Fluorescent behaviour in host-guest interactions. Part 2: Thermal and pH-dependent sensing properties of two geometric isomers of fluorescent amino-β-cyclodextrin derivatives

Article abstract of DOI:10.1039/b105875b

The fluorescent behaviour in aqueous solution of two types of amino-β-cyclodextrin (amino-β-CDx) isomers 1 and 2 bearing the naphthoamide group at the 1- and 2-position as a fluorescent-sensing unit was investigated using mainly fluorescence spectroscopy. The isomers 1 and 2 show both strong temperature- and pH-responsive photophysical properties in aqueous solution. The protonation of the amino groups of 1 and 2 in acidic media affects efficiently their fluorescence intensities. The equilibrium and thermodynamic quantities of the two-state equilibrium model for 1 and 2 have been determined spectrophotometrically. Solution NMR behaviour in a DMSO-D₂O mixed solvent confirms the stereospecific relationship between the appended naphthalene fluorophore and the hydrophobic cavity of CDx. Restricted and/or flexible motion of the naphthalene moiety of 1 and 2 about the bond between the amide group and the amino group at the C-6 carbon atom in the CDx ring is evident from the NMR studies. The potential application of 1 to anion sensing is also discussed.

Full text of DOI:10.1039/b105875b

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Fluorescent behaviour in host–guest interactions. Part 2.† Thermal
and pH-dependent sensing properties of two geometric isomers of
fluorescent amino-ꢀ-cyclodextrin derivatives
2
Hironori Nakashima,a Yasushi Takenaka,a Miwako Higashib and Noboru Yoshida*a
a Laboratory of Molecular Functional Chemistry, Division of Material Science,
Graduate School of Environmental Earth Science, Hokkaido University,
Sapporo 060-0810, Japan
b Center for Cooperative Research and Development, Ibaraki University, Hitachi 316-8511,
Japan
Received (in Cambridge, UK) 3rd July 2001, Accepted 15th August 2001
First published as an Advance Article on the web 16th October 2001
The fluorescent behaviour in aqueous solution of two types of amino-β-cyclodextrin (amino-β-CDx) isomers 1 and 2
bearing the naphthoamide group at the 1- and 2-position as a fluorescent-sensing unit was investigated using mainly
fluorescence spectroscopy. The isomers 1 and 2 show both strong temperature- and pH-responsive photophysical
properties in aqueous solution. The protonation of the amino groups of 1 and 2 in acidic media affects efficiently
their fluorescence intensities. The equilibrium and thermodynamic quantities of the two-state equilibrium model for
1 and 2 have been determined spectrophotometrically. Solution NMR behaviour in a DMSO–D2O mixed solvent
confirms the stereospecific relationship between the appended naphthalene fluorophore and the hydrophobic cavity
of CDx. Restricted and/or flexible motion of the naphthalene moiety of 1 and 2 about the bond between the amide
group and the amino group at the C-6 carbon atom in the CDx ring is evident from the NMR studies. The potential
application of 1 to anion sensing is also discussed.
Introduction
Molecular manufacturing is linked to many areas of science
and technology.1 In particular, research in molecular machinery
requires a design perspective because it aims to describe work-
able systems such as the molecular shuttle.2 Recent use of
cyclodextrins as building blocks for the construction of
supramolecular species3,4 such as rotaxanes, dendrimers and
lipophilic chiral sensors5 in solution is emerging as a new con-
temporary field in CDx chemistry.
To date we have focussed our attention on the molecular
recognition phenomena of several anionic azo compounds by
α-cyclodextrin as these systems provide a suitable dynamic
model for enzyme–substrate binding processes in aqueous
solution.6–14 Also, weak interactions such as electrostatic
forces have been found to be effective in the selectivity and
enhancement of binding properties in amino-β-cyclodextrin
systems15–19 such as 3,16 4,16 518 and 6.18 In particular, for 5,
a one-dimensional supramolecular array with a helically
extended polymeric structure has been found to form in the
solid state by repetition of intermolecular inclusion.18
Fluorescent artificial cyclodextrins have received consider-
able attention in sensory,20 biochemical21 and photoelectronic22
applications. The CDx cavity offering a binding site and a
fluorophore acting as a signaling unit with a linkage group are
indispensable for substrate specific-responsive functions. Iso-
Experimental
Materials and synthesis
mers 1 and 2 are found to possess a wide range of features that
render them attractive as potential sensors for temperature, pH
and anions.
