Tuning the emission of a water-soluble 3-hydroxyflavone derivative by host-guest complexation

Article abstract of DOI:10.1039/c8sm00349a

3-Hydroxyflavone derivatives have great potential as fluorescent probes for bio-labeling in aqueous medium. They were extensively studied in various organic solvents for the "excited state intramolecular proton transfer" process, but seldom addressed in aqueous solution due to the poor water solubility. Herein, an amphiphilic molecule bearing 3-hydroxyflavone and oligo(ethylene oxide) (denoted as 3HF-EO) was designed and synthesized. Different from the fluorescence in organic solvents, 3HF-EO in aqueous solution showed a remarkable single fluorescence emission, which is ascribed to the fluorescence of its anionic species. We found that the fluorescence intensity could be efficiently tuned via host-guest complexation. α-CD has little effect on the emission, while β-CD and γ-CD lead to enhanced and reduced emissions of 3HF-EO, respectively. The ¹H NMR and 2D NOESY NMR spectra indicate that α-CD barely had any interaction with 3HF-EO, while β-CD and γ-CD formed complexes with one and two 3HF-EO molecules, respectively. These results provide a sound explanation for the modulated fluorescence intensity.

Full text of DOI:10.1039/c8sm00349a

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PAPER
Jure Dobnikar et al.
Rational design of molecularly imprinted polymers
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Tuning the emission of a water-soluble 3-hydroxyflavone
derivative by host-guest complexation
Received 00th January 20xx,
Accepted 00th January 20xx
Dahua Li, Yuzhi Xing, Lan Ding, Chengfeng Wu, Guangliang Hou and Bo Song*
DOI: 10.1039/x0xx00000x
3-Hydroxyflavone derivatives have great potential as fluorescence probes for bio-labeling in aqueous medium. They were
extensively studied in various organic solvents on the “excited state intramolecular proton transfer” process, but seldom
addressed in aqueous solution due to the poor water solubility. Herein, an amphiphilic molecule bearing 3-hydroxyflavone
and oligo(ethylene oxide) (denoted by 3HF-EO) was designed and synthesized. Different from the fluorescence in organic
solvents, 3HF-EO in aqueous solution showed a remarkable single fluorescence emission, which is ascribed to the
fluorescence of its anionic species. We found that the fluorescence intensity could be efficiently tuned via host-guest
complexation. α-CD has little effect on the emission, while β-CD and γ-CD lead to enhanced and reduced emission of 3HF-
EO, respectively. The 1H NMR and 2D NOESY NMR spectra indicate that α-CD barely had interaction with 3HF-EO, while β-
CD and γ-CD formed complexes with one and two 3HF-EO molecules, respectively. These results make a sound explanation
for the modulated fluorescence intensity.
www.rsc.org/
alter the nature of the fluorescence emission of 3HF
derivatives.23 Through complexation with cucurbit[7]uril, Seth
et al. modulated the photophysical behavior of 3HF.27 The
1 Introduction
Flavonoids are a group of polyphenolic compounds, which
ubiquitously exist in various plants and foods (e.g. gingko,
honeysuckle, apple and soy product).1, 2 Since the first report
on flavonoids by S. Rusznyák and A. Szent-Györgyi in 1936,3
various bioactive flavonoids have been discovered and applied
in clinic because of their antioxidant and free radical
scavenging activity.4-8 3-Hydroxyflavone (3HF) derivatives
normally possess a large stokes shift and exclusion of self-
absorption,9-11 and thus have great potential as ideal
candidates for fluorescence probes in bio-labeling. This class of
molecules are known for “the excited state intramolecular
proton transfer” process, and extensively studied in organic
solvents,12-22 but seldom addressed in aqueous solution due to
above examples demonstrate that the confinement effect
generated from host-guest interaction should be feasible
method to tune the fluorescence emission of 3HF derivatives.
