Fluorescent β-cyclodextrins modified by isomeric aminobenzamides: Synthesis, conformational analysis, and fluorescent behaviors

Article abstract of DOI:10.1021/jo2007829

Three isomeric fluorescent β-cyclodextrins bearing 2-, 3-, and 4-(2-aminoethyl)amino-N-butylbenzamide, respectively (1-3) have been synthesized. The conformations of these fluorescent CDs have been investigated by 2D NMR and induced circular dichromism. It is confirmed that the ortho isomer 1 takes a butyl-included conformation, while the other two isomers 2 and 3 display a phenyl-included conformation, respectively. The three fluorescent CDs 1-3 exhibited totally different self- and guest-inclusion fluorescence behavior. In the presence of adamantane carboxylate sodium (ADA) or deoxycholate sodium (DCA), the fluorescence intensity of 1 showed an enhancement over 1-fold, while 2 exhibited dramatic fluorescence quenching. Interestingly, the fluorescent responses of 3 toward two guests respectively were highly distinguishable. The fluorescence intensity of 3 only showed a slight increase upon the addition of ADA, but the addition of DCA led to a large decrease in fluorescence intensity. The investigations have been further carried out by 2D NMR, induced circular dichromism, fluorescence spectroscopy and molecular modeling to explore the relationships between the conformations and the fluorescence characteristics of CDs 1-3 in the absence and presence of guest molecules. On the basis of the above investigations, the origins for the different fluorescence behaviors have been proposed.

Full text of DOI:10.1021/jo2007829

ARTICLE
pubs.acs.org/joc
Fluorescent β-Cyclodextrins Modified by Isomeric Aminobenzamides:
Synthesis, Conformational Analysis, and Fluorescent Behaviors
Lei Wang, Cheng Zhong, Peng Xue, and Enqin Fu*
Department of Chemistry, Hubei Key Laboratory on Organic and Polymeric Optoelectronic Materials, Wuhan University, Wuhan
430072, PR China
S Supporting Information
b
ABSTRACT: Three isomeric fluorescent β-cyclodextrins bear-
ing 2-, 3-, and 4-(2-aminoethyl)amino-N-butylbenzamide, re-
spectively (1ꢀ3) have been synthesized. The conformations of
these fluorescent CDs have been investigated by 2D NMR and
induced circular dichromism. It is confirmed that the ortho
isomer 1 takes a butyl-included conformation, while the other
two isomers 2 and 3 display a phenyl-included conformation,
respectively. The three fluorescent CDs 1ꢀ3 exhibited totally
different self- and guest-inclusion fluorescence behavior. In the
presence of adamantane carboxylate sodium (ADA) or deox-
ycholate sodium (DCA), the fluorescence intensity of 1 showed an enhancement over 1-fold, while 2 exhibited dramatic
fluorescence quenching. Interestingly, the fluorescent responses of 3 toward two guests respectively were highly distinguishable.
The fluorescence intensity of 3 only showed a slight increase upon the addition of ADA, but the addition of DCA led to a large
decrease in fluorescence intensity. The investigations have been further carried out by 2D NMR, induced circular dichromism,
fluorescence spectroscopy and molecular modeling to explore the relationships between the conformations and the fluorescence
characteristics of CDs 1ꢀ3 in the absence and presence of guest molecules. On the basis of the above investigations, the origins for
the different fluorescence behaviors have been proposed.
’ INTRODUCTION
surrounded by a hydrophilic environment. The inclusion of a
hydrophobic guest molecule into the cavity of the fluorescent CD
makes the fluorophore locate in a more hydrophobic environ-
ment; thus, the fluorescence intensity increases.
Fluorescence-based sensing has been a growing research area
because of its high sensitivity, simplicity, and diversity.1 However,
up to now, only very limited cases have been achieved in aqueous
media for biomedical analysis.2
Recently, we have reported a new fluorescent cyclodextrin
with an N-butyl-4-(2-aminoethyl)amino-1,8-naphthalimide group
connecting to the primary side of β-CD.7 Upon addition of guest
molecules, an unexpected 8-fold enhancement of the fluores-
cence intensity and a 5 nm blue shift of the fluorescence
maximum were observed. On the basis of the combination of the
fluorescence data and conformation, it is believed that fluores-
cence of this fluorescent CD is quenched by the formation of a
self-inclusion conformation. On the other hand, Campos and
Brochsztain8 reported that when β-CD was added to an aqueous
solution of 4-amino-1, 8-naphthalimide, a blue shift of the fluores-
cence maximum and an increase in the fluorescence intensity
were observed. In other words, the fluorescence behavior of our
fluorophore-appended CD in aqueous solution was opposite to
that of the inclusion complexes between 4-amino-1,8-naphtha-
limide and β-CD (namely, in Campos’s case). Detailed research
has revealed that the orientations of the two fluorophore are
opposite to each other, though in both systems the 4-amino-1,
8-naphthalimide moiety was included in the CD cavity.
Cyclodextrins (CDs) are the most important and promising
natural macrocyclic hosts. They are water-soluble, nontoxic,
commercially available, and readily functionalized. The most
important property of CDs is the inclusion of guest molecules
into their cavity. These properties made them applicable in
various fields, such as enzyme models, drug delivery, chemical
sensors, and enantiomeric separations.3 Among them, the fluor-
escent sensors based on CD derivatives have attracted much
attention due to their potential for biosensing.4 Ueno and co-
workers5 have pioneered the field of fluorophore-appended CD
chemical sensors, which usually adopt a self-inclusion conforma-
tion in aqueous solution. The fluorescent CD exhibited strong
emission in the self-inclusion state because of the hydrophobic
environment of the CD cavity, and the exclusion of fluorophore
from CD cavity to bulk aqueous media must weaken its
fluorescence intensity. But some exceptions have also been
reported,6 and the fluorescence intensity of these fluorescent
CDs was increased by formation of hostꢀguest inclusion com-
plexes. These fluorescent CDs, with a rigid spacer between
CD and fluorophore, could not form self-inclusion complexes.
