U.S. patent application number 12/274174 was filed with the patent office on 2009-05-28 for carbon nanotube based imaging agents.
Invention is credited to Keith Bennett Hartmann, Kyle Ryan Kissell, Lon J. Wilson.
Application Number | 20090136987 12/274174 |
Document ID | / |
Family ID | 38724087 |
Filed Date | 2009-05-28 |
United States Patent
Application |
20090136987 |
Kind Code |
A1 |
Wilson; Lon J. ; et
al. |
May 28, 2009 |
Carbon Nanotube Based Imaging Agents
Abstract
Compositions and methods related to carbon Nanotubes are
provided. More particularly, imaging agents comprising carbon
Nanotubes internally loaded with a contrast agent and associated
methods are provided. One example of a method may involve a method
for imaging comprising: providing an imaging agent comprising a
carbon Nanotube loaded with contrast agent; introducing the imaging
agent into a cell; and imaging the cell to detect the presence of
the imaging agent.
Inventors: |
Wilson; Lon J.; (Houston,
TX) ; Kissell; Kyle Ryan; (Manvel, TX) ;
Hartmann; Keith Bennett; (Houston, TX) |
Correspondence
Address: |
Michelle M. LeCointe;Baker Botts L.L.P.
98 San Jacinto Blvd., Ste. 1500
Austin
TX
78701
US
|
Family ID: |
38724087 |
Appl. No.: |
12/274174 |
Filed: |
November 19, 2008 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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PCT/US2007/069459 |
May 22, 2007 |
|
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12274174 |
|
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60747874 |
May 22, 2006 |
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Current U.S.
Class: |
435/29 ;
423/447.1; 977/742; 977/954 |
Current CPC
Class: |
B82Y 5/00 20130101; A61K
51/00 20130101; A61K 49/0447 20130101; A61K 49/0409 20130101 |
Class at
Publication: |
435/29 ;
423/447.1; 977/954; 977/742 |
International
Class: |
C12Q 1/02 20060101
C12Q001/02; D01F 9/12 20060101 D01F009/12 |
Claims
1. An imaging agent comprising a carbon Nanotube and a contrast
agent, the contrast agent being disposed within the carbon
Nanotube.
2. The imaging agent of claim 1 wherein the carbon Nanotube is an
ultra short carbon nanotube.
3. The imaging agent of claim 1 wherein the Nanotube is substituted
with serinol groups.
4. The imaging agent of claim 1 further comprising a buckysome,
wherein the imaging agent is disposed within the buckysome.
5. The imaging agent of claim 1 wherein the contrast agent is
I.sub.2 or a molecule having an iodine moiety.
6. A method of preparing ultra short carbon Nanotubes comprising:
providing a plurality of single walled carbon Nanotubes produced by
HiPco; fluorinating the tubes; purifying the tubes with
concentrated HCl; and cutting the tubes using pyrolysis.
7. A method of loading Nanotubes with contrast agent comprising:
providing ultra short carbon Nanotubes and a contrast agent; and
allowing the contrast agent to sublime thereby loading the ultra
short carbon nanotubes.
8. The method of claim 7 wherein the contrast agent is I.sub.2.
9. The method of claim 7 further comprising reducing the loaded
tubes using NaH.
10. A method for imaging comprising: providing an imaging agent
comprising a carbon Nanotube loaded with contrast agent;
introducing the imaging agent into a cell; and imaging the cell to
detect the presence of the imaging agent.
11. The method of claim 10 wherein the cell is imaged using
computed tomography.
12. The method of claim 10 wherein the contrast agent is
I.sub.2.
13. The method of claim 10 wherein the imaging agent is disposed
within a buckysome.
14. The method of claim 10 wherein the carbon Nanotube is a single
walled carbon nanotube.
15. The method of claim 10 wherein the carbon Nanotube is an ultra
short carbon nanotube.
16. The method of claim 10 wherein the carbon Nanotube is
substituted.
17. The method of claim 10 wherein the carbon Nanotube is
unsubstituted.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of International
Application No. PCT/US2007/069459, filed May 22, 2007, which claims
the benefit of U.S. Provisional Application Ser. No. 60/747,874,
filed May 22, 2006, both of which are incorporated in this
application by reference.
BACKGROUND
[0002] The discovery of the "buckyball" by Smalley et al. at Rice
in 1985 and its cousin the single-walled carbon Nanotube (SWNT) by
Sumio Iijima in 1991 has sparked two decades of intense research on
possible applications of these novel Nanostructures. SWNTs have
useful properties, such as high tensile strength, low density, high
electrical conductivity, and high thermal conductivity. SWNTs have
demonstrated the ability to translocate into cells opening the
possibility of intracellular diagnostic and therapeutic
applications.
[0003] One such application, computed tomography (CT), sometimes
known as computed axial tomography (CAT), is a powerful diagnostic
imaging tool utilized in thousands of diagnoses annually. In CT,
imaging is achieved by measuring the attenuation of an X-ray,
defined as the loss of energy of the radiant beam due to
absorption, scattering, and beam divergence as it propagates
through a medium. X-ray slice data is generated by rotating an
X-ray source around an object. Detectors opposite the source
measure the intensity of the exiting X-ray, which is directly
proportional to the radiodensity of the scanned object. The X-ray
slices can then be reconstructed into a three-dimensional image for
interpretation. Naturally radiodense objects, such as bone, can be
easily distinguished from fatty tissue using unenhanced CT.
However, for objects with similar radiodensities, such as cancerous
tissue compared to healthy tissue, a contrast agent usually needs
to be employed to achieve the correct diagnosis.
[0004] The majority of existing commercial CT contrast agents are
iodine-based because of two factor: iodine is an effective X-ray
scatterer due to its large number of electrons (atomic number 53)
and current clinical CT X-ray sources operate at 33 keV, an energy
which is also absorbed by the iodine atoms; thereby improving the
overall performance of the contrast agent. The increase in
attenuation at 33 keV for iodine is due to the photoelectric
absorption of X-rays at that specific energy by iodine inner-shell
electrons.
[0005] Many existing CT contrast agents consist of a 1,3,5 tri-iodo
benzene backbone with the other three positions on the benzene ring
consisting of water-solubilizing groups containing alcohol, amine,
amide, and carbonyl functional groups. The major difference between
the various contrast agents on the market is the structure of the
water-solubilizing groups, but the tri-iodo benzene backbone is
nearly universal. These CT agents contain between 25 and 50 percent
by mass iodine, have high water solubility, on the order of 150
mg/mL, and are known as blood pool agents. This means the agent
circulates in the blood pool, but does not translocate into the
interior of cells. Sufficient contrast is achieved solely because
abnormal tissues, such as cancerous tumors, require increased blood
flow to sustain their growth, resulting in higher local
concentrations of contrast agent. Current CT contrast agents are
generally not targeted to specific cell types which lead to
limitations in the detection of diseases such as vulnerable plaque
in the coronary artery.
SUMMARY
[0006] The present disclosure relates to compositions and methods
related to carbon Nanotubes. More particularly, the present
disclosure relates to an imaging agent comprising carbon Nanotubes
internally loaded with a contrast agent and associated methods of
preparation and use.
[0007] The hollow structure of SWNTs may be used as a capsule to
deliver diagnostic and/or therapeutic agents to specific cell-types
of interest, such as cancers.
[0008] Existing CT technology lacks the ability to non-invasively
diagnose critical diseases, such as coronary artery disease
vulnerable plaque. The imaging agents of the present disclosure may
be used as blood pool CT contrast agents, with long circulation
times, avoiding the use of a catheter during x-ray angiography.
[0009] By using a carbon Nanotube as the base structure of the
imaging agent, toxic contrast agents, such as I.sub.2 may be
sequestered within the interior of the Nanotube. This may be
advantageous for in vivo applications, to ensure the iodine
toxicity is completely sequestered within the interior of the
carbon Nanotube. The exterior of the Nanotube may be substituted
with peptides, water-solubilizing groups, and the like, to enhance
the ability of the nanotube to be internalized by cells.
[0010] The features and advantages of the present disclosure will
be readily apparent to those skilled in the art upon a reading of
the description of the embodiments that follows.
DRAWINGS
[0011] Some specific example embodiments of the disclosure may be
understood by referring, in part, to the following description and
the accompanying drawings.
[0012] FIG. 1 shows the three species of I.sub.2 present in
I.sub.2-loaded full-length SWNTs: (A) physisorbed to the outside of
a Nanotube bundle, (B) contained within the interior of the
Nanotube, and (C) intercalated within the interstitial spaces of a
Nanotube bundle.
[0013] FIG. 2 shows thermal gravimetric analysis of raw SWNTs
(blue) and I.sub.2-SWNTs (red).
[0014] FIG. 3 shows a Raman spectrum of (a) raw SWNTs and (b)
I.sub.2-SWNTs.
[0015] FIG. 4 is a TEM image of raw SWNTs (left) and I.sub.2-SWNTs
(right).
[0016] FIG. 5 shows an I 3d.sub.5/2 XPS spectrum (left) and X-ray
induced Auger emission spectrum (right) of I.sub.2-SWNTs.
[0017] FIG. 6 shows a C 1s XPS spectrum for I.sub.2-SWNTs
[0018] FIG. 7 shows an AFM image of raw HiPco SWNTs (left) and
reduced HiPco SWNTs (right).
[0019] FIG. 8 shows AFM height measurements for raw HiPco
SWNTs.
[0020] FIG. 9 shows AFM height measurements for Na.degree./THF
reduced HiPco SWNTs.
[0021] FIG. 10 shows a Raman spectrum of (a) raw HiPco SWNTs and
(b) Na.degree./THF reduced HiPco SWNTs.
