Dual-mode tunable viscosity sensitivity of a rotor-based fluorescent dye

Article abstract of DOI:10.1016/j.tet.2009.12.014

The design and fabrication of new type viscosity sensor on molecular scale will enrich the detection means in both physical and life sciences. In this work, a rotor-containing fluorescent dye was prepared, which can reveal a typical viscosity-sensitive behavior due to the environment-induced non-radiative decay. The viscosity-sensitive behavior of this dye could be tunable (locked and activated) in aqueous environment, either with the reversible light-driven trans/cis-photoisomerization of the cyanostilbene moiety, or with the reversible assembly/disassembly process of β-cyclodextrin (β-CD) to the rotor part. Such dual-mode tunable viscosity sensitivity can be well distinguished by fluorescent spectra. A slope method, on double-logarithmic plots of the fluorescent signal to the corresponding environmental viscosity, makes a quantitative estimation to the tunable viscosity sensitivity, featuring the 'Activated' and the 'Locked' state in this molecular-scale viscometer.

Full text of DOI:10.1016/j.tet.2009.12.014

Tetrahedron 66 (2010) 1254–1260
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Dual-mode tunable viscosity sensitivity of a rotor-based fluorescent dye
*
Liang-Liang Zhu, Da-Hui Qu, Dong Zhang, Zhao-Fei Chen, Qiao-Chun Wang, He Tian
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science & Technology, Shanghai 200237, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The design and fabrication of new type viscosity sensor on molecular scale will enrich the detection
means in both physical and life sciences. In this work, a rotor-containing fluorescent dye was prepared,
which can reveal a typical viscosity-sensitive behavior due to the environment-induced non-radiative
decay. The viscosity-sensitive behavior of this dye could be tunable (locked and activated) in aqueous
environment, either with the reversible light-driven trans/cis-photoisomerization of the cyanostilbene
Received 1 November 2009
Received in revised form 27 November 2009
Accepted 4 December 2009
Available online 23 December 2009
moiety, or with the reversible assembly/disassembly process of b-cyclodextrin (b-CD) to the rotor part.
Such dual-mode tunable viscosity sensitivity can be well distinguished by fluorescent spectra. A slope
method, on double-logarithmic plots of the fluorescent signal to the corresponding environmental vis-
cosity, makes a quantitative estimation to the tunable viscosity sensitivity, featuring the ‘Activated’ and
the ‘Locked’ state in this molecular-scale viscometer.
Ó 2009 Published by Elsevier Ltd.
1. Introduction
medium, for test of the local viscosity by the change of fluorescence
quantum yield.
A b-cyclodextrin (b-CD) polypseudorotaxane
The design and development of viscosity chemosensors or
probes1 is of considerable current interest in modern viscosity test.
In particular, changes in biofluid viscosity are usually linked to the
perturbations and diseases in organisms. Because of its high
sensitive and low detection limit in these fluid media, the mole-
cular-scale viscometers may play a significant role in such areas
where mechanical measurement apparatus are hard to reach.
Generally, the microscopic viscosity test is realized by the sensing
function of a molecular-scale viscometer, whose output signal (e.g.,
the fluorescence) varies indicatively in response to the change of
the environmental viscosity. Hitherto, most of the viscosity tests at
molecular level are continuous and forward.1,2 Sometimes,
temporary halt and reset of the viscosity tests are needed in
a comprehensive determination program. Thus, a tunable way in
practice, to make the viscosity-response ability of the sensory
species controllably locked and activated using simple chemical
switching elements, is of great concern. In this case, we have
focused on the conception of molecular switch or molecular
machinery behaviors,3 and tried to combine such tunable functions
with the viscosity sensitivity in a molecular platform, for control of
the viscosity-sensitive behavior by multiple input operations.
p-(Dialkylamino)-benzylidenemalonitrile derivative is a typical
molecular-rotor architecture.4 Its non-radiative decay of the fluo-
rescent excited state can be influenced by the viscosity of the
system, comprising a light-tunable fluorescent rotor with combi-
nation of cyanostilbene (a light-active moiety) and tetramethylju-
lolidine (a rotator), was reported more recently.5 It showed a clear
photo-lockable viscosity-sensitive behavior with the trans/cis-
photoisomerization process, and this light-driven tunable viscom-
eter could be remotely operated as photon is clean and long-range
control element. For the interest of fabricating multi-responsive
functional dyes and multi-controllable sensors, however, other
more efficient approaches to modulate the rotor’s viscosity sensi-
tivity are required. Considering the suitable space configuration
and hydrophobic structure of the rotor part, we tried the supra-
molecular assembly (host–guest encapsulation) of cyclodextrins,6
to influence and control the rotor’s relative rotation in fluid
together with its viscosity-sensitive behavior.