The supramolecular encapsulation can effectively prevent self-
aggregation and alter the micro-environment of the guest
molecules, and hence can be used to tune the amphiphilicity
and the emission of chromophores.28, 29
To obtain stable and hydrophilic complexes, the selection of
host molecules becomes critically important. On board, we
have crown ether, CD, cucurbituril, calixarene, pillararene, octa
acid and so on.30-41 CDs present a truncated cone with the both
rims displaying hydroxyl groups, which make the outside of the
molecular cavity hydrophilic, whereas the inner surface is
hydrophobic lined with ether-like oxygen atoms and hydrogen
atoms. The hydrophilic CD molecules are able to bind size-fit
organic compounds. Such binding also allows CDs to be used
to increase the water solubility and stability of normally
hydrophobic compounds.41, 42 Therefore, CDs will be ideal host
molecules to encapsulate the 3HF derivatives. Apart from the
complexation, we anticipated that the fluorescence due to the
confinement effect can also be tuned by using different CDs to
encapsulate the guest molecules.43
the poor water solubility.23
From the published literatures,2,
24, 25
3HF derivatives were
often confined by host-guest interactions to promote the
emission of the corresponding tautomer. Chattopadhyay et al.
reported the disruption of probe-solvent cluster formed by a
3HF derivative because of the confinement of the probe with
cyclodextrin (CD) nano-cavity, and the disruption resulted in
the increase in fluorescence anisotropy of the probe compared
to its value in the aqueous solution.26 Rodembusch et al. found
that the confinement effect caused by octa acid was able to
In this study, 3HF was covalently linked to oligo(ethylene
oxide) with click reaction, and the resulting compound is
denoted by 3HF-EO. We found that the cavity size of the CDs is
critical to the host-guest complexation with 3HF-EO. The cavity
of α-CD is too small to encapsulate 3HF-EO, and it has little
effect on the fluorescence emission. In contrast, β-CD and γ-CD
formed complexes with one and two 3HF-EO molecules, and
a.College of Chemistry, Chemical Engineering and Materials Science, Soochow
University, Suzhou 215123, China.
Email: songbo@suda.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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thus resulting in the enhanced and reduced fluorescence dimethylformamide. The mixture was stirred at 80 °C for 12 h.
emission, respectively. This research conducted After cooling to room temperature, the resulting mixture was
a
comprehensive study on the emission of 3HF-EO in aqueous poured into 200 mL of deionized water. The product was
solution, and modulated its emission via host-guest extracted with dichloromethane (6 × 30 mL), and dried over
complexation. It is anticipated that the strategy developed in anhydrous Na2SO4. After removal of the solvent under reduced
this research can be applied to the analogous light-emitting pressure, the residue was purified by silica gel column
chromophores.
chromatography (ethyl acetate/petroleum ether (1:25, v/v)) to
1
afford a faint yellow oil. Yield: 2.5 g, 72%. H NMR (400 MHz,
CDCl3) δ 7.31–7.23 (m, 2H), 6.75 (d, J = 8.1 Hz, 3H), 3.55 (t, J =
5.9 Hz, 2H), 3.46 (t, J = 6.1 Hz, 2H), 3.02 (s, 3H).
2 Experimental
2.3.2. Synthesis of 4-((2-azidoethyl) (methyl) amino)
benzaldehyde (compound 2 in Scheme 1). Under nitrogen
atmosphere, phosphoryl chloride (2.8 mL, 30 mmol) was
added dropwise to dry N,N'-dimethylformamide (20 mL) in an
ice bath. After being stirred for 30 min, the solution of
compound 1 (2.6 g, 15 mmol) in dry N,N'-dimethylformamide
(20 mL) was added dropwise to the above solution. After
warmed to room temperature, the mixture was continuously
stirred for 1 h. Subsequently, the reactant was quenched by
deionized water (150 mL), and continuously stirred for 12 h.
The product was extracted with dichloromethane (6 × 30 mL),
and dried over Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified by silica gel column
chromatography (ethyl acetate/petroleum ether (2:7, v/v)) to
2.1 Materials
Triethylene glycol mono(2-propynyl) ether, p-toluenesulfonyl
chloride, cuprous bromide (CuBr) and 1,1,4,7,7-pentamethyl
diethylenetriamine (PMDETA) were purchased from Aladdin
Reagent Co., Ltd (Shanghai, China). Ethyl acetate, petroleum
ether, dichloromethane, methanol, ethanol, n-hexane,
tetrahydrofuran, N,N'-dimethyl formamide and toluene were
purchased from Yonghua Chemical Technology Co., Ltd
(Jiangsu, China). 2-N-methylanilinoethannol, α-CD, γ-CD,
deuterated chloroform, deuteroxide were purchased from J&K
chemical Ltd. β-CD was purchased from TCI Co., Ltd.
