Pyridinium amide-based simple synthetic receptor for selective recognition of dihydrogenphosphate

Article abstract of DOI:10.1016/j.tetlet.2009.09.043

A new fluorescent receptor 1 built on biphenyl motif has been designed and synthesized. Pyridinium amide moiety .1 acts as binding site and shows selective complexation of isophthalate and H₂PO₄- under the mastery of biphenyl spacer.

Full text of DOI:10.1016/j.tetlet.2009.09.043

Tetrahedron Letters 50 (2009) 6557–6561
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Pyridinium amide-based simple synthetic receptor for selective recognition
of dihydrogenphosphate
a
b
Kumaresh Ghosh a, , Avik Ranjan Sarkar , Amarendra Patra
*
a Department of Chemistry, University of Kalyani, Kalyani, Nadia 741 235, India
b Department of Chemistry, University College of Science, 92 A.P.C Road, Kolkata 700 009, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 July 2009
Revised 5 September 2009
Accepted 9 September 2009
Available online 12 September 2009
A new fluorescent receptor 1 built on biphenyl motif has been designed and synthesized. Pyridinium
amide moiety in 1 acts as binding site and shows selective complexation of isophthalate and H2PO4
ꢀ
under the mastery of biphenyl spacer. Binding-induced increase in emission was used to determine
ꢀ
the selectivity and sensitivity of 1 toward a series of anions such as different dicarboxylates, HSO4
,
ClO4ꢀ, and H2PO4ꢀ. The binding characteristics were established by 1H NMR, UV–vis, and fluorescence
spectroscopic methods.
Keywords:
2,20-Diphenic acid
PET sensor
Ó 2009 Elsevier Ltd. All rights reserved.
Anthracene
Pyridinium amide
Dihydrogenphosphate
Design and synthesis of hydrogen-bonding fluororeceptor for
selective sensing of anions are the focus of interest for chemists
in the past decade due to the important roles of anions in many
biological and chemical systems.1–6 In developing such receptors
searching of new binding sites and their placement onto the differ-
ent rigid and semi rigid spacers are challenging tasks. Among the
different binding motifs for anions, the hydrogen-bonding proper-
ties of NH groups in neutral amines,7 amide,8 urea/thiourea,9,10 in-
dole,11 pyrrole,12 guanidinium,13 and imidazolium14 groups are
well established. In this connection, pyridinium amide motif for
anions is less explored. To investigate the significance of uncon-
ventional C–Hꢁ ꢁ ꢁO hydrogen bonds in highly polar solvents for car-
boxylate ion recognition, Jeong and Cho reported the use of a
pyridinium salt.15 This pyridinium motif was further used by Steed
and co-workers16 in the synthesis of tripodal-shaped receptor for
selective sensing of Clꢀ ion. During the course of our work on anion
binding we placed these pyridinium motifs onto the different scaf-
folds for fluorometric assessment of specific anion.17,18 Later, this
idea was extended by Gong and Hiratani for the synthesis of tripo-
dal receptor for dihydrogenphosphate.19 Selective recognition of
dihydrogenphosphate is an important topic and various receptors
of different topologies are known in the literature.20–22 In the pres-
ent study we report a new fluororeceptor 1 which elegantly shows
selective binding of H2PO4ꢀ, HSO4ꢀ, and isophthalate in CHCl3 con-
taining 2% CH3CN. Binding-induced significant change in emission
intensity of 1 at 513 nm clearly distinguishes H2PO4ꢀ, HSO4ꢀ, and
isophthalate from other anions studied.
-
PF6
H
N
N
O
N
PF6
O
N
H
-
1
The receptor 1 was synthesized according to Scheme 1. Initially,
2,20-diphenic acid was converted to the corresponding diacid chlo-
ride 2 which was subsequently coupled with 3-aminopyridine in
dry CH2Cl2 in the presence of Et3N to afford the diamide 3. Diamide
3 was isolated in low yield due to poor reactivity of 3-aminopyri-
dine. After work-up, unreacted 3-aminopyridine was recovered.
