Fluorescence sensing of tartaric acid: a case of excimer emission caused by hydrogen bond-mediated complexation

Article abstract of DOI:10.1016/j.tetlet.2006.03.044

A novel quinoline based receptor that shows monomer emission quenching followed by intramolecular excimer emission upon hydrogen bond mediated complexation of tartaric acid has been designed and synthesized. The excimer emission has been used to confirm t

Full text of DOI:10.1016/j.tetlet.2006.03.044

Tetrahedron Letters 47 (2006) 3577–3581
Fluorescence sensing of tartaric acid: a case of excimer
emission caused by hydrogen bond-mediated complexation
Kumaresh Ghosh* and Suman Adhikari
Department of Chemistry, University of Kalyani, Kalyani, Nadia 741235, India
Received 10 December 2005; revised 3 March 2006; accepted 9 March 2006
Available online 5 April 2006
Abstract—A novel quinoline based receptor that shows monomer emission quenching followed by intramolecular excimer emission
upon hydrogen bond mediated complexation of tartaric acid has been designed and synthesized. The excimer emission has been used
to confirm the selective recognition of tartaric acid over its nonhydroxy analogue, succinic acid. Binding ability was studied by
1H NMR, UV–vis and fluorescence spectroscopic methods.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Due to many applications in analytical chemistry and
biomedical research, the development of receptors which
have the ability selectively to bind and sense neutral
molecules, anions and cations through an optical
response has attracted much attention in recent years.1
In this regard, one of the recent approaches to the design
of fluorescent signalling systems relies on guest-induced
folding of flexible receptors, which brings the fluoro-
phores close enough as to function as an excimer.2
This excimer emission formation is sometimes used to
‘read out’ the molecular recognition process more
conveniently.
tives,6a unique trench type binding on a porphyrin
for tartaric acid derivatives,6b a colorimetric chemosen-
sing ensemble for tartrate/malate in beverages devel-
oped by Anslyn and co-workers,6c are notable.
Tryptophan-based chiral sensors7a for dibenzoyl tartrate
and anthracene labelled fluorescent chiral sensors7b for
enantiomeric discrimination of tartaric acid are also
interesting. As a result of our research on molecular
recognition,8,4a we herein report the design and synthesis
of a quinoline-based sensor 1 which shows selective
recognition of tartaric acid from its nonhydroxy
analogue succinic acid by exhibiting selective excimer
emission.
Given the importance of dicarboxylic acids due to their
biological relevance,3 the need for fluorescent receptors
as sensors for carboxylic acids in different contexts of
molecular recognition research4 has recently been of
paramount interest. In this respect, tartaric acid, a com-
mon natural product in wines and other grape derived
beverages, has received attention due to its structural
features possessing several hydrogen bond donors and
acceptors. Many hydrogen bonding receptors for the
binding of tartaric acid and its derivatives have been
reported.5
The receptor 1 was synthesized according to Scheme 1
and was isolated in 55% yield.9 The lumophore,
8-hydroxyquinoline was first coupled with 2-N-pivaloyl-
amino-6-bromomethylpyridine (obtained from 2-N-
pivaloylamino-6-methylpyridine by reaction with NBS
in dry CCl4) to give compound 2. Amide hydrolysis of
2 then afforded compound 3 in 80% yield. On coupling
3 with 5-octyloxy-1,3-benzenedicarbonyl chloride (pre-
pared by etherification of diethyl 5-hydroxyisophthalate
with octyl bromide in dry acetone using K2CO3 and
hydrolysis of the esters followed by reaction with oxalyl
chloride) yielded the desired receptor 1.
A binaphthol-based aminopyridyl group for enantio-
selective recognition of diacetyl tartaric acid deriva-
The quinoline moiety has been coupled with a pyridyl
unit to serve as a fluorophore as well as to involve the
quinoline nitrogens as hydrogen bond acceptors. Energy
minimization10 of 1 (Emin = 19.92 kcal/mol) shows the
nearly parallel arrangement of the pendent quinolines
Keywords: Molecular recognition; Excimer emission; Selective binding;
Tartaric acid; Neutral molecule binding.
*
Corresponding author. Tel.: +91 33 25828282x306; fax: +91 33
25828282; e-mail: ghosh_k2003@yahoo.co.in
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.044