Triethylamine and phosphoryl chloride were bought from
Sinopharm Chemical Reagent Co., Ltd. Sodium azide was
acquired from Alfa Aesar (China) chemical Co., Ltd. Milli-Q
water with a resistivity of 18.0 MΩ·cm was used in the study.
2.2 Instruments
1
afford a faint yellow oil. Yield: 2.45 g, 81%. H NMR (400 MHz,
CDCl3) δ 9.77 (s, 1H), 7.76 (d, J = 9.0 Hz, 2H), 6.75 (d, J = 8.1 Hz,
2H), 3.64 (t, J = 6.0 Hz, 2H), 3.52 (t, J = 6.0 Hz, 2H), 3.13 (s, 3H).
2.3.3. Synthesis of (E)-3-(4-((2-azidoethyl) (methyl) amino)
phenyl)-1-(2-hydroxyphenyl) prop-2-en-1-one (Compound 3
in Scheme 1). Under nitrogen protection, potassium tert-
butoxide (673 mg, 6 mmol) was added into the solution of
compound 2 (612 mg, 3 mmol) and 2-hydroxyacetophenone
(542 μL, 4.5 mmol) in toluene (20 mL). The reaction mixture
was stirred for 1 h at room temperature and then poured into
1 mol/L HCl (160 mL). The resulting product was extracted with
dichloromethane (6 × 30 mL), and dried over Na2SO4. After
removal of the solvent under reduced pressure, the residue
was purified by silica gel column chromatography (ethyl
acetate/petroleum ether (1:4, v/v)). Yield: 0.82 g, 85%. 1H NMR
(400 MHz, CDCl3) δ 13.14 (s, 1H), 7.95–7.87 (m, 2H), 7.59 (d, J =
8.7 Hz, 2H), 7.51–7.43 (m, 2H), 7.01 (d, J = 8.4 Hz, 1H), 6.93 (t, J
= 7.8 Hz, 1H), 6.74 (d, J = 8.8 Hz, 2H), 3.63 (t, J = 6.0 Hz, 2H),
3.51 (t, J = 6.0 Hz, 2H), 3.11 (s, 3H).
1H NMR spectra were recorded on an Avance III 400 MHz NMR
spectrometer (Bruker Co.). 2D Nuclear Overhauser effect
spectroscopy (NOESY) spectra were recorded on a 600 MHz
Direct Drive 2 NMR spectrometer manufactured by Agilent
Technologies. Electrospray Ionization Mass spectra (ESI-MS) of
3HF-EO was carried out on
a micro Q-TOF III Mass
spectrometer (Bruker Co.). The MS of complexes of 3HF-EO/β-
CD and 3HF-EO/γ-CD were performed on a Q-Exactive mass
spectrometer with ESI source. The UV-vis spectra were
recorded on a Cary 60 produced by Agilent Technologies
(USA). Steady-state emission spectra (excited by 404 nm) were
recorded on a Hitachi F-2700 fluorescence spectrophotometer
(Japan). Fluorescence quantum yield (QY) was measured at 25
°C using a Flurolog-3 spectrofluorometer with a 450 W Xe lamp
as light source.
2.3 Synthesis and characterization
2.3.4. Synthesis of 2-(4-((2-azidoethyl) (methyl) amino)
2.3.1. Synthesis of N-(2-azidoethyl)-N-methylaniline (compound 1
in Scheme 1). 2-N-methylanilinoethannol (3.0 g, 20 mmol) and
p-toluenesulfonyl chloride (7.6 g, 40 mmol) were dissolved in
dry dichloromethane (60 mL) in an ice bath. Subsequently,
trimethylamine (3.5 mL, 25 mmol) was added dropwise, and
the reaction mixture was then warmed to room temperature.
