A new Hg2+ fluorescent sensors based on 1,3-alternate thiacalix[4]arene (L) and the complex of [L+Hg2+] as turn-on sensor for cysteine

Article abstract of DOI:10.1016/j.tet.2012.01.010

A new thiacalix[4]arene derivative in a 1,3-alternate conformation bearing four naphthalene groups through crown-3 chains has been synthesized, which exhibits high selectivity toward Hg²⁺ by forming a 1:2 complex, among other metal ions (Na⁺, K⁺, Mg²⁺, Ba ²⁺, Ca²⁺, Sr²⁺, Cs⁺, Mn ²⁺, Fe²⁺, Cd²⁺, Co²⁺, Ni ²⁺, Cu²⁺, Li⁺, and Zn²⁺) with a low detection limit (3.30×10^-7 M). The metal ion-binding properties were studied by fluorescence, AFM, and ¹H NMR spectroscopy. The in situ prepared [Hg²⁺+L] complex shows well recognition ability for cysteine with a low detection limit (2.23×10^-7 M) through fluorescence turning on. The mechanism of fluorescence turning on is the host L releasing from [L+Hg²⁺] for [Cys+Hg²⁺] complex formed. Thus the paper reports secondary-sensor design: Hg²⁺ as a first sensor for [L+Hg²⁺] form, cysteine as a second sensor for Hg ²⁺ releasing from the [L+Hg²⁺] complex after cysteine adding in.

Full text of DOI:10.1016/j.tet.2012.01.010

Tetrahedron 68 (2012) 2409e2413
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A new Hg2þ fluorescent sensors based on 1,3-alternate thiacalix[4]arene (L)
and the complex of [LþHg2þ] as turn-on sensor for cysteine
*
Fajun Miao, Junyan Zhan, Zhilong Zou, Deimei Tian, Haibing Li
Key Laboratory of Pesticide and Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new thiacalix[4]arene derivative in a 1,3-alternate conformation bearing four naphthalene groups
through crown-3 chains has been synthesized, which exhibits high selectivity toward Hg2þ by forming
Received 31 October 2011
Accepted 6 January 2012
Available online 12 January 2012
a 1:2 complex, among other metal ions ( Naþ, Kþ, Mg2þ, Ba2þ, Ca2þ, Sr2þ, Csþ, Mn2þ, Fe2þ, Cd2þ, Co2þ
,
Ni2þ, Cu2þ, Liþ, and Zn2þ) with a low detection limit (3.30ꢀ10ꢁ7 M). The metal ion-binding properties
were studied by fluorescence, AFM, and 1H NMR spectroscopy. The in situ prepared [Hg2þþL] complex
shows well recognition ability for cysteine with a low detection limit (2.23ꢀ10ꢁ7 M) through fluores-
cence turning on. The mechanism of fluorescence turning on is the host L releasing from [LþHg2þ] for
[CysþHg2þ] complex formed. Thus the paper reports secondary-sensor design: Hg2þ as a first sensor for
[LþHg2þ] form, cysteine as a second sensor for Hg2þ releasing from the [LþHg2þ] complex after cysteine
adding in.
Keywords:
Mercury(II) sensing
Cysteine sensing
Thiacalix[4]arene
Click
Fluorescent
Ó 2012 Published by Elsevier Ltd.
