Rational design of fluorescent viscosity sensors by the principle of photoinduced electron transfer

Article abstract of DOI:10.1016/j.tetlet.2013.02.111

To establish a new strategy for the development of fluorescent viscosity sensors by the principle of photoinduced electron transfer, three 4-aminonaphthalimide based D-(CH₂)₂-A molecules were designed and synthesized. The effects of solvent polarity and viscosity on the fluorescence spectra of these compounds were investigated. These compounds exhibit viscosity-sensitive fluorescence spectra in ethylene glycol-glycerol mixtures. A mechanism about exciplex formation was proposed to explain their viscosity sensitivity.

Full text of DOI:10.1016/j.tetlet.2013.02.111

Tetrahedron Letters xxx (2013) xxx–xxx
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Rational design of fluorescent viscosity sensors by the principle
of photoinduced electron transfer
Zhiyong Wu a, Jingnan Cui a, , Xuhong Qian b,
⇑
⇑
a State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116012, China
b Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, Shanghai, China
a r t i c l e i n f o
a b s t r a c t
Article history:
To establish a new strategy for the development of fluorescent viscosity sensors by the principle of pho-
toinduced electron transfer, three 4-aminonaphthalimide based D-(CH2)2-A molecules were designed and
synthesized. The effects of solvent polarity and viscosity on the fluorescence spectra of these compounds
were investigated. These compounds exhibit viscosity-sensitive fluorescence spectra in ethylene glycol–
glycerol mixtures. A mechanism about exciplex formation was proposed to explain their viscosity
sensitivity.
Received 12 December 2012
Revised 31 January 2013
Accepted 19 February 2013
Available online xxxx
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Fluorescent viscosity sensors
Photoinduced electron transfer
4-Aminonaphthalimide
Exciplex formation
Introduction
tors is complicated. The relationship between molecular structure
and viscosity sensitivity was not well established. It is difficult to
Viscosity is an important physicochemical parameter which
determines the diffusion rates of solutes in solvents. Changes in
the local microviscosity of biological systems have been linked to
many diseases and disorders.1 The demands of the quantitative
measurements of viscosity on a microscopic scale, where tradi-
tional mechanical methods met with difficulties, led to the devel-
opment of fluorescent viscosity sensors.
Fluorescent viscosity sensors are functional molecules whose
fluorescence properties are dependent upon the viscosity of the lo-
cal environments.1–14 The most reported fluorescent viscosity sen-
develop new fluorescent viscosity sensors with diverse sensitivity
and emission wavelengths to meet the needs of different applica-
tions. Strategies for the rational design of fluorescent viscosity sen-
sors are severely desired.
We focused our efforts on the establishment of a rational strat-
egy to develop fluorescent viscosity sensors by the principle of
photoinduced electron transfer (PET). Photoinduced electron trans-
fer is one of the most employed principles in the design of fluores-
cent sensors.28 The typical structure of an intramolecular PET
system is that an electron donor and an electron acceptor are
linked together by a flexible chain. In the ground state, there are
no electronic interactions between the donor and the acceptor
moieties. In the excited state, electron transfer from the donor
moiety to the acceptor moiety may quench the fluorescence from
the fluorophore. Electron transfer efficiency will be strongly influ-
enced by the steric nature of the flexible chain linking the donor
and acceptor moieties. This is because the steric nature of the flex-
ible chain determines the distance between the donor and the
acceptor moieties and their relative orientations, and therefore,
determines the distance the electron must travel in the electron
transfer process and the extent of the orbital interactions between
the donor and acceptor moieties.29,30 Viscosity may influence the
conformational motions of the flexible chain in the electron trans-
fer process, and thus, affect electron transfer efficiency. Therefore,
it is reasonable to suppose that viscosity sensors can be developed
based on the principle of photoinduced electron transfer. However,
PET fluorescent viscosity sensors were rarely reported.
sors
are
molecular
rotors,
such
as
p-
dialkylaminobenzylidenemalononitriles,2 and their carboxy di-
logs,1,3–6 4-p-dimethylaminostyrylpyridinium salts,7,8 etc. They
usually have a D-p-A structure with an electron donor and an elec-
tron acceptor being linked together by a single bond or single dou-
ble alternative bonds. The internal rotations of the single bonds
linking the different parts are associated with the nonradiative
pathways of the excited states and are influenced by the changes
of the viscosity of the medium.15,16 Benefit from high sensitivity,
fast response and good spatial resolution, these kind of fluorescent
viscosity sensors were widely used in biochemical research.17–27
Their wide applications stimulated the development of new fluo-
rescent viscosity sensors. However, the mechanism of the effects
of solvent viscosity on the fluorescence properties of molecular ro-
⇑
Corresponding authors. Tel./fax: +86 411 84986229.
