Cationic cyclotriveratrylene-based glycoconjugate and its interaction with fullerene

Article abstract of DOI:10.1039/c3ra40432c

Fullerenes exhibit interesting biological activities both in vitro and in vivo. However, the low solubility of fullerenes in aqueous media appears to be a major problem for their biological application. To exploit water-soluble macrocyclic host systems to improve the water-solubility of fullerene, a cationic water-soluble CTV derivative containing glucosamine hydrochloride (CTV-GH) is synthesized and well characterized. The supramolecular complexation between CTV-GH and C₆₀ was investigated in organic solvent and aqueous solution, respectively, and confirmed by fluorescence, UV-vis, and Raman spectra. The CTV derivative exhibits a distinct photoluminescence, which can be used to conveniently detect its interaction with C₆₀ through spectrofluorometric titration. CTV-GH can bind C₆₀ in toluene-DMSO solution with the association constant K_a = 4.36 × 10 ⁵ M^-1 calculated on the hypothesis of forming a supramolecular complex with 1:1 molar ratio at 298 K. In an aqueous solution, C₆₀ has no absorption intensity due to its insolubility. However, in the presence of CTV-GH, a new characteristic peak of C₆₀ at 342 nm in the UV-vis absorption spectrum was observed for the C₆₀-CTV-GH complex and its intensity greatly increases over 24 h, which proves that CTV-GH can bind C₆₀ in aqueous solution to form a water-soluble complex. The host-guest interaction between sugar-bearing CTV and C₆₀ in aqueous solution will boost the potential biological applications of C₆₀.

Full text of DOI:10.1039/c3ra40432c

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Cationic cyclotriveratrylene-based glycoconjugate and
its interaction with fullerene3
Cite this: DOI: 10.1039/c3ra40432c
ab
a
a
a
Li-Juan Feng, Hui Li, Qi Chen* and Bao-Hang Han*
Fullerenes exhibit interesting biological activities both in vitro and in vivo. However, the low solubility of
fullerenes in aqueous media appears to be a major problem for their biological application. To exploit
water-soluble macrocyclic host systems to improve the water-solubility of fullerene, a cationic water-
soluble CTV derivative containing glucosamine hydrochloride (CTV-GH) is synthesized and well
characterized. The supramolecular complexation between CTV-GH and C60 was investigated in organic
solvent and aqueous solution, respectively, and confirmed by fluorescence, UV-vis, and Raman spectra. The
CTV derivative exhibits a distinct photoluminescence, which can be used to conveniently detect its
interaction with C60 through spectrofluorometric titration. CTV-GH can bind C60 in toluene–DMSO
5
21
solution with the association constant K
a
= 4.36 6 10
M
calculated on the hypothesis of forming a
supramolecular complex with 1 : 1 molar ratio at 298 K. In an aqueous solution, C60 has no absorption
intensity due to its insolubility. However, in the presence of CTV-GH, a new characteristic peak of C60 at
Received 25th January 2013,
Accepted 26th February 2013
3
42 nm in the UV-vis absorption spectrum was observed for the C60–CTV-GH complex and its intensity
greatly increases over 24 h, which proves that CTV-GH can bind C60 in aqueous solution to form a water-
DOI: 10.1039/c3ra40432c
soluble complex. The host–guest interaction between sugar-bearing CTV and C60 in aqueous solution will
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boost the potential biological applications of C60.
Thus, it is necessary to exploit water-soluble macrocyclic host
systems to improve the water-solubility of C60 by forming
water-soluble supramolecular complexes.
Introduction
Fullerenes, as a kind of spherical organic molecules with a
cage-like structure and 0.7 nm in diameter, are condensed
aromatic ring compounds with an extended p-conjugated
Cyclotriveratrylene (CTV), as host molecule for the full-
9–11
erene, has been widely reported in recent years.
It has
1
system. A great deal of attention has been focused on their
attracted much attention owing to its good chemical stability,
unique properties. In the past decade, the applications of
fullerenes have been gradually extended to many other
research fields, such as pharmaceutical science and biological
12
small cavity, stable conformation, and facile modification.
Considering its bowl-shape conformation with a molecular
cavity, CTV and its derivatives are well known to bind
fullerenes both in solution and in the solid state.