The fluorophore just covers the upper rim of the CD cavity,
Received: January 22, 2011
Published: May 11, 2011
r
2011 American Chemical Society
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Another unusual fluorescence phenomenon for two diastere-
omeric L/D-Trp-β-CD (where Trp is tryptophan) was also
reported by Liu.9 It is interesting to note that the L-Trp-β-CD
exhibits usual self- and guest-inclusion fluorescence behavior, as
in the case of Ueno’s “turn-off” fluorophore-appended CD, while
the D-Trp-β-CD shows entirely opposite behavior, similar to our
case above. Moreover, two position-isomeric naphthalene-ap-
pended amino-β-cyclodextrins have also been found to exhibit
totally different fluorescent behavior.10
Scheme 1. Synthetic Route for Fluorescent CDs 1ꢀ3
The interesting phenomena described above demonstrated
that the nature of the microenvironment around the fluorophore
(usually expressed in terms of polarity, hydrogen-bonding ability,
hydrophobicity, etc.) is anisotropic, although the interior of the
CD cavity is generally considered as a hydrophobic hole. Thus,
when we investigate the microenvironment effect of CD on
fluorescence, the position and orientation of the fluorophore
moiety relative to the CD cavity should be considered as a key
factor. Therefore, in order to create new and better fluorophore-
appended CD chemical sensors, the relative position and or-
ientation of the fluorophore to the CD cavity should be designed
or controlled by changing the molecular structure of the fluor-
escent CDs, such as by changing the spacer or substitute groups
on the fluorophore or by changing the isomeric connecting sites
on the fluorophore and so on. The investigations on the relation-
ship between conformation and spectroscopic properties are
significant for explaining different fluorescence behaviors and
gathering more information of the microenvironment provided
by CD. Fluorescent molecules are currently used as probes for
the investigation of physicochemical, biochemical, and biological
processes, so the study of microenvironment effects on fluores-
cence behavior should be of great importance for sensing, monitor-
ing, and elucidating various processes in biological systems.
In this paper, we report three isomeric fluorescent CDs 1ꢀ3,
in which 2-, 3-, and 4-(2-aminoethyl)amino-N-butylbenzamide
are connected to the primary side of β-CD, respectively. The
aminobenzoyl moiety is an intramolecular charge-transfer (ICT)
group, which is sensitive to polarity.11,12 This ICT characteristic
is propitious to offer the information about the microenviron-
ment around the fluorophore moiety.13 All these compounds
have a flexible diaminoethyl group as spacer and a butyl group as
terminal on the aminobenzamide moiety to induce the inclusion
into the CD cavity. The three position-isomeric aminobenzoyl
moieties of fluorescent CDs, 1ꢀ3, should take different steric
hindrance effects and control the position and orientation of
fluorophore moiety relative to the CD cavity. 2D NMR and
induced circular dichromism experiments were carried out to
investigate the conformations of the fluorescent CDs 1ꢀ3, and
their spectroscopic properties were also determined. It is inter-
esting that the three fluorescent CDs, 1ꢀ3, exhibit totally
different self- and guest-inclusion fluorescence behavior. The
relationships between their conformations and spectroscopic
properties are discussed.
Conformations of Fluorescent CDs 1ꢀ3. NOESY NMR
experiments in D2O were carried out to determine the con-
formation of 1ꢀ3. Figure 1 shows the 2D NOESY NMR spectra
of 1ꢀ3. In the spectrum of 1, correlation signals between the
protons of CD and the protons of n-butyl group can be found.
Somewhat unexpectedly, no NOE signal can be observed
between the protons of the CD and phenyl group. If the phenyl
moiety is included in the CD cavity, the NOE correlations would
be observed; therefore, it is possible to estimate that the benzene
ring of CD 1 is staying outside the CD cavity. Different from the
ortho isomer 1, meta and para isomers 2 and 3 display clear NOE
correlations between protons of CD and the aromatic protons of
aminobenzamide other than that between CD and butyl. This
result suggests that the benzene ring is included into the CD
cavity and the butyl group has passed through the cavity. The 2D
NOESY NMR experiment confirms that the three compounds all
take self-inclusion conformation in water and the depth of side
chains included in CD cavity are different.
Induced circular dichromism (ICD) spectroscopy was used to
further provide information about the orientation and position of
chromophore relative to the CD cavity. The ICD spectra of 1ꢀ3
are shown in Figure 2, and a broad band can be observed,
respectively, for all three compounds and assigned to the ICT
πꢀπ* transition relative to about 320, 310, and 290 nm absorp-
tion for 1ꢀ3, respectively, in UV spectra (Figure4). In the
absence of the guests, 1 displayed a negative band and fluorescent
CDs 2 and 3 showed a positive band, respectively. According to
the rule proposed by Kajtar, Harata, and Kodaka et al.,14 we can
conclude that the phenyl group, the main body of the fluor-
ophore in 1, is outside the CD cavity, with the benzene plane
parallel to the axis of CD cavity and tightly perching on the upper
rim of the hydrophobic cavity, and the phenyl group in 2 and 3 is
certainly included in the CD cavity. This conclusion is consistent
with the results of 2D NOESY NMR experiments.
On the basis of the above experimental information, the
molecular modeling of the three fluorescent CDs have been
performed by Gaussian 09 program with the density functional
theory (DFT) B97D/SVP/def2SV level. The resulting confor-
mations are shown in Figure 3.
The only difference in the three fluorescent CDs is the relative
positions of the substituted groups in aminobenzamide moiety,
so the position isomerism of side chain is the key factor to yield
the differences in self-inclusion conformations. From Figure 3,
we can see that because free rotation is strictly limited by two
’ RESULTS AND DISCUSSION
Synthesis. The synthetic route is showed in Scheme 1.
Halogen-substituted benzoic acid reacted with thionyl chloride
followed by n-butylamine to afford 4. Then under cuprous catalytic
conditions, 4 and 1,2-ethylenediamine coupled to generate 5.
Finally, through the classic mono-6-tosyl-β-CD derivative meth-
od, the tosyl group was readily displaced by the amine group of 5
to gain the corresponding fluorescent CDs 1ꢀ3.
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Figure 2. Induced circular dichromism spectra of 1, 2 in the absence,
and 3 in the absence and presence of guest molecules in tris-HCl buffer
(10 mM, pH 7.5), concentration: 1 and 2, 0.5 mM; 3: 0.05 mM;
adamantane carboxylate sodium, 2 mM; deoxycholate sodium, 0.4 mM.