After being stirred for 4 h, the resulting mixture was poured
into 150 mL of deionized water, extracted with
dichloromethane (4 × 20 mL). The organic phase was dried
over anhydrous Na2SO4, and then the solvent was removed
under reduced pressure to obtain the crude product 2-
(methyl(phenyl)amino) ethyl 4-methylbenzenesulfonate.
phenyl)-3-hydroxy-4H-chromen-4-one (compound
4
in
Scheme 1). Under nitrogen atmosphere, 5% sodium hydroxide
solution (5 mL) was added into a solution of compound 3 (483
mg, 1.5 mmol) in the mixed solvents of THF (5 mL) and ethanol
(15 mL) in an ice bath. After the mixture solution was warmed
up to room temperature, and then 30% hydrogen peroxide
(600 μL) was dropwise added into the reactant in an ice bath,
and the reactant was then warmed to room temperature and
continuously stirred for 4 h. The product was extracted with
dichloromethane (6 × 30 mL), and dried over Na2SO4. After
removal of the solvent under reduced pressure, the residue
was purified by recrystallization from ethyl acetate to acquire
a yellow solid. Yield: 310 mg, 62%. 1H NMR (400 MHz, CDCl3) δ
Sodium azide (2.6 g, 40 mmol) was added to the above
obtained crude product dissolved in 80 mL of dry N,N'-
2 | J. Name., 2012, 00, 1-3
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8.22 (dd, J = 10.5, 7.9 Hz, 3H), 7.67 (ddd, J = 8.5, 6.9, 1.7 Hz,
1H), 7.57 (d, J = 8.5 Hz, 1H), 7.43–7.36 (m, 1H), 6.91 (s, 1H),
6.84 (d, J = 8.9 Hz, 2H), 3.65 (t, J = 6.0 Hz, 2H), 3.53 (t, J = 6.0
Hz, 2H), 3.13 (s, 3H).
2500
2000
1500
1000
500
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
(a)
(b)
2.3.5.
Synthesis
of
3-hydroxy-2-(4-((2-(4-((2-(2-(2-
hydroxyethoxy) ethoxy) ethoxy) methyl)-1H-1,2,3-triazol-1-yl)
ethyl) (methyl) amino) phenyl)-4H-chromen-4-one (denoted
by 3HF-EO). Under nitrogen atmosphere, 3HF-EO was
synthesized via click reaction between compound 4 and
triethylene glycol mono(2-propynyl) ether. Typically,
compound 4 (168 mg, 0.5 mmol) and triethylene glycol
mono(2-propynyl) ether (94 mg, 0.5 mmol) were dissolved in
dry N,N'-dimethylformamide (60 mL). Subsequently, CuBr (72
mg, 0.5 mmol) and PMDETA (173 mg, 1 mmol) were added
into the mixture and the reaction was then stirred for 24 h.
The product was poured into deionized water (100 mL),
0
0
2
4
6
8
10
350 400 450 500 550 600 650
Wavelength (nm)
Concentration (× 10ꢀ5 mol/L)
(c)
Fig. 1 (a) Normalized UV-vis and PL spectra of 1 × 10-4 mol/L 3HF-EO in aqueous
solution; (b) Plot of fluorescence intensity at 525 nm versus the concentration of 3HF-
EO; (c) The anionic species of 3HF-EO.
extracted with dichloromethane (10 × 20 mL), and dried over As shown in Fig. 1a, the maximum absorption and
Na2SO4. After removal of the solvent under reduced pressure, photoluminescence of 3HF-EO in water located at around 404
the residue was washed 3 times with n-hexane, and purified by and 525 nm, respectively. The large stokes shift (approximately
recrystallization from ethyl alcohol to afford a yellow solid. 120 nm) allows 3HF-EO to have a very little self-absorption
Yield: (159 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = during emitting process. The remarkable single fluorescence
7.7 Hz, 1H), 8.18 (d, J = 8.7 Hz, 2H), 7.68 (t, J = 7.3 Hz, 1H), mission should be assigned to the anionic species, as shown in
7.60–7.49 (m, 2H), 7.40 (t, J = 7.5 Hz, 1H), 6.97 (s, 1H), 6.77 (d, Fig. 1c.23, 45, 46
J = 8.7 Hz, 2H), 4.67 (s, 2H), 4.61 (t, J = 6.1 Hz, 2H), 3.98 (t, J = The emission of 3HF-EO showed a concentration dependent
6.0 Hz, 2H), 3.74–3.67 (m, 2H), 3.68–3.51 (m, 10H), 2.93 (s, feature. As shown in Fig. 1b, the fluorescence intensity
3H), 2.01 (s, 1H). MS (ESI): Calculated for C27H32N4O7, increases with the concentration of 3HF-EO until the
m/z=524.23; found, 524.22.