In this work, we synthesized a novel fluorescent dye (compound
1; see Schemes 1 and 2)7 by introduction the hydrophilic viologen
group linked to the above-mentioned light-active rotor (also a flu-
orophore). Such viologen-containing dye could be easily encapsu-
lated by b
-CD in aqueous environment.8 The long alkyl chain is used
to avoid the intramolecular electron transfer from the rotor to the
viologen group, keeping the individual but viscosity-dependent
fluorescent emission of the rotor itself. A reversible dual-mode
(light-driven trans/cis-photo-isomerization and
b-CD assembly/
disassembly process) switchable system based on compound 1 is
presented. The new format of tunable viscosity-sensitive effect
induced by b-CD supramolecular assembly could be also well dis-
tinguished by fluorescence signals. The two locked viscosity sen-
sitivity states of this dye could be reactivated by corresponding
* Corresponding author. Tel.: þ086 21 64252756; fax: þ86 21 64252288.
E-mail address: tianhe@ecust.edu.cn (H. Tian).
0040-4020/$ – see front matter Ó 2009 Published by Elsevier Ltd.
doi:10.1016/j.tet.2009.12.014

L.-L. Zhu et al. / Tetrahedron 66 (2010) 1254–1260
1255
Scheme 1. Synthetic route of compound 1.
ICD spectra were recorded on a Jasco J-815 CD spectrophotometer in
a1 cmquartzcell. ThephotoirradiationwascarriedonaCHF-XM500-
W high-pressure mercury lamp with a filter for 254 nm in a sealed
Ar-saturated 1 cm quartz cell. The distance between the lamp and the
sample cell was 20 cm. Melting points were determined by using an
X-6 micro-melting point apparatus. The scanning electron micros-
copy (SEM) was tested on JEOL (JSM-6360LV) electron microscope,
while the transmission electric microscopy (TEM) was tested on
a JEOL-JEM2100F electron microscope. Solvent viscosities were car-
ried on a NDJ-79 rotatory viscometer. The surface tension was mea-
sured by Thermo Cahn DCA-315 surface tension analysis system.
2.2. Materials
b
-Cyclodextrin (b-CD), phosphorus oxychloride, 1,10-dibromo-
Scheme 2. Illustration of the dual-mode molecular switch of 1 accompanied with the
interconversions network of its conformational species in water. (The initial state ‘State
1’ can be translated to the photostationary ‘State 2’ by irradiation upon 254 nm for ca.
2 h, while can be reversibly returned by irradiation of visible light; The initial state
‘State 1’ can be also interconversed to encapsulation equilibrium state ‘State 3’ via
decane, 18-Crown-6,4,40-bipyridine and the inorganic reagents
were commercially available and used without further purification.
1-Adamantanol (1-Ada), julolidine, 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) were purchased from Alfa Aesar and used as received.
Dextran (70 kDa average MW) was purchased from Tokyo Chemical
Industry Corp. Pyridine was dried over potassium hydroxide while
DMF and dichloromethane were dried over calcium hydride, and
then distilled under reduced pressure. Acetone and acetonitrile
were dried by 4A molecular sieve and distilled before used.
addition of 10 equiv of
b-CD at room temperature, while can be disassembled via
addition of excessive 1-adamantanol to form a competitive complex.).
visible-light irradiation or supramolecular disassembly of
b-CD,
and it exhibits a promising application in the area of multi-mode
tunable viscosity detection.
2.2.1. Preparation of 9-formyl-julolidine. POCl3 (5 ml) was slowly
added to 11 ml anhydrous DMF under argon at 0 ꢀC. The mixture
was vigorously stirred for 2 h and then julolidine (5 g, 28.9 mmol)
dissolved in 10 ml anhydrous DMF was added. After stirring for 12 h
at room temperature under argon, the solution was added drop-
wise to ice and then NaOAc (aq) was added until pH of 7–8 was
achieved. A great deal of yellow solid was gradually crystallized
from the solution. The solid was filtered, washed with petroleum
2. Experimental part
2.1. Instruments
1H NMR,13C NMR, and 2D-ROESY NMR spectra were measured on
a Bru¨ker AV-400, or AV-500 spectrometer with tetramethylsilane
(TMS) as the internal standard. The high-resolution ESI mass spec-
trum was tested on a HP5989 mass spectrometer. Absorption spectra
were done on a Varian Cary 500 UV/Vis spectrophotometer (1 cm
quartz cell used). Fluorescent spectra were recorded on a Varian Cary
Eclipse fluorescence spectrophotometer. All the fluorescent spectra
recorded in this work were on an excitation at 370 nm. Fluorescence
lifetime measurements were performed on an Edinburgh FL 900
ether several times and then dried in vacuo. Yield was 67.6%. Mp
1
70–72 ꢀC. H NMR (400 MHz, CDCl3, 25 ꢀC, TMS):
d
¼9.60 (s, 1H),
7.30 (s, 2H), 3.30 (t, J¼6.0 Hz, 4H), 2.77 (t, J¼6.4 Hz, 4H), 1.97 (tt,
J1¼6.4 Hz, J2¼6.0 Hz, 4H).