Modification with appending functional groups can extend
side-arms to the upper rim on the basic CTV platform, which
expands the cavity effectively and enhances the binding ability
to C60 in solution. Therefore, various cyclotriveratrylene
derivatives with extended-cavity have been developed through
versatile functionalization. The CTV-based receptor that has
three 2-ureido-4-(1H)-pyrimidinone side-arms can form hydro-
gen-bonded self-assembled capsules binding fullerenes inside,
which was further applied to the isolation of C and C84 from
2
science. It is reported that fullerene derivatives can be used in
3
photodynamic therapy or as inhibitors against HIV reverse
4
5
transcriptase and HCV RNA polymerase. Fullerene deriva-
tives with novel molecular skeletons could be lead compounds
6
in the development of antiviral agents. In addition, they
exhibit antiproliferative activity by inducing apoptosis related
to the generation of reactive oxygen species. Certain fullerene
derivatives also have the potential to be anticancer drugs.
However, fullerenes are almost insoluble in aqueous media,
which, to some extent, hampers its biological application.
7
8
7
0
1
3,14
complex mixtures of fullerenes.
Attaching aromatic exTTF
a
moieties to the basic CTV platform can afford another host
exTTF-CTV, which shows a very effective association with both
National Center for Nanoscience and Technology, Beijing 100190, China.
E-mail: hanbh@nanoctr.cn; chenq@nanoctr.cn; Tel: +86 10 8254 5576
Tel: +86 10 8254 5708
1
5
C
60 and C70
.
These derivatives form stable complexes with
b
Department of Bioengineering, Zunyi Medical College (Zhuhai Campus), Zhuhai
fullerenes in organic solvent, and can be used to purify
5
19041, China
1
6,17
fullerenes efficiently from crude soot or fullerite mixtures.
3
Electronic supplementary information (ESI) available: Absorption spectra of
1
13
Two CTV derivatives containing peripheral triethyleneglycol
chains also have the ability to form water-soluble supramole-
aqueous CTV-Glc and C60–CTV-Glc solution, and C60 in water; H NMR, C NMR
and MS spectra of the key compounds. See DOI: 10.1039/c3ra40432c
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on the hypothesis that a supramolecular complex is formed
with 1 : 1 molar ratio at 298 K. As for CTV-L, a similar complex
with a lower association constant can also be formed. Both
CTV-G and CTV-L can transfer C60 into aqueous solution
through supramolecular interactions. To extend the CTV-
based glycoconjugate family and deepen insight into the
effects of the sugar nature on the abilities of CTV-based
glycoconjugate host to form water-soluble supramolecular
complexes with C60, a novel cationic cyclotriveratrylene-based
glycoconjugate (CTV-GH) was herein prepared by grafting
glucosamine hydrochloride moieties to the CTV motif and was
found to possess a better binding ability to fullerene in both
organic solvent and water.
Results and discussion
The synthetic route to sugar-bearing CTV is outlined in
Scheme 1. Like the cyclotriveratrylene parent, which is
prepared from veratrole, functionalized cyclotriveratrylene
analogues are typically synthesized by aromatic electrophilic
Fig. 1 Structures of cyclotriveratrylene-based glycoconjugates.
2
0
substitution of appropriate benzyl alcohols. Propargylation
of vanillyl alcohol with propargyl bromide under basic
conditions can quantitatively afford phenolic propargyl ether
of vanillyl alcohol 1, which actually undergoes smooth
trimerization in the presence of perchloric acid to furnish
cular complexes with
candidates for biological applications.
C60, and make them interesting
1
8
We have introduced neutral sugar moieties into the CTV
platform to furnish a novel water-soluble glycoconjugate host
3
the C -cyclotriveratrylene derivative 2. Cu(I)-catalyzed azide–
1
9
for fullerene, considering that appending sugar chains not
only provides CTV a good solubility in water, but also extends
its cavity. Two water-soluble CTV derivatives functionalized by
glucose and lactose residues (CTV-G and CTV-L in Fig. 1) were
synthesized and their interaction with C60 was investigated in
organic solvent and aqueous solution. CTV-G can associate
with C60 to form a supramolecular complex in organic solvent
alkyne ‘‘click’’ ligation between progargylated CTV 2 and
azido-functionalized sugar derivatives (3) was chosen to
introduce three sugar groups into the CTV platform, owing
to the efficiently selective ligation and mild reaction condi-
tions based on the ‘‘click’’ reaction. Formation of the triazole
ring is confirmed by the chemical shift at nearly 7.91 ppm in
1
the H NMR spectrum and the peaks at nearly 122.1 and 144.2
5
21
1
3
a
and the association constant K is 4.36 6 10 M calculated
ppm on the C NMR spectrum of the corresponding desired
Scheme 1 Synthetic route to CTV-GH and CTV-Glc.