[0022] FIG. 11 shows a) I 3d.sub.5/2 XPS spectrum of I.sub.2-SWNTs
(black) and I.sub.2@SWNTs (red) reduced by the Na.degree./THF
reaction and then quenched by water. b) X-ray induced Auger
emission spectrum over the I MNN region for I.sub.2-SWNTs (black)
and I.sub.2@SWNTs (red) reduced by the Na.degree./THF reaction and
then quenched by water. The peaks due to externally-adsorbed
I.sub.2 are denoted by an asterisk.
[0023] FIG. 12 shows a) Variable-temperature XPS study of
I.sub.2-SWNTs under high vacuum and b) X-ray induced Auger emission
spectrum of I.sub.2-SWNTs at room temperature (black), at
100.degree. C. (green), at 200.degree. C. (blue), at 300.degree. C.
(red), and reduced by the Na.degree./THF reduction reaction
(yellow). All spectra were acquired under high vacuum. Possible
instrument error is +10.degree. C. and +0.1% Iodine.
[0024] FIG. 13 shows an I 3d.sub.5/2 XPS spectrum for
twice-Na.degree./THF-reduced I.sub.2-SWNTs.
[0025] FIG. 14 shows an x-ray induced Auger emission spectrum over
the I MNN region for twice-Na.degree./THF-reduced I.sub.2-SWNTs
[0026] FIG. 15 shows a) Raman spectrum of raw (a) raw SWNTs, (b)
I.sub.2-SWNTs, (c) Na.degree./THF reduced I.sub.2-SWNTs, (d)
I.sub.2-SWNTs heated to 400.degree. C., and (e) I.sub.2-SWNTs
heated to 1000.degree. C. b) The low energy region of a) magnified.
The .nu. (I-I) stretching mode peak is denoted by an asterisk.
[0027] FIG. 16 shows micro CT images of (a) raw SWNTs, (b)
I.sub.2-SWNTs, and (c) Na.sup.0/THF reduced I.sub.2@SWNTs.
[0028] FIG. 17 shows AFM image of US-tubes. Only 20-40 nm in
length, the US-tubes are seen as bright dots in a 2 .mu.m.sup.2
image.
[0029] FIG. 18 shows AFM height measurements for US-tubes.
[0030] FIG. 19 shows a Raman spectrum of (a) raw SWNTs and (b)
US-tubes.
[0031] FIG. 20 shows AFM height measurements for Na.degree./THF
reduced US-tubes
[0032] FIG. 21 shows Raman spectrum of I.sub.2-US-tubes.
[0033] FIG. 22 shows an XPS spectrum (left) and X-ray induced Auger
emission spectrum (right) of I.sub.2-US-tubes. In the Auger
emission spectrum, the peaks assigned previously to external
I.sub.2 for full-length I.sub.2-SWNTs are denoted by asterisks.
[0034] FIG. 23 shows a Raman spectrum of Na.degree./THF reduced
I.sub.2-US-tubes.
[0035] FIG. 24 shows a micro CT images of (a) empty US-tubes, (b)
I.sub.2-US-tubes, and (c) Na.degree./THF reduced I.sub.2-US-tubes.
The calculated radiodensities are 4366 HU, 43,716 HU, and 4395 HU
respectively.
[0036] FIG. 25 shows a) Variable-temperature XPS study of
I.sub.2-US-tubes under high vacuum and b) X-ray induced Auger
emission spectrum of I.sub.2-US-tubes at room temperature (black),
at 100.degree. C. (green), at 200.degree. C. (blue), and at
300.degree. C. (red). All spectra were acquired under high vacuum.
Possible instrument error is .+-.10.degree. C. and .+-.0.1%
iodine.
[0037] FIG. 26 shows a Raman spectrum of (a) Na.degree./THF reduced
I.sub.2-US-tubes, (b) NaH reduced I.sub.2@US-tubes, and (c)
Na.degree./THF reduced I.sub.2@SWNTs. The region of interest is
enlarged in the right image.
[0038] FIG. 27 shows an I 3d.sub.5/2 XPS spectrum (left) and X-ray
induced Auger emission spectrum (right) of NaH reduced
I.sub.2@US-tubes.
[0039] FIG. 28 shows a reaction scheme for the synthesis of
PEG-US-tubes.
[0040] FIG. 29 shows an alternative reaction scheme for
PEG-US-tubes.
[0041] FIG. 30 shows a reaction scheme for serinol
amide-US-tubes.
[0042] FIG. 31 shows molecular structure of amphifullerene,
AF1.
[0043] FIG. 32 shows CT image of 50 mg of unloaded SWNTs (left) and
an equal amount of I.sub.2@SWNTs (right) as solids. The lines
beneath the samples are a support material for the sample
holders.
[0044] FIG. 33 shows an I 3d.sub.5/2 XPS spectrum of I.sub.2 loaded
US-tubes substituted with serinol after NaH reduction. The position
of the peak is 619 eV, consistent with all previous
measurements.
[0045] FIG. 34 shows an XAES spectrum of I.sub.2 loaded US-tube
substituted with serinol (black), I.sub.2 loaded US-tube
substituted with serinol after EtOH washing (blue), and I.sub.2
loaded US-tube substituted with serinol after 10 mins NaH reduction
(red). The black and blue spectra have all 3 I.sub.2 peaks, meaning
they contain both internal and external I.sub.2. Only after the NaH
reduction is all external I.sub.2 removed.
[0046] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the Office
upon request and payment of the necessary fee.
[0047] While the present disclosure is susceptible to various
modifications and alternative forms, specific example embodiments
have been shown in the figures and are herein described in more
detail. It should be understood, however, that the description of
specific example embodiments is not intended to limit the invention
to the particular forms disclosed, but on the contrary, this
disclosure is to cover all modifications and equivalents as
illustrated, in part, by the appended claims.
DESCRIPTION
[0048] The present disclosure relates to compositions and methods
related to carbon Nanotubes. More particularly, the present
disclosure relates to an imaging agent comprising carbon Nanotubes
internally loaded with a contrast agent and associated methods of
preparation and use.
[0049] In one embodiment, the present disclosure relates to imaging
agents comprising a carbon Nanotube and a contrast agent. As used
herein, the term "contrast agent" refers to any agent which is
detectable by any means. As used herein, the term "carbon nanotube"
refers to a type of fullerene having an elongated, tube-like shape
of fused five-membered and six-membered rings that is approximately
1 nm in diameter. Examples of carbon Nanotubes that may be used in
conjunction with the methods of the present disclosure include, but
are not limited to, single walled carbon Nanotubes (SWNTs) and
ultra-short carbon Nanotubes (US-tubes).
[0050] SWNTs, also known as single walled tubular fullerenes, are
cylindrical molecules consisting essentially of sp.sup.2 hybridized
carbons. In defining the size and conformation of single-walled
carbon Nanotubes, the system of nomenclature described by
Dresselhaus et al., Science of Fullerenes and Carbon Nanotubes, Ch.
19, ibid. will be used. Single walled tubular fullerenes are
distinguished from each other by a double index (x,y), where x and
y are integers that describe how to cut a single strip of hexagonal
graphite such that its edges join seamlessly when the strip is
wrapped onto the surface of a cylinder. When x=y, the resultant
tube is said to be of the "arm-chair" or (x,x) type, since when the
tube is cut perpendicularly to the tube axis, only the sides of the
hexagons are exposed and their pattern around the periphery of the
tube edge resembles the arm and seat of an arm chair repeated n
times. When y=0, the resultant tube is said to be of the "zig-zag"
or (x,0) type, since when the tube is cut perpendicular to the tube
axis, the edge is a zig zag pattern. Where x.noteq.y and y.noteq.0,
the resulting tube has chirality. The electronic properties of the
Nanotube are dependent on the conformation, for example, arm-chair
tubes are metallic and have extremely high electrical conductivity.
Other tube types are metallic, semi-metals or semi-conductors,
depending on their conformation. Regardless of tube type, all SWNTs
have extremely high thermal conductivity and tensile strength. The
SWNT may be a cylinder with two open ends, a cylinder with one
closed end, or a cylinder with two closed ends. Generally, an end
of an SWNT can be closed by a hemifullerene, e.g. a (10, 10) carbon
Nanotube can be closed by a 30-carbon hemifullerene. If the SWNT
has one or two open ends, the open ends can have any valences
unfilled by carbon-carbon bonds within the single wall carbon
Nanotube filled by bonds with hydrogen, hydroxyl groups, carboxyl
groups, or other groups. SWNTs can also be cut into ultra-short
pieces, thereby forming US-tubes. As used herein, the term "US
tubes" refers to ultra short carbon Nanotubes with lengths from
about 20 nm to about 100 nm.
[0051] Generally, the carbon Nanotubes, more particularly, the
SWNTs may be produced by the HiPco process or by electric arc
discharge. Virtually all previous research about loading SWNT
samples was performed with electric-arc discharge-produced SWNTs as
opposed to other SWNT production methods, such as high-pressure
carbon monoxide (HiPco), because arc-produced SWNTs have a larger
diameter than HiPco SWNTs (1.4 nm average diameter for arc vs. 1.0
nm diameter for HiPco) and arc SWNTs are generally believed to
contain more sidewall defects than HiPco SWNTs, thereby
facilitating loading. For medical applications, however, the
uniformity and purity of HiPco SWNTs is advantageous. Suitable
commercially available carbon Nanotubes may be obtained from Carbon
Nanotechnologies Inc., Houston, Tex.