On refluxing diamide 3 in the presence of 9-chloromethylanthra-
cene in dry CH3CN and DMF solvent mixture for 36 h, the chloride
salt 4 was obtained in 22% yield. Due to poor solubility of diamide
3 in CH3CN the chloride salt 4 was isolated in low yield. The anion
exchange using NH4PF6 gave the receptor 1 as light yellow solid.
Compound 1 was fully characterized by 1H NMR, 13C NMR, and
mass spectroscopy.23
Prior to study the complexation, gas phase optimization of 1
* Corresponding author. Tel.: +91 33 25828750; fax: +91 33 258282.
E-mail address: ghosh_k2003@yahoo.co.in (K. Ghosh).
was performed at AM1 level.24 The conformational behavior of
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.043

6558
K. Ghosh et al. / Tetrahedron Letters 50 (2009) 6557–6561
-
PF6
H
N
N
O
N
O
N
-
PF6
H
1
H
N
i
COOH
COOH
COCl
COCl
N
ii
O
iii
O
N
N
H
2
3
Cl-
H
iv
N
O
N
1
+
+
N
Cl-
O
N
H
4
Scheme 1. Reagents and conditions: (i) PCl5, dry C6H6; (ii) 3-aminopyridine, Et3N, in dry CH2Cl2 (isolated yield: 39%); (iii) 9-chloromethylanthracene in dry CH3CN and DMF
mixture, reflux for 36 h (isolated yield: 22%); and (iv) NH4PF6, aq CH3OH (yield: 57%).
biphenyl system provides a well-defined cleft for complexation
400
(Fig. 1). In the energetically favorable conformation anthracenes
0
Receptor1
Acetate
are aligned in the same face showing a distance of 4.48 ÅA.
The ability of the receptor 1 toward anion recognition was eval-
uated by 1H NMR, fluorescence, and UV–vis spectroscopic meth-
ods. The fluorescence spectrum of 1 in CHCl3 containing 2%
CH3CN solution showed a strong emission band at 413 nm attrib-
uting to the anthryl group (excitation at 370 nm) along with a
weak emission at 513 nm. The emission at 513 nm is aroused
due to the formation of excimer between the closely spaced
anthracene.25 Upon addition of H2PO4ꢀ, HSO4ꢀ, ClO4ꢀ, and differ-
ent dicarboxylates in the form of their tetrabutylammonium
(TBA) salts, the emission intensity at 413 nm was increased mar-
ginally. In comparison, the emission at 513 nm was enhanced
and it varied with the nature of the guest. Figure 2 represents
the change in emission of 1 in the presence of 10 equiv amounts
of different guests. As can be seen from Figure 2, only upon addi-
tion of H2PO4ꢀ a marked change in emission at 513 nm is observed.
Other anions such as acetate and different dicarboxylates exhibit
weak effect. Among the isomeric aromatic dicarboxylates, iso-
Glutarate
H2PO4-
300
200
100
0
Isophthalate
Malonate
Succinate
Terephthalate
Phthalate
HSO4-
Perchlorate
400
450
500
550
600
650
Wavelength (nm)
Figure 2. Change in fluorescence emission of 1 (c = 6.617 ꢂ 10ꢀ5 M) in the presence
of 10 equiv amounts of tetrabutylammonium salt of different guests.
Figure 1. (a) AM1-optimized geometry (E = ꢀ327.542 au), (b) positions of HOMO, and (c) LUMO in 1.

K. Ghosh et al. / Tetrahedron Letters 50 (2009) 6557–6561
6559
phthalate shows stronger interaction. A similar effect is observed
500
400
300
200
100
0
in the presence of HSO4ꢀ. Perchlorate anion did not show any mea-
surable interaction. Figure 3 shows the comparison of change in
emission of 1 at 513 nm in the presence of 10 equiv amounts of a
particular guest in CHCl3 containing 2% CH3CN. It is evident from
Figure
3 that the receptor 1 has a clear-cut selectivity for
H2PO4ꢀ. Figures 4 and 5 display the change in emission of 1 upon
ꢀ
gradual addition of H2PO4 and isophthalate into the solution of 1
in CHCl3 containing 2% CH3CN, respectively.