Here, we describe the novel temperature and pH sensing
ability of 1 and 2. The thermodynamic quantities of these pro-
cesses and their potential application to anion sensing are also
reported.
Analytical grade β-cyclodextrin (Wako Pure Chemical Ind.
Ltd.) was used without further purification. Monotosylated
β-CDxots at the O-6 position of the -glucopyranosyl rings of
β-CDx was synthesized by the reaction of β-CDx with toluene-
p-sulfonyl chloride in pyridine at room temperature for
1.5 h (Scheme 1).16 The β-CDxots thus obtained was dissolved
in excess diethylenetriamine bis(2-aminoethyl)amine (Tokyo
Kasei) and the solution was heated at 70 ЊC for 3 h with stirring.
† For Part 1 see ref. 16(b).
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J. Chem. Soc., Perkin Trans. 2, 2001, 2096–2103
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b105875b

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Scheme 1 Synthesis of 1 and 2. Reagents and conditions: (a) p-TsCl, pyridine, room temp, 1.5h; (b) diethylenetriamine, 70 ЊC, 3 h; (c) cation
exchange column chromatography; (d) 1-naphthoic acid, DCC, HOSu, DMF, 0 ЊC, 1 h, and then room temp; (e) 2-naphthoic acid, DCC, HOSu,
DMF, 0 ЊC, 1 h, and then room temp; (f ) cation-exchange column chromatography.
The reaction mixture was poured into a large amount of
acetone and the resultant white precipitate was collected and
dried in vacuo. Purification of mono[6-N-(5-amino-3-aza-
pentyl)amino-6-deoxy]-β-cyclodextrin (β-CDxdien) as a pre-
cursor of the functionallized β-CDx derivatives was carried out
by ion-exchange column chromatography through a cation-
exchange resin (Toyopearl 650 M; 0.05 mol dmϪ3 NH4HCO3
aqueous solution as eluent). The purified β-CDxdien was then
coupled with 1- and 2-naphthoic acid by the usual 1,3-dicyclo-
hexylcarbodiimide (DCC) method and precipitation with acet-
one and cation-exchange chromatography gave 1 (yield, 48%
based on β-CDxdien) and 2 (yield, 10% based on β-CDxdien),
respectively (Scheme 1). The elemental analysis of 1 and 2 was
satisfactory, although solvent water molecules were usually
bound [Found for 1: C, 46.23; H, 6.56; N, 2.71. Calc. for
C57H87N3O35ؒ6H2O: C, 46.18; H, 6.73; N, 2.83%. Found for 2:
C, 47.87; H, 6.44; N, 3.18. Calc. for C57H87N3O35ؒ3H2O: C,
47.93; H, 6.56; N, 2.94%].
45.99–50.10 (methylene spacer and C-6 carrying NH), 60.72–
66.64 (C-6 (CDx ring)), 70.95–74.20 (C-2, C-3, C-5), 81.81–
84.86 (C-4), 102.64–103.35 (C-1), 122.12–134.89 (naphthalene
moiety) and 168.67 (carbonyl). Mass spectral data also coincide
with the structural formula [MS(FAB, m-nitrobenzyl alcohol
(m-NBA) as matrix) m/z 1374 (MHϩ) for 1 and 1374 (MHϩ),
1396 (M ϩ Na)ϩ, and 1413 (M ϩ K)ϩ for 2.
Measurement of physical quantities
Equilibrium constants (K) for the temperature-dependent pro-
cess of 1 and 2 were determined by fluorescence spectroscopy
using a Shimadzu RF-5000 recording fluorescence spectro-
meter. The pH values in solution were obtained using a Horiba
pH meter B-112. Below pH 5.5, HCl–HEPES (N-(2-hydroxy-
ethyl)piperazine-NЈ-ethanesulfonic acid) at low concentration
(<0.01 mol dmϪ3) was used and above this pH, HEPES and
NaOH were used. The temperature of the solution was con-
trolled by means of an external circulating water bath (Thomas
Kagaku Co. Ltd., TRL-108H). Relative fluorescence intensities
were measured at a constant wavelength around the emission
maximum. The NMR spectra of 1 and 2 were obtained at vari-
ous temperatures with a JEOL EX400 FTNMR spectrometer.