3578
K. Ghosh, S. Adhikari / Tetrahedron Letters 47 (2006) 3577–3581
O(CH2)7CH3
COCl
K2CO3 in dry DMF/ TBAB and KI;
4% KOH in aq. EtOH
N
N
ClOC
1
O
N
O
N
O
16 h reflux
, 80%
dry CH Cl , Et N
, 55%
70%
2
2
3
N
Br
N
H
N
OH
2
3
NH
NH2
O
Scheme 1. The synthesis of receptor 1.
˚
with a separation of distance of 4.01 A and the open
binding cleft assumes a nonplanar shape (Fig. 1). The
hydrogen bonding groups in the cavity are well arranged
for complexation of hydroxydicarboxylic acids.
Determination of the association constants was, however
impossible because of the negligible change in the posi-
tion of the amide protons after forming the 1:1 complex.
The absorption spectra of 1 and its 1:1 complexes with
D-(À)-tartaric, rac-malic, and succinic acids in CHCl3
were recorded to investigate the interactions in the
ground state. Chloroform solutions of the 1:1 complexes
were diluted gradually with chloroform and the change
in intensity, as a function of the concentration was linear
in each case. Figure 3 shows the effect of dilution on the
UV spectra of the tartaric acid 1:1 complex with 1. This
change in the UV–vis spectra was used conveniently to
study the binding since the lower concentration used
led to a more accurate determination of the values of
the association constants11 for the acids (Table 1). The
hydroxy analogues of succinic acid show higher binding
constants due to the greater number of hydrogen bonds.
Interestingly, the binding values were reduced 10-fold as
the number of –OH groups decreases. The binding con-
stant values in our case, however, are greater in magni-
tude than the previously reported naphthyridine-based
receptors.5b
The sensitivity and the selectivity of receptor 1 were
evaluated by observing the change in H NMR, UV–
vis and fluorescence emission in CHCl3.
1
1H NMR of the receptor 1 in CDCl3 (5.83 · 10À3 M)
revealed the position of the amide protons at d
8.96 ppm. The addition of powdered D-(À)-tartaric
acid to this solution showed clear dissolution after
sonication. This was evident from the downfield shift
of the amide protons (d 8.96–9.90 ppm = Dd
0.94 ppm) of 1 as well as from the appearance of a
new peak at d 4.97 ppm due to methine protons in
the 1:1 complex (Fig. 2). The integration ratio of
tartaric acid methine protons to the receptor amide
protons in the NMR spectrum of the complex
(Fig. 2; top) clearly revealed the formation of a 1:1
complex. On dilution of the 1:1 complex, there was
practically no shift of the receptor amide protons.
This suggests strong complexation of tartaric acid into
the open cleft of the receptor 1 as in the mode shown
in complex A (Fig. 1).
The fluorescence spectra of the receptor 1 were simulta-
neously recorded in CHCl3 both in the presence and
OR
OR
O
O
O
O
NH
HN
NH
HN
O
N
O
OH
N
N
N
HO
H
O
HO
N
H
OH
O
O
O
N
N
N
Complex A
1
R = C8H17
R = C8H17
Figure 1. Energy minimized structure of 1.

K. Ghosh, S. Adhikari / Tetrahedron Letters 47 (2006) 3577–3581
3579
Figure 2. 1H NMR (in CDCl3) spectra of receptor 1 (bottom) and the 1:1 complex with tartaric acid (top).
350
1.2
2.5
a
1.0
a. Receptor 1 in CHCl3(2.1 x 10-5M)
b. 1:1 complex with succinic acid
c. 1:1 complex with rac-malic acid
d. 1:1 complex with tartaric acid
300
0.8
2.0
250
0.6
0.4
1.5
1.0
0.5
0.0
200
150
100
50
0.2
0.0
b
c
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
[Complex] x 10-5
M
d
0
300
240
260
280
300
320
340
360
350
400
450
500
550
Wavelength (nm)
Wavelength (nm)
Figure 3. UV spectra of complex A and its change of absorbance on
dilution; (inset) plot of absorbance versus concentration of the
complex of tartaric acid with 1.
Figure 4. Fluorescence change of 1 in CHCl3 in the presence of
dicarboxylic acids (kex = 290 nm).
2.4
2.2
2.0
1.8
1.6
1.4
1.2
1.0
0.8
Table 1. Association constants determined by UV (CHCl3)
Guest
Association constant Ka (MÀ1
)
D-(À)-Tartaric acid
rac-Malic acid
Succinic acid
9.81 · 105
4.96 · 104
9.38 · 103
absence of dicarboxylic acid guests. Figure 4 shows the
fluorescence spectra of 1 and its 1:1 complexes with
D-(À)-tartaric, rac-malic and succinic acids in CHCl3.
On complexation with these acids significant fluores-
cence quenching takes place.
0.000000 0.000005 0.000010 0.000015 0.000020 0.000025
[Complex] M
However, the degree of quenching is dependent on
the nature of the acid. The magnitude of the quenching
Figure 5. Plot of the ratio of excimer to monomer emission versus
concentration of the complex of 1 with tartaric acid.