The observed increase in emission upon complexation is attrib-
uted to the inhibition of PET process occurring in-between the ex-
cited state of anthracene and pyridinium amide-binding site. The
assignment of HOMO and LUMOs in the optimized geometry of 1
(see Fig. 1) clearly demonstrates the direction of PET process in
the uncomplexed state. The strong enhancement of emission at
ꢀ
400
450
500
550
600
650
513 nm in the presence of tetrahedral-shaped H2PO4 is corrobo-
Wavelength (nm)
rated by its strong hydrogen bonding and charge–charge interac-
tions into the binding cleft according to the mode A (host/
guest = 1:1) shown in Figure 6. At the higher concentration of
Figure 4. Change in emission of 1 (c = 6.617 ꢂ 10ꢀ5 M) in the presence of increasing
ꢀ
amounts of H2PO4 (10 equiv) in CHCl3 containing 2% CH3CN.
ꢀ
H2PO4 the binding may take place via mode B involving either
1:1 (guest/host) or 2:1 (guest/host) binding stoichiometry and this
may remain in equilibrium with mode A in solution (Fig. 6). How-
ever, binding of H2PO4 in mode A results in a subtle conforma-
500
1.5
ꢀ
tional change of 1 for which anthracene moieties are pulled more
closely for the formation of stable and stronger excimer.
400
1.0
This is indeed found less effective in the presence of dicarboxyl-
ates although isophthalate exhibited a weak change in emission of
the excimer. This has presumably happened due to bulkier nature
of the dicarboxylate guest that weakens the binding in the mode A
as shown in Figure 6. This was supported by the titration experi-
ment of 1 with AcOꢀ. Upon increasing the addition of AcOꢀ to
the solution of 1 the excimer emission at 513 nm was almost
unperturbed (see Supplementary data). This underlines the fact
that simultaneous coordination of the two arms of 1 via hydrogen
bonding and charge–charge interactions are necessary for a change
in emission intensity at 513 nm.
300
0.5
200
0.0
300
350
400
450
Wavelength (nm)
100
0
400
450
500
550
600
650
To realize the ground state interaction, simultaneous UV–vis
titration experiments of 1 with the guests were carried out under
controlled conditions. The change in absorbance of 1 was apprecia-
Wavelength (nm)
Figure 5. Change in emission of 1 (c = 6.617 ꢂ 10ꢀ5 M) in the presence of increasing
amounts of isophthalate; inset: UV–vis titration spectra of 1 (c = 6.617 ꢂ 10ꢀ5 M)
upon gradual addition of isophthalate (10 equiv) in CHCl3 containing 2% CH3CN.
ꢀ
ble in the presence of H2PO4 anion. Other anions, that is, the dif-
ferent dicarboxylates (both aliphatic and aromatic) interacted
weakly thereby resulting in minor changes in UV–vis spectra of 1
(see Supplementary data). Figure 7 shows the UV–vis titration
spectra of 1 upon gradual addition of H2PO4ꢀ. Inset of Figure 5 indi-
cates the change in absorbance of 1 in the presence of isophthalate.
In order to understand the binding potencies and selectivities of
1 for the anions studied, fluorescence and UV–vis titration data
were used to calculate the binding constant values (Table 1).26 It
is evident from Table 1 that the receptor 1 exhibits a selectivity
for H2PO4 accompanying with a higher binding constant value.
The binding constant for H2PO4 is particularly found to be higher
ꢀ
ꢀ
Perchlorate
Acetate
in the excited state and it is presumably due to more polar charac-
ter of the receptor in the excited state. On the other hand, iso-
phthalate was bound strongly compared to its isomers and other
aliphatic dicarboxylates. It is suggested that when receptor 1 binds
with isophthalate, the two binding arms in the non-planar cavity
are cooperatively involved for compact chelation for which the ap-
pended anthracenes form excimer with significant intensity. This is
in contrast to phthalate where the excimer intensity is less com-
pared to the case of isophthalate and the excimer is disrupted at
high concentration of phthalate (see Supplementary data). Thus
the non-planar arrangement of the binding groups around the
biphenyl spacer of 1 has an influence in discriminating the iso-
meric dicarboxylates. The stoichiometries of the complexes were
ascertained from the break of the fluorescence titration curves
(Fig. 8). From the broadening nature of the curve for H2PO4ꢀ shown
in Figure 8, it was difficult to determine the exact stoichiometry of
the complex of 1 with H2PO4ꢀ. For other anions, curvature at [G]/
Succinate
Glutarate
malonate
Phthalate
terephthalate
Hydrogensulphate
Isophthalate
Dihydrogenphosphate
0
2
4
6
8
10 12 14 16 18
ΔI/I0
Figure 3. Fluorescence ratio (
upon addition of 10 equiv tetrabutylammonium salt of a particular anion.