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3
intermediates 5 (see the ESI ). After removing all the acetyl
groups with MeONa–MeOH and deprotecting N-Boc groups in
M aqueous HCl–THF solution, the desired water-soluble
4
CTV-GH was obtained in an excellent yield (90% in two steps)
by a one-pot procedure. Similarly, glucopyranosyl-bearing CTV
(
CTV-Glc) was also prepared for the control studies. Compared
1
with the H NMR spectrum of protected precursor 5, we can
find that the peak intensities of Boc (d = 1.19 ppm), Ac (d = 2.04
ppm), and NH-Boc (dN–H = 5.99 ppm) groups in compound 5
disappear after final efficient global deprotection and the peak
+
of the NH
(
3
group (d = 8.56 ppm) in CTV-GH appears clearly
), which confirms the successful preparation of
see the ESI
3
the hydrochloride salt. The protected sugar-bearing CTVs, are
readily soluble in common solvents such as methylene
chloride, chloroform, and tetrahydrofuran, but insoluble in
methanol, ethanol, and water. The solubility of the resulting
cationic glycoconjugate CTV-GH is different from its precur-
sor, exhibiting a good solubility in DMF, DMSO, toluene–
DMSO (1 : 1, v/v), and water. As for the neutral glycoconjugate
CTV-Glc, it just shows a slight solubility in water due to the
lower water-solubility compared with the cationic counterpart
CTV-GH.
2
Fig. 2 Fluorescence spectra of CTV-GH (5.0 6 10 M) in the absence and
6
presence of various concentrations of C60 in the toluene–DMSO solution at
2
6
room temperature (lex = 310 nm). The concentrations of C60 (610 M) are 0,
1.25, 2.5, 5.0, 7.5, 10.0, 12.5, 15.0, and 17.5, respectively. The inset is the plot of
2
]
1
DI vs. [C60
.
2
6
solution. When sugar-bearing CTV interacts with C60, the
photo-induced intermolecular electron transfer from sugar-
bearing CTV donors to C60 takes place and leads to the
fluorescence quenching of sugar-bearing CTV. Meanwhile, a
CTV-GH displays an emission maximum peak at 356 nm
with a shoulder peak at 328 nm in toluene–DMSO (1 : 1, v/v)
solution. The fluorescence in the region from 340 to 390 nm
probably results from the formation of a ground-state dimer
because of the interactions between the benzene rings upon
16 nm red-shift (from 356 to 372 nm) of its emission
2
1
maximum was observed, which might be attributed to further
enhanced planar conformation of the CTV part when binding
with the C60 or the aggregation of sugar-bearing CTV complex
due to the increasing concentration of C60. The fluorescence
intensity of CTV-GH gradually decreased and was significantly
quenched by 90% when concentration of C60 is up to 17.5 mM
(Fig. 2). As a comparison, fluorescence intensity of CTV-G is
finally quenched by 80% when concentration of C60 is up to
excitation or excimeric emission caused by the interaction
2
2
between the phenyl groups. As for sugar-bearing CTV,
besides the reasons aforementioned, the fluorescence might
be ascribed to the enhanced planar conformation of the
cyclotriveratrylene ring derived from the spatial effect of bulky
branch chains. When excited at 310 nm, the fluorescence
intensity of CTV derivative 2 is very low. After incorporation of
three sugar groups into the CTV platform, the obtained sugar-
bearing CTV possesses a distinct photoluminescence.