1. Introduction
and also of great significance. Keeping these in mind and encour-
aged by the recent brilliant achievements of competitive binding
The development of highly selective and sensitive fluorescent
sensors, which are capable with dual monitoring of metal ions and
amino acids, have attracted considerable attention because of their
wide impacts on environment and biological monitoring.1 Among
the metal ions, Hg2þ is attracted much more attention because it
could cause a variety of symptoms in vivo, including digestive,
cardiac, kidney, and neurological diseases.2 Generally, the damage
of Hg2þ mainly takes place through the process of complex in-
teractions between mercury and sulfur, which provided by amino
acids and peptides in vivo.3 In particular, Hg2þ ions are inactive
toward other amino acids except cysteine in terms of the previous
reports.4 As one of the indispensable amino acids, cysteine plays
vital and important roles in human body.5 Therefore, detecting and
sensing mercury and cysteine based on one fluorescent sensor with
dual functionality is feasible, and which is more economical, con-
venient and also of great significance. There are several reports
upon recognizing Hg2þ and cysteine individually. For the sake of
Hg2þ detection, plenty of receptors have been applied, such as calix
[4]crowns,6 rhodamine,7 calix[4]arene-diaza-crown ether,8 and
dipyrene-diamide.9 Fluorescent sensors based on amino recogni-
tion also have been reported.10 Therefore, detecting and sensing
mercury and cysteine based on one fluorescent sensor with dual
functionality is feasible, and which is more economic, convenient,
assays, such as Mirkin’s.11 As a result, a specific host for Hg2þ rec-
ognition and second detection of cysteine is quite demanded. Being
famous for its excellent skeleton structure serving as molecular
platform,12 calixarene based on numerous derivative molecules
have achieved wonderful recognization performances. Especially
combined with the universal and popular ‘click chemistry’ tech-
nology, which endows the calixarene more recognization sites,
such as triazole groups.13 On the basis of the wonderful cooperative
interactions between triazole and metal ions,14 to achieve the Hg2þ
recognization and secondary detection of cysteine by a clicked
fluorescent calixarene is reasonable and meaningful. And to the
best of knowledge, such a secondary sensor of cysteine recog-
nization followed by Hg2þ detection has been no report.
Herein, we exploited a novel functionalized thiacalix[4]arene (L)
by means of the classic ‘click chemistry’ methodology.15 1-(2-(2-(2-
azidoethoxy)ethoxy)ethoxy)naphthalene were chosen to graft onto
the thiacalix[4]arene for the following two reasons: (i) thiacalix[4]
arene considered as a desirable platform, the pre-formed triazole
groups provided binding sites. (ii) The naphthalene groups offered
fluorescent signals for the sensitive fluorescent detection. The
prepared L was characterized by 1H NMR, MS, elementary analysis.
The verification performance of L toward recognition of metal ions
is subsequently investigated. High selectivity and sensitivity upon
Hg2þ was accomplished. Most significantly, the formed [Hg2þþL]
complex in the first step shows specific recognition of cysteine with
high selectivity and sensitivity. The characteristic changes observed
* Corresponding author. Tel.: þ86 27 67867958; e-mail address: lhbing@
mail.ccnu.edu.cn (H. Li).
0040-4020/$ e see front matter Ó 2012 Published by Elsevier Ltd.
doi:10.1016/j.tet.2012.01.010

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F. Miao et al. / Tetrahedron 68 (2012) 2409e2413
in the fluorescence spectroscopy during the sensing of Hg2þ as well
cysteine are represented schematically in Scheme 1.
1.0
0.8
0.6
0.4
0.2
0.0
700
600
500
400
300
200
100
0
0
1
2
3
4
5
Scheme 1. Schematic representation of the primary and secondary sensing properties
of L.
2+
equiv of Hg
2. Results and discussion
2.1. Synthesis
320 340 360 380 400 420 440 460 480 500
Wavelength (nm)
The receptor molecule, L, has been synthesized as given in Fig. 1.
All of these molecules including L were characterized satisfactorily
by 1H NMR, 13C NMR, HRMS, and elemental analysis. The compound
Fig. 2. Fluorescence spectra (lexc¼300 nm) of L (7ꢀ10ꢁ6 M) in CH3CN/H2O (v/v, 3/1)
with increasing amount of Hg2þ (0e3 equiv) in CH3CN/H2O (v/v, 3/1). Inset shows
variation of fluorescence intensity against equivalents of Hg2þ. The excitation wave-
length was 300 nm.
1
with 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)naphthalene was
carried out in DMF at 90 ꢂC, with copper(II) sulfate and sodium
ascorbate, to afford L (Fig. S4). A well-defined and simple 1H NMR
spectrum showed a highly symmetric structure for receptor L. The
tBu groups and aromatic protons of the thiacalix[4]arene moiety
titration experiments. The titration curves were analyzed by the
Hyperquad 2003 program17 and the binding constants were cal-
culated to be log K11¼8.75(2) and log K12¼14.23(4).
appeared as singlets at
d 1.08 ppm and d 7.41 ppm, respectively.
