Anthracene coupled trans-pyridylcinnamide: a new fluororeceptor for selective sensing of dicarboxylates

Article abstract of DOI:10.1016/j.tetlet.2008.02.095

trans-Pyridylcinnamide has been established as an alternative hydrogen bonding synthon, in place of urea for carboxylate binding. This alternative motif has been used in the design and synthesis of new fluorescent 'On-Off' signalling chemical sensor 1, which is found to bind aliphatic dicarboxylates with moderate binding constants. The recognition ability has been established by fluorescence, UV-vis and ¹H NMR spectroscopic methods. The receptor is found to be selective for long chain pimelate.

Full text of DOI:10.1016/j.tetlet.2008.02.095

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2592–2597
Anthracene coupled trans-pyridylcinnamide:
a new fluororeceptor for selective sensing of dicarboxylates
Kumaresh Ghosh *, Goutam Masanta
Department of Chemistry, University of Kalyani, Kalyani, Nadia 741 235, India
Received 17 December 2007; revised 13 February 2008; accepted 16 February 2008
Available online 21 February 2008
Abstract
trans-Pyridylcinnamide has been established as an alternative hydrogen bonding synthon, in place of urea for carboxylate binding.
This alternative motif has been used in the design and synthesis of new fluorescent ‘On–Off’ signalling chemical sensor 1, which is found
to bind aliphatic dicarboxylates with moderate binding constants. The recognition ability has been established by fluorescence, UV–vis
1
and H NMR spectroscopic methods. The receptor is found to be selective for long chain pimelate.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: trans-Pyridylcinnamide; Anthracene; Dicarboxylate recognition; Fluorescent receptor
The development of new hydrogen bonding synthons
and their use in the construction of new chemosensors
for the selective recognition of important anions is of great
interest in host–guest chemistry.1–4 In this aspect, dicarb-
oxylates are important target anions because of their con-
siderable roles in numerous metabolic processes such as
the generation of high energy phosphate bonds and the
biosynthesis of important intermediates.5–7 Dicarboxylate
anion binding by various hydrogen bonding receptors has
been demonstrated.8–11 In general, most of these receptors
consist of urea/thiourea,6,8 imidazolium cations,12 guanid-
inium ions13,14 etc., as the hydrogen bonding synthons
attached to different fluorophores. However, the use of
the trans-pyridylcinnamide motif as a new hydrogen bond-
ing synthon, having both more polar NH and less polar
CH groups, in the design of hydrogen bonding fluorescent
receptor for anions is unknown to the best of our
knowledge. It is well established that the weak C–HÁ Á ÁO
hydrogen bonds extensively exist just like their strong
counterparts15,16 and are found widely in proteins and
many organic crystals.17–19 Although it is much weaker in
comparison to the usual strong hydrogen bond, X–HÁ Á ÁY
(X, Y = N, O, F), this kind of interaction has aroused
significant interest in recent times. In this aspect, reports
concerning the occurrence of this weak C–HÁ Á ÁO interac-
tion in solution are still rare.20,21 Although the idea of such
C–HÁ Á ÁO interactions is familiar,22 more recently their exis-
tence and importance as a weak, but forceful, secondary
interactions has been widely accepted.23 To explore the
scope of such weak interactions in molecular recognition
processes we herein report the design and synthesis of
new fluororeceptor 1 for the selective sensing of dicarbox-
ylate anions.
Receptor 1 was synthesized according to Scheme 1. The
hydrogen bonding site N1-(3-pyridyl)-(E)-3-phenyl-2-pro-
penamide (also known as trans-pyridylcinnamide) 3 was
initially prepared by reacting 3-aminopyridine with trans-
cinnamic acid chloride in the presence of triethylamine
in dry CH2Cl2. Subsequent coupling of 3 with 9,10-bis-
(chloromethyl)anthracene followed by anion exchange
using NH4PF6 afforded receptor 1 in 85% yield.24
Receptor 1 can exhibit different types of conformations
in solution. Molecular modelling25 studies indicate that
both the syn- and anti-forms of receptor 1 are close in
*
Corresponding author. Tel.: +91 33 25828750; fax: +91 33 25828282.
E-mail address: ghosh_k2003@yahoo.co.in (K. Ghosh).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.095