centration was ~ 4 ×
10-5 mol/L, and thereafter the
fluorescence intensity showed little increase with
concentration. This phenomenon should be attributed to the
aggregation caused quenching, which is categorized as static
quenching due to the formation of ground state complexes.47
The confinement effect supplied by host-guest complexation
can possibly disrupt the ground state aggregates, so that
modulating the emission of the 3HF-EO. Therefore, α-CD, β-CD
and γ-CD were applied as hosts to assemble with 3HF-EO. To
make a parallel comparison, the concentrations of 3HF-EO
were all controlled to 1 × 10-4 mol/L, and 8 equivalents of α-
CD, β-CD or γ-CD was added into the aqueous solution. During
the measurement, the temperature of the solution was kept at
25 °C (our experiment indicated that 3HF-EO is quite sensitive
3 Results and discussion
The amphiphilic molecule 3HF-EO was designed and
synthesized by using the synthetic route illustrated in Scheme
1. Briefly, the synthesis of 2-(4-((2-azidoethyl) (methyl) amino)
phenyl)-3-hydroxy-4H-chromen-4-one (i.e. compound
4 in
scheme 1) referred to the literature,19 and the detailed
description is shown in the experimental section. The rigid 3HF
and the flexible oligo(ethylene oxide) residue linked by a
triazole group with click reaction, which happens in mild
conditions to avoid the damage of 3HF derivative during
synthesis. The 3HF moiety is hydrophobic and acts as the light-
emitting chromophore, and the oligo(ethylene oxide) provides
hydrophilicity. The target molecule was characterized by 1H
NMR and mass spectra, as shown in Figure S1.
4000
No CD
with αꢀCD
with βꢀCD
with γꢀCD
3000
2000
1000
0
450
500
550
600
650
Wavelength (nm)
Fig. 2 The PL spectra of 3HF-EO upon addition of 8 equivalents of α-CD, β-CD and
γ-CD. The concentration of 3HF-EO was 1 × 10-4 mol/L.
Scheme 1 The synthetic route of 3HF-EO.
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3HFꢀEO ×2 + γꢀCD + Na
3HFꢀEO + βꢀCD + Na
to temperature). As shown in Fig. 2, α-CD had little effect on
the PL spectrum of 3HF-EO; whereas β-CD and γ-CD showed
opposite effect on the emission intensity: the former
enhanced the fluorescent emission, and the latter suppressed
the emission. These results suggest that the three CDs should
have different interactions with 3HF-EO.
(a)
(b)
Theoretical
Theoretical
Experimental
Experimental
QY was determined to confirm the steady state fluorescence
results. The QY of neat 3HF-EO in aqueous solution was 14.8%.
The addition of α-CD did not cause significant change of QY,
and a value of 14.4% was acquired. Addition of equimolar β-CD
and γ-CD led to the enhanced and reduced QY to 22.7% and
10.5%, respectively. The QY changes are consist with the
results indicated by the steady fluorescence spectra. It is worth
to note that the QY of 3HF-EO also depends on the amount of
β-CD. A QY as high as 62.7% was acquired as 8 equivalents of
β-CD was added into the solution. In comparison, the QY of
3HF-EO did not show further decrease as adding more than
one equivalents of γ-CD in the solution.
1682
1684
1686
1688
1690
2368
2370
2372
2374
2376
1700 1750 1800 1850
m/z
2400
2450
m/z
2500
Fig. 4 ESI-MS of the complexes of (a) 3HF-EO/β-CD, (b) 3HF-EO/γ-CD. Inset: magnified
theoretical isotopic distributions for the complexes.
a
b
k
4
g
h
6
3
e f
5
A
c
2
B
C
1
j
d
i
(a)
We speculated that fluorescence difference upon addition of
these three CDs should be caused by the host-guest
complexation. The cavity of α-CD is too small to encapsulate
3HF-EO, while the cavity of β-CD and γ-CD are both big enough
for host-guest interactions. To verify this assumption, a series
of experiments were designed as follows.