The CD spectra were measured using a JASCO J-600C circular
dichrometer. In order to obtain an adequate signal-to-noise
ratio, we used a computer for multiple scanning and averaging.
Each memory unit in the computer stored the CD signal for a
spectral band of 0.2 nm.
The 1H NMR spectrum (external TMS, JEOL 400 MHz
NMR spectrometer) of 1 shows characteristic peaks of the α-
protons to the amino nitrogen at δ 2.6–3.0 in D2O (pD 10): 1, δH
2.6–3.0 (8H, N-CH2), 3.3–3.6 (14H, 2-H and 4-H), 4.8–5.1 (7H,
1-H), and 3.5–4.0 (28H, 3-H, 5-H and 6-H) for the β-CDx ring
protons and 7.5–8.3 (7H, aromatic protons). It is noteworthy
that the C1-H protons of the -glucopyranosyl moiety of the β-
CDx ring of 1 shows seven different resonances. 13C NMR
(D2O) for 1: δC 39.83 (α-carbon to NHCO), 47.50–48.68
(methylene spacer and C-6 carrying NH), 60.33–60.60 (C-6
(CDx ring)), 70.85–73.80 (C-2, C-3, C-5), 81.36–84.09 (C-4),
102.22–102.56 (C-1), 125.27–133.88 (naphthalene moiety) and
172.84 (carbonyl). The 1H NMR spectrum of 2 is also identical
to that of 1 except for the spectral pattern in the aromatic
region. 13C NMR (D2O) for 2: δC 39.23 (α-carbon to NHCO),
Results and discussion
Temperature-responsive fluorescence spectra of 1 and 2
The effect of temperature on the fluorescence spectrum of 1 is
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shown in Fig. 1. A progressive decrease in temperature results in
quite an enhancement in emission intensity. Fig. 2 shows the
fluorescence intensity (IF) vs. temperature plot for 1 at the emis-
sion maximum wavelength (λem(max)), which has a hyperbola
profile with an inflection point at ca. 35 ЊC. Fluorescent amino-
β-cyclodextrin derivative 2 bearing an amide-linkage at the 2-
position of the naphthalene ring also exhibits a similar IF–T
profile as shown in Fig. 2 and an inflection point at ca. 50 ЊC,
but its fluorescent intensity is much greater than that of 1 even
at the 3.0 nm bandwidth used for both emission and excitation.
In order to clarify the strong temperature-dependent fluor-
escence spectra of 1 and 2, we measured their 1H NMR spectra
at various temperatures (30, 40 and 60 ЊC). Fig. 3 shows the
(H-1) of the native β-CDx exhibit only one degenerated reson-
ance, those of the derivative 1 showed six separated resonances.
Mono modification at the C-6 position of β-CDx causes the
seven -glucopyranosyl rings to have a magnetically inequiv-
alent environment.23 Therefore, the slight change in the spectral
pattern in Fig. 3 for the anomeric protons at the higher
temperature suggest a subtle change in the motion of each
-glucopyranosyl ring of 1. However, the relationship between
the self-inclusion (inside–outside isomerisation equilibrium)
of the naphthalene unit of 1 into the CDx cavity and the
temperature-dependent fluorescence spectra for 1 is not clear.
1
temperature-dependent H NMR spectra of the naphthalene
and CDx ring moieties of 1. The protons in the naphthalene
moiety show a small shift. Although the anomeric protons
Fig. 1 Temperature-dependent fluorescence spectrum of 1. [1] = 1.25 ×
10Ϫ5 mol dmϪ3 and pH = 7.0. 10 (1), 20 (2), 30 (3), 40 (4), 50 (5), 60 (6),
70 (7) and 80 ЊC (8). The excitation (λex = 295 nm) and emission
bandwidth were both set at 5.0 nm.