(The ICD spectra of 1 and 2 with guests are absent because the
concentration of two guests cannot satisfy the need for the ICD
experiment.)
group in the CD cavity, so it adopts a conformation similar to that
of 2. In both cases, hydrophobicity and the shape-matching effect
make the phenyl group stay in the CD cavity and allow the butyl
group to pass through the bottom rim of CD into the aqueous
solution.
Spectroscopic Properties. The emission spectra (in Figure 6)
of all three compounds are characterized by a typical ICT band
corresponding to the longest wavelength absorption band in
absorption spectra, about 320, 310, and 290 nm for 1ꢀ3, respec-
tively (Figure 4), which originates mainly from the amino group
to the carbonyl group transfer. The excitation wavelengths (λex)
for 1, 2, and 3 are 326, 315, and 292 nm, respectively, and the
maximum emission wavelengths (λmax) of 1, 2, and 3 are 428,
418, and 357 nm, respectively.
Since fluorescent chromophores based on the electron donor/
acceptor system are very sensitive to the pH value, the relation-
ship of emission intensity and pH value has been tested. From
Figure 5, we can observe that with the increased solution acidity
the fluorescence intensity of 2 and 3 enhanced gradually, while in
the case of 1, the change of fluorescence intensity with the
increased solution acidity exhibits an opposite tendency. The
fluorescenceꢀpH relationships of 2 and 3 show a typical photo-
induced electron transfer (PET) feature; namely, with the
increased protonation of the amino group directly connected
to CD, the PET process was blocked resulting emission en-
hancement. For the case of 1, at low pH value, the increased
protonation of arylamine quenches the fluorescence emission.
The fluorescence titration of compounds 1ꢀ3 was performed
in 0.01 M pH 7.5 Tris-HCl (tris-(hydroxymethyl)aminomethane)
buffer. Well known as having highly affinity to β-CD, adamantane
analogues15 and bile salts16 could be tightly bound by β-cyclo-
dextrin and displace the chromophore in the CD cavity. Thus,
adamantane carboxylate sodium (ADA) and deoxycholate sodium
(DCA) were chosen as the guests to investigate the fluorescent
behavior, while the fluorophore of CDs 1ꢀ3 stayed outside the
CD cavity. The results of the fluorescence titration of com-
pounds 1ꢀ3 toward these two guests are shown in Figure 6. It
was found that the sensing behaviors of the three fluorescent CDs
Figure 1. 2D NOESY NMR spectra of 1ꢀ3 with water suppression in
D2O (mixing time = 600 ms).
adjacent substituent groups, the side chain of 1 can only take a
folding shape, which holds the benzene ring on the upper rim of
the CD cavity, resulting in a butyl-included conformation. In the
case of 2, the meta-substituted side chain provides relatively
better flexibility than the side chain in 1, consequently the
aminobenzamide moiety can be induced deeply into the CD
cavity by butyl group and give a phenyl-included conformation.
As for 3, the linear side chain makes it easier to inlcude the phenyl
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Figure 3. Possible geometry structures of 1ꢀ3.
Figure 4. Absorption spectra of 1ꢀ3 in water, concentration (mM): 1
and 2, 0.5; 3, 0.05.
Figure 5. Plots of fluorescence intensity of 1ꢀ3 versus pH value in
aqueous solution. Measured wavelengths for 1ꢀ3 are 428, 418, and
357 nm respectively.
toward these two guests are highly inconsistent. With the gradual
addition of ADA or DCA, the fluorescence intensity of 1 showed
continuous enhancement. An over 1-fold enhancement of the
fluorescence intensity and about 2 nm red shift of the fluores-
cence maximum were observed when the equilibrium was
reached. In the case of compound 2, a large decrease of the
fluorescence intensity and about 18 nm red shift of the fluores-
cence maximum were observed with the addition of the two
guests, respectively. Compared with compounds 1 and 2, the
fluorescent respondses of 3 toward two guests are highly
distinguishable. The fluorescence intensity of 3 only showed a
slight increase upon the addition of ADA, but the addition of
DCA led to a large decrease in fluorescence intensity, and in both
cases the fluorescence maximum was red-shifted 5 and 7 nm,
respectively. Furthermore, the fluorescence titrations of 3 with
1-adamantanol and taurocholate as guest molecules, respectively,
have been carried out, and the same distinguishable emission
spectra were obtained in the two situations (see Figures S2 and
S3, Supporting Information). This guest-responsive variation of
the fluorescence intensity allowed 3 to be used as an effective
fluorescent sensor for molecule discrimination.
fluorescent CDs 1ꢀ3 and two guests were calculated by using a
nonlinear least-squares curve-fitting method17 as shown in Table 1.
The order of binding constants of fluorescent CDs 1ꢀ3 with
ADA is 3 < 2 < 1, which reflects the order of steric hindrance
caused by the relative substitutions on the benzene ring in
aminobenzamide moiety. It indicates the strength of the isomeric
side chains being self-included by CD cavity of these modified
CDs is 3 > 2 > 1. Very large and almost equal KS values for 1ꢀ3
with DCA show that the combining capacity between DCA and CD
cavity are much larger than that of the self-included side chain.
In order to analyze the relationships between the conforma-
tion and fluorescent behavior of fluorescent CDs 1ꢀ3 in detail,
the fluorescent spectra of 5a, 5b, and 5c (the fluorophore moiety
of 1ꢀ3) at the same test conditions as that for 1ꢀ3 and as well in
different solvents were recorded for comparison (as shown in
Figure 7 and 8). It should be noted that the effect of the polarity
(the polarizability effects and hydrogen bonding ability) of
solvents on the fluorescent property of fluorophore moiety with
more than one functional group is not easy to predict.19 The
complicacy could be demonstrated by the spectra of 5a, 5b ,and
5c in different solvents (Figure8).