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K. Ghosh, S. Adhikari / Tetrahedron Letters 47 (2006) 3577–3581
OR
O
OR
O
OR
O
O
O
O
O
O
NH
HN
NH
HN
NH
HN
O
N
N
N
N
HO
N
N
HO
OH
HO
HO
OH
O
O
O
O
O
O
O
O
O
HO
HO
HO
N
N
N
N
N
N
6
4
5
R = C8H17
Figure 6. Possible hydrogen bonding structures of 1 with rac-malic acid.
efficiency (/Q)12 follows the order of D-(À)-tartaric acid
(0.92) > rac-malic acid (0.87) > succinic acid (0.53),
reflecting the stabilities of the complexes (see the binding
constant values in Table 1). In the case of D-(À)-tartaric
acid, an additional peak at 453 nm along with monomer
emission at 377 nm was noticed due to excimer forma-
tion. The excimer emission resulted from the intramole-
cular excimer, rather than intermolecularly, as indicated
by the dilution experiments at different concentrations in
which the intensities of the ratio of excimer to monomer
emission changed gradually (Fig. 5). The formation of
this excimer in the presence of D-(À)-tartaric acid could
be attributed to the tartaric acid templated hydrogen
bond induced organization of the quinoline moieties.
Such excimer formation was not observed in the case
of succinic acid due to the lack of –OH groups which
are necessary to bring closer together the pendant quin-
oline groups of the binding arms via hydrogen bond
formation. This was confirmed using rac-malic acid
where the excimer emission was observed (Fig. 4) due
to the possibility of hydrogen bonding structure 4 which
may remain in equilibrium with 5 and 6 (Fig. 6). It is,
therefore, worth noting that the conformation of 1
was changed substantially only on binding with hydroxy-
dicarboxylic acids rather than with a dicarboxylic acid
of the same chain length.
References and notes
1. (a) Chemosensors of ion and Molecule Recognition; Des-
vergne, J. P., Czarnik, A. W., Eds.; NATO ASI Series;
Kluwer Academic: Dordrecht, 1997; Vol. 492; (b) De
Silva, A. P.; Gunaraine, H. Q. N.; Gunnlaugsson, T.;
Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice,
T. E. Chem. Rev. 1997, 97, 1515; (c) Pfeffer, F. M.;
Gunnlaugsson, T.; Jensen, P.; Kruger, P. E. Org. Lett.
2005, 7, 5357, and references cited therein.
2. (a) Aoki, I.; Harada, T.; Sakaki, T.; Kawahara, Y.;
Shinkai, S. J. Chem. Soc., Chem. Commun. 1992, 1341;
(b) Liao, J.-H.; Chen, C.-T.; Fang, J.-M. Org. Lett. 2002,
4, 561; (c) Bai, Y.; Zhang, B.-G.; Xu, J.; Duan, C.-Y.;
Dang, D.-B.; Liu, D.-J.; Meng, Q.-J. New J. Chem. 2005,
29, 777; (d) Nishizawa, S.; Kaned, H.; Uchida, T.;
Teramae, N. J. Chem. Soc., Perkin Trans. 2 1998,
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3. Styrer, L. Biochemistry, 3rd ed.; Freeman: New York,
1988; p 188; pp 373–394; p 376; pp 575–625.
4. (a) Goswami, S.; Ghosh, K.; Dasgupta, S. J. Org. Chem.
2000, 65, 1907; (b) Yang, D.; Li, X.; Fan, Y.-F.; Zhang,
D.-W. J. Am. Chem. Soc. 2005, 127, 7996, and references
cited therein.
5. (a) Zhao, J.; Davidson, M. G.; Mahon, M. F.; Kociok-
Kohn, G.; James, T. D. J. Am. Chem. Soc. 2004, 126,
16179; (b) Goswami, S.; Ghosh, K.; Mukherjee, R.
Tetrahedron 2001, 57, 4987; (c) Hernandez, J. V.; Almaraz,
M.; Raposo, C.; Martin, M.; Lithgow, A.; Crego, M.;
Cabellero, C.; Moran, J. R. Tetrahedron Lett. 1998, 39,
7401.
6. (a) Garcia-Tellado, F.; Albert, J.; Hamilton, A. D. J.
Chem. Soc., Chem. Commun. 1991, 1761; (b) Kuroda, Y.;
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Soc. 1994, 116, 10338; (c) Lavigne, J. J.; Anslyn, E. V.
Angew. Chem., Int. Ed. 1999, 38, 3666.
In pursuit of a fluorescent sensor we have demonstrated
that hydrogen bond-mediated complexation of tartaric
acid with 1 results in monomer emission quenching fol-
lowed by intramolecular excimer emission. This excimer
emission is moderate and convenient for practical use to
distinguish tartaric acid from its nonhydroxy analogue
succinic acid. Further study on this subject is underway
in our laboratory.
7. (a) Xu, K.-X.; He, Y.-B.; Qin, H.-J.; Qing, G.-Y.; Liu,
S.-Y. Tetrahedron 2005, 16, 3042; (b) Zhao, J.; James,
T. D. Chem. Commun. 2005, 1889.
8. (a) Ghosh, K.; Masanta, G. Supramol. Chem. 2005, 17,
331; (b) Goswami, S.; Ghosh, K.; Dasgupta, S. J. Org.
Chem. 2000, 65, 1907–5504.
Acknowledgements
9. Receptor 1: Mp 110–111 ꢁC, 1H NMR (CDCl3, 400
MHz): d 8.96 (s, 2H, –NHCO–), 8.95 (d, 2H, J = 8 Hz),
8.26 (d, 2H, J = 8 Hz), 8.19 (s, 1H), 8.12 (d, 2H, J = 8 Hz),
7.71 (t, 4H, J = 8 Hz), 7.42 (m, 2H), 7.37–7.33 (m, 6H),
We thank CSIR [01(1922)/04/EMR-II], New Delhi,
India, for financial support and DST-FIST, for provid-
ing the facilities in the Department.