d e jb a
(b)
c
f
i
k
h
g
Hꢀ5
Hꢀ2
Hꢀ6
Hꢀ3
//
(c)
Hꢀ1
// //
Firstly, the association ratio between 3HF-EO and β-CD (or γ-
CD) was determined through Job’s plot using the change of
chemical shift (∆δ) of proton H-f on 3HF-EO as variable.48 The
corresponding NMR spectra are presented in the supporting
information (Figure S2 and S3). Thus, the value of ∆δ (for β-CD)
or -∆δ (for γ-CD) times the concentration of 3HF-EO (denoted
as C1) was plotted against the molar ratio of 3HF-EO in the
mixed solution of 3HF-EO and β- (or γ-CD) (denoted by R). As
shown in Fig. 3, the intersections of the linear fitting meet at
approximately 0.52 and 0.66 for the systems containing β-CD
and γ-CD, respectively. These results indicate that the
association ratio between 3HF-EO and β-CD is 1:1, and
between 3HF-EO and γ-CD is 2:1. The above results was further
supported by ESI-MS data. As shown in Fig. 4, the experimental
isotopic distributions of the complexes of 3HF-EO/β-CD and
3HF-EO/γ-CD agreed well with corresponding theoretical
predictions.
Hꢀ4
Fig. 5 1H NMR spectra of (a) 3HF-EO, (b) 3HF-EO in the presence of equimolar α-CD, (c)
α-CD. The concentration of 3HF-EO is 1 × 10-4 mol/L. The solvent is D2O.
as well as the mixture of 3HF-EO and the respective CDs were
recorded. The H-3 and H-5 protons locate inside of the
hydrophobic cavity, and H-2, H-4 and H-6 protons reside on
the outer surface of the corresponding CDs. The chemical
shifts of H-3 and H-5 protons are readily affected as guest
molecule threads into the cavity of CD, which is because that
the guest molecule will cause a shielding effect on the interior
protons. Therefore, this characteristic is often used as an
indicator to judge the formation of host-guest complexation.49
As shown in Fig. 5, the addition of α-CD did not cause any
change of chemical shift of the protons of 3HF-EO or α-CD,
which indicates that there is no interaction between 3HF-EO
and α-CD. This result is consistent with that being reflected by
steady state fluorescence spectra.
1
Secondly, H NMR spectra were applied to investigate the
host-guest complexation formed by 3HF-EO and the CDs. For
this purpose, the NMR spectra of the neat 3HF-EO and the
CDs,
The addition of β-CD into the aqueous solution of 3HF-EO
induced chemical shift of protons on 3HF-EO and β-CD (shown
in Fig. 6). Most of the chemical shifts of protons on β-CD
moved to up-field, especially for that of the H-3 and H-5
protons, which indicates that β-CD and 3HF-EO formed host-
guest complex. As for 3HF-EO, the chemical shifts of almost all
protons on aromatic region moved to down-field, which
should be explained by the reduced electron density around
the protons owing to the formation of host-guest complex.50
Herein, the concentration of 3HF-EO was 1 × 10-4 mol/L, and
the 3HF-EO molecules are apt to aggregate, which should
result in a relatively dense electron density around the
protons.
16
(a)
(b)
16
12
8
12
8
4
4
0
0
0
0.2 0.4 0.6 0.8 1.0
0
0.2 0.4 0.6 0.8 1.0
R
R
Fig. 3 The Job’s plot for determining the association ratio of 3HF-EO to (a) β-CD or (b) γ-
CD. The total concentration of 3HF-EO and β-CD (or γ-CD) was kept at 3 × 10-4 mol/L.
4 | J. Name., 2012, 00, 1-3
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Hꢀ3
Hꢀ3
(a)
F1 (ppm)
F1 (ppm)
2
2
(a)
(b)
g
g
3
4
5
3
4
5
(b)
(c)
6f
6f
7
7
8e
8
9
Hꢀ5
Hꢀ2
Hꢀ6
Hꢀ3
//
Hꢀ1
9
Hꢀ4
9
8
7
6
5
4
3
2
9
8
7
6
5
4
3
2
F2 (ppm)
F2 (ppm)
//
//
Fig. 8 2D NMR NOESY spectra of 3HF-EO in the presence of (a) β-CD or (b) γ-CD in D2O
Fig. 6 1H NMR spectra of (a) 3HF-EO, (b) 3HF-EO in the presence of equimolar β-CD, (c)
β-CD. The concentration of 3HF-EO is 1 × 10-4 mol/L. The solvent is D2O.
in Fig. 8, the H-3 protons of β-CD and H-e, H-f, H-g protons of
3HF-EO showed strong correlations, and the NOE effect
between the H-3 and H-e protons was weaker than that
between the H-3 and H-f protons, implying that the H-3 proton
should be spatially closer to H-f proton. These results further
confirm that β-CD should bind to benzene ring B of 3HF-EO.