2.2.2. Preparation of Compound 4. 4-(Cyanomethyl) phenyl ace-
Fluorescence Spectrometer equipped with a laser (
l¼372 nm). The
tate5 (3.0 g, 17.1 mmol), 9-formyl-julolidine (3.6 g, 17.9 mmol), and

1256
L.-L. Zhu et al. / Tetrahedron 66 (2010) 1254–1260
DBU (4.8 g, 28.2 mmol) were dissolved in pyridine (17 ml) and
stirred for 48 h at 120 ꢀC under argon, then cooled, and poured into
de-ionized water (120 ml). Here the product had hydrolyzed to be
a corresponding phenol. The solution was extracted three times
with dichloromethane (150 ml) and the underlayer was washed
with water (80 ml). After drying with anhydrous MgSO4 and con-
centrated in vacuo, the residue was applied to silica gel chroma-
tography (petroleum ether–ethyl acetate¼5:1) to afford orange
compound 4 (2.83 g, 52.4%). Mp 198–201 ꢀC. 1H NMR (400 MHz,
4H), 1.67–1.76 (m, 2H), 1.22–1.44 (m, 12H). HRMS (ESI): m/z:
313.2000 [1ꢁBrꢁI]2þ
.
3. Results and discussion
3.1. Conformational switches of compound 1 with photo-
isomerization and b-CD inclusion
Compound 1 has an excellent solubility and exists as a free
monomeric form in some high-polar solvents such as DMSO. In this
case, 1H NMR signals of 1 can be well assigned (Fig. 1A). As expected,
the trans-cyanostilbene unit of compound 1 was photo-isomerized
upon 254 nm irradiation to its cis-form. It resulted in a cluster of new
peaks of rotor part arising in 1H NMR spectrum with a photo-
isomerization efficiencyof nearly 70%(Fig.1B). When 1 was dispersed
in water, it self-organized to an aggregated form immediately if
onlyaboveitscriticalaggregateconcentration(CAC:1.70ꢂ10ꢁ5 M,see
Supplementary data, Fig. S5). In this case, compound 1 shows some
surfactantproperties,whichresultsinarelativelowsolubilityatroom
temperature with the surface tension falling down to 55.23 mN/m. As
shown in Figure 1C, the Ha–Hd and Hi–Hn signals, which belong to the
rotor and the alkyl chain part, respectively, are obviously turned to be
broad. But the signals of He–Hh and Ho, which are associated with the
viologenpart, stillkeepsplit.Hence,itisinferredthatthehydrophobic
part of 1 is stacked up to each other, whereas hydrophilic viologen
unitisexposedtotheaqueousenvironment.8 Thisaggregatedvesicles
can be clearly observed from SEM image (Fig. 2A). Trans-to-cis pho-
toisomerization process of 1 could also take place in water. The ag-
gregationwouldbeslightlyweakened, which should becausedbythe
CDCl3, 25 ꢀC, TMS):
d
¼7.48 (d, J¼8.0 Hz, 2H), 7.39 (s, 2H), 7.17 (s,1H),
6.86 (d, J¼8.0 Hz, 2H), 3.26 (t, J¼6.0 Hz, 4H), 2.77 (t, J¼6.4 Hz, 4H),
1.97 (tt, J1¼6.4 Hz, J2¼6.0 Hz, 4H). 13C NMR (500 MHz, CDCl3):
d
¼156.117, 145.231, 141.850, 129.332, 127.520, 121.639, 120.475,
116.435, 103.477, 54.111, 50.667, 30.391, 28.376, 22.231. HRMS (EI):
m/z: 316.1573.
2.2.3. Preparation of Compound 3. Compound 4 (2.2 g, 6.9 mmol)
was added with magnetic stirring to 1,10-dibromodecane (20.7 g,
69 mmol) acetone solution. The mixture was then added upon
K2CO3 (1.9 g, 13.9 mmol) and trace of 18-Crown-6. The solution was
stirred refluxing for 8 h under Ar protection. The solution was
poured into 200 ml ethanol and the mixture was concentrated in
vacuo to ca. 60 ml left. A great deal of solid was crystallized from
the solution while cooled in an ultrasonator. The solid was filtered,
washed with 300 ml petroleum ether overnight, and then with
100 ml water to obtain orange compound 3 (2.5 g, 67.1%). Mp 73–
74 ꢀC. 1H NMR (500 MHz, CDCl3, 25 ꢀC, TMS):
d
¼7.51 (d, J¼8.6 Hz,
2H), 7.39 (s, 2H), 7.17 (s, 1H), 6.90 (d, J¼8.6 Hz, 2H), 3.97 (t, J¼6.6 Hz,
2H), 3.41 (t, J¼6.8 Hz, 2H), 3.25 (t, J¼6.0 Hz, 4H), 2.77 (t, J¼6.4 Hz,
4H), 1.97 (tt, J1¼6.4 Hz, J2¼6.0 Hz, 4H), 1.75–1.88 (m, 4H), 1.20–1.51
(m, 12H). 13C NMR (500 MHz, CDCl3):
d
¼159.589, 145.287, 141.619,
129.290, 127.229, 121.580, 121.490, 120.505, 115.477, 103.520,
68.808, 54.106, 50.613, 34.731, 33.503, 30.111, 30.030, 30.001,
29.894, 29.421, 28.841, 28.394, 26.681, 22.261. HRMS (EI): m/z:
534.2247 (79Br), 536.2239 (81Br).