K. Ghosh, G. Masanta / Tetrahedron Letters 49 (2008) 2592–2597
Table 1
2593
O
Hp
O
H
c
Change in chemical shift values of receptor 1 in 1:1 complexes with various
anions
PF6
+
N
H
N
H
N
PF6
+
N
N
Ho
H
H
H
a
Guest
Dd for Hb (ppm) Dd for Ho (ppm) Dd for Hp (ppm)
b
Acetate
+0.08
+0.02
+0.0
+0.14
+0.12
+0.24
+0.28
À0.10
À0.09
À0.11
À0.10
À0.11
À0.15
À0.14
+0.16
+0.10
+0.10
+0.10
+0.09
+0.18
+0.31
+0.32
+0.35
Malonate
Succinate
Glutarate
Adipate
Pimelate
Suberate
H
N
H
N
H
N
N+
N+
PF6
PF6
O
O
H
1
2
Terephthalate +0.36
energy, and the anti-form is more stable by 3.87 kcal/mol
(Fig. 2). The cavity of the syn-form (E = 127.48 kcal/mol)
can accommodate dicarboxylates of required chain length
involving both pyridylcinnamides as binding sites in a
cooperative fashion. The non-cooperation of pyridylcinn-
amide in the anti-form of 1 can induce a dynamic supra-
molecular structure with dicarboxylates that are too short
to bridge the binding sites.
‘+’ indicates downfield chemical shift.
‘À’ indicates upfield chemical shift.
for the complexation of carboxylate anions (Fig. 1). Such
weak C–HÁ Á ÁO hydrogen bonds are not an unusual phe-
nomenon. The result is consistent with the previous
reports.19,26 In this connection, the involvement of the vinyl
protons of the a,b-unsaturated amide motif in the complex-
ation of thymine by acrylamido pyridine is worthy of men-
tion.27 During complexation, the pyridyl ortho protons
(Ho) showed an upfield shift, presumably, due to either a
desolvation effect as DMSO is displaced from the cavity
by an anion or a complexation induced conformational
change in the receptor. The simultaneous downfield shifts
of Hp (Table 1) upon complexation were appreciable. This
may be either due to the participation of Hp in the forma-
tion of C–HÁ Á ÁO hydrogen bonds that stabilize the cinna-
mylamide–carboxylate complex via the dynamic mode C
among the other possible equilibrium forms A and B or
closer approach of the amide carbonyl oxygen to Hp upon
complexation via mode A/B (Fig. 3). These observations
are consistent with our previously reported urea analogue
2 for dicarboxylates28 and also with the results reported
by Jeong and Cho.29 The representative spectra of 1 in
The anion binding ability of 1 was initially established
by H NMR in DMSO-d6. To the receptor solution of 1
1
in DMSO-d6, aliphatic dicarboxylates of various chain
lengths and AcOÀ ions were added as their tetrabutylam-
monium salts in 1:1 stoichiometries. In the presence of ace-
tate ions the amide proton (Ha) underwent a downfield
shift (Dd = 0.74 ppm) and became broad. The more acidic
vinyl proton (Hb) also showed
a downfield shift
(Dd = 0.08 ppm). Similar findings were noticed in the pres-
ence of dicarboxylate anions. Both the amide (Ha) and the
vinyl protons (Hb) of 1 moved downfield in the presence of
dicarboxylate anions owing to the formation of receptor–
dicarboxylate anion complexes. Surprisingly, the less acidic
vinyl proton (Hc) did not show any change in its chemical
shift thereby indicating its non-involvement in complex-
ation. The extent of change in the chemical shift of vinyl
proton (Hb) was different for aliphatic dicarboxylates of
different chain lengths. As can be seen from Table 1, the
shift is significant in the case of terephthalate and long
chain dicarboxylates such as pimelate and suberate. The
amide signal in each case was difficult to detect accurately
due to broadening upon complexation. We believe that
such measurable downfield chemical shifts of vinyl proton
(Hb) are caused by the formation of a weak C–HÁ Á ÁO
hydrogen bond with the carboxylate anion. The simulta-
neous involvement of amide proton (Ha) and vinyl proton
(Hb) of the trans-cinnamide motif in 1 can thus be consid-
ered as an alternative hydrogen bonding synthon of urea
O
H
O
R
R
R
N
H
N
H
N
H
H
O
O
O
O
A
R'
R'
B
Fig. 1. Hydrogen bonding structures of carboxylate with cinnamide (A)
and urea derivatives (B).
O
Cl
N
N
H
+
NH2
O
trans-cinnamic acid chloride
9,10-bis(chloromethyl)anthracene
in dry CH3CN, reflux, 13 h 82%
N
dry CH Cl
,
Et3N
75%
N
2
2
N
H
H
N
+
N
3
4
Cl
CH3OH, NH4PF6
85%
O
1
Scheme 1. Synthesis of receptor 1.