Under the above conditions, as shown in Fig. 3, the fluorescence
of L (7ꢀ10ꢁ6 M) at 354 nm was strongly quenched by Hg2þ, no
significant spectral changes occurred in the presence of 4 equiv
These
d values are in good agreement with the values obtained for
1,3-alternate conformers reported elsewhere.16
each of Naþ, Kþ, Mg2þ, Ba2þ, Ca2þ, Sr2þ, Csþ, Mn2þ, Fe2þ, Cd2þ, Co2þ
,
Ni2þ, Cu2þ, Liþ, and Zn2þ. To find out whether L can detect Hg2þ
selectively even in the presence of other metal ions, competitive
metal ion titrations were carried out. Of practical significance is
that even 14 equiv each of these metal ions did not interfere in the
sensing of Hg2þ, and the results of the competition experiments are
shown in Fig. 4. The origin of the fluorescence quenching may re-
sult from the electron or energy transfer from the excited naph-
thalene fluorescence to the Hg2þ ion. Alkali and alkaline earth
metal ions showed no interaction with L, which may be due to their
hard acid properties. Other transition and heavy metal ions pro-
duced insignificant fluorescence changes. Thus, while Hg2þ ion can
be detected quantitatively in the presence of a number of bi-
ologically relevant Mnþ ions.
90
80
800
700
600
500
400
300
200
100
0
+
free, Li , Na , K , Mg , Ca , Ba
+
+
2+
2+
2+
+
70
60
50
40
30
20
10
0
,
Fig. 1. Synthesis of the receptor L.
2+ 2+ 2+ 2+ 2+
,
Co , Ni , Zn
Hg , Mn , Ag ,
+
Cs ,Fe ,Cd ,Sr ,Pb
+
2+ 2+
3
2+
2.2. The properties of L in the selective recognition of Hg2D
2+
Hg
2.2.1. Fluorescence titration studies. The fluorescence spectrum of L
lexc¼300 nm) in CH3CN/H2O (v/v, 3/1) exhibited a characteristic
(
emission band at 354 nm. Upon addition of increasing amounts of
Hg2þ to a solution of L in CH3CN/H2O (v/v, 3/1), quenching of
fluorescence at 354 nm was observed instantaneously. Fluores-
cence titration of L (7ꢀ10ꢁ6 M) was conducted in CH3CN/H2O (v/v,
3/1) by the addition of Hg2þ from 0 to 2.1ꢀ10ꢁ5 M (Fig. 2). About
2 equiv of Hg2þ makes the quenched fluorescence reach a mini-
mum. As the result, excess Hg2þ cannot achieve further quenching
of fluorescence. Based on the mole ratio method, mole ratio be-
tween L and Hg2þ is 1:2, and meanwhile, the job’s plots highly
indicated a 1:2 mol ratio (Fig. S8). The detection of Hg2þ is about
3.3ꢀ10ꢁ7 M. Given the binding between the host and the guest, the
binding constants could be calculated from the fluorescence
320 340 360 380 400 420 440 460
Wavelength (nm)
Hg Zn Mn Ni Na K Cd CoMg Cs Ca Ba Sr Ag Li Fe Cu pd
Metal ions
Fig. 3. Quench ratio [(I0ꢁI)/I0] of L (7ꢀ10ꢁ6 M) in CH3CN/H2O (v/v, 3/1) upon addition
of 4 equiv of metal ions. The excitation wavelength was 300 nm. I0 is the fluorescent
emission intensity of the host at 354 nm, I is the fluorescent intensity after adding
metal ions. Inset shows fluorescence intensity changes for L in CH3CN/H2O upon ad-
dition of metal ions.

F. Miao et al. / Tetrahedron 68 (2012) 2409e2413
2411
the fluorescence spectra changes (Fig. 2), which were observed for
the complex [LþHg2þ].
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
2.2.3. AFM studies. To determine whether the L reaction with Hg2þ
is reflected in their nano structural features, AFM studies were
performed with L, [LþHg2þ], and the corresponding micrographs
and particle size distributions are shown in Fig. 6.
The micrographs show spherical particles in the case of L
(Fig. 6a). The size particles are in the range of 312e396 nm, the
height of these particles is in the range of 8.046e8.885 nm. The size
present in these particles is similar to that observed in case of the
aggregate of calix[4]arene as reported by recently.19 When
Hg(NO3)2 is added to L, the shape is changed to saclike, and the size
of the particles is increased drastically to 323e690 nm (Fig. 6b).