Fig. 2 Plots of fluorescence intensity at λem(max) vs. temperature (ЊC)
for 1 and 2 at pH = 7. [1] = [2] = 1.25 × 10Ϫ5 mol dmϪ3. The excitation
and emission bandwidth for 2 were both set at 3.0 nm.
Fig. 3 1H NMR spectra of 1 at various temperatures in D2O (ext. ref TMS). The aromatic region (a) and C1-H protons of the CDx ring (b) for 1
are shown. Numberings refer to those in Scheme 1. [1] = 7.28 × 10Ϫ3 mol dmϪ3
.
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ring of 2 are also appreciably affected (Fig. 5(b)); each of the
peaks shift downfield and converge to some extent.
Fig. 6 shows the plot of chemical shifts vs. temperature. The
protons H-1, H-3, and H-4 at the periphery of the amide link-
age show only a little shift, while the protons H-5, H-6, H-7 and
H-8 show a large shift as mentioned above.
Stereospecific intramolecular and/or intermolecular inclu-
sion takes place efficiently in 2 judging from the temperature
1
dependence of the H NMR spectrum. Perhaps, the difference
in the linkage between the naphthalene unit and the amide
group at the 1- or 2-position could determine whether such
an inclusion process occurs. The suitable linkage position
(2-isomer) for 2 led smoothly to the inclusion of the naph-
thalene unit into its CDx cavity. On the other hand, the amide
group at the 1-position of 1 may result in a much shallower
self-inclusion due to steric hindrance between the naphthalene
moiety and the CDx cavity.
Fig. 4 Induced circular dichroism spectra of 1 at 10 (a), 25 (b), 40 (c),
60 (d) and 80 (e) ЊC. [1] = 1.25 × 10Ϫ5 mol dmϪ3
.
Fig. 4 shows the induced circular dichroism (ICD) spectrum
of 1 at various temperatures. The ICD spectral change provides
precise structural information such as the orientation of
the chromophore in the CDx cavity.24 If the polarization of
the π–π* transition of the chromophore is almost parallel to the
symmetry axis of CDx, the relatively strong positive ICD sign
should be observed. The ICD sign at lower temperatures of 1
shows a larger positive value and its intensity gradually
decreases upon increasing the temperature in solution. These
ICD data suggest that the long-axis polarized π–π* transition
of the chromophore is inclined against the CDx axis upon
increasing the temperature, as shown in Scheme 2. This subtle
It is noteworthy that the intermolecular inclusion process
shown in Scheme 3 may be formed in the concentrated solution
Scheme 3
(10Ϫ3 mol dmϪ3 under NMR conditions) and in the solid state.
For example, type (c) complex has been found in the case of
host 5 by X-ray crystallographic analysis.18 Takahashi and
Hattori also suggested this type of complex to occur in mono-
1
substituted cyclodextrins based on their H NMR analysis.25
Furthermore, the existence of type (a)26 and type (b)27 has
been also pointed out by some authors. Since the H NMR
Scheme 2
1
of 2 is found to be concentration-dependent, the strongly
temperature-dependent 1H NMR spectrum of 2 shown in Fig. 5
is due to one of the intermolecular inclusion processes shown in
1
conformational change may not be detected by the H NMR
spectrophotometric method. Furthermore, the concentration
dependence (5.00 × 10Ϫ6, 2.50 × 10Ϫ5, 5.00 × 10Ϫ5, 2.50 × 10Ϫ4
mol dmϪ3) of the ICD of 1 was not observed.
1
Scheme 3. On the other hand, the H NMR of 1 is almost
concentration-independent. Furthermore, self-inclusion of the
naphthalene probe of 2 may occur in dilute aqueous solution
(10Ϫ5 mol dmϪ3) judging by its smaller ICD spectral change at
various temperatures.