For the complexation of 3HF-EO and γ-CD, the correlations
between the H-3 and H-f, H-g protons were observed. This
result also indicates that 3HF-EO are thread in the cavity of γ-
CD. Combining the 2D NMR results with that obtained from
Job’s plot, we can conclude that every γ-CD should
encapsulate two 3HF-EO molecules due to the larger cavity of
γ-CD. These results are in good accordance with those
obtained from the Job’s plot and 1H NMR spectra.
(a)
(b)
Hꢀ5
Hꢀ2
Hꢀ6
Hꢀ3
//
(c)
Hꢀ1
//
Hꢀ4
//
Fig. 7 1H NMR spectra of (a) 3HF-EO, (b) 3HF-EO in the presence of equimolar γ-CD, (c)
γ-CD. The concentration of 3HF-EO is 1 × 10-4 mol/L. The solvent is D2O
The formation of 3HF-EO/β-CD complex will definitely alleviate
this effect, so that leading to the decrease of electron density
around the protons. In addition, the up-field shift of the
protons on benzene ring B (H-e and H-f, marked in the
molecular structure) and the H-h, H-i, H-j and H-k protons in
the vicinity are more obvious than that of the rest, suggesting
that β-CD should mainly bond to the benzene ring B of 3HF-EO.
As shown in Fig. 7, the addition of γ-CD into solution of 3HF-EO
also caused the change of NMR spectra of 3HF-EO and γ-CD,
but the situation is different with that happened in the 3HF-EO
and β-CD system. The chemical shifts of the H-3 and H-5
protons on γ-CD moved to much higher field, which indicates
that γ-CD formed inclusion complex with 3HF-EO. Most of the
protons in aromatic part of 3HF-EO shifted to high-field upon
addition of γ-CD. These results suggest that strong interaction
between 3HF segments should exist in the complex, which is
consistent with the 1:2 association ratio of γ-CD and 3HF-EO.
As 3HF-EO was encapsulated with γ-CD, two molecules of 3HF-
EO was confined in one cavity. This effect should be similar
with the formation of aggregates of 3HF-EO, and the π–π
stacking interaction should be even stronger. This explains the
decrease of fluorescence intensity as well as the quantum yield
This result also explains the broadened NMR signals of 3HF-EO
upon addition of γ-CD due to the retarded mobility of 3HF-EO
molecule.51
4 Conclusions
A novel amphiphilic molecule 3HF-EO containing 3HF and
oligo(ethylene oxide) was designed and synthesized. Being
dispersed in water, 3HF-EO showed a remarkable single
fluorescence emission, which can be assigned to the emission
of its anionic species. The complexation with different CDs was
employed to modulate the fluorescence intensity. α-CD with
relatively small cavity is unable to encapsulate 3HF-EO, and
hence it has little effect on the fluorescence emission. β-CD
and γ-CD own suitably-sized cavity, and form complexes with
one and two 3HF-EO molecules, respectively. The different
type of complexation resulted in different effect on the
fluorescence emission. β-CD showed enhancement effect, and
reached to a QY as high as 62.7% in aqueous solution. On the
contrary, γ-CD showed moderate reduction effect on the
emission of 3HF-EO, and a relatively low QY of 10.5% was
acquired.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
Protons in distance less than 0.4 nm can produce cross
correlation named by Nuclear Overhauser Effect (NOE).52
Therefore, 2D NOESY spectra are often used to investigate the
spatial proximity of protons in host-guest complex by
monitoring the intermolecular dipolar correlations. As shown
We thank the financial support of the National Natural Science
Foundation of China (21674075), the Natural Science
Foundation of Jiangsu Province (BK20161211), Key University
Science Research Project of Jiangsu Province (17KJA150007),
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The remarkable single fluorescence emission of a water-soluble 3-hydroxyflavone
derivative was modulated by host-guest complexation with different cyclodextrins.