[0052] Current methods known in the art to produce US tubes from
SWNTs require full-length SWNTs to be cut into short pieces by a
four-step process. First, residual iron catalyst particles are
removed by oxidation via exposure to wet-air or SF.sub.6 followed
by a strong acid (HCl) treatment to extract the oxidized iron
particles. The purified SWNTs are then fluorinated by a gaseous
mixture of 1% F.sub.2 in He at elevated temperatures for up to 2
hours and cut into short pieces by pyrolysis under argon at
900.degree. C. The fluorination reaction produces F-SWNTs, with a
stoichiometry of CF.sub.x (x<0.2), which consist of bands of
flurorinated-SWNT separated by regions of pristine SWNT. Pyrolysis
under Ar liberates volatile fluorocarbons, thereby cutting the
SWNTs into pieces with lengths corresponding to the areas of
pristine SWNT. While this method known in the art is effective at
producing cut SWNTs, improvements can be made; specifically, the
separate purification step is unnecessary and can be
eliminated.
[0053] To overcome the inefficiencies of current methods to produce
US tubes, a three-step process may be used to produce US tubes.
First, as produced HiPco SWNTs are fluorinated in a monel steel
apparatus by a mixture of 1% F.sub.2 in He at 100.degree. C. for 2
hours. During this process, both the SWNTs and the iron catalyst
particles become fluorinated. Subsequent exposure to concentrated
HCl removes the fluorinated catalyst particles without affecting
the F-SWNTs, which have a stoichiometry of .about.C.sub.10F after
the acid treatment. The, now-purified, F-SWNTs are cut into
US-tubes by pyrolysis under Ar at 900.degree. C. The resulting
US-tubes have lengths ranging from 20-80 nm, with the majority
being .about.40 nm in length. Utilizing this method, the amount of
iron catalyst is reduced from .about.25 mass percent in raw SWNTs
to .about.1 mass percent for US-tubes. Therefore, this method is
ideal for the purification of SWNTs, but only as a precursor to
producing US-tubes. This is because the fluorine remaining, after
the HCl acid treatment, is very hard to remove, making the F-SWNTs
only viable for subsequent cutting. Furthermore, the time to
produce US tubes from SWNTs using this method is significantly
reduced.
[0054] Typically, carbon Nanotubes are of micron-length. Such
lengths may reduce the ability of the carbon Nanotubes to
internalize into the cells. The carbon Nanotubes of the present
disclosure may be of a length of about 100 nm to about 5 .mu.m,
alternatively 100 nm or less, alternatively of about 50 nm or less,
and alternatively from about 20 nm to about 50 nm. Generally,
carbon Nanotubes of Nano-length may be suited for internalization
by cells. In certain embodiments, the carbon Nanotubes used in the
compositions of the present disclosure may comprise US tubes of
length in the range of about 20 nm to about 80 nm. In certain
embodiments, the carbon Nanotubes used in the compositions of the
present disclosure may comprise SWNTs of a length of less than 100
nm.
[0055] The carbon Nanotube can be substituted or unsubstituted. By
"substituted" it is meant that a group of one or more atoms is
covalently linked to one or more atoms of the carbon Nanotube.
Generally, Bingel chemistry may be used to substitute the Nanotube
with appropriate groups. Examples of groups suitable for use
include, but are not limited to, malonate groups, serinol
malonates, groups derived from malonates, serinol groups, serinol
amide, carboxylic acid, dicarboxyilic acid, polyethyleneglycol
(PEG), and the like. In certain embodiments, the carbon Nanotube is
substituted with one or more water-solubilizing groups.
Water-solubilizing groups are polar groups (that is, groups having
a net dipole moment) that render the generally hydrophobic Nanotube
soluble in water. Such groups may allow for greater
biocompatibility of the carbon Nanotube and enhanced diffusion
through the cell membrane. In certain embodiments, the carbon
Nanotube may be substituted before loading of the contrast agent
within the tube. For example, in certain embodiments using US
tubes, the US tubes may be substituted with serinol groups prior to
loading of a contrast agent within the tube. The degree of
lipophilicity of the substituted Nanotube should roughly parallel
the degree of lipophilicity of the groups covalently linked to the
surface of the nanotube.
[0056] The imaging agents of the present disclosure also comprise a
contrast agent. In certain embodiments, the contrast agent is
I.sub.2. In other embodiments, the contrast agent may be any iodine
moiety. In other embodiments, the contrast agent may be magnetic
metallic particles, such as Gd.sup.3+. Examples of contrast agents
include, but are not limited to, MRI contrast agents (e.g. magnetic
metal particles), CT contrast agents (e.g. hyperpolarized gas),
X-ray contrast agents, nucleosan contrast agents, and ultrasonic
contrast agents, among others.
[0057] The contrast agents of the present disclosure are generally
sequestered within the carbon Nanotube. Generally all or a portion
of the carbon Nanotube may be loaded with contrast agent. The
carbon Nanotubes may be loaded through the ends of the carbon
nanotubes and/or through the side wall defects. Examples of
suitable methods that may be used to load the carbon Nanotubes with
contrast agent include, but are not limited to, solution phase
method, molten phase method, and sublimation. One of ordinary skill
in the art, with the benefit of the disclosure will realize what
method would be suitable for loading the carbon Nanotube based on
the properties of the contrast agent to be loaded.
[0058] To prepare the imaging agents of the present invention,
loading by sublimation may be effective when using materials that
sublime at relatively low temperatures, such as I.sub.2. In certain
embodiments, carbon Nanotubes are loaded with I.sub.2 in high
yields via sublimation. In certain embodiments, HiPco SWNTs are
loaded with a contrast agent, such as I.sub.2. Typically, HiPco
SWNTs are not used for loading experiments because the interior of
the HiPco SWNT was thought to be inaccessible for loading due to
the lack of sidewall defects and the presence of the iron catalyst
particle, which blocks the open end of the SWNT. However, such
HiPco produced tubes do load with I.sub.2 without exposure to
strong acids, known to create sidewall defects in the Nanotube that
would facilitate loading. It may be possible for I.sub.2 to react
with the iron catalyst particle to remove it from the end of the
SWNT, thus allowing loading through the open end of the SWNT. US
tubes may also be loaded in the same manner as SWNTs.
[0059] Though the Nanotubes are able to be loaded, exterior
adsorbed I.sub.2 must be removed. In certain embodiments, a
chemical reduction procedure may be performed to debundle carbon
Nanotubes after loading with the contrast agent to ensure that the
contrast agent is completely sequestered within the carbon
Nanotubes. In particular, procedures useful for debundling SWNTs
are known in the art. One such procedure, a Na.sup.0/THF reduction
reaction, results in the SWNTs becoming highly charged (.about.10
electrons/nm), which creates an electrostatic repulsion resulting
in the debundling of the Nanotubes into mostly individual SWNTs. In
the case of I.sub.2 loaded SWNTs, this debundling would allow for
any I.sub.2 intercalated within the surface spaces of a SWNT bundle
to be chemically reduced to I.sup.- and washed away. In other
embodiments, the I.sub.2 loaded SWNTs may be heated to 300.degree.
C. without reduction to remove I.sub.2 adsorbed to the exterior
surface of the Nanotube. In these embodiments, the resulting loaded
Nanotubes are stable and loaded contrast agent will not be lost
even after further reduction steps or additional heating.
[0060] In certain embodiments, the carbon Nanotubes are US tubes
and such reduction methods for SWNTs result in the unloading of
contrast agent, I.sub.2, from the interior of the US tubes. In
these embodiments, the US tubes may be reduced using NaH. Such
reduction methods, however, are time-dependent. The length the
reaction is allowed to proceed will depend on the presence or
absence of internally loaded I.sub.2. Generally, in these
embodiments, when reduction reactions are performed on carbon
Nanotubes loaded with contrast agents, the reaction should not
proceed for longer than one hour to ensure that contrast agent
remains loaded within the tubes. In other embodiments, the removal
of externally adsorbed I.sub.2 may occur by heating the loaded
Nanotubes to 400.degree. C.
[0061] In certain other embodiments, the imaging agents of the
present disclosure may comprise carbon Nanotubes that are US tubes.
In these embodiments, the US tubes may be substituted with serinol
groups prior to loading with contrast agent. The contrast agent may
be I.sub.2 and may be loaded after the US tubes have been
substituted via sublimation. To remove the any exterior adsorbed
contrast agent, the US tubes may be reduced using NaH to form a
substituted and loaded US tube imaging agent.
[0062] In certain embodiments, the imaging agents of the present
disclosure may be enclosed within a buckysome. As used herein, the
term "buckysome" refers to amphifullerenes, AF1, (FIG. 31) that
have self assembled into unilamellar vesicles which resemble
unilamellar liposomes. As used herein, the term "unilamellar"
refers to having only one bilayer around an aqueous core. The
imaging agents of the present disclosure may be entrapped within
the fullerene cage of the buckysome. Buckysomes have been found to
be temperature and pH sensitive. In certain embodiments, under high
temperature and pH, the imaging agents may be released at much
higher rates than at low temperature and low pH. This pH dependent
release is due to the protonation and deprotonation of the
carboxylic acid groups of the individual AF1 groups. Upon
deprotonation, the carboxylic acid moieties become negatively
charged and may repel one another, resulting in a more fluid
structure which increases the release of imaging agent from the
vesicles. An acidic environment results in a more tightly packed
structure. Additionally, the AF1 molecule has potential for an
almost unlimited degree of further derivatization of its structure,
which gives it "tunability" with respect to imaging agent
release.
[0063] In certain embodiments, the imaging agents of the present
disclosure may be used to diagnose diseases. Examples of such
diseases include, but are not limited to, coronary heart disease
resulting from vulnerable plaque, intracranial hemorrhages, acute
and chronic lung conditions such as cancer, emphysema, or
pneumonia, and several abdominal conditions such as kidney stones
or appendicitis. In these embodiments, the imaging agents may be
internalized by cells of interest. Imaging techniques known in the
art may be used to detect the presence of imaging agent after
internalization by the cells. Such imaging techniques include, but
are not limited to, CT, MRI, X-Ray, and the like.