D
I/I0) of receptor 1 (c = 6.617 ꢂ 10ꢀ5 M) at 513 nm

6560
K. Ghosh et al. / Tetrahedron Letters 50 (2009) 6557–6561
H
O
H
O
O
P
O
N
O
N
O
-
PF6
-
-
N
H
H
N
H2PO4
H2PO4
H
N
H
N
H
N
O
O
N
O
O
N
H
O
H
P
N
-
H
PF6
O
O
H
H
O
N
1
N
H
O
P
mode B
H
mode A
O
O
H
O
H
ꢀ
Figure 6. Possible hydrogen bonding modes of complexation of 1 with H2PO4
.
1.5
1.0
0.5
0.0
500
400
300
200
100
0
H2PO -
Isopht4halate
Malonate
Succinate
Glutarate
Terephthalate
Phthalate
HSO4-
300
350
400
450
500
0
2
4
6
8
10
Wavelength (nm)
[G]/[H]
Figure 7. Change in UV–vis spectra of 1 (c = 6.617 ꢂ 10ꢀ5 M) in the presence of
Figure 8. Plot of change in emission of 1 at 513 nm versus the ratio of guest to host
concentration.
ꢀ
increasing amounts of H2PO4 (10 equiv) in CHCl3 containing 2% CH3CN.
Table 1
Binding constant values for 1 with the guests in CHCl3 containing 2% CH3CN
2.0x10-5
a,e
Guests
Ka (Mꢀ1
)
Ka (Mꢀ1
)
b,e
c
Acetated
6.61 ꢂ 102
8.35 ꢂ 103
1.39 ꢂ 103
6.04 ꢂ 102
2.98 ꢂ 103
3.40 ꢂ 102
9.65 ꢂ 102
2.45 ꢂ 102
5.29 ꢂ 102
8.31 ꢂ 102
1.5x10-5
Dihydrogenphosphated
Hydrogen sulfated
Perchlorate
Isophthalate
Phthalate
1.22 ꢂ 104
2.36 ꢂ 103
(G:H = 1:1)
c
1.0x10-5
2.73 ꢂ 103
8.37 ꢂ 102
5.03 ꢂ 102
1.71 ꢂ 102
3.52 ꢂ 102
6.95 ꢂ 102
(G:H = 2:1)
Terephthalate
Glutarate
Malonate
5.0x10-6
0.0
Succinate
a
b
c
Determined by UV method at 375 nm.
Determined by fluorescence at 513 nm.
Not determined due to irregular and minor changes.
d
e
0.0
0.2
0.4
0.6
0.8
1.0
Based on K11
.
XG
Error <10%.
ꢀ
Figure 9. UV–vis Job plot of 1 with H2PO4
.
[H] = 1 stated 1:1 binding mode. The 1:1 stoichiometry of the com-
plexes was further proved by Job plots (see Supplementary data).
Figure 9 represents the UV Job plot for 1 with H2PO4ꢀ. In the plot,
a maximum at 0.5 mol fraction was observed along with a small
inflection at 0.66 mol fraction of the guest. This, indeed, underlines
the fact that the receptor 1 initially forms 1:1 complex with
ꢀ
job (Supplementary data) was noticed. Like H2PO4ꢀ, HSO4 exhib-
ited an equilibrium between 1:1 and 2:1 stoichiometries of the
complexes (see Supplementary data).