Strongly temperature-dependent 1H NMR spectrum of 2
1
By contrast, the H NMR spectra of 2 were strongly temper-
ature dependent as exemplified by its behaviour in D2O
(Fig. 5(a)). The most noticeable upfield shift upon decreasing
the temperature was observed for the H-5, H-6, H-7 and H-8
naphthalene protons far from the amide linkage. Such an
upfield shift in the NMR signal suggests that a regiospecific
inclusion complexation between these protons and the CDx
cavity may be involved.16 The aromatic region of the 1H NMR
spectrum of 2 at 70 ЊC is almost similar to that of reference
compound 7 in D2O, indicating that the naphthalene fluoro-
phore is situated outside the CDx cavity. Furthermore, the
spectral pattern due to the anomeric H-1 protons of the CDx
Energetic preferences for the inclusion process for 1 and 2
The temperature-dependent fluorescence change could be
analysed thermodynamically by
a two-state equilibrium
model.28 The equilibrium constant K for the equilibrium
between 1 and 2 in eqn. (1) can be expressed by eqn. (2), where
If, lower temp., If, higher temp. and If, obs denote the fluorescence inten-
sity at λem for the lower-temperature and higher-temperature
species and the observed experimental fluorescence intensity in
Fig. 1, respectively. The temperature dependence of the equi-
librium constant K is given by eqn. (3), where R and T are the
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Fig. 5 1H NMR spectra of 2 at various temperatures in D2O (ext. ref. TMS). Aromatic region (a) and C1-H protons of CDx ring (b) for 2 are
shown. [1] = 7.28 × 10Ϫ3 mol dmϪ3
.
Fig. 7 Plot of ln K vs. T Ϫ1 for the inside–outside isomerisation of the
appended naphthalene of 1.
Fig. 6 Plots of the chemical shift [δ(ppm)] of appended naphthalene
protons for 2 vs. temperature in aqueous solution.
(2)
(3)
gas constant and absolute temperature, respectively. The least-
squares fit for eqn. (3) has been carried out using the postulated
values of If, lower temp. and If, higher temp until a good linear relation-
ship in the ln K vs. T Ϫ1 plot could be obtained. An optimised
linear plot of ln K for 1 against T Ϫ1 could be obtained as shown
in Fig. 7 on the assumption that If, lower temp and If, higher temp are
equal to 400 at Ϫ10 ЊC and 5 at 100 ЊC, respectively.
The values of ∆HЊ and ∆SЊ were calculated from the slope
and intercept through the van’t Hoff plot in Fig. 7. A series of
similar procedures were also carried out for derivative 2.
(1)
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Table 1 Thermodynamic parameters for the inside–outside isomerization of 1 and 2 at 20 ЊC in aqueous solution
K (20 ЊC)
∆HЊ/kcal molϪ1
∆SЊ/cal KϪ1 molϪ1
∆GЊ/kcal molϪ1
1
2
1.27
0.92
7.13
5.48
24.7
18.5
Ϫ0.14
0.06
Table 2 Change in the chemical shift (δ (ppm)) of the naphthalene protons of 1 in the absence and presence of NaClO4 at 30 and 70 ЊC in D2O
H-2
H-3
H-4
H-5
H-6
H-7
H-8
a
δa b
7.966
7.980
0.014
7.996
0.016
7.571
7.580
0.009
7.602
0.022
7.896
7.922
0.026
7.940
0.018
7.676
7.663
0.013
7.669
0.006
7.541
7.610
8.136
δb
7.527
Ϫ0.014
7.548
7.598
Ϫ0.012
7.621
8.036
Ϫ0.050
8.130
∆δ = δb Ϫ δa
c
δc
∆δ = δc Ϫ δb
0.021
0.023
0.017
a At 30 ЊC and [NaClO4] = 0 mol dmϪ3
.
b At 30 ЊC and [NaClO4] = 2 mol dmϪ3
.
c At 70 ЊC and [NaClO4] = 2 mol dmϪ3
.
Thermodynamic parameters for the two-state equilibria of 1
and 2 are given in Table 1.