[0064] To facilitate a better understanding of the present
disclosure, the following examples of certain aspects of some
embodiments are given. In no way should the following examples be
read to limit, or define, the entire scope of the invention.
EXAMPLES
Example 1
Synthesis of I.sub.2 Loaded SWNTs (Hereinafter I.sub.2-SWNTs)
[0065] A raw Nanotube sample of SWNTs, produced by the HiPco
process, with an average diameter of 1.0 nm and containing 25% by
weight iron catalyst impurities was obtained from Carbon
Nanotechnologies Inc. The, as received, SWNT sample was not
purified by exposure to a strong acid treatment which is known to
create additional defects in the sidewalls. Loading of raw,
full-length SWNTs with contrast agent, I.sub.2 was accomplished via
sublimation of I.sub.2 (.about.100.degree. C.) in the presence of
SWNTs for one hour in a closed glass vessel. In all cases, SWNTs
and I.sub.2 were kept separate to ensure loading was via I.sub.2
sublimation and not via molten iodine. In a typical experiment, 50
mg of raw SWNTs were used and the SWNT sample gained approximately
80% mass during the loading process (total mass after loading was
90 mg). However, not all of this mass gain is due to
internally-loaded I.sub.2; in fact, a central question surrounding
loaded SWNTs is whether the loading material is contained within
the interior of the SWNT or adsorbed to its exterior surface.
Nanotubes aggregate into large bundles which are difficult to
separate (.about.1 eV/nm binding energy) and hydrophobic molecules,
e.g. I.sub.2, can become intercalated in the surface spaces within
a SWNT bundle. As shown in FIG. 1, there are actually 3 possible
I.sub.2 species present; I.sub.2 adsorbed to the exterior of a
Nanotube bundle, I.sub.2 intercalated within the surface spaces of
a nanotube bundle, but not loaded within any one SWNT, and I.sub.2
loaded within the interior of a SWNT.
Example 2
Thermal Gravimetric Analysis of I.sub.2-SWNTs
[0066] Thermal gravimetric analysis (TGA) in air measures the mass
loss of the I.sub.2-SWNTs as a function of temperature (FIG. 2).
Raw SWNTs, with no loaded I.sub.2, exhibit very little loss of mass
until temperatures greater than 400.degree. C. are reached, at
which point the SWNTs combust. For I.sub.2-SWNTs, mass loss is
observed much earlier, around 150.degree. C., as I.sub.2 is
liberated. The total mass lost from 150.degree. C. to 400.degree.
C., when the SWNTs again combust, is approximately 35%, which is in
good agreement with the observed mass gain from the loading
process. However, no distinction can be made as to which species of
I.sub.2 is liberated and only a quantification of the total amount
of iodine removed can be made. For raw SWNTs, the mass remaining at
600.degree. C. is iron oxide residue from iron catalyst particles
present in raw SWNTs; 19 mass percent of iron oxide remaining
corresponds to an initial iron content of 25% by mass. In the case
of the I.sub.2-SWNTs, only 7 mass percent remains at 600.degree. C.
This is not necessarily because iron is being removed during the
loading process. The added iodine mass due to the loading process
results in a lower overall mass percent of iron in the
I.sub.2-SWNTs.
Example 3
Raman Spectroscopy of I.sub.2-SWNTs
[0067] Raman spectroscopy provides additional structural
information about the I.sub.2-SWNTs but is also unable to
distinguish the multiple species of I.sub.2 present. Comparative
Raman spectra of raw SWNTs and I.sub.2-SWNTs are shown in FIG. 3.
Characteristic SWNT bands at 1590 cm.sup.-1 (sp.sup.2 hybridized
carbon), 1350 cm.sup.-1 (sp.sup.3 hybridized carbon), and in the
region of 100-300 cm.sup.-1 (radial breathing modes for SWNTs of
various diameters) are present in both the raw SWNT and
I.sub.2-SWNT samples. However, the I.sub.2-SWNTs exhibit an
additional band at 159 cm.sup.-1 which is not present in the raw
SWNT spectrum. This peak disappears when the I.sub.2-SWNTs are
heated to 1000.degree. C. and reappears after a second I.sub.2
sublimation treatment, therefore it can confidently be assigned to
the .nu.(I-I) stretching mode. The position of this .nu.(I-I) band
for I.sub.2-SWNTs, 159 cm.sup.-1, is somewhat surprising, because
it does not correspond with either the .nu.(I-I) stretching mode
observed at 178 cm.sup.-1 for crystalline I.sub.2 or at 211
cm.sup.-1 for gaseous I.sub.2. Thus, the interior of a SWNT or SWNT
bundle is a unique chemical environment. While this is interesting
information, Raman spectroscopy alone is not able to identify or
quantify the multiple species of I.sub.2 present; thus other
techniques, such as electron microscopy, must be explored.
Example 4
Transmission Electron Microscopy of I.sub.2-SWNTs
[0068] High-resolution transmission electron microscopy (HRTEM) has
thus far been the method of choice for characterizing loaded SWNT
samples. While HRTEM is a powerful technique and is able to
visualize individual atoms of loading material, HRTEM does have
several disadvantages. The long acquisition time, inability to
characterize bulk samples, and inability to quantify each species
present of HRTEM indicate that better techniques are needed for
complete characterization. Perhaps the greatest disadvantage of the
HRTEM used in the previous work is its uniqueness; very few labs in
the world have the equipment and software necessary to perform this
type of HRTEM analysis. Due to the limited availability of the
equipment, only regular TEM could be performed on the
I.sub.2-SWNTs. In addition to the disadvantages experienced by
HRTEM, the resolution of regular TEM is too low to visualize
individual I.sub.2 molecules. In fact, very little difference can
be seen between raw SWNTs and I.sub.2-SWNTs (FIG. 4). Energy
Dispersive X-ray spectroscopy (EDAX) does confirm the presence of
iodine loaded in the I.sub.2-SWNTs and the absence of iodine in raw
SWNTs, but certainly this method cannot be used to identify or
quantify the multiple species of I.sub.2 present.
Example 4
X-Ray Photoelectron Spectroscopy of I.sub.2-SWNTs
[0069] After loading, the I.sub.2-SWNTs contained 5.3 atomic % of
iodine by XPS (36% by mass) which agrees well with the mass gain
observed during the loading process. The position of the
I-3d.sub.5/2 peak in the XPS spectrum (FIG. 5) at 619.5.+-.0.2 eV
is consistent with accepted values for I.sub.2 (as opposed to
polyiodide chains such as I.sub.3.sup.- and I.sub.5.sup.-),
indicating that I.sub.2 does not react with SWNTs to form C--I
bonds. This is also confirmed by the absence of a second peak in
the C 1s spectrum (FIG. 6), which would also indicate C--I bond
formation, for the I.sub.2-SWNT sample. However, only one peak is
observed in the I-3d.sub.5/2 region and no shoulders are visible
which would indicate the presence of a hidden second peak.
Therefore, it would appear that XPS cannot distinguish between the
I.sub.2 species. However, inspection of the X-ray-induced Auger
emissions reveals several features of interest (FIG. 5). For
I.sub.2-SWNTs, the X-ray induced Auger emission spectrum exhibits
peaks at kinetic energies of 507.5.+-.0.2 eV and 519.0.+-.0.2 eV.
Additionally, there is a prominent shoulder observed on the 507.5
eV peak, with a maximum at .about.510 eV. The 507.5 and 510.0 eV
peaks stem from I-M.sub.5N.sub.45N.sub.45 emissions, whereas the
519.0 peak stems from I-M.sub.4N.sub.45N.sub.45 emissions.
Unfortunately, despite lengthy efforts curve-fitting the various
peaks in the X-ray induced Auger emission spectrum; no conclusive
discrimination of individual I.sub.2 species could be made. It
became obvious that the only method to definitively identify any
single I.sub.2 species was to debundle the SWNTs; this would result
in the intercalated I.sub.2 becoming accessible to an organic
solvent or a reactive species, leading to the removal of this
unwanted, external I.sub.2 species.
Example 5
Chemical Reduction of SWNTs
[0070] A method of debundling SWNTs via chemical reduction in
tetrahydrofuran (THF) was published by Petit et al. 50 milligrams
of raw SWNTs were added to a dry 250 mL round bottom flask with a
2:1 molar excess of sodium metal (100 mg). Then, 150 mL of dry THF
was added to the flask, and the flask was purged with N.sub.2(g),
capped, and bath sonicated for one hour. After one hour, the
reduction reaction was quenched with DI water and the sample was
isolated using a glass frit filter (Pyrex #36060). Atomic force
microscopy (AFM) confirmed the debundling of the SWNTs by the
Na.degree./THF reduction reaction into mostly individuals (FIG. 7).
The AFM image was acquired before the addition of water, although
the SWNTs are likely quenched via exposure to the atmosphere.
Height measurements taken for several points in the reduced SWNT
sample measure 1 nm, corroborating individual SWNTs (FIGS. 8 and
9).
2. Example 6
Raman Spectroscopy of Na.sup.0/THF Reduced SWNTs
[0071] Raman spectroscopy was used to assess structural changes in
the SWNTs as a result of the Na.sup.0/THF reduction reaction. Such
changes could be either residual delocalized negative charge not
quenched by the addition of water as suggested in the original
work, or protonation (similar to the Birch reaction) of the charged
SWNTs upon quenching by water. As shown in FIG. 10, the Raman
spectrum before and after the Na.degree./THF reduction is nearly
identical, with the exception of a small increase in the disorder
band at .about.1300 cm.sup.-1. This band is indicative of
sp.sup.3-hybridized carbon which suggests that some degree of
protonation of the SWNTs has occurred. This was confirmed by an
elemental analysis performed by Galbraith Laboratories which showed
increased hydrogen content in the Na.sup.0/THF reduced SWNTs, with
a C:H ratio of .about.20:1 measured for Na.degree./THF reduced
SWNTs as opposed to a C:H ratio of >150:1 measured for raw SWNTs
(Table 1). Once the effects of the Na.degree./THF reduction
reaction on raw SWNTs were understood, a Na.degree./THF reduction
was performed on I.sub.2-SWNTs under the same reaction conditions
to determine if removal of intercalated I.sub.2 was achieved.