2.2.4. Preparation of Compound 2. A solution of compound 3 (2.5 g,
4.7 mmol) and 4,40-bipyridine (4.4 g, 28 mmol) in acetonitrile
(100 ml) was stirred for two days at 80 ꢀC. The solvent was removed
in vacuo, and the residue was dissolved in some acetone to applied
to silica gel chromatography (dichloromethane–methanol¼50:3) to
afford orange compound 2 (1.12 g, 34.8%). Mp 118–120 ꢀC. 1H NMR
(500 MHz, CDCl3, 25 ꢀC, TMS):
d¼9.46 (d, J¼6.4 Hz, 2H), 8.87
(d, J¼6.4 Hz, 2H), 8.32 (d, J¼6.4 Hz, 2H), 7.67 (d, J¼6.4 Hz, 2H), 7.50
(d, J¼8.6 Hz, 2H), 7.38 (s, 2H), 7.17 (s,1H), 6.89 (d, J¼8.6 Hz, 2H), 4.96
(t, J¼7.4 Hz, 2H), 3.97 (t, J¼6.6 Hz, 2H), 3.24 (t, J¼6.0 Hz, 4H), 2.77 (t,
J¼6.4 Hz, 4H), 1.98–2.08 (m, 2H), 1.97 (tt, J1¼6.4 Hz, J2¼6.0 Hz, 4H),
1.72–1.84 (m, 2H), 1.22–1.49 (m, 12H). 13C NMR (500 MHz, DMSO-
d6): 152.223, 150.939, 146.943, 145.243, 140.807, 137.587, 134.814,
128.302, 127.615, 126.099, 125.348, 122.386, 121.853, 120.205,
115.192, 114.904, 108.251, 67.532, 60.347, 52.395, 49.131, 30.641,
28.768, 28.635, 28.548, 28.305, 27.156, 27.000, 25.3087, 20.0666.
HRMS (ESI): m/z: 611.3757 [2ꢁBr]þ
2.2.5. Preparation of Compound 1. Compound 2 (1.12 g, 1.62 mmol)
was dissolved in 40 ml acetonitrile. The solution was then added
upon iodomethane (1.6 g, 11.3 mmol) and stirred for one day at
60 ꢀC. A great deal of orange solid was gradually crystallized from
the solution. The solid was filtered, washed with acetonitrile
several times and then dried in vacuo to afford Compound 1
(1.02 g, 75.6%). Mp 219–220 ꢀC. 1H NMR (500 MHz, DMSO-d6,
25 ꢀC, TMS):
d
¼9.39 (d, J¼6.4 Hz, 2H), 9.28 (d, J¼6.4 Hz, 2H), 8.79
(d, J¼6.4 Hz, 2H), 8.76 (d, J¼6.4 Hz, 2H), 7.54 (d, J¼8.6 Hz, 2H),
7.50 (s, 1H), 7.39 (s, 2H), 6.98 (d, J¼8.6 Hz, 2H), 4.67 (t, J¼7.4 Hz,
2H), 4.43 (s, 3H), 3.99 (t, J¼6.6 Hz, 2H), 3.25 (t, J¼6.0 Hz, 4H), 2.64
(t, J¼6.4 Hz, 4H), 1.92–2.02 (m, 2H), 1.88 (tt, J1¼6.4 Hz, J2¼6.0 Hz,
Figure 1. 1H NMR spectra (500 MHz, 293 K) of 1, (A) in DMSO-d6, (B) in DMSO-d6 upon
sufficient irradiation at 254 nm, (C) in D2O, (D) in the presence of excessive b-CD in
D2O, and (E) after addition of excessive 1-adamantanol in D2O. The concentration of 1
was maintained at 1.5ꢂ10ꢁ3 M.

L.-L. Zhu et al. / Tetrahedron 66 (2010) 1254–1260
1257
unfavorable
duced vesicle-size showninFigure2B. For the encapsulationbehavior
of the -CD cavity to a configuration matched guest, the hydrophobic
part of compound 1 could be complexed with -CD in water. In-
troduction of 10 equiv of -CD to the aggregated system of 1 in water
would lead to a new monomeric form. It was indicated by the re-
production of the peaks of Ha–Hd and Hi–Hn in 1H NMR spectrum
(Fig. 1D), as well as a disappearance of aggregated vesicles observed
from SEM image (Fig. 2C).
p
–
p
stack of the cis-fluorophore confirmed by the re-
The maximum absorption band for compound 1 in water ap-
pears at wavelength of around 420 nm, which decreases re-
markably upon irradiation with UV light at 254 nm. When the
b
b
complex of compound 1 with b-CD was formed, the maximum
b
absorption was red-shifted about 20 nm (see Fig. 3). A sufficient
transformation of 1 to the encapsulation complex at 1.01ꢂ10ꢁ4 M
concentration needs ten-fold
b-CD, attribute to a relative small
association constant K (4.82ꢂ102 Mꢁ1, see Supplementary data,
Fig. S6) between 1 and b-CD. The 2D ROESY spectrum (see Sup-
plementary data, Fig. S3) of 1 mixed with excessive
generation of positive induced circular dichroism (ICD) signal at
around 425 nm (attributed to transition of the rotor part, see
the inset of Fig. 3), indicate that the cyanostilbene unit is located in
the cavity of -CD in this system, because a positive ICD signal
b-CD and the
p
/p
*
b
arises when the electric transition dipole moment of the guest in-
side the host cavity is aligned parallel to the axis of the chiral host.9
This location is also confirmed by the finding of a similar ICD signal
and locked viscosity-sensitive behavior of the encapsulation com-
plex of compound 4 and
Compound 1 will be extruded from the
aggregated form while excessive 1-adamantanol (1-Ada) is added,
b
-CD (see Supplementary data, Fig. S7).
b-CD cavity to reform an
due to a very high association constant between the b-CD host and
the 1-Ada guest. This process is also confirmed by 1H NMR spec-
troscopy (shown in Fig. 1E and 1C).