K. Ghosh, S. Adhikari / Tetrahedron Letters 47 (2006) 3577–3581
3581
6.95 (d, 2H, J = 8 Hz), 5.32 (s, 4H), 4.08 (t, 2H, J = 8 Hz),
1.85–1.80 (m, 2H), 1.46 (m, 2H), 1.33–1.15 (m, 8H),
0.86 (t, 3H, J = 6 Hz). 13C (CDCl3, 125 MHz): d 165.2,
160.3, 155.4, 154.3, 151.6, 149.7, 140.7, 139.5, 136.4, 136.1,
129.8, 126.9, 122.1, 120.5, 118.1, 118.0, 117.9, 113.7, 109.9,
71.1, 69.1, 32.2, 29.7, 29.6, 29.5, 26.3, 23.4, 14.5. HRMS
calcd for C46H44N6O5: 760.3363. Found: 760.3382. FTIR
(KBr) mmax: 3300, 2924, 2853, 1674, 1597, 1577, 1457,
10. MM2 calculations were performed using CS Chem 3D
version 6.0.
11. Colquhoun, H. M.; Goodings, E. P.; Maud, J. M.;
Stoddart, J. F.; Wolstenholme, J. B.; Williams, D. J. J.
Chem. Soc., Perkin Trans. 2 1985, 607.
12. The quenching efficiency was determined using the equa-
tion: /Q = (Ihost À Icomplex)/Ihost, where Ihost and Icomplex
are the fluorescence intensities (377 nm) of 1 and its
complex, respectively.
1109 cmÀ1
.