1
9
25.0 mM, implying that CTV-GH exhibits a better binding
ability to fullerene than CTV-G under these conditions. The
spatial structure of CTV-GH with three sugar moieties is more
suitable to accommodate C60, so the photo-induced inter-
molecular electron transfer tends to take place. On the basis of
The binding of C60 to the extended-cavity CTV derivatives
2
3
can be studied by crystal X-ray diffraction, mass spectrum
1
5
and optical spectroscopy. Optical spectroscopy assay has
drawn much attention in the investigation of C60–CTVs
binding, because it is highly sensitive, convenient, and cost-
effective. The supramolecular interaction between sugar-
bearing CTV and C was studied by spectrofluorometric
2
1
linear fitting of the plot of DI vs. [C60
that the complex is formed by host and C60 is 1 : 1 ratio, and
the association constants K of host CTV-GH with C60 in
toluene–DMSO solution is 4.36 6 10
]
and the hypothesis
6
0
a
2
4,25
5
21
2
titrations
in toluene–DMSO (1 : 1, v/v) at 25 uC. Both sugar-
M
at 298 K (R =
bearing CTV and C60 are soluble in the co-solvent. Continuous
fluorescence quenching was observed in the fluorescence
spectra of sugar-bearing CTV upon successive additions of the
fullerene (0–17.5 mM) to the host solutions. As aforemen-
tioned, the fluorescence of sugar-bearing CTV might be
ascribed to the enhanced planar conformation of the
cyclotriveratrylene ring derived from the spatial effect of the
bulky sugar moieties. The enhanced planar conformation of
the cyclotriveratrylene ring makes the p-electron delocalization
and excitation much easier. As for the ground-state C60, it
possesses remarkable electron acceptor properties and is
capable of accommodating as many as six electrons in
0.995), which is slightly higher than that of neutral host CTV-G
with C60 under the same condition.
The host–guest interaction of sugar-bearing CTV hosts and
C
60 was further investigated in aqueous solution, which is
beneficial to improve the solubility of fullerenes in aqueous
media. Preparation of water soluble supramolecular com-
plexes between CTV-based host systems and fullerenes can be
done by stirring an aqueous solution of CTV-GH or CTV-Glc
2
5
(5.0 6 10
M) containing C60 solid (>99%) for 24 h and
centrifugation. Fig. 3 shows the UV absorption spectra of C60
,
CTV-GH, and C60–CTV-GH complex, respectively, in aqueous
solution after centrifugation. As expected, C60 has no absorp-
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CTV-GH with C60 in water. The interaction of sugar-bearing
CTV hosts with C60 can be visually monitored by a color
change of the corresponding solutions. For instance, the
aqueous solution of CTV-GH is almost colorless, after addition
of C60 and followed by centrifugation, the color of aqueous
C
60–CTV-GH solution gradually changes into yellow (inset of
Fig. 3).
This novel cationic CTV host with peripheral sugar chains
exhibits a higher water-solubility and shows a better ability to
60
form water-soluble supramolecular complexes with C .
Moreover, the special structure effects also play key roles in
the supramolecular interaction. The sugar–triazole cluster
structure based on the bowl-shape CTV can provide an internal
cavity capable of encapsulating the hydrophobic C60 guest,
thus preventing aggregation in aqueous solutions due to the
stronger water–water interactions. Multiple hydroxyl groups
from sugar moieties make the supramolecular complexes
water-soluble. The hydrophobic triazole groups and six-
member ring skeleton of sugars can increase the hydrophobic
and van der Waals interactions between the inner surface of
sugar-bearing CTV hosts and C60, which are useful to enhance
the major driving forces for the formation of supramolecular
complexes.
Fig. 3 Absorption spectra of aqueous CTV-GH and C60–CTV-GH solution, and
25
C60 in water (concentration of CTV-GH is 5.0 6 10 M). Inset shows the
photographs of aqueous CTV-GH (left) and C60–CTV-GH (right) solutions.
tion intensity, due to its insolubility in aqueous solution.
However, in the presence of CTV-GH, a new absorption peak at
342 nm (characteristic signal peak of C60 in UV-vis region) was
observed for C60–CTV-GH complex and its intensity greatly
increases after 24 h, which proves that CTV-GH can bind C60 in
aqueous solution to form a water-soluble complex. Further
study with Raman spectra shows the existence of C60 in C60
–
2
1
Conclusions
CTV-GH complex, in which the featured peak at 1470 cm
was assigned to the totally symmetric pentagonal pinch mode
On the basis of macrocyclic host CTV, a water-soluble CTV
derivative (CTV-GH) modified with cationic glucosamine
hydrochloride is synthesized and exhibits a distinct photo-
luminescence, which can be used to conveniently detect its
interaction with C60 through spectrofluorometric titration. The
supramolecular complexation between CTV-GH and C60 was
investigated in organic solvent and aqueous solution, respec-
tively, and was confirmed by fluorescence, UV-vis, and Raman
spectra. CTV-GH can bind C60 to form supramolecular
complexes in toluene–DMSO solution. The association con-
2
7
of C60
.