In general, cyclodextrin inclusion for various guests is
enthalpically driven (∆HЊincl < 0) and the standard entropy
change is either negative or positive.6,9,12,28 Therefore, the
positive ∆HЊ values (Ϫ∆HЊincl) in our case indicate that the
exclusion of the naphthalene unit from the CDx cavity is endo-
thermic for both 1 and 2. The more positive value of ∆HЊ for 1
suggests restrictive motional freedom of the naphthalene ring
when the amide linkage is at the 1-position. In all cases the
inclusion is enthalpically favoured (∆HЊincl < 0) but entropically
unfavoured (∆SЊincl < 0). It is noteworthy that the comparative
contribution of ∆SЊ to the Gibbs energy term ∆GЊ shows a
positive value which results from two different contributions:10
the changes in (i) randomness and (ii) solvation which are
associated with the two-state inclusion model.
Effect of anions
Upon addition of several inorganic salts, the considerable
fluorescence quenching and/or large enhancement in intensity
were observed only in the 1–anion system. Addition of ClϪ and
2Ϫ
SO4 anions has little effect on the fluorescence intensity (If)
of 1. On the other hand, BrϪ, IϪ, and SCNϪ quench the fluor-
escence intensity appreciably. Interestingly, the addition of a
Ϫ
Ϫ
bulky hydrophobic anion such as ClO4 and PF6 results in a
large enhancement in If. This unexpected enhancement in If is
not observed in 2. It is well known that ClO4Ϫ and PF6Ϫ can be
included into the β-CDx cavity,30 so perhaps, derivative 1 would
have enough space in its cavity to accommodate such anions.
Table 2 shows the change in the chemical shift of the naph-
thalene protons of 1 in the presence of NaClO4. The upfield
shift (∆δ = δb Ϫ δa) of H-6, H-7 and H-8 indicates the shallower
induced-inclusion into the β-CDx cavity upon addition of the
anions (Scheme 4). This upfield shift is reduced (∆δ = δc Ϫ δb >
Fig.
8
Temperature-dependence of the fluorescence intensity at
λem(max) for 1 at various NaClO4 concentrations at pH = 6.8. [1] = 1.25
× 10Ϫ5 mol dmϪ3. [ClO4Ϫ] = 0 (a), 0.01 (b), 0.1 (c), 0.5 (d), 2 (e) mol
dmϪ3
.
predominant. The application of derivative 1 to anion sensing
is now in progress in our laboratories.
pH dependent fluorescence of 1 and 2
Fluorescent amino-β-cyclodextrin isomers 1 and 2 have two
amine sites that may be protonated. The protolytic equilibrium
of the amine site linked to the fluorophore may enhance and/or
quench the fluorescence of 1 and 2 owing to the chelation-
enhanced fluorescence31 or photo-induced electron-transfer
(PET) mechanism.32 Fig. 9 shows the pH dependence of the
fluorescence intensity (If) at λem(max) of 1 and 2. The drastic
decrease in If of 1 upon increasing the pH from 3 to 6 could be
ϩ
ascribed to the deprotonation of the ϪNH2 proton as shown
Scheme 4
in Scheme 5. At pH 8.5, which is closely related to the second
protolytic equilibrium in Scheme 5, a much smaller decrease in
If of 1 is observed. At pH >10, the amine sites of 1 are almost
completely deprotonated and its fluorescence is consequently
very low.
Since the naphthalene unit of 2 is deeply included within the
CDx cavity compared with that of 1, moderate quenching
due to the first protolytic equilibrium at pH 3–6 is observed.
0) upon increasing the temperature to 70 ЊC. Fig. 8 shows the
temperature dependence of If for 1 on the concentration of
NaClO4. At lower temperatures, the magnitude of the fluor-
escence enhancement in the presence of NaClO4 is particularly
large. The effect of ClO4Ϫ anions on the two-state inclusion of 1
Ϫ
is summarized in Table 3. At higher ClO4 concentrations
(>0.01 mol dmϪ3), the higher-temperature species seems to be
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Table 3 Thermodynamic parameters for the inside–outside isomerization of 1 in the presence of NaClO4 at 20 ЊC in aqueous solution
[NaClO4]/M
K (20 ЊC)
∆HЊ/kcal molϪ1
∆SЊ/cal KϪ1 molϪ1
∆GЊ/kcal molϪ1
0
1.27
1.16
1.21
1.50
4.60
7.13
9.11
9.45
11.2
9.40
24.7
31.3
32.5
39.0
34.8
Ϫ0.14
Ϫ0.09
Ϫ0.11
Ϫ0.24
Ϫ0.89
0.01
0.10
0.50
2.00
Scheme 5
Fig. 10 1H NMR spectra of 2 at various temperatures in 10% (v/v)
DMSO–D2O mixed solvent systems (ext. ref. TMS) at 30 (a), 40 (b),
60 (c) and 70 (d) ЊC.
for the two-state inclusion of the appended naphthalene unit.