2594
K. Ghosh, G. Masanta / Tetrahedron Letters 49 (2008) 2592–2597
Fig. 2. Energy minimized structures of the syn- (A) and anti-forms (B) of
receptor 1.
the aromatic region in the presence of both AcOÀ and
pimelate anions are shown in Figures 4 and 5.
Once it had been established that the vinyl proton (Hb)
and the amide proton (Ha) are cooperatively involved in
hydrogen bonding with the carboxylate anion like urea
(see Fig. 1), the sensitivity and selectivity of receptor 1
was ascertained by fluorescence and UV–vis spectroscopic
studies. The UV–vis experiments on receptor 1 with anions
were performed in DMSO. As shown in Figure 6, upon
complexation of pimelate as its tetrabutylammonium salt
with receptor 1 (c = 3.40 Â 10À5 M), the absorption peaks
at 362 nm, 384 nm and 405 nm for anthracene were
increased significantly with a simultaneous decrease of
the absorption peak at 306 nm. Similar findings were noted
for other anions as mentioned in Table 1. The change in
absorbance of the peak at 384 nm as a function of [G]/
[H] is shown in Figure 7. From the break of the titration
curves (Fig. 7) it is noted that all the anions except pime-
late, suberate and terephthalate exhibit 2:1 (host–guest)
stoichiometry. The long chain dicarboxylates pimelate,
suberate and the aromatic dicarboxylate terephthalate bind
in 1:1 stoichiometries. The change in absorption of the
peak at 384 nm as a function of added guest concentration
was used to determine the binding constant values (Table
2). The results in Table 2 demonstrate that the open cavity
of 1 has marked selectivity for the long chain pimelate.
Fig. 4. 1H NMR spectra of 1 (c = 2.43 Â 10À3 M) with acetate in DMSO-
d6, (a) 1 only; (b) [G]/[H] = 1.
Fig. 5. 1H NMR spectra of 1 (c = 2.43 Â 10À3 M) with pimelate in
DMSO-d6, (a) 1 only; (b) [G]/[H] = 1.
In fluorometric studies, when the solution of
1
(c = 7.79 Â 10À5 M) in DMSO was excited at 384 nm,
receptor 1 gave a characteristic emission spectrum of
anthracene along with a weak emission at 506 nm due to
the anthracene–pyridinium complex (exciplex). With a
gradual increase in the concentration of the guest anions
as reported in Table 2, the fluorescent emission of 1 was
quenched or switched off significantly and behaved oppo-
sitely to that of our previously reported receptor 2.28 The
O
O
H
H
Ph
Ph
O
O
Hp
H
H
N
H
H
-
N
N
H
N
PF6
b
+
-
PF6
N
Ph
O
N
N
+
H
+
a
-
H
O
PF6
O
Ho
H
O
O
O
H
H
O
O
Ph
O
O
H
H
+
N
-
PF6
H
+ N
-
N
N
Ph
+
PF6
H
N
H
-
PF6
O
Ph
H
H
O
C
O
O
B
H
A
Fig. 3. Possible structures of the hydrogen bonded complexes of 1 with dicarboxylates in solution.