15
6
c
10
5
b
5
0
4
a
-5
3
350 375 400 425 450 475
Wavelength/nm
a
2
c
1
b
0
300
350
400
450
500
550
600
Wavelength/nm
Figure 3. Absorption spectra of 1 (curve a), after irradiation at 254 nm to photosta-
tionary state (curve b) and 1 mixed with excessive -CD (curve c). The inset shows
b
their corresponding ICD signals. These optical spectra of 1 were measured in water
with the concentration of 1.01ꢂ10ꢁ4 M at 293 K.
3.2. Viscosity response of compound 1 detected
by fluorescent spectroscopy
The rotor part of 1 belongs to a class of fluorophore, which can
form twisted intramolecular charge transfer (TICT) states upon
photo-excitation. The competition of fluorescence emission and
non-radiative decay is environmental viscosity or fluid flow de-
pendent. The intramolecular rotation of the phenyl group (here is
the julolidine group) is relatively free when the fluid outside is not
sheared, whereas it is readily inhibited by high viscosity of the
microenvironment. Hence the balance of relaxation will shift with
the variation of environmental viscosity and the fluorescence in-
tensity increases with increased viscosity of the solvent.2,4
The viscosity sensitivity of compound 1 described by fluorescent
intensity 10 could be clearly observed in mixtures of ethylene glycol
and glycerol with different ratio. Increased glycerol content is
known to increase viscosity with only minimal changes of solvent
polarity. Glycerol contents of 0, 20, 40, 60, 80% resulted in viscosi-
ties of 19, 32, 72, 155 and 368 mPa s, respectively. Fluorescence
measurements of 1 made in glycol/glycerol mixtures of different
Figure 2. SEM images of (A) 1, (B) after sufficient irradiation at 254 nm and (C) 1
mixed with excessive
b
-CD. The concentration of 1 is 1.01ꢂ10ꢁ4 M, which is larger than
its critical aggregate concentration (CAC) (1.70ꢂ10ꢁ5 M).

1258
L.-L. Zhu et al. / Tetrahedron 66 (2010) 1254–1260
viscosities (Fig. 4A), show that the fluorescence intensity increases
dramatically with increasing solvent viscosity. Interestingly, the
logarithm of its fluorescence has a good linear relationship with the
3.3. Viscosity sensitivity of compound 1 in aqueous
environment
}
logarithm of viscosity according to the Forster–Hoffmann equation
With the growing importance of viscosity measurements in
aqueous solutions or biofluids, the viscosity sensitivity of compound
1 is required to be tested in water. The dextran was added to make
the following weight/volume aqueous solutions, 2.5, 5.0, 7.5, and
10.0%, leading to viscosities of 1.6, 2.6, 4.2, and 6.5 mPa s, re-
spectively. The monomeric form of 1 at the concentration of
1.01ꢂ10ꢁ5 M (below CAC) shows a good solvent-dependent viscos-
ity-sensitive behavior. As shown in Figure 5A, the emission intensity
of the fluorescent dye boosts obviously with the increase of the
solvent’s viscosity, i.e., from 4.5 to 8.3 a.u. in the viscosity test range.
(Eq. 1).11 This result also suggest this fluorescent dye has a repre-
sentative viscosity response.
Figure 4. (A) Emission spectra of 1 (1.01ꢂ10ꢁ5 M, 293 K) in mixtures of ethylene glycol
and glycerol with different viscosity (ex¼370 nm). The insets show double-logarithmic
plot between fluorescent intensity at 480 nm of 1 and the corresponding viscosity. (B)
The changes of fluorescence lifetime for
1 as another indication of viscosity
(ex¼372 nm). The insets show double-logarithmic plot between fluorescence lifetime
of 1 and the corresponding viscosity.
log I ¼ xlog
h
þ C
(1)
Figure 5. Emission spectra of 1 (A) 1.01ꢂ10ꢁ5 M and (B) 1.01ꢂ10ꢁ4 M in aqueous solutions
at 293 K of dextran at different concentrations (ex¼370 nm). The insets show double-log-
arithmic plot between fluorescent intensity at 480 nm of 1 and the corresponding viscosity.
I¼fluorescent emission intensity;
h
¼solvent viscosity; x¼dye-de-
pendent constant; C¼conc. and temp. constant.