TABLE-US-00001 TABLE 1 Carbon and hydrogen elemental analysis of
raw HiPco SWNTs and Na.degree./THF reduced HiPco SWNTs Atomic
Percent Sample Carbon Hydrogen Raw HiPco SWNTs 69.49 <0.5
Na.sup.0/THF reduced HiPco SWNTs 67.91 3.21
Example 6
XPS of Na.sup.0/THF Reduced I.sub.2-SWNTs
[0072] After an I.sub.2-SWNT sample was reduced by the Na.sup.0/THF
reaction, 2.8 atomic % or 22% by weight I.sub.2 remained in the
sample, which approximates to be 3.1 atoms of iodine/nm of SWNT. A
slight shift of the I-3d.sub.5/2 peak to a lower binding energy
(619.1.+-.0.2 eV) is observed in the reduced I.sub.2@SWNT sample;
however, the shift is within experimental error and is not large
enough to provide conclusive evidence as to the removal of
exterior-adsorbed I.sub.2. Additionally, this value is still within
those accepted for I.sub.2, which indicates the remaining I.sub.2
in the sample has not been reduced to some polyiodide form
(I.sub.3.sup.- or I.sub.5.sup.-) as a result of the Na.degree./THF
reaction. This would likely occur only if the remaining I.sub.2 was
sequestered within the interior of the hydrophobic Nanotube and
therefore, inaccessible to chemical reduction.
[0073] Inspection of the X-ray induced iodine Auger emission
spectrum reveals significant differences between the I.sub.2-SWNT
sample and the Na.sup.0/THF reduced I.sub.2@SWNTs. As described
above, the unreduced I.sub.2-SWNT sample exhibits peaks at kinetic
energies of 507.5.+-.0.2 eV and 519.0.+-.0.2 eV, with a prominent
shoulder observed on the 507.5 eV peak (maximum at .about.510 eV).
The reduced I.sub.2@SWNT sample, on the other hand, exhibits a
single peak at 510.0.+-.0.2 eV with a shoulder at approximately 517
eV. This shoulder is initially hidden in the I.sub.2-SWNT spectrum
by the I.sub.2 peak at 519 eV and is likely also due to internal
I.sub.2. This phenomenon is also observed in the Auger temperature
studies discussed below (red trace in FIG. 12b). Representative
spectra comparing the iodine photoelectron and X-ray induced Auger
emissions for the I.sub.2-SWNT (black) and reduced I.sub.2@SWNT
(red) samples are shown in FIG. 11. As discussed above, the 507.5
and 510.0 eV peaks stem from I-M.sub.5N.sub.45N.sub.45 emissions,
whereas the 519.0 peak stems from I-M.sub.4N.sub.45N.sub.45
emissions. This allows for the calculation of Auger parameters for
each peak, a valuable tool in deriving chemical state
information.
[0074] Since the I-M.sub.4N.sub.45N.sub.45 emissions appear at 11.5
eV lower kinetic energy than I-M.sub.5N.sub.45N.sub.45 emissions,
addition of this value allows for Auger parameters to be derived.
Such parameters are an effective method of deriving additional
chemical state information. Auger parameters are derived by adding
the I-3d.sub.5/2 peak binding energy to the
I-M.sub.4N.sub.45N.sub.45 kinetic energy, or by adding the
I-3d.sub.5/2 peak binding energy to the I-M.sub.5N.sub.45N.sub.45
kinetic energy plus 11.5 eV. For the unreduced I.sub.2-SWNT sample,
Auger parameter values of 1138.5 eV for the 507.5 eV peak, 1141.0
eV for the 510.0 eV shoulder, and 1138.5 eV for the 519.0 eV peak
are derived. A value of 1141.0 eV is derived for the peak at 510.0
eV in the Na.sup.0/THF reduced I.sub.2@SWNT sample.
[0075] The Auger peak at 510.0 eV is thus assigned to
internally-loaded I.sub.2, while those at 507.5 eV and 519.0 eV are
attributed to externally-adsorbed I.sub.2. The difference in the
kinetic energies of these Auger emissions represents a definitive
method of distinguishing between internal and external I.sub.2.
Auger parameters of 1138 eV are consistent with I.sub.2, confirming
once again that the external-adsorbed iodine is I.sub.2, not a
polyiodide or a C--I species. The shift observed in the Auger
parameter, from 1138.5 eV to 1141 eV, for internal I.sub.2, is
likely due to the unique chemical environment experienced by
I.sub.2 confined within the interior of a SWNT.
Example 7
Inductively-Coupled Plasma Analysis
[0076] The removal of iodine from the I.sub.2-SWNTs during the
Na0/THF reduction reaction was also confirmed by
inductively-coupled plasma/atomic emission detector (ICP-AE)
analysis of the THF/water filtrate. After the Na.degree./THF
reaction was quenched with water, the reduced I.sub.2@SWNTs were
isolated by a glass frit filter. The THF/water filtrate was heated
to remove the THF, and ICP-AE confirmed the presence of iodine
(present as NaI) in the filtrate after the reduction reaction. A 20
mL sample contained 550 mg/L of I-, which corresponds to 10 mg of
I.sub.2 removed from the I.sub.2-SWNT sample during the reduction
reaction. This is consistent with the change observed in the atomic
% of I.sub.2 by XPS.
[0077] To confirm the stability of the internal I.sub.2 with
respect to chemical reduction, a second Na.sup.0/THF reaction was
performed on the already reduced I.sub.2-SWNTs (hereinafter
I.sub.2@SWNTs) under the same conditions. After a second
Na.degree./THF reduction, 2.3 atomic % of iodine remained which is
unchanged (within error) from the amount of I.sub.2 present in the
I2-SWNT sample after the first reduction. Additionally, the peak
positions for iodine in the XPS and X-ray induced Auger emission
spectra were unchanged from the peak positions after the first
reduction (FIGS. 13 and 14) ICP-AE also confirmed that no iodine
(as NaI) was present in the filtrate after the second reduction.
These results establish that internal I.sub.2 is truly sequestered
within the interior of the Nanotube (I.sub.2@SWNTs) and is
impervious to chemical reduction by Na.degree./THF.
Example 8
Variable-Temperature XPS Studies
[0078] Variable-temperature XPS analysis was performed on an
I.sub.2-SWNT sample to assess the thermal stability of the internal
I.sub.2 vs. external I.sub.2. A sample of the unreduced
I.sub.2-SWNTs was heated from room temperature to 800.degree. C.
under high vacuum. During this process, a mass spectrum analysis
indicated I.sub.2.sup.+ (254 amu) and I.sup.+ (127 amu) were the
only positive ion species liberated from the I.sub.2-SWNT sample in
the temperature range of 200.degree. C.-800.degree. C. XPS spectra
and X-ray induced Auger emission spectra were acquired every
100.degree. C. As shown in FIG. 12a, a linear loss of iodine is
observed by XPS from room temperature until 300.degree. C. From
300.degree. C. to 500.degree. C., the iodine content remains
constant, and above 500.degree. C. linear loss of iodine is again
observed. The atomic % of iodine remaining at 400.degree. C. is
.about.2.0%, a value consistent with the amount of
internally-loaded I.sub.2 from the reduction experiments. As also
shown in FIG. 12b, the X-ray induced Auger emission spectra of the
I.sub.2-SWNTs at room temperature (black), 100.degree. C. (green),
200.degree. C. (blue), 300.degree. C. (red), and after the
Na.sup.0/THF reduction reaction (yellow) confirm that the decrease
in the atomic % of iodine observed by XPS is due to the removal of
exterior-adsorbed I.sub.2. The Auger peaks at 507.5 eV and 519.0
eV, assigned above to externally-adsorbed I.sub.2, decrease in
intensity from room temperature until their disappearance at
.about.300.degree. C. This is illustrated by the shift from an
unresolved doublet in the 505-510 eV region at room temperature
(black trace in FIG. 9b, maxima at 507.5 eV and 510 eV) to a single
peak at 300.degree. C. (red trace in FIG. 12b, maximum at 510 eV).
As discussed above, a shoulder is once again observed at .about.517
eV after the external I.sub.2 is removed from the SWNT sample (red
trace in FIG. 12b). The Auger peak at 510.0 eV, assigned to
internal I.sub.2, is largely unchanged during the temperature
study. The Auger emission spectrum of I.sub.2-SWNTs at 300.degree.
C. (red trace in FIG. 12b) and the spectrum for reduced
I.sub.2@SWNTs (yellow trace in FIG. 12b) are identical with respect
to the features at 507.5 and 519.0 eV. Heating to 300.degree. C.
thus provides an alternative method for removing
externally-adsorbed I.sub.2. It is possible to also remove the
interior I.sub.2 from the SWNT sample, but temperatures upwards of
800.degree. C. are required.