Most obvious, that the height of these particles is reduced drasti-
cally to 2.886e3.87 nm. Thus, both the size and shape of the par-
ticles differ between L and [LþHg2þ], suggesting that it is possible
to identify the complex formation between L and Hg2þ by using
nano structural features.
i
n
K
L
Sr
Al
Ca
Na
Ba
Cd
Co
+
Cu
+
+
M
+
+
+
+
+
+
+
+
Hg
g+Zn
Hg
g+Fe
Hg
H
Hg
Hg
Hg
Hg
Hg
Hg
Hg
H
Hg
Hg
Fig. 4. Quench ratio [(I0ꢁI)/I0] of fluorescent intensity of L (7ꢀ10ꢁ6 M) in CH3CN/H2O
(v/v, 3/1) upon the addition of 2 equiv of Hg2þ in the presence of 14 equiv of back-
ground metal ions. I0 is the fluorescent emission intensity of the host at 354 nm, I is the
fluorescent intensity after adding metal ions.
2.2.2. 1H NMR study. To get first hand information about the co-
ordinatingsitesofreceptorLandHg2þ,1HNMRofL (inDMSO-d6)was
carried out with Hg(NO3)2 (in DMSO-d6) (Fig. 5). From the 1H NMR
spectra of L, upon the addition of Hg(NO3)2, absence of any changes
observed in the chemical shift of aromatic and/or tert-butyl protons
rules out any interaction between the arene of thiacalixarene and
Hg2þ. If the Hg2þ were to be interacting with the arene cavity of the
thiacalixarene, the protons would show corresponding shifts as re-
ported in the literature by Shinkai and co-workers.18 In the presence
of 2.0 equiv of Hg2þ, the peak of the protons Ha on the triazole ring is
shifted downfield by 0.216 ppm, whereas the OCH2etriazole linker
Hb is shifted downfield by 0.144 ppm. These 1H NMR changes, es-
pecially the move of triazole proton Ha, suggest that the Hg2þ ion of
the complex [LþHg2þ] may be located in the negative cavity formed
by the nitrogen-rich triazole. These results are also fully in line with
Fig. 6. AFM images of (a) L in CH3CN/H2O (v/v, 3/1). (b) [LþHg2þ] in CH3CN/H2O (v/v, 3/
1). (c) {[LþHg2þ]þCys} in CH3CN/H2O (v/v, 3/1).
2.3. Secondary sensor behavior of [LDHg2D] and selective
recognition of cysteine among naturally occurring amino
acids
Since L recognizes Hg2þ clearly, the utility of [LþHg2þ] complex
toward selective recognition of amino acid has been studied so that
this complex can act as a secondary sensor.
2.3.1. Fluorescence titration. The chemosensing ensemble used in
these titrations was prepared in situ by mixing L and Hg2þ in a 1:2
ratio. Out of 15 amino acids studied for their interaction, only Trp
did not yield interpretable results owing to their strong emission
that overlaps with the emission of L. The chemosensing mixture
was titrated with all of the remaining naturally occurring 14 amino
acids, where the fluorescence spectrum of [LþHg2þ] is altered only
in the presence of cysteine (Fig. 7). After adding 5 equiv cysteine to
the complex, the emission band at 354 nm was enhanced obviously.
This is exactly reverse to what happens when L is titrated with
Hg2þ, as reported in this paper, the Hg2þ is being removed from the
complex by cysteine to release free L and thus the recognition of
cysteine by [LþHg2þ] complex as a secondary sensor. The release of
L in the titration of cysteine is followed by the formation of
[CysþHg2þ] complex, as it can form a stable complex with the thiol
functionality.1b,20 Under the above conditions, [LþHg2þ] has also
been studied for its interaction with cysteine, which shows fluo-
rescence recovery, as the concentration of cysteine increases.
Fluorescence titration of [LþHg2þ] was conducted in CH3CN/H2O
(v/v, 3/1) by the addition of cysteine from 0 to 1.2ꢀ10ꢁ5 M (Fig. 8).
Fig. 5. NMR spectral changes of L by the addition of Hg(NO3)2 at 600 MHz in DMSO-d6.