Currently, a new approach to image local viscosity using the
fluorescence lifetime has been demonstrated,12 as this measure-
ment is also a reflection of environmental parameters and in-
dependent of fluorophore concentration. Fluorescence lifetime
measurement has also been carried out on compound 1. The cali-
bration plot of fluorescence lifetime versus solvent viscosity for 1 is
shown in Figure 4B, which is well described by Eq. 2.11 The plot of
On the other hand, although compound 1 comes to be aggre-
gated form at the concentration above CAC, this rotor moiety can
still feel the environmental viscosity change and show a similar
linear relationship of the fluorescent intensity to the solvent vis-
cosity (see Fig. 5B). In this case, the linear relationship here shows
the non-radiative decay is also mainly affected by the viscosity
change rather than the self-organized effect. It is suggested that the
viscosity response of this dye is very sensitive in water.
log
s versus log h (Fig. 4B, inset) is fitted by a straight line in
agreement with the regularity that emission intensity changed
with viscosity.
3.4. Dual-mode tunable viscosity sensitivity in aqueous
environment
s
¼
z
k
0ha
(2)
s
¼fluorescence lifetime;
h¼solvent viscosity; k0¼radiative rate
The cyanostilbene moiety of 1 undergoes trans-to-cis photo-
isomerization by irradiation at 254 nm in water. The maximum
constant; ¼constant.
z,
a

L.-L. Zhu et al. / Tetrahedron 66 (2010) 1254–1260
1259
absorption of 1 is weakened by the photoisomerization, along with
a stronger blue-shifted emission peak. After irradiation at 254 nm
to the photostationary state, the new emission spectra of 1 (cis-
form) almost does not change with the increase of the solvent’s
viscosity (Fig. 6A). A similar phenomenon was found when exces-
in the cavity of cyclodextrins. Thus the intramolecular rotation of the
rotator in compound 1 should be prevented, together with its en-
vironmental-viscosity sensitivity shielded. In this way, this process
could be regarded as a supramolecular assembly induced tunable
viscosity-sensitive behavior. High-temperature is unfavorable for
this locked viscosity sensitivity (see Supplementary data, Fig. S10).
sive
fluorescent intensity of the rotor was overall enhanced because of
the -CD inclusion, it remains a same level despite the environ-
b-CD was introduced to the initial system of 1. Although the
b
3.5. Reversible and repetitive operation of the tunable
viscosity sensitivity of compound 1
mental viscosity change (Fig. 6B).
The locked viscosity-sensitivity state of 1, resulted from the
dual-mode switch effect, generated much stronger fluorescent
emissions than the ones in the corresponding initial state. In this
way, the reversibility of these two switch processes could be simply
described by the change of the fluorescent spectra. The photo-
isomerized cis-form of 1 would turn back to trans-form upon the
irradiation of visible-light, with the decrease of the emission nearly
to the original level. On the other hand, compound 1 complexed
with
1-Ada. Moreover, the 1-Ada encapsulated in the
extracted out by introducing dichloromethane into this system;
thereby the -CD will be reassembled to compound 1. These pro-
b
-CD would be recovered to the initial conformation by adding
b
-CD cavity can be
b
cesses are obviously featured by the alternant fluorescent change
(see Supplementary data, Fig. S11), indicating the dual-mode tun-
able viscometer could be repeatedly operated.
3.6. Quantitative estimation of the tunable viscosity-sensitive
state by double-logarithmic scaled slopes
To a quantitative data processing of this dual-mode switch, we
establish a methoddcomparing the slope of logarithm of the nor-
malized fluorescent intensity to the logarithm of viscositydto
judge the tunable viscosity-sensitive effect in a logic way. To this
rotor system, the logarithm of its fluorescence has a good linear
relationship with the logarithm of viscosity according to the
}
Forster–Hoffmann equation, but the activated and the locked vis-
cosity-sensitive states exhibit significant difference on the slopes.
Herein we recorded their normalized fluorescent intensity at
480 nm13 and plotted in a double-logarithmic scale with respect to
the environmental viscosity. Three straight lines, corresponding to
an initial state and two converted states of 1, are shown in Figure 7
with significant differences on the slopes. A threshold can be set
between these slopes, displaying the ‘Activated’ state of 1 in initial
Figure 6. Emission spectra of (A) 1 after irradiation at 254 nm to photostationary state
and (B) 1 mixed with excessive
b-CD in aqueous solutions of dextran at different
concentrations (ex¼370 nm). The concentration of 1 is kept as 1.01ꢂ10ꢁ4 M at 293 K,
and the solvent’s viscosity was basically adjusted by addition of dextran at that test
concentration of compound 1.
Both the locked viscosity-sensitive phenomena are generally
originated from the conformational restriction of the rotor part.