K. Ghosh, G. Masanta / Tetrahedron Letters 49 (2008) 2592–2597
2595
phore–spacer–receptor’ model as proposed by de Silva
and, therefore, the compound could act as a simple PET
sensor.30,31 Thus the quenching of fluorescence of 1 is pre-
sumably attributed to the activation of PET (photo-
induced electron transfer) either from the electronically
rich binding site after complexation to the excited anthra-
cene or the reverse. The changes in fluorescence intensity
of 1 as a function of [G]/[H] are plotted in Figure 10 and
the sharp break in the curves for pimelate, suberate and
terephthalate at [G]/[H] = 1 indicated 1:1 stoichiometry
of the complexes. The stoichiometry of the complexes
was further confirmed by fluorescence Job plots. In this
regard, Figure 11 demonstrates the Job plot for pimelate
with receptor 1 which confirms the 1:1 stoichiometry. The
lower homologues such as malonate, succinate, glutarate
and adipate ions are shown to bind in 2:1 (guest–host)
stoichiometries.
3.0
2.5
2.0
1.5
1.0
0.5
0.0
300
350
400
450
Wavelength (nm)
Fig. 6. Changes in the UV–vis spectra of 1 (c = 3.40 Â 10À5 M) in DMSO
upon the addition of tetrabutylammonium pimelate.
The binding constant values were also evaluated by fluo-
rescence titration methods considering the change in emis-
sion at 433 nm and showed similar trends to those obtained
0.60
0.55
__
acetate
0.50
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
0.00
__
__
__
__
__
__
__
malonate
succinate
glutarate
adipate
pimelate
suberate
terepthalate
__
__
__
__
__
__
__
__
acetate
16
14
12
10
8
malonate
succinate
glutarate
adipate
pimelate
suberate
terepthalate
6
4
0
1
2
3
4
5
6
7
8
2
[G]/[H]
0
0
10
20
30
40
50
Fig. 7. UV–vis titration curves ([Guest]/[Host] vs change in absorbance)
[G].10-5M
for 1 (measured at 384 nm) with various anions.
Fig. 8. Stern–Volmer plot for 1 at 433 nm.
Table 2
Binding constants for 1 with the guest anions
Guest anion
Receptor 1
50
Ka in MÀ1
a
Ka in MÀ1
b
Acetate
2.85 Â 104
2.09 Â 104
1.15 Â 104
4.21 Â 104
4.68 Â 104
8.60 Â 104
7.29 Â 104
4.75 Â 104
1.94 Â 104
4.80 Â 103
2.10 Â 103
1.22 Â 104
2.08 Â 104
3.53 Â 104
2.86 Â 104
1.88 Â 104
40
30
20
10
0
Malonate
Succinate
Glutarate
Adipate
Pimelate
Suberate
Terephthalate
a
Determined by fluorescence methods in DMSO.32
Determined by UV methods in DMSO.32
b
degree of quenching varied with the chain length of the
dicarboxylates as evidenced from the Stern–Volmer plot
(Fig. 8). The change in emission spectra of 1 upon gradual
addition of pimelate is displayed in Figure 9. Receptor 1
falls into the category of the ‘receptor–spacer–fluoro-
400
450
500
550
600
650
Wavelength (nm)
Fig. 9. Changes in the fluorescence spectra of 1 (c = 7.79 Â 10À5 M) in
DMSO upon the addition of tetrabutylammonium pimelate.