3. Example 8
Raman Spectroscopy of Na.sup.0/THF Reduced I.sub.2-SWNTs
[0079] Raman spectroscopy is used to characterize changes in the
I-I stretching mode present in the I.sub.2-SWNT sample as a result
of the removal of external I.sub.2, either by heating or
Na.degree./THF reduction. As discussed above and shown in FIG. 15,
there is an additional band at 159 cm.sup.-1 in the Raman spectrum
of I.sub.2-SWNTs (FIG. 15b), which is not present in the raw SWNT
spectrum (FIG. 15a). This band is therefore assigned to the
.nu.(I-I) stretching mode. Interestingly, this .nu.(I-I) stretching
mode decreases significantly when the I.sub.2-SWNTs are reduced by
the Na.degree./THF reduction reaction or heated to 400.degree. C.
(FIGS. 15c and 15d respectively). Upon heating to 1000.degree. C.,
which removes all I.sub.2, the 159 cm.sup.-1 band completely
disappears (FIG. 15e) and the Raman spectrum is once again
identical to that for the raw SWNT sample (FIG. 15a). Thus, Raman
spectroscopy can also be used to discriminate between internal and
external I.sub.2, by way of the relative intensities of the
.nu.(I-I) stretching mode, but only in conjunction with XPS
spectral data.
Example 9
Micro Computed Tomography (MicroCT)
[0080] Finally, MicroCT experiments confirm that I.sub.2@SWNTs are
functional computed tomography contrast agents. Solid samples of
raw SWNTs, I.sub.2-SWNTs, and Na.degree./THF reduced I.sub.2@SWNTs
were placed in a cylindrical polyethylene holder and analyzed by a
Skyscan 1172 microcomputed tomography scanner. The raw SWNTs, as
expected, exhibit very little X-ray attenuation; qualitatively, raw
SWNTs appear similar to the polyethylene holder. The attenuation
for raw SWNTs, which contain no iodine, is most likely due to the
presence of iron catalyst particles which also scatter X-rays,
although not nearly as effectively as iodine (26 electrons for iron
compared to 57 for iodine). The I.sub.2-SWNTs, on the other hand,
display extremely high attenuation. I.sub.2@SWNTs, as expected,
demonstrate much higher attenuation than the raw SWNTs, but not as
high as the I.sub.2-SWNTs. This is, of course, because
I.sub.2-SWNTs contain both internal and external I.sub.2 (5.3
atomic %) whereas I.sub.2@SWNTs contain only internal I.sub.2 (2.8
atomic %). Comparative 2-D MicroCT images for raw SWNTs,
I.sub.2-SWNTs, and I.sub.2@SWNTs are shown in FIGS. 16 and 32.
[0081] To quantify the performance of each sample, Hounsfield Units
(HU) were calculated. The Hounsfield scale, established by Sir
Godfrey Hounsfield, one of the developers of computed tomography,
is a quantitative way of describing radiodensity. Specifically,
distilled water is defined as 0 HU and air is defined as -1000 HU.
Using these values, Hounsfield units of 14,927 HU, 46,438 HU, and
28,400 HU were calculated for raw SWNTs, I.sub.2-SWNTs and
I.sub.2@SWNTs, respectively.
Example 10
Modified Approach Using Fluorination for Purification
[0082] US-tubes, with lengths ranging from 20-80 nm, were prepared
via a modification of a known process. Currently, full-length SWNTs
are cut into short pieces by a four-step process. First, residual
iron catalyst particles are removed by oxidation via exposure to
wet-air or SF.sub.6 followed by a strong acid (HCl) treatment to
extract the oxidized iron particles. The purified SWNTs are then
fluorinated by a gaseous mixture of 1% F.sub.2 in He at elevated
temperatures for up to 2 hours and cut into short pieces by
pyrolysis under argon at 900.degree. C. The fluorination reaction
produces F-SWNTs, with a stoichiometry of CF.sub.x (x<0.2),
which consist of bands of flurorinated-SWNT separated by regions of
pristine SWNT. Pyrolysis under Ar liberates volatile fluorocarbons,
thereby cutting the SWNTs into pieces with lengths corresponding to
the areas of pristine SWNT. While this method is effective at
producing cut SWNTs, improvements can be made; specifically, the
separate purification step is unnecessary and can be
eliminated.
[0083] US-tubes were prepared via a three-step process. First, as
produced HiPco SWNTs are fluorinated in a monel steel apparatus by
a mixture of 1% F.sub.2 in He at 100.degree. C. for 2 hours. During
this process, both the SWNTs and the iron catalyst particles become
fluorinated. Subsequent exposure to concentrated HCl removes the
fluorinated catalyst particles without affecting the F-SWNTs, which
have a stoichiometry of .about.C.sub.10F after the acid treatment.
The, now-purified, F-SWNTs are cut into US-tubes by pyrolysis under
Ar at 900.degree. C. The resulting US-tubes have lengths ranging
from 20-80 nm, with the majority being .about.40 nm in length.
Utilizing this method, the amount of iron catalyst is reduced from
.about.25 mass percent in raw SWNTs to .about.1 mass percent for
US-tubes. Therefore, this method is ideal for the purification of
SWNTs, but only as a precursor to producing US-tubes. This is
because the fluorine remaining, after the HCl acid treatment, is
very hard to remove, making the F-SWNTs only viable for subsequent
cutting.
Example 11
Atomic Force Microscopy of US-Tubes
[0084] Atomic force microscopy (AFM) analysis of the US-tubes
illustrates the effectiveness of the cutting process. Shown in FIG.
17, all US-tubes are between 20 and 80 nm in length, with the
majority being .about.40 nm. No evidence of SWNTs longer than TOO
nm can be found. Height measurements (FIG. 18) confirm that the
US-tubes exist as small bundles, with heights between 3 and 7
nm.
Example 12
Raman Spectroscopy of US-Tubes
[0085] Raman spectroscopy evaluates the structural changes to the
SWNT resulting from the cutting procedure. The increase in the band
at 1350 cm.sup.-1, indicative of sp.sup.3-hybridized carbon,
confirms additional sidewall defects are created as a result of the
cutting process. Comparative Raman spectra for SWNTs and US-tubes
are shown in FIG. 19.
[0086] Atomic force microscopy also confirms that the
Na.degree./THF reduction reaction debundles empty US-tubes into
individuals. Shown in FIG. 20, height measurements substantiate
individual US-tubes (diameters of .about.1 nm). This is a
significant result because it represents the first example of
individual US-tubes in suspension. This is critical to the sidewall
functionalization of US-tubes.
Example 13
Loading Procedures for US-Tubes
[0087] The loading and characterization procedures of US-tubes are
taken directly from the full-length SWNT model system. Loading of
US-tubes is again accomplished via sublimation of I.sub.2 in a
closed glass vessel at 100.degree. C. The mass gain observed for
US-tubes is slightly higher than that observed for full-length
SWNTs; typically a 50 mg sample of US-tubes increases 100-120% by
mass during the loading process (final mass=100-110 mg) as opposed
to the 80% mass increase observed for full-length SWNTs. This is
likely due to the increased surface area of the US-tubes as
compared to full-length SWNTs. XPS also confirms that
I.sub.2-US-tubes contain a greater amount of iodine than do
I.sub.2-SWNTs. Values of 8-9 atomic % iodine (.about.57% iodine by
mass) are obtained for I.sub.2-US-tubes in contrast to 5.3 atomic %
for I.sub.2-SWNTs (36% iodine by mass). This increase in atomic
percent iodine is once again consistent with the mass increase
observed during the I.sub.2 sublimation process. The Raman spectrum
for I.sub.2-US-tubes, shown in FIG. 21, displays the peak, at 159
cm.sup.-1, proven to be the .nu.(I-I) stretching mode, once more
confirming the presence of I.sub.2.
Example 14
XPS of I.sub.2-US-Tubes
[0088] The I 3d.sub.5/2 peak position, shown in FIG. 22, for
I.sub.2-US-tubes is 619.2.+-.0.2 eV, consistent with both the
I.sub.2-SWNT data and accepted values for I.sub.2 from the
literature. The X-ray induced Auger emission spectrum for
I.sub.2-US-tubes, also shown in FIG. 22, again shows the same
general features as I.sub.2-SWNTs. Peaks are once again observed at
507.5 eV and 519 eV, with a shoulder at 510 eV. Thus, US-tubes and
full-length SWNTs behave identically with respect to the loading
process; however, the stability of the internal I.sub.2 is
dramatically reduced for I.sub.2-US-tubes.
[0089] In the case of full-length SWNTs, the internal I.sub.2 is
remarkably stable with respect to either chemical reduction or
elevated temperatures. In contrast, the internal I.sub.2 in
I.sub.2-US-tubes is completely removed by either the Na.sup.0/THF
reduction reaction or temperatures above 300.degree. C. This is
likely a consequence of the sidewall defects created during the
cutting process, which allows Na.degree.
(Na.degree..fwdarw.Na.sup.++e.sup.-) access to the US-tube interior
and permits escape of internal I.sub.2 from the US-tube at elevated
temperatures.
Example 15
Raman Spectroscopy of Na.degree./THF Reduced I.sub.2-US-Tubes
[0090] I.sub.2-US-tubes were reduced via the Na.degree./THF
reaction using the same conditions described previously for
I.sub.2-SWNTs. The Raman spectrum of the Na.degree./THF reduced
I.sub.2-US-tubes, shown in FIG. 19, exhibits no peak in the
vicinity of 159 cm.sup.-1, indicating complete removal of I.sub.2.
XPS analysis confirms no iodine present in the Na.degree./THF
reduced I.sub.2-US-tubes. Therefore, the Na.sup.0/THF reduction of
I.sub.2-US-tubes to remove external I.sub.2 is not a viable option,
because the reduction also removes the internal I.sub.2.
[0091] Comparing empty US-tubes (FIG. 16a) and empty SWNTs (FIG.