E-mail address: jncui@dlut.edu.cn (J. Cui).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.02.111
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Z. Wu et al. / Tetrahedron Letters xxx (2013) xxx–xxx
In order to develop PET fluorescent viscosity sensors, three D-
(CH2)2-A molecules (1–3, Fig. 1) with N-alkyl anilines as electron
donors and 4-aminonaphthalimides as electron acceptors were de-
signed and synthesized. 4-Aminonaphthalimide was chosen as the
fluorophore for its excellent photophysical properties, such as high
fluorescence efficiency, long emission wavelengths and good
photostability.31–33 The chain length of the alkyl substituent on
the N atom of the aniline moiety was purposely altered to investi-
gate the effect of substituent on viscosity sensitivity. Compound A
which has no aniline moieties connected was used as a reference to
determine the electron transfer efficiency.31
Results and discussion
The synthesis procedures of 1–3 are shown in Scheme 1. N-Bu-
tyl-4-bromo-1,8-naphthalimide (4) was refluxed with N-methyl-2-
aminoethanol in 2-methoxyethanol with triethylamine as catalyst
to give N-butyl-4-(N-methyl-2-hydroxyethylamino)-1,8-naphthal-
imide (5). Compound 5 was treated with phosphorous tribromide
in dichloromethane to get N-butyl-4-(N-methy-2-bromoethylami-
no)-1,8-naphthalimide (6). The bromine atom of 6 was substituted
by N-alkyl anilines to give 1–3.
Firstly, we examined the photophysical properties of 1–3 in sol-
vents with different polarity. The absorption spectra of 1–3 in var-
ious solvents (Supplementary data, Table S1, Figs. S1–S5) indicate
that there are no appreciable interactions between the aniline
and the 4-aminonaphthalimide moieties on the ground state. The
absorption maxima of 1–3 are about 20 nm shorter than those of
A in the solvents tested. This can be attributed to the steric inter-
action between the 4-amino group and the 5-H atom of the naph-
thalene ring, which prevents the 4-amino group from conjugating
well with the naphthalene ring.
Scheme 1. Synthesis procedures of 1–3.
Figure 2 displays the fluorescence efficiency of A and 1–3 in sol-
vents with different polarity (see also Supplementary data,
Table S1). The fluorescence efficiency of A decreases progressively
with the increase of solvent polarity, indicating an intramolecular
charge transfer (ICT) character.31 Compared to that of A, the fluo-
rescence of 1–3 is extensively quenched both in nonpolar and polar
solvents, which indicates that efficient electron transfer takes place
in these compounds. With the increase of solvent polarity, the fluo-
rescence intensity of 1–3 decreases steeply. In moderate polar sol-
vents, such as tetrahydrofuran, the fluorescence of these
compounds is almost fully quenched.
Figure 3 shows the emission maxima of A and 1–3 in solvents
with different polarity. The emission maximum of A increases lin-
early with the increase of solvent polarity. This is also a character
of an ICT emission. Interestingly, in nonpolar solvents, 1–3 exhibit
much longer emission maxima than those of A. For example, in tol-
Figure 2. Fluorescence efficiency of A and 1–3 in solvents with different polarity.
Solvents, from left to right are hexane, toluene, tetrahydrofuran, dichloromethane,
acetonitrile, ethanol, ethylene glycol, and glycerol.
Figure 3. Emission maxima of A and 1–3 in solvents with different polarity. The
straight line is the linear fitness of the emission maxima of A to the solvent polarity
parameter, ET (30). Solvents, from left to right are hexane, toluene, tetrahydrofuran,
dichloromethane, acetonitrile, ethanol, ethylene glycol, and glycerol.
Figure 1. Structures of A and 1–3.
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Z. Wu et al. / Tetrahedron Letters xxx (2013) xxx–xxx
3
uene, the maximal emission wavelength of 3 (543 nm) is about
60 nm longer than that of A (481 nm). This phenomenon indicates
that an excited state with much larger charge separation character
than that of an ICT state is formed. The emission maxima of 1–3
shift to red when the solvent changes from hexane to toluene. In
solvents more polar than toluene, this long-wavelength emission
is quenched, and 1–3 exhibit emission maxima similar to those
of A. Some representative fluorescence spectra of 1–3 are shown
in Figure 4 (see also Supplementary data, Figs. S6–S8).