The stoichiometry of hostꢀguest complexes was determined
by the Job’s method of continuous variations (Supporting Informa-
tion). It was confirmed that compounds 1ꢀ3 all formed a 1:1
complex with the guest. On the basis of the stoichiometry and the
fluorescence titration data, the binding constants (KS) between
In Figure 7, the spectrum of 1 alone exhibits a weak fluorescent
peak at 428 nm, while an over one fold enhancement of emission
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Figure 6. Emission spectra of 10 μM 1ꢀ3 in the presence of various concentrations of guests in pH 7.5 tris-HCl buffer. Adamantane carboxylate sodium
(μM): (1) 0, 20, 40, 60, 79, 98, 116, 151, 186, 235; (2) 0, 20, 40, 60, 88, 116, 251, 327; (3) 10, 20, 40, 60, 79, 98, 134. Deoxycholate sodium (μM): (1) 0,
0.5, 2, 3.8, 5.6, 10, 14, 17; (2) 0, 0.5, 1.5, 3.8, 6.5, 11, 15; (3) 0, 1, 2, 3, 4, 4.7, 6.5, 8.2, 10, 14, 20. The excitation wavelength of 1ꢀ3 are 326, 315, and
292 nm, respectively.
is noticed for 1þADA and 1þDCA, respectively, the intensity is
nearly the same as that of 5a, besides the enhancement of
emission, an about 2 nm red shift of fluorescence maximum is
also observed in both situations. Combining above spectrum data
and the initial conformation of 1, it is clear that in the cases of
1þADA and 1þDCA, the butyl group, which is self-included in
the CD cavity of fluorescent 1, has been already expelled by guest
molecule leading whole fluorophore moiety in 1 exposed to bulk
aqueous solution, resulting a concomitant enhancement of
fluorescence emission. Namely, the fluorescence of 1 is quenched
when it keeps initial conformation, which is the reason for the
fluorescence enhancement respond to the guest molecules.
The fluorescence enhancement response is an unusual phe-
nomenon for fluorophore-modified CDs. This phenomenon is
often explained by a mechanism which was mentioned pre-
viously. However, this mechanism is not suitable for 1. According
to the initial conformation, the fluorophore of 1 should be partially
included by the upper rim of the CD cavity, and the exclusion of
the fluorophore from the relative hydrophobic environment to
bulk aqueous media should weaken its fluorescence intensity.
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Table 1. Binding Constants of 1ꢀ3 with Guests
KS (104 Mꢀ1
)
host
ADA
DCA
1
2
3
2.47 ( 0.03
1.49 ( 0.03
0.46 ( 0.06
11.67 ( 1.6
13.07 ( 1.9
12.03 ( 1.7
Figure 8. Fluorescent spectra of 5a, 5b, and 5c in different solvents.
hydrophobic and close environment avoiding the influence of
water molecule, which strongly increases the strength of IHB. On
the basis of the above deduction, we postulate that a possible
photoinduced proton transfer process via the IHB may be
responsible for the fluorescence quenching of 1. In the presence
of the guest molecule, the IHB, which has been exposed to bulk
aqueous solution, is broken due to the competition of water
molecules; thus, the photoinduced proton transfer was stopped,
so as to restore the emission of fluorescence. From the spectra of
5a in different solvents (In Figure 8), it is clear that the effect of
solvent polarity and hydrogen banding ability on the emission
intensity and fluorescence maximum of 5a is consistent with that
on the fluorescent behavior of 1. This comparison further
supports the above hypothesis. Moreover, Stalin and Mataga18
also confirm that 2-aminobenzoic acid exhibits much weaker
fluorescence intensity in nonpolar or hydrophobic solvents than
in polar solvents.
Figure 7. Fluorescent spectra of 10 μM 5a, 5b, and 5c compared with
the corresponding CD compounds in the absence and presence of the
guest molecules in pH 7.5 tris-HCl buffer.
It should be noted that only fluorescent CD 1 exhibits
significant fluorescence enhancement to the guest molecule
among these three position isomers. Therefore, the ortho sub-
stitution on the benzene ring in the fluorophore moiety of 1
should play an important role in the fluorescent behavior. It is
expected from this structure that the adjacent amino group and
carbonyl group on the benzene ring suitably form a six-member
intramolecular hydrogen bond (IHB).18 From the conformation
of 1, we can see that the butyl group is enfolded in the CD cavity
and the benzene ring is located on the upper rim of the cavity.
The special conformation makes the IHB stay in a relative
In the same way, we explore the relationship between the
conformation and fluorescent behavior of 2. From Figure 7, we
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Figure 9. NOESY spectra of 3þADA with water suppression in D2O
(mixing time = 600 ms).
can find that 2 alone exhibits a relative strong fluorescent
emission at 418 nm, while in the case of 2þADA and 2þDCA,
a large decrease of the fluorescence emission and about 18 nm
red shift has been noticed. The final intensity and florescence
maximum of both are nearly the same as those of 5b. This
comparison further confirms the phenyl-included conformation
of 2 and concludes that the decrease of the emission intensity in
the presence of guest should be attributed to the change of
polarity experienced by the fluorophore through the process of
being expelled from the cavity. The red shift of florescence
maximum in the case of 2 with the addition of the guest is much
larger than that of the ortho and para isomers. This property is in
accordance with the performance of 5b compared to 5a and 5c
with the increasing polarity (the polarizability effects and hydro-
gen bonding ability) from dichloromethane to water (Figure 8).
Different from 1 and 2, compound 3 has exhibited differ-
ent fluorescent respondses, respectively, toward two guests
(Figure 6). It is interesting to explore the origin of this difference.
In Figure 7, we find that 3 alone exhibits a strong fluorescent
emission at 357 nm, and the emission intensity is much stronger
than that of 5c. This comparison confirms that 3 also takes a
phenyl-included conformation. In the situation of 3þADA, a
slight increase of emission intensity and about 5 nm red shift of
florescence maximum are observed, however in the situation of
3þDCA, a large decrease in fluorescence intensity and a 7 nm red
shift of fluorescence maximum occur, and the final intensity and
florescence maximum are nearly the same as that of 5c. These
results suggest that the fluorophore moiety in the complex of
3þADA is located in a more hydrophobic environment than that
of 3 alone, while in the situation of 3þDCA, the environment
polarity around the fluorophore is similar to bulk aqueous media.