(Fig. 4) Similar phenomena were also found for CTV-
) However, the
Glc upon addition of C . (Fig. S1 in the ESI
3
6
0
absorption intensity of the C60–CTV-Glc ensemble is much
lower than that of the C60–CTV-GH complex under the same
condition probably due to the lower ability of CTV-Glc to form
a supramolecular complex with C60 and move into aqueous
phase. It also should be noted that the absorption intensity of
the C60–CTV-GH complex (24 h) is about 10 times higher than
that of C60–CTV-G complex (30 h) under similar conditions,
which indicates the higher binding ability of cationic host
5
21
stant K of host CTV-GH with C is 4.36 6 10 M calculated
a
60
on the hypothesis that the supramolecular complex is formed
with 1 : 1 molar ratio at 298 K. This novel cationic CTV host
with peripheral sugar chains exhibits higher water-solubility
and shows a better ability to form water-soluble supramole-
cular complexes with C . Moreover, the special structure
6
0
effects also play key roles in the supramolecular interaction.
The host–guest interaction between sugar-bearing CTV and
C60 in aqueous solution will boost the potential biological
applications of C60
.
Experimental section
Materials and characterization
All chemical reagents are commercially available and used as
received unless otherwise stated. Azido-functionalized sugar
2
8
29
derivatives (3 or 4 ) were prepared according to reporting
Fig. 4 Raman spectra of C60–CTV-GH, CTV-GH and C60
.
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methods. Ultrapure water (18.2 MV cm) was purified with a
115.7, 113.6, 85.6, 80.0, 74.4, 71.7, 67.8, 65.1, 62.7, 61.4, 55.9,
27.4, 27.2, 20.6, 20.2, 20.1. MALDI-TOF-MS calcd. for
C H N O33, 1812.71 (m/z), found 1835.82 (M + Na),
84 108 12
Millipore Purification System (Milli-Q water).
1
13
The H NMR and C NMR spectra were recorded on a
Bruker DMX400 NMR spectrometer. Mass spectra were
recorded with a Microflex LRF MALDI-TOF mass spectrometer.
Ultraviolet–visible (UV-vis) spectra were measured using a
Perkin–Elmer Lamda 950 UV-vis-NIR spectrophotometer and
quartz cells with 1 cm path length. The fluorescence spectra
were measured in a conventional cell with 1 cm path length
using a Perkin–Elmer LS55 spectrophotometer. Raman spectra
were recorded with a Renishaw inVia Raman spectrometer
1851.86 (M + K).
Glucopyranosyl CTV derivative 6
Glucopyranosyl CTV derivative 6 was obtained from com-
pounds 2 and 4 using the same procedure as for the
preparation of glucosamine CTV derivative 5 as a foamy solid
1
(92%). H NMR (DMSO-d ) d (ppm) 8.52 (s, 3H), 7.11 (d, J =
6
10.0 Hz, 3H), 6.37 (d, J = 8.8 Hz, 3H), 5.68 (t, J = 9.2 Hz, 3H),
5.55 (t, J = 9.6 Hz, 3H), 5.18 (t, J = 9.6 Hz, 3H), 5.10 (d, J = 12.4
Hz, 3H), 5.02 (d, J = 12.4 Hz, 3H), 4.73 (d, J = 13.2 Hz, 3H), 4.40–
4.29 (m, 6H), 4.16–4.00 (m, 6H), 3.73 (d, J = 6.0 Hz, 9H), 3.52 (d,
J = 12.8 Hz, 3H), 2.08 (s, 3H), 2.03 (s, 9H), 1.99 (s, 6H), 1.98 (s,
(
Renishaw plc, UK) by dropping the sample solutions CTV-GH
or CTV-Glc onto a slide glass or silicon wafer after air drying.
60 was tested in powder form on a slide glass.