2412
F. Miao et al. / Tetrahedron 68 (2012) 2409e2413
Fig. 9. The proposed structure of [LþHg2þ] for HSCH2CH2NH3Cl, and increasing con-
centrations of HSCH2CH2NH3Cl in DMSO-d6 at 298 K.
simple L from the [LþHg2þ]. Since fluorescence changes occur only
in the presence of cysteine and not with the other amino acids, the
role of the eSH function in Hg2þ binding was further confirmed by
studying the 1H NMR titration of [LþHg2þ] with cysteamine hy-
drochloride, because there only eSH function in the cysteamine
hydrochloride, the result of the 1H NMR titration can provide
powerful evidence for this.
Fig. 7. Enhance ratio [(IꢁI0)/I0] of fluorescent intensity of [LþHg2þ] upon addition of
5 equiv of amino acids. The excitation wavelength was 300 nm. I0 is the fluorescent
emission intensity of [LþHg2þ] at 354 nm, I is the fluorescent intensity after adding the
14 amino acids. Inset: fluorescence intensity changes for [LþHg2þ] in CH3CN/H2O (v/v,
3/1) upon addition of the 14 amino acids, 5 equiv.
340
320
2.3.3. AFM studies. To determine whether the release of L from the
reaction of [LþHg2þ] with cysteine is reflected in their nano
structural features, AFM studies were performed with {[LþHg2þ]þ
Cys}, and the corresponding micrographs and particle size distri-
butions are shown in Fig. 6c. Upon addition of cysteine to the
complex, the saclike nano was completely disappeared, and there
were appeared many white micron grade sphere. The micrographs
are filled with particles arising from L and [Hg2þþCys] complex.
The white micron grade sphere may be the precipitation of
[Hg2þþCys], except for the micron grade sphere, all other spherical
particles are in the range of 236e410 nm, these results are also fully
in line with the range of L in the Fig. 6a. So these results also directly
proved the release of L from reaction of [LþHg2þ] with cysteine.
300
280
260
240
220
200
180
160
140
120
100
80
2.2
2.0
1.8
1.6
1.4
1.2
1.0
2
4
6
8
10
-5
C
(
* 10
)
M
60
40
20
0
320 340 360 380 400 420 440 460 480 500
wavelength (nm)
3. Conclusion
In conclusion, we have synthesized a new 1,3-alternate de-
rivative of thiacalix[4]arene L, which exhibited a highly selective
toward Hg2þ. L is sensitive and selective toward Hg2þ over 15 other
Fig. 8. Fluorescence spectra (lexc¼300 nm) of [LþHg2þ] (5
m
M) in CH3CN/H2O (v/v, 3/1)
M, respectively) in
M) at 354 nm
with increasing amount of cysteine (0, 1.85, 3.7, 5.5, 7.4, 10.2
m
CH3CN/H2O (v/v, 3/1). Inset: fluorescence intensity of [LþHg2þ] (5
m
ions studied, viz., Naþ, Kþ, Mg2þ, Ba2þ, Ca2þ, Sr2þ, Csþ, Mn2þ, Fe2þ
,
versus the concentration of cysteine added.
Cd2þ, Co2þ, Ni2þ, Cu2þ, Liþ, and Zn2þ, as demonstrated by individual
as well as competitive metal ion titrations. The complex formation
between L and Hg2þ has been further followed by measuring 1H
NMR spectra as a function of added mercuric nitrate concentration.
Comparison of the changes observed in the chemical shifts of dif-
ferent protons, suggests Hg2þ binding located in the negative cavity
formed by the nitrogen-rich triazole in the thiacalixarene platform.
The nano structural features of L and its complex of Hg2þ differ
substantially to differentiate the complex from that of simple L.
Most significantly, the [LþHg2þ] complex selectively recognizes
cysteine among the naturally occurring amino acids to a lowest
concentration of 2.23ꢀ10ꢁ7 M. The release of L has also been fur-
ther proven on the basis of NMR titration. The present studies also
demonstrate the necessity of the eSH function in removing the
Hg2þ from its complex of L based on NMR titration. That is, to say, L
acts as a primary sensor toward Hg2þ and as a secondary sensor
toward cysteine.
About 2 equiv of cysteine makes the quenched fluorescence reach
restore to the largest. Excess cysteine cannot achieve further en-
hancing of fluorescence. It is found that cysteine increase the FL
intensity of [LþHg2þ] in a concentration dependence (Fig. 8), that is,
best described by a Langmuir-type equation.21 A very high linearity
(R2¼0.97133) is observed throughout the entire concentration
range 1.85e10 mM of cysteine. The detection limit of cysteine is
about 2.23ꢀ10ꢁ7 M.