The 2D NOESY NMR experiments of 3 in the presence of the
two guests have been carried out, respectively, to obtain some
structural information. No correlation signal between the pro-
tons of CD and fluorophore moiety of 3 is found in Figures 9 and
10, respectively, which suggests that the fluorophore moiety in
both situations has been expelled from the CD cavity. The clear
correlation signals between all protons of ADA and H3, H5 of
CD in Figure 9 indicate the deep immersion of ADA into CD
cavity. Because the size and shape of ADA is almost exactly fit for
the cavity of β-CD, the hydrophobic main body of ADA should be
tightly accommodated by the cavity, with the charged carboxylic
Figure 10. NOESY spectra of 3þDCA with water suppression in D2O
(mixing time = 600 ms).
group exposed to the bulk aqueous solution at the wider opening
of the host CD.20 In the case of 3þDCA, the clear correlation
signals between H3, H5, H6 of CD and the protons of the DCA
main body can also be found in Figure 10. In comparison with
ADA, DCA is a larger molecule with an elongated shape, and it is
clear that there is no enough room for the whole hydrophobic
main body of DCA inside the CD cavity. The above correlation
signals should be the averages of the spectra of the species in
dynamic equilibrium, in which different parts of DCA could be
alternately bounded in the CD cavity. The correlation signal
between Hb of DCA and H6 of CD is also observed, which
indicates that the carboxyl group in DCA also faces to wider side
of CD cavity.
The ICD spectra of 3 in the presence of two guests have also
been measured, respectively (Figure 2), to determine the posi-
tion and orientation of the fluorophore moiety relative to the CD
cavity in both situations (3þADA and 3þDCA). Compared
with the ICD spectra of 3, a weaker positive band, at the same
position as the original, is observed, respectively, in both cases. It
can be assigned to the ICT πꢀπ* transition of the fluorophore
moiety outside CD cavity with perpendicular orientation. This
further confirms that the fluorophore moiety of 3 has been
expulsed from the CD cavity by guest molecule and suggests
that the fluorophore moiety of 3 in two complexes might cover
on the upper rim of CD.
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maximum of 3þADA could be attributed to the changes of the
microenvironment polarity around the fluorophore moiety. In
comparison, the large size and elongated shape of DCA leads the
complex of 3þDCA to adopt a guest partly included structure in
which the fluorophore moiety has been raised by DCA and
covers the top of the guest molecule. From the final intensity and
florescence maximum of 3þDCA, which are nearly the same as
those of 5c, it could be inferred that the gap between the
fluorophore moiety and the upper rim of CD should allow the
accommodation of water molecules. Therefore, the real polarity
experienced by the fluorophore moiety might be like the situa-
tion of the moiety entirely exposed in water, which might be the
reason for the dramatic quenching of fluorescence emission
by DCA.
’ CONCLUSIONS
Figure 11. Possible geometry structures of hostꢀguest complexes
3þADA and 3þDCA.
In summary, we have synthesized three isomeric fluorescent-
β-CDs bearing 2-, 3-, and 4-(2-aminoethyl)amino-N-butylben-
zamide, respectively (1, 2, and 3). By comparative study of their
structures, conformations, and fluorescence characteristics, it can
be deduced that the relative position of the substituted groups on
the benzene ring in the fluorophore moiety is the key factor in
yielding different conformations and fluorescence behaviors of
1ꢀ3. In the situation of 1, the two adjacent substituted groups on
benzene ring can offer not only the ability to form an intramo-
lecular hydrogen bond (IHB) but also the butyl-included con-
formation. The suitable location of benzene ring makes the
aminobenzoyl moiety of 1 form a strong IHB, therefore under-
going a photoinduced proton transfer via the IHB results in a
concomitant fluorescence quenching. Inclusion of the guest is
accompanied by an increase in the intensity of emission due to
changing the environment around the fluorophore from the
hydrophobic interior to the polar water environment.
In contrast, compound 2, in which the side chain has better
flexibility, takes a phenyl-included conformation as a fluorescent
CD bearing an intramolecular charge-transfer group and exhibits
a usual fluorescence behavior. The decrease in the intensity of
emission in the presence of guest should be attributed to the
change of polarity experienced by the fluorophore through the
process of being expelled from the cavity.
Compound 3 with a linear side chain has a phenyl-included
conformation similar to that of 2 and the strongest self-
inclusion ability among three isomers. The distinguishable
fluorescent response to two guests should be attributed to the
tiny difference between two guest-included conformations of
3. The differences in the size and shape of two guests (ADA or
DCA) let the fluorophore suffer from different changes in
environment, yielding an entirely different fluorescence re-
sponse. This guest-responsive variation of the fluorescence
intensity allows 3 to be used as effective fluorescent sensor for
molecule discrimination.
This investigation has demonstrated that the different
relative position and orientation of the fluorophore to the
CD cavity can be obtained by changing the molecular struc-
ture of fluorescent CDs. This approach allows us to go deep
into the relationship between conformation and spectroscopic
properties of fluorescent CDs and also to gather more
information about the microenvironment effect of the CD
cavity on fluorescence. This study provided some significant
information for sensing, monitoring, and elucidating various
processes in biological systems.
The most stable conformations of 3þADA and 3þDCA have
been obtained by molecular dynamics simulation of hostꢀguest
complexes in water and shown in Figure 11. They are consistent
with the experimental data we have obtained so far. As expected,
in the complex of 3þADA, the size and shape of ADA suitably
match the cavity of CD, and the fluorophore moiety closely
covers on the upper rim of CD. While in the complex between 3
and DCA, obviously, the hydrophobic main body of DCA has
penetrated the CD cavity thoroughly, and a small part of DCA is
out of the narrow side of the cavity. Thus, the fluorophore moiety
could not closely cover the CD cavity.
Combining the structures of two complexes with the results of
the fluorescence titrations of 3 with different guest molecules, it
could be inferred the interesting fluorescent phenomenon of 3,
respectively, toward to two guests do not be caused by the
interaction between the fluorophore moiety of host molecule and
the special functional groups in the guests (see Figures S2 and S3,
Supporting Information). All results let us realize that the
distinguishable fluorescent responds toward to two guests should
be attributed to the tiny difference between two guest-included
conformations of 3. On this basis, possible mechanisms have
been provided here to explain the specific fluorescent behavior of
3. In aqueous solution, 3 alone has adopted a self-included
conformation, and the fluorophore moiety is located in a relative
hydrophobic microenvironment. Upon the addition of ADA,
guestꢀhost association must be accompanied by release of
surface/cavity neighboring waters.6,9,21 The suitable size and
shape of ADA must lead to the tight combination of 3 and ADA.
The formed complex of 3þADA has a guest full-included
structure in which the fluorophore moiety could closely cover
the upper rim of CD.20 In this complex, the fluorophore moiety's
location is relatively complicated; the microenvironment below
the fluorophore moiety must become more hydrophobic because
of the deep immersion of the hydrophobic main body of ADA
and the accompanied release of surface/cavity neighboring
waters, but the upper side of the fluorophore moiety is exposed
in bulk aqueous solution. The effect on fluorescent property
should come from the changes of the microenvironment polarity.