C
Propargyl-carrying CTV (2)
1
3
6
1
1
6
H), 1.96 (s, 9H) , 1.80 (s, 3H). C NMR (DMSO-d ) d (ppm)
To the solution of vanillyl alcohol (500 mg, 3.24 mmol) and
propargyl bromide (0.35 mL, 3.64 mmol) in acetone (15 mL)
69.9, 169.5, 169.3, 168.4, 147.6, 145.9, 143.7, 132.8, 131.8,
31.4, 128.6, 123.5, 115.5, 114.0, 83.8, 73.2, 72.1, 70.1, 67.4,
were added anhydrous K CO (450 mg, 3.24 mol) and Bu NBr
2
3
4
62.0, 61.7, 55.9, 20.4, 20.3, 20.1, 19.8, 19.7, 18.6, 18.4. MALDI-
(37 mg, 0.115 mmol). The reacting mixture was refluxed
TOF-MS calcd. For C H N O , 1641.54 (m/z), found 1664.52
7
5
87 9 33
overnight and cooled to room temperature. After removing the
solvent, the residue was mixed with water (15 mL) and further
extracted with dichloromethane (25 mL). The organic phase
was separated and concentrated under reduced pressure to
yield crude (605 mg) propargyl-bearing vanillyl alcohol as
syrup. Without further purification, the above intermediate (1)
was dissolved in methanol (20 mL) and cooled with an ice
bath. To the solution was added 1.7 mL of 70% perchloric acid
dropwise. And then the resulting mixture was stirred at room
temperature under nitrogen protection for 18 h. After dilution
with dichloromethane (50 mL), the final solution was
thoroughly washed with water until neutral. The organic
phase was dried over sodium sulfate and evaporated under
vacuum to afford an oil residue, which was purified by
recrystallization in dichloromethane–ethanol to furnish pro-
(
M + Na),1680.53 (M + K).
CTV-GH
To a solution of compound 5 (55 mg, 42 mmol) in methanol (15
mL), 1 M sodium methoxide in methanol was added drop-wise
until the pH = 10. The reaction mixture was stirred at room
temperature overnight. After removal of the solvent under
reduced pressure, the residue was dissolved in 5 mL THF and
1
0 mL aqueous HCl (4 M) solution, and then stirred for 24 h at
room temperature. The solvent was removed and 10 mL of
acetonitrile was added to precipitate the crude product. A
foamy product of CTV-GH was obtained as a light-yellow solid
after purification on a Bio-gel P2 column (38 mg, 90%).
NMR (DMSO-d
3
3
3
3
1
H
6
) d (ppm) 8.56 (s, 3H), 8.44 (bs, 9H), 7.37 (s,
H), 7.20 (s, 3H), 6.06 (d, J = 9.2 Hz, 3H), 5.17 (d, J = 12.0 Hz,
H), 5.00 (d, J = 12.0 Hz, 3H), 4.77 (d, J = 12.8 Hz, 3H), 3.78–
.74 (m, 15H), 3.68 (d, J = 10.0 Hz, 3H), 3.58 (d, J = 13.2 Hz,
1
pargyl-carrying CTV (2) (170 mg, 30%). mp 213 uC. H NMR
(CDCl
3
) d (ppm) 7.02 (s, 3H), 6.88 (s, 3H), 4.77(d, J = 13.6 Hz,
3
3
1
H), 4.72 (d, J = 2.4 Hz, 6H), 3.86 (s, 9H), 3.58 (d, J = 13.6 Hz,
13
H), 3.52–3.44 (m, 9H), 3.43–3.34 (m, 9H). C NMR (DMSO-d6)
1
3
H), 2.46 (t, J = 2.4 Hz, 3H). C NMR (DMSO-d
44.8, 133.0, 131.5, 115.9, 113.8, 79.6, 77.7, 56.0, 55.7, 35.1.
, 522.20 (m/z), found
6
) d (ppm) 147.7,
d (ppm) 147.4, 146.0, 143.4, 132.7, 131.9, 125.0, 115.1, 113.8,
3.5, 80.0, 72.7, 69.1, 61.9, 60.1, 55.9, 55.8, 54.1. MALDI-TOF-
MS calcd. For C51 18, 1242.39 (m/z), found 1135.56
M 2 3Cl), 1157.60 (M 2 3Cl + Na) .
8
MALDI-TOF-MS calcd. for C33
23.21(M + 1).