2.3.2. 1H NMR titration of [LþHg2þ] with cysteine and cysteamine
hydrochloride. The release of L and the formation of the complex of
Hg2þ have been further proven through 1H NMR titration carried
out between [LþHg2þ] and cysteine/cysteamine hydrochloride. The
titration of [LþHg2þ] with cysteine could not be continued beyond
1 equiv owing to precipitation, therefore, the detailed titrations
were carried out using cysteamine hydrochloride instead of cys-
teine, as the fluorescence behavior of both of these was found to be
same. During the titration, the changes observed in the chemical
shift can be seen in Fig. 9, as the concentration of cysteamine hy-
drochloride increases, the proton signals of eOCH2, eNCH, are
shifted and moved toward simple L. Thus it has been found that
cysteamine hydrochloride removes Hg2þ from the binding core of
calixarene using its eSH function, resulting in the recovery of
4. Experimental section
4.1. General remarks
All reactions were carried out in the oven-dried glassware. Every
progress of the reactions was monitored by thin layer silicon,

F. Miao et al. / Tetrahedron 68 (2012) 2409e2413
2413
purification was by column chromatography using silica gel
Supplementary data
(200e300 mesh). All chemicals used were of analytical reagent
grade. NMR spectra were recorded at 600 (1H) and 150 (13C) MHz
on a Bruker Avance DPX-300 FT NMR spectrometer. MALDI-TOF MS
were obtained on a Bruker BIFLEXIII mass spectrometer. Fluores-
cence spectra were measured on a Hitachi F-4500 spectrometer.
Metal ions as their salts were commercial and used without further
treatment.
Supplementary data related to this article can be found online at
doi:10.1016/j.tet.2012.01.010.
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4.3. Ligand L
Compound 2 (0.752 g, 2.5 mmol), calix[4]arene 1 (0.43 g,
0.5 mmol), CuSO4 (0.5 g, 3.125 mmol), and sodium ascorbate (1.5 g,
7.5 mmol) were stirred in dry DMF (40 mL). The mixture was heated
at 90 ꢂC for 10 h, and then diluted with ethyl acetate (40 mL), and
washed with water (3ꢀ30 mL). The organic phase was dried over
MgSO4, filtered, and the solvent removed under reduced pressure.
The crude product was purified by column chromatography (SiO2,
CH3Cl/MeOH, v/v¼20/1), yielding L as a white powder (440 mg,
75%). 1H NMR (DMSO-d6,
d ppm): d 8.13 (s, 4H, CCH2N), 7.78 (dd,
J¼11.2, 8.8 Hz, 8H, NaeH), 7.73 (d, J¼8.1 Hz, 4H, NaeH), 7.47 (s, 8H,
ArH), 7.42 (s, 4H, NaeH), 7.32 (d, J¼7.6 Hz, 4H, NaeH), 7.26 (s, 4H,
NaeH), 7.11 (dd, J¼8.9, 2.4 Hz, 4H), 4.92 (s, 8H, OCH2C), 4.49 (s, 8H,
NeCH2), 4.21e4.11 (m, 8H, OCH2), 3.84 (d, J¼5.1 Hz, 8H, OCH2), 3.77
(d, J¼4.2 Hz, 8H, OCH2), 3.59 (d, J¼3.6 Hz, 18H, OCH2CH2O), 0.96 (s,
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36H, C(CH3)). 13C NMR (CDCl3,
d ppm) d 156.74 (s), 154.30 (s), 146.06
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(s), 143.78 (s), 134.32 (s), 131.14 (s), 128.55 (s), 127.31 (s), 126.26 (s),
125.70 (s), 125.47 (s), 125.01 (s), 123.82 (s), 121.88 (s), 120.32 (s),
104.76 (s) (ArC, NaeC, CHN), 70.58 (d, OCH2), 69.48 (d, OCH),
69.09e68.75 (m, OCH2CH2O), 67.67 (s, OCH), 64.03 (s, OCH), 49.78
(s, NCH), 33.96 (s, C(CH3)3), 31.00 (s,CH3). EI(þ) MS m/z¼2078.89
([M]þ 100%). Anal. calcd for C116H134N12O16S4: C, 66.96; H, 6.49; N,
8.08.
Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (21072072), Program for New Century
Excellent Talent in University (NCET-10-0428).