11a); it is apparent that empty SWNTs demonstrate higher X-ray
attenuation. This is because iron catalyst particles, which scatter
X-rays, are present in raw SWNTs but are removed during the
preparation of US-tubes. Thus, US-tubes are very poor at
attenuating X-rays and have a radiodensity of only 4366 HU. In
stark contrast, I.sub.2-US-tubes, which contain 57 mass % iodine by
XPS, exhibit extraordinary X-ray attenuation. The radiodensity of
I.sub.2-US-tubes, again as a solid, is 43,716 HU. Even though this
value is actually less than that of I.sub.2-SWNTs (FIG. 11b,
radiodensity=46,438 HU), I.sub.2-US-tubes are likely superior X-ray
attenuators due to their greater amount of iodine. In these
experiments, the radiodensities of I.sub.2-SWNTs and
I.sub.2-US-tubes are similar only because both attenuate the X-ray
beam the maximum that can be measured.
[0092] I.sub.2-US-tubes which have been reduced by the
Na.degree./THF reaction are shown in FIG. 16c. As expected based on
the previous XPS and Raman results, very little X-ray attenuation
is demonstrated because all I.sub.2 has been removed by the
Na.sup.0/THF reduction reaction. The radiodensity of the
Na.degree./THF reduced I.sub.2-US-tubes is only 4395 HU as opposed
to the 28,400 HU obtained for Na.degree./THF reduced I.sub.2-SWNTs
(FIG. 14c).
Example 16
Variable-Temperature XPS Study on I.sub.2-US-Tubes
[0093] An XPS temperature study demonstrates that elevated
temperatures also result in the removal of internal I.sub.2 from
I.sub.2-US-tubes. The atomic percent of iodine in I.sub.2-US-tubes,
as shown in FIG. 21, decreases much more rapidly with respect to
temperature as compared to I.sub.2-SWNTs. By 300.degree. C., a
temperature at which 2.8 atomic % of internal I.sub.2 still remains
in I.sub.2-SWNTs, nearly all I.sub.2 has been removed from
I.sub.2-US-tubes. The X-ray induced Auger emission temperature
study, also shown in FIG. 18, does provide encouraging results. The
same behavior exhibited by I.sub.2-SWNTs, the disappearance of the
X-ray induced Auger peaks at 507.5 and 519 eV as external I.sub.2
is removed and the relative stability of the internal I.sub.2 peak
at 510 eV, is also demonstrated by I.sub.2-US-tubes, albeit at
lower temperatures. Thus, in spite of the sidewall defects present
in US-tubes, the internal I.sub.2 is more stable than external
I.sub.2, at least with respect to temperature.
[0094] While careful heating could provide a method of producing
internally-loaded I.sub.2@US-tubes, a chemical reduction method
that does not remove internal I.sub.2 would seem more advantageous,
particularly with respect to functionalization of the
I.sub.2@US-tubes. US-tubes, even more so than full-length SWNTs,
are very difficult to suspend in any solvent. Full-length SWNTs can
be suspended, as individual tubes, in aqueous solvents via
surfactant wrapping and, in both organic and aqueous solvents via
Na.degree./THF reduction, thereby allowing functionalization
reactions to take place on individual SWNTs as opposed to bundled
SWNTs. US-tubes, in contrast, can not be suspended via surfactant
wrapping and, as illustrated above, the Na.degree./THF reaction can
not be used to suspend I.sub.2-US-tubes. Therefore, it is
imperative that an alternate chemical reduction method be found
that does not remove the internal I.sub.2 from
I.sub.2-US-tubes.
Example 17
NaH Reduction of I.sub.2-US-Tubes
[0095] Fortunately, experimentation with NaH, a reducing agent used
as the first step in the Bingel cyclopropanation reaction, suggests
that I.sub.2 remains in the I.sub.2-US-tubes after exposure to NaH
for 1 hour. In a typical experiment, 10 mg I.sub.2-US-tubes are
added to a round bottom flask containing 20 mL toluene in a dry
box. Then, 20 mg dimethylsulfoxide, DMSO, and 40 mg NaH are added
to the flask and the reaction is allowed to proceed for one hour.
After one hour, the reaction is quenched by the careful addition of
ethanol. The reduced I.sub.2@US-tubes are then isolated by
filtration on a glass frit filter, washed with three 10 mL portions
of EtOH and dried overnight at 40.degree. C.
Example 18
Raman Spectroscopy of NaH Reduced I.sub.2-US-Tubes
[0096] Raman analysis reveals that I.sub.2 remains after the NaH
reduction. Shown in FIG. 23 are comparative Raman spectra for (a)
Na.degree./THF reduced I.sub.2-US-tubes, (b) NaH reduced
I.sub.2@US-tubes, and (c) Na.degree./THF reduced full-length
I.sub.2@SWNTs containing only internal I.sub.2. The spectrum for
the NaH reduced I.sub.2@US-tubes exhibits a similar peak at 159
cm.sup.-1 as the Na.sup.0/THF reduced I.sub.2@SWNTs. The
Na.sup.0/THF reduced I.sub.2-US-tubes, in contrast, exhibit no such
peak. Thus, Raman spectroscopy indicates that I.sub.2, most likely
internal I.sub.2, survives a 1 hour NaH reduction reaction.
Example 19
Micro CT of Na.sup.0/THF Reduced I.sub.2-US-Tubes
[0097] Micro computed tomography (MicroCT) experiments illustrate
the extremely high X-ray attenuation of I.sub.2-US-tubes and the
low X-ray attenuation of Na.sup.0/THF reduced I.sub.2-US-tubes
which, as a result of the Na.sup.0/THF reduction, no longer contain
I.sub.2. Shown in FIG. 24 are MicroCT images of a) empty US-tubes,
b) I.sub.2-US-tubes, and c) Na.sup.0/THF reduced
I.sub.2-US-tubes.
[0098] Comparing empty US-tubes (FIG. 24a) and empty SWNTs (FIG.
14a); it is apparent that empty SWNTs demonstrate higher X-ray
attenuation. This is because iron catalyst particles, which scatter
X-rays, are present in raw SWNTs but are removed during the
preparation of US-tubes. Thus, US-tubes are very poor at
attenuating X-rays and have a radiodensity of only 4366 HU. In
stark contrast, I.sub.2-US-tubes, which contain 57 mass % iodine by
XPS, exhibit extraordinary X-ray attenuation. The radiodensity of
I.sub.2-US-tubes, again as a solid, is 43,716 HU. Even though this
value is actually less than that of I.sub.2-SWNTs (FIG. 14b,
radiodensity=46,438 HU), I.sub.2-US-tubes are likely superior X-ray
attenuators due to their greater amount of iodine. In these
experiments, the radiodensities of I.sub.2-SWNTs and
I.sub.2-US-tubes are similar only because both attenuate the X-ray
beam the maximum that can be measured.
[0099] I.sub.2-US-tubes which have been reduced by the
Na.degree./THF reaction are shown in FIG. 24c. As expected based on
the previous XPS and Raman results, very little X-ray attenuation
is demonstrated because all I.sub.2 has been removed by the
Na.degree./THF reduction reaction. The radiodensity of the
Na.degree./THF reduced I.sub.2-US-tubes is only 4395 HU as opposed
to the 28,400 HU obtained for Na.degree./THF reduced I.sub.2-SWNTs
(FIG. 16c).
Example 20
Variable-Temperature XPS Study on I.sub.2-US-Tubes
[0100] An XPS temperature study demonstrates that elevated
temperatures also result in the removal of internal I.sub.2 from
I.sub.2-US-tubes. The atomic percent of iodine in I.sub.2-US-tubes,
as shown in FIG. 251, decreases much more rapidly with respect to
temperature as compared to I.sub.2-SWNTs. By 300.degree. C., a
temperature at which 2.8 atomic % of internal I.sub.2 still remains
in I.sub.2-SWNTs, nearly all I.sub.2 has been removed from
I.sub.2-US-tubes. The X-ray induced Auger emission temperature
study, also shown in FIG. 25, does provide encouraging results. The
same behavior exhibited by I.sub.2-SWNTs, the disappearance of the
X-ray induced Auger peaks at 507.5 and 519 eV as external I.sub.2
is removed and the relative stability of the internal I.sub.2 peak
at 510 eV, is also demonstrated by I.sub.2-US-tubes, albeit at
lower temperatures. Thus, in spite of the sidewall defects present
in US-tubes, the internal I.sub.2 is more stable than external
I.sub.2, at least with respect to temperature.
Example 21
NaH Reduction of I.sub.2-US-Tubes
[0101] Fortunately, experimentation with NaH, a reducing agent used
as the first step in the Bingel cyclopropanation reaction, suggests
that I.sub.2 remains in the I.sub.2-US-tubes after exposure to NaH
for 1 hour. In a typical experiment, 10 mg I.sub.2-US-tubes are
added to a round bottom flask containing 20 mL toluene in a dry
box. Then, 20 mg dimethylsulfoxide, DMSO, and 40 mg NaH are added
to the flask and the reaction is allowed to proceed for one hour.
After one hour, the reaction is quenched by the careful addition of
ethanol. The reduced I.sub.2@US-tubes are then isolated by
filtration on a glass frit filter, washed with three 10 mL portions
of EtOH and dried overnight at 40.degree. C.
Example 22
Raman Spectroscopy of NaH Reduced I.sub.2-US-Tubes
[0102] Raman analysis reveals that I.sub.2 remains after the NaH
reduction. Shown in FIG. 26 are comparative Raman spectra for (a)
Na.degree./THF reduced I.sub.2-US-tubes, (b) NaH reduced
I.sub.2@US-tubes, and (c) Na.degree./THF reduced full-length
I.sub.2@SWNTs containing only internal I.sub.2. The spectrum for
the NaH reduced I.sub.2 US-tubes exhibits a similar peak at 159
cm.sup.-1 as the Na.sup.0/THF reduced I.sub.2@SWNTs. The
Na.degree./THF reduced I.sub.2-US-tubes, in contrast, exhibit no
such peak. Thus, Raman spectroscopy indicates that I.sub.2, most
likely internal I.sub.2, survives a 1 hour NaH reduction
reaction.
