
with polymers and
alloys (prosthetics)
Internal functionalization
External
functionalization
On the ends and defects
of tubes
On the walls of tubes
GENERAL STRATEGY OF FUNCTIONALIZATION OF CNT
GENERAL STRATEGY OF COVALENT FUNCTIONALIZATION OF CNT
IMMOBILIATION OF STREPTAVIDIN ON CNT
CNT AS KILLERS OF CANCER CELLS
 NANOBOMBS (near IR-light)
 HYPERTHERMIA (near IR-light)
 DELIVERY of radioisotopes, cytochrome C, cytostatics
etc.
(Folic acid – provides selectivity of meeting CNT with cancer cells)
Destruction of cancer cells in blood vascular with use of CNT at
illumination by near IR-light (on Balaji Panchapakesan)
TRANSPORT OF OBJECTS INTO CELL
BY MEANS OF CNT
(In cytoplasm and in nucleus)
 Transport of medicines (antibiotic – amphotericin B)
 Transport of vaccines (peptide of virus foot-and-mouth disease virus)
 Transport of proteins (streptavidin, fibrinogen, protein A,
erythropoetin, apolipoprotein)
 Transport of nucleic acids
ANTICARCINOGENIC PREPARATIONS ON
THE BASIS OF PLATINUM
cis - [Pt (NH3) 2Cl2)]
Cisplatin
Complex Pt (IV) and
Complex Pt (IV) covalent connected
with SWNT.
Viability of tumor cells (%) at fourdays influence of free complex Pt
(IV) and the similar complex
attached to SWNT.
APPLICATION OF CNT AS CARRIERS OF
BIOPREPARATES
Authors
Conjugates
Result
Pantarotto et al,
2003
Functionalized SW CNT + small peptide
sequence from the foot-and-mouth disease
virus (FMDV)
SW CNT-FMDV peptide complex induced a specific antibody
response in vivo. It was maintained and recognized by monoand polyclonal antibodies
Pantarotto et al,
2004
Functionalized SW CNT + peptide fragment
from the α-subunit of the Gs protein (αs)
SWCN-αs complex was able to cross the cell and nucleic
membranes (human 3T6 and murine 3T3 cells)
Kam et al, 2004
Purified and shortened SW CNT + streptavidin
SW CNT- streptovidin conjugate caused extensive cell death,
which was attributed to the delivery of streptavidin to the cells
(proleukemia cells of human and T-lymphocytes)
Wu et al, 2005
CNT + amphotericin B;
Amphotericin B got into various cells and increased its activity
Bianco et al,
2005
CNT + different proteins of < 80 kDa
(fibrinogen, protein A, erythropoietin, and
apolipoprotein)
CNT-TEG-short protein complex quickly got at fibroblasts and
other cells, sometimes migrated to their nuclei. Proteins
executed own biological functions
Lu et al, 2004
SW CNT + RNA polymer
Successful transportation of SW CNT-RNA polymer complex
into cytoplasm and nucleus of cell
Pantarotto et al,
2004
SW CNT and MW CNT + plasmid DNA
All conjugates influenced on regulative expression of marker
genes in human cells
Cai et al, 2005
SW CNT + plasmid DNA, with nickel under the
influence of a magnetic field
High efficiency of transduction of SW CNT-DNA conjugates in
lymphoma cells (Ball 7 B-lymphoma)
Kam et al, 2005,
2006
SW CNT + cytochrome C, RNA, DNA
CNT transferred cytochrome C to the cancer cells;
accumulation of SW CNT-RNA conjugates in cytoplasm and
nucleus of HeLa cells
NANOSENSORS (vertical oriented CNT
on surface of electrode)
NANOSENSORS
(vertical orientation of CNT on electrode)
NANOSENSORS
(usage of CNT in form of fibers or nets)
Joining of antibodies to grids from CNT allows to create nanosensors. At
linkage of antibodies with a corresponding antigens (for example, the
specific protein of cancer cells) changes conductivity of fibers from CNT,
that is fixed by a current between electrodes.
(Balaji Panchapakesan, University of Delaware, USA)
CONCLUSIONS:
Manufacture and use of carbon nanotubes are:
Expensive (small yields, special physical, chemical
and biological methods of enriching, fractioning,
separations, reception of great volumes with
reproduced properties; the powerful and expensive
equipment for the control of properties and
characterization is also required);
Unsafe (influence on alive organisms at cellular level
and on environment; necessity to develop
nanotoxicology with all expenses needed for it);
Perspective (for medicine it is new class of
preparations, delivery systems of medicines, vaccines,
serums, a vector for gene engineering, nanosensors,
nanoinstruments).
CONCLUSIONS
 We actually use the first method of spin probes to study the
cytotoxicity of nanomaterials (CNT) and the development of
nanotechnology (drug delivery systems, medical
biotechnology) has shown its great potential.
 Advantages of the method associated with an instant
assessment of the influence of parameters of the
microenvironment of the probe (microviscosity, polarity,
micro-relief surface, red-ox potential) on the parameters of
their EPR spectra, as well as the small size of the probes
(<< 1 nm), which fits well with the size range studied
nanostructures and significantly less than the size of
biological objects (proteins, cells, subcellular structures, etc.).
 Another important aspect of the effectiveness of spin
probes is that the method allows to work with very complex,
optically opaque biological objects and to judge the status of
their individual structures or fragments by detecting changes
in the parameters of the microenvironment of the
paramagnetic proper tags.
THANK YOU FOR ATTANTION !
БЛАГОДАРЮ ЗА ВНИМАНИЕ !
ДЯКУЮ ЗА УВАГУ !