In quest of application of this simple receptor in aqueous sys-
tem we performed the complexation study of 1 in aq CH3CN
(CH3CN/H2O = 4:1 v/v) with different phosphate salts. Surprisingly,
ꢀ
H2PO4 ion and then equilibrates to a 2:1 stoichiometry in the
ꢀ
presence of excess H2PO4 ion. A similar situation in fluorescence

K. Ghosh et al. / Tetrahedron Letters 50 (2009) 6557–6561
6561
Hm
-
PF6
N
H
Ho'
Hb
N
Hp
O
N
PF6
O
Hb
-
N
Ho
Ha
1
Hc
Figure 10. Partial 1H NMR (300 MHz, CDCl3 containing 2% CD3CN) spectra of (a) 1 and its 1:1 complexes with (b) H2PO4 and (c) isophthalate.
ꢀ
the excimer emission of 1 at longer wavelength was completely
destroyed in aq CH3CN and no measurable change in monomer
emission was observed during titration with the phosphate salts
(see Supplementary data). This suggested weak or no interactions
of 1 in aq CH3CN.
Supplementary data
Supplementary data (Figures showing the change in absorption
and fluorescence spectra and the Job plots of receptor 1 in presence
of the guests, Binding constant curves, Change in emission of 1 in
presence of different phosphate salts in aq CH3CN are available)
associated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2009.09.043.
However, the expected strong interaction between 1 and
ꢀ
H2PO4 in CDCl3 containing 2% CD3CN was further confirmed by
1H NMR (Fig. 10). As shown in Figure 10, the amide proton Ha,
pyridinium proton Ho of 1 underwent downfield chemical shifts
of 0.97 and 0.28 ppm, respectively, in the presence of equivalent
References and notes
amount of H2PO4ꢀ. During interaction the pyridinium proton Ho
0
moved to the downfield direction (Dd = 0.26). Similarly, the pyrid-
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inium proton Hp, which appeared at 7.92 ppm underwent a down-
field chemical shift of 0.13 ppm upon complexation suggesting its
involvement in the binding process. This is evident from the
molecular modeling (Fig. 1) where one of the binding arms of 1
provides Hp toward the cavity for complexation. A similar findings
in 1H NMR were observed when equivalent amount of isophthalate
was added to the solution of 1
DdH = 0.24, DdH = 0.36, DdH = 0.36,
0
a o
o
and dH = 0.09; Fig. 10c). During the interaction of 1 with the
D
p
guests, the signal for Hb protons of 1 was split into two doublets
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In conclusion, we have designed a new type of dihydrogenphos-
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provides well-defined structure for efficient and selective com-
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ꢀ
plexation of H2PO4 with 1:1 binding stoichiometry. Although
the sensing and binding of 1 with isophthalate are not extremely
strong in the present study, the binding selectivity is high in com-
parison with isomeric and other dicarboxylate anions. Addition of
H2PO4ꢀ, HSO4ꢀ, and isophthalate to the solution of 1 in CHCl3 con-
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ꢀ
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are due to the combined effects of semi-rigid structures, charge–
charge interactions, and the involvement of both N–Hꢁ ꢁ ꢁO and C–
Hꢁ ꢁ ꢁO hydrogen bonds.
23. Mp 225 °C; 1H NMR (DMSO-d6, 400 MHz): d 11.07 (s, NH, 2H), 8.80 (s, 4H), 8.70
(s, 2H), 8.38 (br s, 2H), 8.34 (d, 4H, J = 6.4 Hz), 8.20 (d, 4H, J = 7 Hz), 7.95 (br s,
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125.3, 61.7; FTIR:
m
cmꢀ1 (KBr): 3375, 3062, 1665, 1627, 1591, 1556, 1499; m/z
Acknowledgments
(ES+): 921.6 [MꢀPF6ꢀ]+, 775.7 [Mꢀ1–2PF6ꢀ]+.
24. AM1 calculation was performed using minimal valance basis as STO 3G in
ArgusLab 4.0.1, copyright (c) 1997–2004 Mark Thompson and Planaria
Software LLC, http://www.arguslab.com.
We thank CSIR, Government of India for financial support. A.R.S.
thanks the University of Kalyani for providing a university research
fellowship. K.G. thanks DST, Government of India for providing
facilities in the department under FIST program.
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