2596
K. Ghosh, G. Masanta / Tetrahedron Letters 49 (2008) 2592–2597
Acknowledgements
45
40
35
30
25
20
15
10
5
__
__
__
__
__
__
__
__
acetate
malonate
We thank DST (SR/FTP/CS-18/2004) and CSIR,
Government of India for financial support. G.M. thanks
CSIR, Govt. of India for a fellowship.
succinate
glutarate
adipate
pimelate
suberate
terepthalate
References and notes
1. Schmidtchen, F. P. Coord. Chem. Rev. 2006, 250, 2918–2928.
2. Amendola, V.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. Acc.
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4476.
0
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2
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7
8
4. Schmidtchen, F. P.; Berger, M. Chem. Rev 1997, 97, 1609–1646.
5. Voet, D.; Voet, J. G. Biochemistry, 2nd ed.; Wiley: New York, NY,
1995.
[G]/[H]
Fig. 10. Fluorescence titration curves ([Guest]/[Host] vs change in
emission) for 1 (measured at 433 nm) with various anions.
6. Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.; Glynn, M. Org. Lett.
2002, 4, 2449–2452 and references cited therein.
7. Kral, V.; Andrievsky, A.; Sessler, J. L. J. Am. Chem. Soc. 1995, 117,
2953–2954.
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Y.-K.; Yang, R.-H. Org. Lett. 2005, 7, 5825–5828.
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117, 8447–8455.
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Hamilton, A. D. J. Org. Chem. 2001, 66, 7313–7319 and references
cited therein.
12. Kim, S. K.; Kang, B. G.; Koh, H. S.; Yoon, Y. J.; Jung, S. J.; Jeong,
B.; Lee, K.-D.; Yoon, J. Org. Lett. 2004, 6, 4655–4685 and references
cited therein.
13. Raker, J.; Glass, T. E. J. Org. Chem. 2002, 67, 6113–6116.
14. Jadhav, V. D.; Scmidtchen, F. P. Org. Lett. 2006, 8, 2329–2332 and
references cited therein.
34
32
30
28
26
24
22
20
18
16
15. Desiraju, G. R. Acc. Chem. Res. 2002, 35, 565–573.
16. Hobza, P.; Havlas, Z. Chem. Rev. 2000, 100, 4253–4264.
17. Steiner, T.; Saenger, W. J. Chem. Soc., Chem. Commun. 1995, 2087–
2088.
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
XG
18. Thallapally, P. K.; Katz, A. K.; Carrell, H. L.; Desiraju, G. R. Cryst.
Eng. Commun. 2003, 5, 87–92.
Fig. 11. Fluorescence Job plot of 1 with pimelate.
19. Schmuck, C.; Lex, J. Eur. J. Org. Chem. 2001, 1519–1523 and
references cited therein.
20. Huggins, M. T.; Lightner, D. A. J. Org. Chem. 2001, 66, 8402–
8410.
21. Marques, M. P. M.; da Costa, A. M. A.; Ribeiro-Claro, P. J. A. J.
Phys. Chem. A 2001, 105, 5292–5297.
22. Sutor, D. J. Nature 1962, 195, 68–69.
23. For a recent review on C–HÁ Á ÁO bonds see: Desiraju, G. R.; Steiner,
T. The weak Hydrogen Bonds in Structural Chemistry and Biology,
Oxford University Press, Oxford, 1999.
24. Receptor 1: Mp 270–274 ° C; 1H NMR (DMSO-d6, 400 MHz): d 11.2
(s, 2H, –NHCO–), 9.42 (s, 2H), 8.66–8.51 (br m, 8H), 8.08 (br s, 2H),
7.80 (br s, 4H), 7.62 (br s, 6H), 7.45 (br s, 6H), 7.13 (br s, 4H), 6.70 (d,
2H, J = 16 Hz); 13C NMR (DMSO-d6, 125 MHz): 165.5, 143.6, 140.4,
139.4, 135.2, 134.8, 134.5, 132.2, 131.4, 129.9, 129.4, 129.2, 128.9,
127.0, 125.5, 120.9, 57.1; FTIR: m cmÀ1 (KBr): 3373, 3106, 2926, 1682,
1623, 1589, 1547, 1499, 1454; UV (DMSO): (c = 3.40 Â 10À5 M) kmax
(nm) 306, 362, 384, 405. Mass (ES+): 797.0 [(MÀPF6)+1]+, 764.9,
651.2.
25. Energy minimization was carried out by MMX (PC Model Serena
Software 1993). Molecular modelling was performed using standard
constants, and the dielectric constant was maintained at 1.5.
26. Quinn, J. R.; Zimmerman, S. C. Org. Lett. 2004, 6, 1649–1652. and
references cited therein.
by the UV method (Table 2). From the values in Table 2, it
is clear that the open cleft of receptor 1 has marked selec-
tivity for pimelate over a wide range of dicarboxylates
more in the excited state than in the ground state. The con-
ventional N–HÁ Á ÁO, unconventional C–HÁ Á ÁO hydrogen
bonds and the charge–charge interactions are the responsi-
ble forces, which cooperatively contribute to the selectivity
of 1.
In conclusion, we have synthesized fluorescent receptor
1 based on a trans-pyridylcinnamide motif and investigated
its binding properties towards aliphatic dicarboxylates of
various chain lengths. It showed moderate selectivity for
long chain pimelate over a wide range of dicarboxylates
by exhibiting good ‘On–Off’ switchability, and more
importantly, the switching mode was opposite to that of
the previously reported urea analogue 2. This selectivity
was attributed to the simultaneous interplay of N–HÁ Á ÁO
and C–HÁ Á ÁO hydrogen bonds and charge–charge inter-
actions during complexation. We are presently exploring
the scope of this new hydrogen bonding synthon for the
design and synthesis of new task specific receptors.
27. Li, Z.; Ding, J.; Robertson, G.; Day, M.; Tao, Y. Tetrahedron Lett.
2005, 46, 6499–6502.

K. Ghosh, G. Masanta / Tetrahedron Letters 49 (2008) 2592–2597
2597
28. Ghosh, K.; Masanta, G.; Chattopadhyay, A. P. Tetrahedron Lett.
2007, 48, 6129–6132.
29. Jeong, K.-S.; Cho, Y. L. Tetrahedron Lett 1997, 38, 3279–3282.
30. de Silva, A. P.; Gunaratne, H. Q. N.; McCoy, C. P. Nature 1993, 364,
42–44.
linear relationship, indicating the 1:1 stoichiometry of the receptor/
carboxylate complex. The ratio for the intercept versus slope gives the
association or binding constant (Ka) for the receptor–guest complex
shown in Table 2. In a similar way the emission values obtained
during fluorescence titrations of 1 with the same guests were used to
evaluate the binding constant values. Chou, P. T.; Wu, G. R.; Wei, C.
Y.; Cheng, C. C.; Chang, C. P.; Hung, F. T. J. Phys. Chem B. 2002,
104, 7818.
31. de Silva, A. P.; Sandanayake, K. R. A. S. Angew. Chem., Int. Ed.
Engl. 1990, 29, 1173–1175.
32. For the complexes of receptor 1, with guests, [A0/(A À A0)] as a
function of the inverse of carboxylate (guest) the concentration fits a