30 6
H O
3 12
H69Cl N O
5
(
Glucosamine CTV derivative 5
CTV-Glc
To the mixture of 2 (120 mg, 0.27 mol) and glucosamine azide
derivative 3 (350 mg, 0.82 mol) in THF–water (2 : 1, 10 mL)
To a solution of compound 6 (60 mg) in methanol (15 mL), 1 M
sodium methoxide in methanol was added drop-wise until the
pH = 10. The reaction mixture was stirred at room temperature
overnight. After neutralization with Amberlite IR120 acidic
were added ascorbate sodium (15 mg) and CuSO (10 mg) as
4
catalyst. After refluxing for 6 h, the reaction mixture was
cooled to room temperature and then extracted with ethyl
acetate (2 6 25 mL). The combined organic layer was
concentrated and then purified by silica gel chromatography
resin and filtration, the solvent was removed under reduced
1
pressure to give the desired product (98%). H NMR (DMSO-d )
6
d (ppm) 8.43 (s, 3H), 7.32 (s, 3H), 7.15 (s, 3H), 5.54 (d, J = 9.2
Hz, 3H), 5.12 (dd, J = 4.4, 12.0 Hz, 3H), 4.99 (dd, J = 7.2, 11.6
Hz, 3H), 4.75 (d, J = 13.6 Hz, 3H), 3.78 (t, J = 9.2 Hz, 3H), 3.73 (s,
(
9
petroleum ether : ethyl acetate = 1 : 1) to yield 5 (329.6 mg,
1
6%) as a foamy solid. H NMR (CDCl
3
) d (ppm) 7.91 (s, 3H),
7.06 (s, 3H), 6.84 (s, 3H), 5.99 (t, J = 10.0 Hz, 3H), 5.46 (t, J = 9.6
9
9
1
H), 3.70–3.66 (m, 6H), 3.55(d, J = 13.2 Hz, 3H), 3.45–3.41(m,
Hz, 3H), 5.22–5.18 (m, 6 H), 4.97 (dd, J = 8.8, 13.6 Hz, 3H), 4.70
1
3
H), 3.38–3.32 (m, 12H). C NMR (DMSO-d ) d (ppm) 147.5,
6
(
(
(
d, J = 13.6 Hz, 3H), 4.31–4.23 (m, 6H), 4.14–4.07 (m, 6H), 3.97
46.1, 143.9, 132.6, 131.7, 124.8, 114.8, 113.5, 88.9, 82.8, 79.5,
br, 3H), 3.84–3.79 (m, 9H), 3.52 (dd, J = 13.2, 8.8 Hz, 3H), 2.04
1
3
74.4, 70.1, 61.9, 55.9, 54.0. MALDI-TOF-MS calcd. For
s, 27H), 1.19 (s, 27H). C NMR (CDCl ) d (ppm) 170.2, 170.0,
3
C H N O , 1137.41 (m/z), found 1160.79 (M + Na).
5
1
63 9 21
169.0, 154.5, 147.9, 146.1, 144.2, 132.6, 130.4, 128.3, 122.1,
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Studies of CTV-GH–C60 interaction based on
spectrofluorometric titration
8 M. Tadahiko, N. Dai, T. Kyoko, U. Noriko, Y. Takao,
S. Masako, E. Toyoshige and M. Masataka, Bioorg. Med.
Chem. Lett., 2003, 13, 4395.
A solution of CTV-GH was prepared in toluene–DMSO (1 : 1, v/
v). Aliquots of C60 in the same solvent were added to the
solution. The final concentration of CTV-GH is 5 6 10 M.
After each addition, the sample was allowed to equilibrate for
9
J. L. Atwood, A. M. Bond, W. J. Miao, C. L. Raston, T. J. Ness
and M. J. Barnes, J. Phys. Chem. B, 2001, 105, 1687.
2
6
10 H. Mstsubara, S. Oguri, K. Asano and K. Yamamoto, Chem.
Lett., 1999, 431.
2
h prior to recording a spectrum. Additions of C60 were
11 Y. Y. Shi, J. T. Yu, Z. T. Huang and Q.-Y. Zheng, Sci. China B,
continued until no significant change in the fluorescence
signal was observed. The excitation wavelength was 310 nm
and the emission scan ranged from 320 nm to 550 nm.
2009, 39, 329.
1
1
2 M. J. Hardie, Chem. Soc. Rev., 2010, 39, 516.
3 J. de Mendoza, E. Cequier and E. Huerta, Chem. Commun.,
2
007, 5016.