Example 23
XPS of NaH Reduced I.sub.2-US-Tubes
[0103] This indication is confirmed by XPS and X-ray induced Auger
spectral analysis. XPS analysis verifies that 1.3 atomic % iodine
remains in the NaH reduced I.sub.2@US-tubes. The position of the I
3d.sub.5/2 peak in the XPS spectrum of NaH reduced I.sub.2@US-tubes
is 619.2.+-.0.2 eV, consistent with all previous measurements (FIG.
27). The X-ray induced Auger emission spectrum of NaH reduced
I.sub.2@US-tubes contains one peak, at 510 eV, with a visible
shoulder at .about.515 eV as shown in FIG. 27. This is consistent
with the X-ray induced Auger emission spectrum, shown in FIG. 11,
of Na.sup.0/THF reduced I.sub.2@SWNTs which contain only internal
I.sub.2; thus, the NaH reduced I.sub.2@US-tubes also contain only
internal I.sub.2. The I 3d.sub.5/2 XPS spectrum and X-ray induced
Auger emission spectrum of NaH reduced I.sub.2@US-tubes are shown
in FIG. 23. Unfortunately, unlike I.sub.2@SWNTs, which do not lose
additional I.sub.2 with repeated reduction treatments or extended
exposure to the reduction reagent, the internal I.sub.2 stability
of I.sub.2@US-tubes is short-lived. As described above, the NaH
reduction reaction is quenched after one hour and, under these
conditions, I.sub.2 remains. However, if the reaction is allowed to
proceed for 24 hours, all I.sub.2 is removed. Therefore, given
enough time, the internal I.sub.2 in I.sub.2@US-tubes is accessible
to the NaH reduction. This result has important consequences for
I.sub.2@US-tube sidewall functionalization reactions.
Example 24
I.sub.2 Loading Before PEG Functionalization
[0104] The first attempt at synthesizing PEG-I.sub.2@SWNTs involves
first loading US-tubes with I.sub.2 followed by sidewall
functionalization of the I.sub.2-US-tubes with PEG using the
reaction scheme shown in FIG. 28. This would be the ideal method of
producing PEG-I.sub.2@US-tubes because it would unequivocally
ensure that any I.sub.2 present in the final product is contained
within the interior of the US-tube. The first step of this method,
the attachment of diethyl malonate, requires the presence of NaH
which also removes all external I.sub.2. Thus, there would be no
risk of I.sub.2 interfering with subsequent reactions or reacting
with PEG itself Unfortunately, the attachment of the diethyl
malonate requires overnight exposure to NaH and, this results in
the complete removal of all I.sub.2. A one hour reaction, which
does leave some internal I.sub.2, is insufficient and does not
result derivatization with diethyl malonate groups. XPS
measurements confirm that no iodine is seen in the final product
using this method. To counteract the removal of all I.sub.2 by NaH,
an alternate method of diethyl malonate attachment can be used, as
shown in FIG. 29.
Example 25
I.sub.2 Loading Before Alternate PEG Functionalization
[0105] This method circumvents the problem of 24 hour exposure of
I.sub.2@US-tubes to NaH by utilizing an alternate functionalization
method. In this method, initial attachment of the diethyl malonate
groups is achieved by a reaction with carbon tetrabromide
(CBr.sub.4) and 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), a strong
organic base, in THF. For this method, US-tubes are again loaded
with I.sub.2 prior to any functionalization reactions.
Unfortunately, as mentioned previously, US-tubes are extremely
difficult to suspend in any solvent. In fact, the only known method
of suspending US-tubes in THF, or any organic solvent for that
matter, is, of course, chemical reduction, which cannot be
performed on I.sub.2-US-tubes without removal of all I.sub.2.
Sonication of the I.sub.2-US-tubes for 1 hour in several organic
solvents, without the presence of a reducing agent, did not result
in suspension of the I.sub.2-US-tubes, therefore the diethyl
malonate reaction could not occur.
[0106] This method was also attempted with US-tubes which were
first reduced by the Na.sup.0/THF reaction prior to I.sub.2
loading, but this was also unsuccessful. While empty US-tubes are
usually able to be resuspended after the Na.sup.0/THF reduction and
subsequent drying, US-tubes which were Na.sup.0/THF reduced, then
loaded with I.sub.2 did not resuspended in organic solvents with
sonication. It is unclear, but likely, that the I.sub.2 loading
process resulted in the inability to resuspended the reduced
I.sub.2-US-tubes. Regardless, these attempts illustrate that
I.sub.2 is not stable enough within the interior of a US-tube to
survive Bingel reaction conditions. Therefore, even though I.sub.2
loading after the PEGylation of the US-tubes is not the ideal
scenario, the instability of the internal I.sub.2 necessitates this
approach.
Example 26
I.sub.2 Loading After Complete PEG Functionalization
[0107] The I.sub.2 loading of PEG-US-tubes is not an ideal method
for three reasons. First, the PEG groups are bulky and may prevent
I.sub.2 from entering the SWNT. Second, since I.sub.2 loading is
the last step in this process, additional washing steps and
characterization must be performed to ensure that any I.sub.2
present is contained within the SWNT and not adsorbed to the
exterior. Finally, experiments must be developed to make certain
that I.sub.2 does not react with the PEG itself Nevertheless,
US-tubes were first functionalized with PEG via the Bingel
reactions (FIG. 28). The PEG-US-tubes were then isolated using a
glass frit filter and dried overnight. Solid PEG-US-tubes were then
subjected to I.sub.2 loading conditions as described previously and
washed with three 20 mL portions of ethanol to remove excess
I.sub.2. The first two ethanol washings produced a dark orange and
pale yellow color, respectively, indicative of I.sub.2. The third
ethanol washing did not produce any color, indicating excess
I.sub.2 removal was complete. However, XPS of the
PEG-I.sub.2-US-tubes indicated no iodine present. Therefore, it can
be concluded that the PEG groups prevent I.sub.2 access to the
US-tube interior. It can also be deduced that I.sub.2 does not
react with the hydroxyl groups in PEG, which is important for
future experiments involving serinol amide-I.sub.2@US-tubes. These
three methods demonstrate that I.sub.2 loading cannot be either the
first or last step in the PEG functionalization process. Therefore,
the only logical choice remaining is I.sub.2 loading between steps
of the Bingel reactions.
Example 27
I.sub.2 Loading After Diethyl Malonate Reaction
[0108] Since this reaction scheme (FIG. 28) is a three step process
and previous attempts have illustrated that I.sub.2 loading cannot
occur either before the first step or after the last step, only two
choices remain; I.sub.2 loading after the attachment of diethyl
malonate or after conversion of the diethyl malonate to acid
chloride. Because taking an acid chloride to dryness is generally a
bad idea, only one logical choice remains. Thus the fourth and
final attempt to synthesize PEG-I.sub.2@US-tubes involves
performing the diethyl malonate functionalization on empty
US-tubes, followed by I.sub.2 loading. After I.sub.2 loading,
excess I.sub.2 is removed by washing with ethanol then the acid
chloride and PEGylation reactions are performed.
[0109] First, US-tubes are functionalized with diethyl malonate via
Reaction 1 in FIG. 28. The resulting product is again isolated
using a glass frit filter, dried overnight, then loaded with
I.sub.2 via sublimation. XPS confirms that these diethyl
malonate-US-tubes load with I.sub.2, unlike PEG-US-tubes; 5.6
atomic % iodine is present after the loading process. However,
after three washings with 20 mL portions of ethanol, 0 atomic %
iodine is measured by XPS. It is unclear whether the iodine present
after the loading of diethyl malonate-US-tubes is all
externally-adsorbed, which would explain its easy removal, or if
I.sub.2 is contained within the diethyl malonate-US-tubes, but
removed by ethanol washing. Regardless, the I.sub.2 does not
survive the remaining reactions and XPS confirms no iodine
remaining in the PEG-US-tubes utilizing this method.
Example 28
I.sub.2 loaded US Tubes Substituted with Serinol Groups
[0110] I.sub.2 loaded US-tubes substituted with serinol groups have
been made by performing the serinol functionalization on empty
US-tubes as shown by the reaction scheme in FIG. 30. Then the
functionalized US-tubes are filled with I.sub.2 via sublimation as
described above. External I.sub.2 is removed by a very short (10
minute) exposure to NaH. XPS and XAES analyses confirm that iodine
remains after the reduction, that it is only internal I.sub.2, and
that the serinol moieties are not affected. The final product
contains 1.2 atomic % iodine, or about 10% by weight.
[0111] The XPS and XAES spectra (FIGS. 33 and 34) which give the
atomic % iodine and prove that it is only internally-loaded I.sub.2
due to the disappearance of the XAES peaks at 507.5 eV and 519 eV,
which illustrates the removal of external I.sub.2. The peak at 510
eV is due to internal I.sub.2. The nitrogen % in the XPS data is
due to the serinol amide moiety.
[0112] Notwithstanding that the numerical ranges and parameters
setting forth the broad scope of the invention are approximations,
the numerical values set forth in the specific examples are
reported as precisely as possible. Any numerical value, however,
inherently contain certain errors necessarily resulting from the
standard deviation found in their respective testing
measurements.
[0113] Therefore, the present invention is well adapted to attain
the ends and advantages mentioned as well as those that are
inherent therein. While numerous changes may be made by those
skilled in the art, such changes are encompassed within the spirit
of this invention as illustrated, in part, by the appended
claims.
* * * * *