Furthermore, this type of inclusion process may be controlled
by the presence of an organic solvent such as DMSO. In fact,
the two-state inclusion of 2 is fully shifted to the higher-
temperature species in pure DMSO even at lower temperatures.
This inclusion process is appreciably retarded by addition of
10% (v/v) DMSO into an aqueous solution of 2 as shown in
Fig. 10 and is completely blocked in 50% (v/v) DMSO–water
media.
Fig. 11 shows the temperature dependence of the chemical
shift of the most shifted H-7 proton in the naphthalene moiety
at various DMSO content. At lower concentrations of DMSO,
the competitive interaction between the bulk solvent and the
naphthalene moiety of 2 and/or the inclusion of a DMSO
molecule leading to the formation of higher-temperature
species takes place. Although the unfavourable entropic
contribution (∆SЊincl < 0) to the Gibbs free energy term is very
large, classical hydrophobic interactions (∆SЊhydrophobic > 0,
∆HЊhydrophobic > 0 and ∆GЊhydrophobic < 0), where the water is the
driving force for complexation, may be less important in the
inclusion process for 2.
Fig. 9 Effect of pH on the fluorescence intensity at λem(max) for 1 and
2 at 25 ЊC. The excitation and emission bandwidth for 1 and 2 were both
set at 5.0 and 3.0 nm, respectively. [1] = [2] = 1.25 × 10Ϫ5 mol dmϪ3
.
However, the change in If for 2 at pH ca. 8–10 is greater than
that for 1. Therefore, the pH-responsive fluorescence of 1 and 2
is controlled by two factors; the protolytic equilibria of the
amine protons and to a lesser extent the pH-dependent two-
state inclusion process of the naphthalene unit. 1H NMR
analysis at various pD values supports a reasonable correlation
between the protonation–deprotonation equilibrium at the
amine site and the inside–outside isomerisation of the naphthal-
ene fluorophore.
Solvent-dependent 1H NMR spectrum of 2
The driving force for inclusion of a guest into the CDx cavity is
not yet clear to date,9,10 but water inclusion in the CDx cavity
and the hydrated structure around the guest molecule are
crucial influencing factors in a number of host–guest systems
in aqueous solution. Therefore, the inclusion process by CDx
should cause a significant change both in the solvation and
conformation of the naphthalene moiety and the CDx ring.
The 1H NMR analysis of 2 at various temperatures revealed
that the derivative 2 behaves most excellently as a NMR probe
Conclusion
In this paper we have shown that the photophysical properties
of two fluorescent amino-β-cyclodextrin isomers, 1 and 2, bear-
ing a naphthalene moiety linked via an amide bond to the CDx
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ring, are greatly influenced by subtle conformational, steric and
electronic differences. Quite excellent temperature and pH
responses of the fluorescence of 1 and 2 in aqueous solution
can be explained by a two-state inclusion model and proton-
ation of the amino nitrogen group. The fluorescence of deriv-
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1
but its H NMR signal is silent. By contrast, derivative 2 is
found to be a good temperature probe by both fluorescence and
1H NMR spectroscopy. It is likely that the conformational
mobility of the naphthalene unit for 2 gives a more size-
compatible fit in the CDx cavity. Furthermore, derivative 1 also
has the possibility of acting as an anion sensor, particularly
Ϫ
toward a hydrophobic anion such as ClO4 and PF6Ϫ. The
1
temperature–dependent H NMR could be controlled by the
presence of an organic solvent such as DMSO. Thus, the
regiospecific separation between the fluorophore and the CDx
ring using the amide–amine linkage renders 1 and 2 more
attractive as a fluorescence sensor.
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