According to our previous research,5 the photo-lockable viscosity-
sensitive behavior is induced by the UV stimuli. In that case, the
cyanostilbene moiety is photoisomerized and the rotatory motion of
julolidine moiety (the rotator) is hindered by the steric factor of the
aromatic rings in the cis-isomer. That could be considered as a light-
driven tunable viscosity sensitivity. Otherwise, the locked viscosity-
sensitive behavior in this system can be also caused by the
b-CD
encapsulation. This phenomenon should be the result of the rigidity
Figure 7. Double-logarithmic plot between normalized fluorescent intensity and vis-
cosity corresponding to compound 1 (line a), after full irradiation at 254 nm (line b)
of the b-CD ring while locating on the fluorophore. Many structural
experiments or theoretic calculations in the relative reports6 in-
terpret that guests are often prone to a unique optimized geometry
and compound 1 mixed with excessive
threshold slope (0.18).
b-CD (line c). The dash line represents the

1260
L.-L. Zhu et al. / Tetrahedron 66 (2010) 1254–1260
aqueous environment as the slope is big (S1>0.18), compared with
the ‘Locked’ state when this system reaches photostationary state or
encapsulation equilibrium state as the slopes are small (S2,
S3<0.18). The ‘Activated’ and ‘Locked’ states in this system are just
corresponding to the turnon and turnoff of the fluorescent viscosity
sensor function. By the way, S3¼0.01231 is smaller than
S2¼0.06255, which features the fact that the conversion rate of
supramolecular assembly is higher than that of photoisomerization
in this system, for the fluorescence of some residual unconverted
species will slightly ascend with increase of viscosity.
with this article can be found in the online version, at doi:10.1016/
j.tet.2009.12.014.
References and notes
1. (a) Kuimova, M. K.; Botchway, S. W.; Parker, A. W.; Balaz, A.; Collins, H. A.;
Anderson, H. L.; Suhling, K.; Ogilby, P. R. Nat. Chem. 2009, 1, 69–73; (b)
Haidekker, M. A.; Brady, T. P.; Lichlyter, D.; Theodorakis, E. A. Bioorg. Chem.
2005, 33, 415–425; (c) Ghiggino, K. P.; Hutchison, J. A.; Langford, S. J.; Latter,
M. J.; Lee, M. A. P.; Lowenstern, P. R.; Scholes, C.; Takezaki, M.; Wilman, B. E.
Adv. Funct. Mater. 2007, 17, 805–813; (d) Luby-Phelps, K.; Mujumdar, S.;
Mujumdar, R. B.; Ernst, L. A.; Galbraith, W.; Waggoner, A. S. Biophys. J. 1993,
65, 236–242.
4. Conclusions
2. (a) Zhu, D.; Haidekker, M. A.; Lee, J.-S.; Won, Y.-Y.; Lee, J. C.-M. Macromolecules
2007, 40, 7730–7732; (b) Haidekker, M. A.; Brady, T. P.; Lichlyter, D.; Theo-
dorakis, E. A. J. Am. Chem. Soc. 2006, 128, 398–399.
In summary, a new rotor-containing fluorescent dye has been
synthesized and shows a good viscosity-sensitive behavior due to
the environment-dependent non-radiative decay. With the re-
versible dual-mode switch driven by photoirradiation or assembly/
3. (a) Blanco, M.-J.; Jime´nez, M. C.; Chambron, J.-C.; Heitz, V.; Linke, M.; Sauvage,
J.-P. Chem. Soc. Rev. 1999, 28, 293–305; (b) Balzani, V.; Credi, A.; Venturi, M.
ChemPhysChem 2008, 9, 202–220; (c) Browne, W. R.; Feringa, B. L. Nat.
Nanotechnol. 2006, 1, 25–35; (d) Kinbara, K.; Aida, T. Chem. Rev. 2005, 105,
1377–1400; (e) Pease, A. R.; Jeppesen, J. O.; Stoddart, J. F.; Luo, Y.; Collier, C. P.;
Heath, J. R. Acc. Chem. Res. 2001, 34, 433–444; (f) Tian, H.; Wang, Q. C. Chem.
Soc. Rev. 2006, 35, 361–374; (g) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew.
Chem., Int. Ed. 2007, 46, 72–191; (h) van Delden, R. A.; Ter Wiel, M. K. J.;
Pollard, M. M.; Vicario, J.; Koumura, N.; Feringa, B. L. Nature 2005, 437, 1337–
1340; (i) de Silva, A. P.; Uchiyama, S. Nat. Nanotechnol. 2007, 2, 399–410; (j)
Kottas, G. S.; Clarke, L. I.; Horinek, D.; Michl, J. Chem. Rev. 2005, 105, 1281–
1376; (k) Willner, I.; Basnar, B.; Willner, B. Adv. Funct. Mater. 2007, 17, 702–717;
(l) Guo, X.-F.; Zhang, D.-Q.; Zhang, G.-X.; Zhu, D.-B. J. Phys. Chem. B 2004, 108,
11942–11945; (m) Ji, F. Y.; Zhu, L.-L.; Zhang, D.; Chen, Z.-F.; Tian, H. Tetrahedron
2009, 65, 9081–9085.
disassembly process of b-cyclodextrin, the viscosity sensitivity of
this molecular rotor could be locked and activated. These tunable
viscosity-sensitive states can be distinguished by fluorescent sig-
nals. With establishment of a slope method, the viscosity-sensitive
‘Activated’ and the ‘Locked’ states of this dye could be quantita-
tively estimated.