Because of the anisotropy of the microenvironment, its effect on
fluorescent property should be much more complicated than that
in a homogeneous solvent system. Therefore, the slight increase
of emission intensity and about 5 nm red shift of florescence
4881
dx.doi.org/10.1021/jo2007829 |J. Org. Chem. 2011, 76, 4874–4883

The Journal of Organic Chemistry
ARTICLE
’ EXPERIMENTAL SECTION
Synthesis of 1ꢀ3. Mono-6-O-(p-tolylsulfonyl)-β-cyclodextrin (4.2
mmol), 5 (4.2 mmol), and Et3N (0.5 mL) were added to 10 mL of dry
DMF. The resulting solution was stirred at 80 °C under argon atmo-
sphere for 20 h and cooled to room temperature. Afterward, the solution
was added to 200 mL of acetone dropwise to form precipitates. The
precipitates were collected, washed with acetone followed by ether, and
dried in vacuum. The product was dissolved in water, and the solution
was layered on a column packed with YMC GEL ODS-A (2.5 ꢁ 10 cm,
pre-equilibrated with water). A step gradient elution was applied. The
fractions containing title compounds were combined, and EtOH was
removed under reduced pressure.
Mono-6-deoxy-6-(2-(2-aminoethyl)amino-N-butylbenzamide)-
β-CD (1). 20% yield based on 5a. MS (ESI): m/z 1352 (M). 1H NMR
(D2O): δH 0.96 (3H, t, J = 7.2), 1.34 (2H, m), 1.53 (2H, m), 2.67 (2H,
m), 2.84 (1H, m), 2.95 (1H, s), 2.98(1H, s), 3.2ꢀ3.9 (43H, m),
4.96ꢀ5.03 (7H, m), 6.76 (1H, t, J = 7.6), 6.92 (1H, d, J = 8.4), 7.22
(1H, d, J = 8), 7.38 (1H, t, J = 8). 13C NMR (DMSO-d6): δC 11.0, 16.9,
28.5, 39.2, 45.3, 57.0, 67.3, 70.2, 78.8, 80.2, 99.2, 108.5, 111.6, 112.9,
General Procedures. 1H NMR and 13C NMR spectra were
recorded on a 300 MHz NMR spectrometer, and 2D NOESY NMR
was carried out at room temperature on a 400 MHz instrument.
Chemical shifts were referenced to the solvent values, and J values are
reported in hertz. Fluorescence spectra were recorded in a conventional
quartz cell (10 mm ꢁ 10 mm ꢁ 45 mm) on an F-4500 spectro-
fluorometer. Absorption spectra were carried out on a UV 2550 spectro-
photometer. Circular dichroism (CD) spectra were recorded on a J810
spectropolarimeter. Elemental analyses were performed on an EL III
instrument.
Calculations. The calculations reported here utilized Gromacs 4.5.2
and Gaussian 09 programs.22 The optimizations of 1ꢀ3 utilized Grimme’s
B97D functional, which includes dispersion correction and Aldrich SVP
as basis set. Molecular dynamics simulation of hostꢀguest complexes in
water used Gromacs program with parameters as follows: opls-aa force
field, 1 fs time step, and running in the NVT ensemble for 20 ns.
Materials. DMF was dry by CaH2, and other regents were used as
reagent grade without further purification. 6-O-p-Toluenesulfonyl-β-cyclo-
dextrin was prepared according to reported methods.23 Tris(hydroxymethyl)-
aminomethane was dissolved in distilled, deionized water and adjusted
by HCl to make a 0.01 M pH 7.5 Tris-HCl buffer for fluorescence
spectral titration.
125.4, 129.5, 146.2, 166.4. Anal. Calcd for C55H89N3O35 8H2O: C,
3
44.14; H, 7.07; N, 2.81. Found: C, 44.29; H, 7.15; N, 2.99.
Mono-6-deoxy-6-(3-(2-aminoethyl)amino-N-butylbenzamide)-
β-CD (2). 17% yield based on 5b. MS (ESI): m/z 1352 (M). 1H NMR
(D2O): δH 0.96 (3H, t, J = 7.6), 1.39 (2H, m), 1.6 (2H, m), 2.71 (1H,
m), 2.77 (2H, m), 3.01 (1H, s), 3.05 (1H, s), 3.19 (2H, m), 3.37 (3H,
m), 3.53ꢀ3.92 (38H, m), 5.02ꢀ5.04 (7H, m), 6.87 (1H, d, J = 9.2), 6.99
(1H, s), 7.01 (1H, s), 7.26 (1H, t, J = 8). 13C NMR (DMSO-d6): δC 10.7,
16.6, 28.2, 39.7, 45.1, 45.8, 56.9, 69.0, 69.3, 70.0, 78.5, 80.1, 98.9, 107.5,
Synthesis of 4. The corresponding halogen-substituted benzoic acid
(20 mmol), 25 mL of thionyl chloride, and 1 drop of DMF reacted under
reflux until the solid disappeared. Excessive thionyl chloride was
removed by vacuum distillation. The residue was dissolved in 30 mL
of chloroform and added dropwise to a mixture of n-butylamine
(20 mmol) and triethylamine (60 mmol) in 50 mL of chloroform under
0 °C. The mixture was stirred for 4 h. Dilute hydrochloric acid (80 mL)
was added, the mixture shaken, and the organic layer was extracted with
water and saturated brines. The chloroform layer was dried with
anhydrous sodium sulfate and concentrated under vacuum.
2-Iodo-N-butylbenzamide (4a). 1H NMR (CDCl3): δH 0.99 (3H, t,
J = 7.2), 1.32ꢀ1.7 (m, 4H), 3.48 (2H, m), 5.84 (NH, s, br), 7.12 (1H,
m), 7.37 (2H, m), 7.88 (1H, d, J = 8.1).
111.3, 111.7, 125.6, 132.6, 145.8, 163.9. Anal. Calcd. for C55H89N3O35
3
5H2O: C, 45.80; H, 6.92; N, 2.91. Found: C, 45.65; H, 7.02; N, 2.79.