Preparation of sugar-bearing CTV–C60 complexes in aqueous
solution
1
1
1
1
4 E. Huerta, G. A. Metselaar, A. Fragoso, E. Santos, C. Bo and
J. de Mendoza, Angew. Chem., Int. Ed., 2007, 46, 202.
5 J. de Mendoza, N. Mart ´ı n, E. Huerta, H. Isla, E. M. P ´e rez
and C. Bo, J. Am. Chem. Soc., 2010, 132, 5351.
6 C. L. Raston, M. Makha, A. Purich and A. N. Sobolev, Eur. J.
Inorg. Chem., 2006, 2006, 507.
7 R. D. Webster, S. A. Olsen, A. M. Bond, R. G. Compton,
G. Lazarev, P. J. Mahon, F. Marken, C. L. Raston and V. Tedesco, J.
Phys. Chem. A, 1998, 102, 2641.
The aqueous solutions of sugar-bearing CTV–C60 complexes
were prepared by stirring an aqueous solution of CTV-GH or
2
5
CTV-Glc (5.0 6 10 M) containing C60 solid (>99%) for 24 h.
After centrifugation, clear aqueous solutions containing sugar-
bearing CTV–C60 complex were obtained for further studies.
1
1
2
2
2
2
2
2
2
2
2
2
8 Y. Rio and J. F. Nierengarten, Tetrahedron Lett., 2002, 43,
Acknowledgements
4321.
The financial support of the National Science Foundation of
China (Grants 21002017 and 21274033) and the Ministry of
Science and Technology of China (National Basic Research
Program, Grant 2011CB932500) is acknowledged.
9 F. Yang, Q. Chen, Q.-Y. Cheng, C.-G. Yan and B.-H. Han, J.
Org. Chem., 2012, 77, 971.
0 C. Josette, C. Andre and G. Giovanni, J. Am. Chem. Soc.,
1
984, 106, 5997.
1 H. Itagaki, Y. Inagaki and N. Kobayashi, Polymer, 1996, 37,
553.
2 C. W. Frank, D. J. Henker and J. W. Thomas, Polymer, 1988,
9, 437.
3
References
2
1
2
3
M. Prato, J. Mater. Chem., 1997, 7, 1097.
3 J. L. Atwood, J. W. Steed, P. C. Junk, C. L. Raston, M. J. Barnes and
R. S. Burkhalter, J. Am. Chem. Soc., 1994, 116, 10346.
4 Y. Liu, B.-H. Han, X.-X. Sun, T. Wada and Y. Inoue, J. Org.
Chem., 1999, 64, 1487.
M. Prato and T. D. Ros, Chem. Commun., 1999, 663.
E. Nakamura, H. Tokuyama and S. Yamago, J. Am. Chem.
Soc., 1993, 115, 7918.
4
5
6
7
M. Tadahiko, S. Kumiko, I. Noriko, N. Dai, O. Kensuke,
T. Kyoko, N. Shigeo and M. Masataka, Bioorg. Med. Chem.
Lett., 2005, 15, 1107.
G. L. Kenyon, S. H. Friedman, D. L. DeCamp, R.
P. Sijbesma, G. Srdanov and F. Wudl, J. Am. Chem. Soc.,
5 Y. Liu, B.-H. Han and Y.-T. Chen, J. Phys. Chem. B, 2002,
106, 4678.
6 D. M. Guldi, M. Maggini, G. Scorrano and M. Prato, J. Am.
Chem. Soc., 1997, 119, 974.
7 M. Moskovits, K. L. Akers, C. Douketis and T. L. Haslett, J.
Phys. Chem., 1994, 98, 10824.
8 Q. Chen, Q.-Y. Cheng, Y.-C. Zhao and B.-H. Han, Macromol.
Rapid Commun., 2009, 30, 1651.
9 Q. Chen, N. Bian, C. Cao, X.-L. Qiu, A.-D. Qi and B.-H. Han,
Chem. Commun., 2010, 46, 4067.
1993, 115, 6506.
N. E. Fedorova, S. M. Adueva, A. A. Medzhidova, V. S. Romanova,
Z. N. Parnes, G. A. Galegov and A. A. Kushch, Vopr. Virusol., 2002,
47, 30.
C. Nishizawa, N. Hashimoto and S. Yokoo, Free Radical
Res., 2009, 43, 1240.
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