This system provides a paradigm for the design and construction
of multi-tunable molecular-scale viscosity sensor with character-
4. (a) Haidekker, M. A.; Theodorakis, E. A. Org. Biomol. Chem. 2007, 5, 1669–1678;
(b) Loutfy, R. O.; Arnold, B. A. J. Phys. Chem. 1982, 86, 4205–4211; (c) Iwaki, T.;
Torigoe, C.; Noji, M.; Nakanishi, M. Biochemistry 1993, 32, 7589–7592.
5. Zhu, L.-L.; Li, X.; Ji, F. Y.; Ma, X.; Wang, Q. C.; Tian, H. Langmuir 2009, 25, 3482–3486.
6. (a) Liu, Y.; Chen, Y. Acc. Chem. Res. 2006, 39, 681–691; (b) Wenz, G.; Han, B. H.;
Mu¨ller, A. Chem. Rev. 2006, 106, 782–817; (c) Klotz, E. J. F.; Claridge, T. D. W.;
Anderson, H. L. J. Am. Chem. Soc. 2006, 128, 15374–15375; (d) Qu, D. H.; Wang,
Q. C.; Ren, J.; Tian, H. Org. Lett. 2004, 6, 2085–2088; (e) Sakamoto, K.; Taka-
shima, Y.; Yamaguchi, H.; Harada, A. J. Org. Chem. 2007, 72, 459–465; (f) Qu, D.
H.; Wang, Q. C.; Tian, H. Angew. Chem., Int. Ed. 2005, 44, 5296–5299; (g)
Coulston, R. J.; Onagi, H.; Lincoln, S. F.; Easton, C. J. J. Am. Chem. Soc. 2006, 128,
14750–14751; (h) Park, J. W.; Song, H. J.; Cho, Y. J.; Park, K. K. J. Phys. Chem. C
2007, 111, 18605–18614; (i) Ma, N.; Wang, Y.; Wang, Z.; Zhang, X. Langmuir
ized and read by fluorescent outputs. Indeed, the b-cyclodextrin
encapsulation in this system performs efficiently and precisely on
the tunable viscosity-sensitive behavior. There is a drawback of the
relative inconvenient operation of the assembly/disassembly pro-
cess yet. Our next goal is to translate this kind of molecular vis-
cometers to a rotaxane-like architecture, which may bring in
a high-speed tunable way with molecular-scale movement.
Acknowledgements
}
2006, 22, 3906–3909; (j) Xu, Y.; Bolisetty, S.; Ballauff, M.; Muller, A. H. E. J. Am.
This work was supported by NSFC/China (20972053, 20603009),
National Basic Research 973 Program (2006CB806200), partially by
Scientific Committee of Shanghai.
Chem. Soc. 2009, 131, 1640–1641.
7. Compound 1 was fully characterized by 1H NMR, 13C NMR spectroscopy and high-
resolution mass spectrometry (HRMS) as described in Supplementary data.
8. (a) Park, J. W.; Song, H. J. Org. Lett. 2004, 6, 4869–4872; Wang, Y.; Ma, N.; Wang,
Z.; Zhang, X. Angew. Chem., Int. Ed. 2007, 46, 2823–2826.
Supplementary data
9. (a) Kodaka, M. J. Phys. Chem. A 1998, 102, 8101–8103; (b) Zhu, L. L.; Ma, X.; Ji, F. Y.;
Wang, Q. C.; Tian, H. Chem.dEur. J. 2007, 13, 9216–9222; (c) Liu, Y.; Zhao, Y. L.;
Zhang, H. Y.; Fan, Z.; Wen, G. D.; Ding, F. J. Phys. Chem. B 2004,108, 8836–8843; (d)
Wang, Q. C.; Ma, X.; Qu, D. H.; Tian, H. Chem.dEur. J. 2006, 12, 1088–1096.
10. If only the absorbed light intensity Iab is known, the emission intensity Iem and
13C NMR, and HRMS (ESI) spectra of compound 1; 2D ROESY
NMR spectrum of 1 mixed with b-CD; TEM images for a further
magnified observation of Self-organized Conformational Switches
the quantum yield are directly and proportionally related through IemNIabF
.
Thus we could directly make use of fluorescent intensity readout in this
measurement.
of 1 in water; the measurement of CAC; the association constant
between 1 and b-CD; the inclusion of 4 and b-CD; Data for the
11. Fo¨rster, T.; Hoffmann, G. Z. Physiol. Chem. 1971, 75, 63–76.
12. (a) Kuimova, M. K.; Yahioglu, G.; Levitt, J. A.; Suhling, K. J. Am. Chem. Soc. 2008,
130, 6672–6673; (b) Levitt, J. A.; Kuimova, M. K.; Yahioglu, G.; Chung, P.-H.;
Suhling, K.; Phillips, D. J. Phys. Chem. C. 2009, 113, 11634–11642.
13. Here the normalized fluorescent intensity is defined as F/F0, while F is the
emission signals under each the viscosity condition, whereas F0 is the one in
the solvent without any addition of dextran.
fluorescence life-time of compound 1 in mixtures of ethylene glycol
and glycerol with different viscosity; Lockable viscosity sensitivity
of 1 expressed by fluorescent emissions below CAC; Repetitive
cycles of light-and ring-induced lockable viscosity sensitivity of 1
described in fluorescence signal. Supplementary data associated