Mono-6-deoxy-6-(4-(2-aminoethyl)amino-N-butylbenzamide)-
β-CD (3). 27% yield based on 5c. MS (ESI): m/z 1352 (M). 1H NMR
(D2O): δH 0.86 (3H, t, J = 7.6), 1.31 (2H, m), 1.53 (2H, m), 2.5ꢀ2.8
(3H, m), 3.0 (1H, d), 3.1 (1H, m), 3.2ꢀ3.9 (43H, m), 4.8ꢀ5.0 (7H, m),
6.6 (2H, d, J = 8.8), 7.6 (2H, d, J = 8.4). 13C NMR (D2O/DMSO-d6): δC
11.6, 17.9, 29.3, 37.7, 58.4, 68.1, 70.3, 71.5, 79.0, 79.5, 82.0, 99.7, 100.3,
110.2, 119.6, 127.1, 149.9, 167.3. Anal. Calcd for C55H89N3O35 4H2O:
3
C, 46.38; H, 6.86; N, 2.95. Found: C, 46.45; H, 6.99; N, 2.90.
3-Iodo-N-butylbenzamide (4b). 1H NMR (CDCl3): δH 0.96 (3H, t,
J = 7.1), 1.3ꢀ1.66 (m, 4H), 3.45 (2H, m), 6.11 (NH, s, br), 7.16 (1H,
m), 7.11ꢀ7.22 (2H, m), 8.10 (1H, d, J = 8.1).
’ ASSOCIATED CONTENT
4-Bromo-N-butylbenzamide (4c). 1H NMR (CDCl3): δH 0.95 (3H,
t, J = 6.79), 1.39 (2H, m), 1.54 (2H, m), 3.31 (2H, m), 7.52 (2H, d, J =
8.8), 7.75 (2H, d, J = 7.6).
S
Supporting Information. Job’s method of continuous
b
variations, 2D NOESY NMR spectrum of 3 and ADA, copy of
1ꢀ3 NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
Synthesis of 5. A mixture of 4 (0.012 mol), anhydrous K2CO3 (0.024
mol), CuI (0.0006 mol), and 1,2-ethylenediamine (50 mL) was stirred
and heated to reflux under argon atmosphere for 24 h. After being cooled
to room temperature, the resulting solution was collected by filtration
and concentrated under reduced pressure. The residue was dissolved in
CHCl3 and purified by preparative thin layer plates (PLC). The PLC
developing solvent was CHCl3/CH3OH/Et3N = 50:5:1 by volume.
2-(2-Aminoethyl)amino-N-butylbenzamide (5a). MS (ESI): m/z
235 (M). 1H NMR (CDCl3): δH 0.95 (3H, t, J = 6), 1.40 (2H, m), 1.57
(2H, m), 2.95 (2H, t, J = 5.4), 3.22 (2H, t, J = 5.7), 3.38 (2H, t, J = 6.3),
6.22 (NH, s, br), 6.58 (1H, t, J = 7.2), 6.70 (1H, d, J = 8.1), 7.31 (2H, m),
7.63 (NH, s, br).
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: fueq@whu.edu.cn.
’ ACKNOWLEDGMENT
We gratefully acknowledge support from the Natural Science
Foundation of China (No. 20672085).
3-(2-Aminoethyl)amino-N-butylbenzamide (5b). MS (ESI): m/z
235 (M). 1H NMR (CDCl3): δH 0.94 (3H, t, J = 7.2), 1.37 (2H, m), 1.58
(2H, m), 2.94 (2H, t, J = 5.7), 3.21 (2H, s), 3.43 (2H, m), 4.30 (NH, s,
br), 6.29 (NH, s, br), 6.74 (1H, d, J = 6.9), 6.98 (1H,), 7.08 (1H, s), 7.18
(1H, t, J = 7.5).
4-(2-Aminoethyl)amino-N-butylbenzamide (5c). MS (ESI): m/z
236.2 (M þ 1). 1H NMR (CDCl3): δH 0.97 (3H, t, J = 7.2), 1.41 (2H,
m), 1.60 (2H, m), 2.99 (2H, s) 3.23 (2H, s), 3.44 (2H, m), 4.77 (NH, s,
br), 5.97 (NH, s, br) 6.62 (2H, d, J = 6), 7.63 (2H, d, J = 8.1).
’ REFERENCES
(1) (a) Trapp, O. Angew. Chem., Int. Ed. 2008, 47, 8158. (b) Feng, X.;
Liu, L.; Wang, S.; Zhu, D. B. Chem. Soc. Rev. 2010, 39, 2411. (c) Terai, T.;
Nagano, T. Curr. Opin. Chem. Biol. 2008, 12, 515.
(2) (a) Tang, B.; Cao, L.; Xu, K.; Zhuo, L.; Ge, J.; Li, Q.; Yu, L. Chem.
—Eur. J. 2008, 14, 3637. (b) Martínez-Tomꢀe, M. J.; Esquembre, R.;
Mallavia, R.; Mateo, C. R. J. Pharm. Biomed. Anal. 2010, 51, 484. (c) Han,
C.; Li, H. Anal. Bioanal. Chem. 2010, 397, 1437. (d) Chen, Y.; Liu, Y.
Chem. Soc. Rev. 2010, 39, 495.
4882
dx.doi.org/10.1021/jo2007829 |J. Org. Chem. 2011, 76, 4874–4883

The Journal of Organic Chemistry
ARTICLE
(3) (a) Ueno, A. Supramol. Sci. 1996, 3, 31. (b) Ogoshi, T.; Harada,
A. Sensors 2008, 8, 4961. (c) Cucinotta, V.; Contino, A.; Giuffrida,
A.; Maccarrone, G.; Messina, M. J. Chromatogr. A 2010, 1217, 953.
(d) Manakker, F.; Vermonden, T.; Nostrum, C. F.; Hennink, W. E.
Biomacromolecules 2009, 10, 3157. (e) Juvancz, Z.; Kendrovics, R. B.;
Ivꢀanyi, R.; Szente, L. Electrophoresis 2008, 29, 1701.
(4) (a) Patra, D. Biosens. Bioelectron. 2010, 25, 1149. (b) Suzuki, I.;
Ui, M.; Yamauchi, A. J. Am. Chem. Soc. 2006, 128, 4498. (c) Xu, M.; Wu,
S.; Zeng, F.; Yu, C. Langmuir 2010, 26, 4529. (d) Ludden, M. J. W.;
Li, X.; Greve, J.; Amerongen, A.; Escalante, M.; Subramaniam, V.;
Reinhoudt, D. N.; Huskens, J. J. Am. Chem. Soc. 2008, 130, 6964.