Then, we investigated the fluorescence spectra of 1–3 in ethyl-
ene glycol–glycerol mixtures with varied viscosity. The fluores-
cence intensity of 1 and 2 (Supplementary data, Figs. S9 and S10)
is weakly sensitive to solvent viscosity. The fluorescence intensity
of 3 increases about 10-fold when solvent viscosity increases from
50 to 1000 cP (Fig. 5, see also Supplementary data, Fig. S12). As
shown in the inset of Figure 5, the fluorescence intensity of 3 is lin-
early related to solvent viscosity, which can be described well by
Förster–Hoffmann equation (Eq. 1):34
Figure 5. Fluorescence emission spectra of
3
in ethylene glycol/glycerol (v/v)
mixtures: (a) 7:3; (b) 6:4; (c) 5:5; (d) 4:6; (e) 3:7; (f) 2:8; (g) 1:9; and (h) glycerol
only. [3] = 4 ꢀ 10ꢁ5 M, All the spectra were recorded at 20 °C and kex = 435 nm. The
inset shows the linear relationship of logI and logg.
logI ¼ C þ xlog
g
ð1Þ
where I = fluorescent emission intensity;
g
= solvent viscosity;
x = dye-dependent constant; C = concentration and temperature
constant. The slope x, an indicator of viscosity sensitivity, is 0.8
for 3. This value is higher than most of the reported fluorescent vis-
cosity sensors, where the slope x 60.66.3–6 These phenomena indi-
cate that substituent effects have great influence on the viscosity
sensitivity of this kind of fluorescent viscosity sensors and that
higher viscosity sensitivity than that of molecular rotors can be ob-
tained in PET fluorescent viscosity sensors.
Finally, we proposed a mechanism of exciplex formation to ex-
plain the fluorescence properties of these compounds, which is
shown in Scheme 2. Exciplexes are intermediates of photoinduced
electron transfer, and are characterized by partial charge separa-
tion and large dipole moments.29 We suppose that, when 4-amino-
naphthalimide is photoexcited, an ICT state is formed with the 4-N
atom partially positively charged.31 The N atom of the aniline moi-
ety gives its lone-pair electrons to the positively charged N atom of
4-aminonaphthalimide to form a charge-transfer exciplex. When
this exciplex is formed, the fluorescence from the ICT state is
quenched and an emission from the exciplex appears. Due to the
extended charge separation of the exciplex relative to that of the
ICT state, exciplex formation leads to the decrease of the fluores-
cence intensity and the red-shift of the emission wavelengths.29
The broad and long-wavelength emissions of these compounds in
nonpolar solvents give support in this suggestion. The decrease
Scheme 2. The proposed mechanism of exciplex formation.
of the fluorescence intensity and the red-shift of the emission max-
ima of these compounds with the increase of solvent polarity can
be accounted for by assuming that the extent of the charge separa-
tion of this exciplex increases with the increase of solvent polar-
ity.35–37 In polar solvents, this exciplex may separate to ion pairs,
and the fluorescence of 1–3 is fully quenched. This exciplex may
also be considered as a three-electron N–N
r bond formed be-
tween these two N atoms with both of them partially positively
charged.16,38
We suppose that orbital overlapping between the N atom of the
4-amino group and the N atom of the aniline moiety is necessary
for this exciplex formation. On the ground state, the most stable
conformation of the flexible chain is an extended conformation
and the two N atoms are far from each other. On the excited state,
a conformational change from an extended conformation to a
folded conformation is required for orbital overlap between these
two N atoms. The increase of the solvent viscosity hinders this con-
formational change and prevents the formation of this exciplex,
which leads to the resuming of the fluorescence from the ICT state
and the increase of the total fluorescence intensity. This is the rea-
son why 1–3 are sensitive to solvent viscosity.
The relationship between viscosity sensitivity and the chain
length of the alkyl substituent on the aniline moiety can also be ac-
counted for by this mechanism. Increasing the length or volume of
the substituent on the donor moiety increases the activation en-
ergy of the bond rotations of the flexible chain, so that the confor-
mational changes in the electron transfer process are more easily
affected by the changes in solvent viscosity. It is reasonable to sup-
pose that the viscosity sensitivity of these kind of fluorescent vis-
cosity sensors can be finely tuned by simply altering the length
or volume of the substituent on the donor moiety.
Figure 4. The fluorescence spectra of
3 in different solvents: (a) hexane; (b)
toluene; (c) tetrahydrofuran; (d) dichloromethane; (e) acetonitrile; (f) ethanol; (g)
ethylene glycol; and (h) glycerol. [3] = 1 ꢀ 10ꢁ5 M. All the spectra were recorded at
20 °C and excited at the maximal absorption wavelengths.
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4
Z. Wu et al. / Tetrahedron Letters xxx (2013) xxx–xxx
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In conclusion, a new strategy for the rational design of fluores-
cent viscosity sensors was established, by which, three 4-amino-
naphthalimide based PET fluorescent viscosity sensors (1–3)
were developed. Among these compounds, 3 exhibits higher vis-
cosity sensitivity than most of the reported fluorescent viscosity
sensors. The clear-cut relationship between substituent and viscos-
ity sensitivity indicates the potential use of this strategy in the ra-
tional design of fluorescent viscosity sensors. More sensitive PET
fluorescent viscosity sensors are expected to be developed by this
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