(5) (a) Ueno, A.; Ikeda, A.; Ikeda, H.; Ikeda, T.; Toda, F. J. Org.
Chem. 1999, 64, 382. (b) Ikeda, H.; Li, Q.; Ueno, A. Bioorg. Med. Chem.
Lett. 2006, 16, 5420. (c) Ikunaga, T.; Ikeda, H.; Ueno, A. Chem.—Eur. J.
1999, 5, 2698. (d) Ikeda, H.; Nakamura, M.; Ise, N.; Oguma, N.;
Nakamura, A.; Ikeda, T.; Toda, F.; Ueno, A. J. Am. Chem. Soc. 1996,
118, 10980. (e) Murayama, T.; Tanabe, T.; Ikeda, H.; Ueno, A. Bioorg.
Med. Chem. 2006, 14, 3691.
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.;
Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.;
Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich,
S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.;
Fox, D. J. Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford, CT,
2009.
(23) Brady, B.; Lynam, N.; O’Sullivan, T.; Ahern, C.; Darcy, R. Org.
Synth. 2000, 77, 220.
(6) (a) Ikeda, H.; Murayama, T.; Ueno, A. Org. Biomol. Chem. 2005,
3, 4262. (b) Ikeda, H.; Ueno, A. Chem. Commun. 2009, 4281.
(7) Zhong, C.; Mu, T.; Wang, L.; Fu, E.; Qin, J. Chem. Commun.
2009, 4091.
(8) Campos, I. B.; Brochsztain, S. J. Inclusion Phenom. Macrocycl.
Chem. 2002, 44, 207.
(9) Wang, H.; Cao, R.; Ke, C. F.; Liu, Y.; Wada, T.; Inoue, Y. J. Org.
Chem. 2005, 70, 8703.
(10) Nakashima, H.; Yoshida, N. Org. Lett. 2006, 8, 4997.
(11) Introduction to Fluorescence Sensing; Demchenko, A. P., Ed.;
Springer Science: New York, 2009.
(12) Molecular Fluorescence: Principles and Applications; Valeur, B.,
Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, 2001.
(13) (a) Saroja, G.; Soujanya, T.; Ramachandram, B.; Samanta, A.
J. Fluoresc. 1998, 8, 405. (b) Sahu, K.; Mondal, S. K.; Ghosh, S.;
Bhattacharyya, K. Bull. Chem. Soc. Jpn. 2007, 80, 1033.
(14) (a) Harata, K.; Uedaira, H. Bull. Chem. Soc. Jpn. 1975, 48, 375.
(b) Kodaka, M. J. Phys. Chem. 1991, 95, 2110. (c) Kodaka, M. J. Am.
Chem. Soc. 1993, 115, 3702. (d) Shimizu, H.; Kaito, A.; Hatano, M. Bull.
Chem. Soc. Jpn. 1979, 52, 2678. (e) Shimizu, H.; Kaito, A.; Hatano, M.
Bull. Chem. Soc. Jpn. 1981, 54, 513.
(15) (a) Zhao, Y. L.; Hu, L.; Gruner, G.; Stoddart, F. S. J. J. Am.
Chem. Soc. 2008, 130, 16996. (b) Fathalla, M.; Neuberger, A.; Li, S. C.;
Schmehl, R.; Diebold, U.; Jayawickramarajah, J. J. Am. Chem. Soc. 2010,
132, 9966. (c) Voskuhl, J.; Stuart, M. C.; Ravoo, B. J. Chem.—Eur. J.
2010, 16, 2790. (d) Wang, H.; Wang, S.; Su, H.; Chen, K. J.; Armijo,
A. L.; Lin, W. Y.; Wang, Y.; Sun, J.; Kamei, K.; Czernin, J.; Radu, C. G.;
Tseng, H. R. Angew. Chem., Int. Ed. 2009, 48, 4344.
(16) (a) Ollila, F.; Pentik€ainen, O. T.; Forss, S.; Johnson, M. S.;
Slotte, J. P. Langmuir 2001, 17, 7107. (b) Liu, Y.; Yang, Y. W.; Cao, R.;
Song, S. H.; Zhang, H. Y.; Wang, L. H. J. Phys. Chem. B 2003, 107, 14130.
(c) Liu, Y.; Shi, J.; Guo, D. S. J. Org. Chem. 2007, 72, 8227. (d) Liu, Y.;
Song, Y.; Chen, Y.; Li, X. Q.; Ding, F.; Zhong, R. Q. Chem.—Eur. J. 2004,
10, 3685.
(17) Principles and Methods in Supramolecular Chemistry; Schneider,
H. J., Yatsimirsky, A., Eds.; John Wiley & Sons: Chichester, 2000.
(18) (a) Mataga, N. Bull. Chem. Soc. Jpn. 1963, 36, 654. (b) Stalin, T.;
Rajendiran, N. J. Photochem. Photobiol., A 2006, 182, 137.
(19) Principles of Fluorescence Spectroscopy; Lakowicz, J. R., Ed.;
Springer Science: Baltimore, 2006.
(20) (a) Harries, D.; Rau, D. C.; Adrian Parsegian, V. J. Am. Chem.
Soc. 2005, 127, 2184. (b) Goto, H.; Furusho, Y.; Yashima, E. J. Am. Chem.
Soc. 2007, 129, 109. (c) Rudiger, V.; Eliseev, A.; Simova, S.; Schneider,
H. J.; Blandamer, M. J.; Cullis, P. M.; Meyer, A. J. J. Ghem. Soc., Perkin
Trans. 2 1996, 2119. (d) May, B. L.; Clements, P.; Tsanaktsidis, J.;
Easton, C. J.; Lincoln, S. F. J. Chem. Soc., Perkin Trans. 1 2000, 463.
(21) (a) Engeldinger, E.; Armspach, D.; Matt, D. Chem. Rev. 2003,
103, 4147. (b) Szejtli, J. Chem. Rev. 1998, 98, 1743.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
4883
dx.doi.org/10.1021/jo2007829 |J. Org. Chem. 2011, 76, 4874–4883