A selective chromogenic chemosensor for carboxylate salt recognition

Article abstract of DOI:10.1039/c0cc05537a

A new heteroditopic chromogenic chemosensor bearing a crown ether substituted at the intraannular position with a nitrophenylthiourea moiety has been synthesized. The binding behavior of this sensor was investigated by ¹H NMR spectroscopy and U

Full text of DOI:10.1039/c0cc05537a

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COMMUNICATION
A selective chromogenic chemosensor for carboxylate salt recognitionw
Piotr Pia˛tek*
Received 13th December 2010, Accepted 24th February 2011
DOI: 10.1039/c0cc05537a
A new heteroditopic chromogenic chemosensor bearing a crown
ether substituted at the intraannular position with a nitrophenyl-
thiourea moiety has been synthesized. The binding behavior of
this sensor was investigated by 1H NMR spectroscopy and
UV-vis spectroscopy. The receptor binds in a cooperative fashion
to both a potassium cation and a carboxylate anion whereas a
sodium cation sequesters an anion from the anion–receptor
complex. The binding events are confirmed by selective color
changes of the chemosensor solution.
The simultaneous complexation of alkali metal cations and
accompanying anions by heteroditopic molecular receptors
has received increasing attention over the past decade. The
development of this area of supramolecular chemistry is
stimulated by the considerable benefits gained from binding
an ion pair. The complexation of both the cation and anion by
Fig. 1 Proposed binding mode for the complex of 1 and KAcO.
a ditopic receptor enhances salt lipophility, thus facilitating its
solubilization, extraction and membrane transport.1 Further-
more, the binding of the first ion can affect the subsequent
coordination of the counterion. This cooperative effect can
significantly increase the binding affinity between the receptor–
cation complex and anions which poorly coordinate to mono-
topic molecular receptors (i.e. BrÀ, NO3À, ClO4À).2
Subsequent addition of Na+ or Li+ results in loss of the
orange-red color.
We report herein the design, synthesis, salt binding and
sensing ability of novel heteroditopic molecular sensor 1 which
features both a cation binding site in the form of benzocrown
ether and an anion binding site/chromophore in the form of a
nitrophenylthiourea moiety (Fig. 1). The most challenging
problem in the design of convergent heteroditopic receptors
is the proper spatial arrangement of the binding sites. There-
fore, to ensure close proximity of the binding domains, the
thiourea pendant group was situated at an intraannular posi-
tion of the benzocrown moiety. Furthermore, the urea and
crown ether subunits were linked through a five-atom spacer
containing an oxygen atom (an additional cation binding site).
The synthesis of the target receptor was accomplished in
three steps starting from known 2-hydroxy-1,3-xylyl-21-
crown-6 (Scheme 1).7 The alkylation of the phenolic group
with 2-(2-Cbz-aminoethoxy)ethyl tosylate in the presence of
K2CO3 and subsequent cleavage of the protecting group gave
the amino derivative, which after acylation with nitro-
phenylthiocyanate led to receptor 1 in 40% overall yield as
pale-yellow crystals.
Although a number of chromogenic chemosensors capable
of sensing alkali metal cations or anions are known, systems
that are able to detect and differentiate alkali metal salts are
rare.3 The pioneering work in chromogenic sensing of alkali
metal ion-pairs was reported by Kim and Hong, who prepared
a Zn–porphyrin (anion binding site, chromophore) crown
ether (cation binding site) conjugate.4 This receptor binds in
a ditopic fashion selectively to NaCN, resulting in a dramatic
color change. Miyaji, Tucker and coworkers have synthesized
a ditopic receptor that contains nitrophenylurea and crown
ether units linked by a ferrocene moiety.5 The color change of
the receptor solution occurs only in the presence of fluoride,
and in the absence of a potassium cation. Similarly, addition
of fluoride to the solution of the heteroditopic receptor
reported by Yen and coworkers causes the color of the
solution to change from light-yellow to orange-red.6
The binding properties of receptor 1 were initially investi-
gated by 1H NMR spectroscopic titration methods in CD3CN
solution. Addition of alkali metal cations to the 2 mM solution
of 1 causes small, nonlinear upfield shifts of aliphatic and
benzylic protons of the macrocycle, indicating cation binding
to the crown ether subunit. Nonlinear regression of the
Department of Chemistry, University of Warsaw, Pasteura 1,
02-093 Warsaw, Poland. E-mail: ppiatek@chem.uw.edu.pl;
Fax: +48 22 822 5996; Tel: +48 22 822 0211
w Electronic supplementary information (ESI) available: Synthesis
and characterization data for compound 1, general procedures used
for 1H NMR and UV-vis titration experiments. See DOI: 10.1039/
c0cc05537a
c
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Chem. Commun., 2011, 47, 4745–4747 4745

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Table 2 Anion association constants data
Anion
AcOÀ
Cation
Ka/MÀ1 a
TBA+
K+
103 000
278 000
83 000
273 000
16 000
PhCOOÀ
TBA+
K+
TBA+
À
H2PO4
a
Determined at a receptor concentration of 5.8 Â 10À5 M in dry
CH3CN at 295 K by UV-vis spectroscopic titration, errors estimated
to be o10%. Cations and anions were added as their hexafluoro-
phosphate and tetra-n-butylammonium salts, respectively.
absorption band at ca. 465 nm is an indication of the anion-
induced deprotonation of one of the thiourea NH hydrogen
atoms.9 Moreover, the presence of two sharp isosbestic points
at 256 and 350 nm implies that only two species coexist at the
equilibrium point. The 1 : 1 binding stoichiometry was verified
by a Job plot analysis. The association constants calculated by
the nonlinear regression analysis of binding isotherms are
presented in Table 2.10
Scheme 1 The synthesis of compound 1.
Table 1 Cation association constants data
Association constants/MÀ1 a
The receptor 1 binds strongly to the Y-shaped carboxylate
anions, which is a typical feature of thiourea based receptors.11
The binding of tetrahedral anions, like dihydrogenphosphate,
is significantly weaker. No perturbations of the UV-vis spectrum
of 1Àare observed upon addition of ClÀ, BrÀ, NO2À, HSO4À or
BF6 ions (tetra-n-butylammonium salts) in the presence or
absence of metal cation (hexafluorophosphate) salts.
Na+
K+
TBA+ b
Receptor
c
—
1
70
1270
a
Determined in dry CD3CN at 295 K by the 1H NMR technique,
errors estimated to be o10%. Cations were added as their hexafluoro-
b
phosphate salts. TBA—tetra-n-butylammonium cation. No binding.
c
The presence of various alkali metal cations significantly
alters the anion binding ability of receptor 1 (Table 2). Specifi-
cally, titration of a solution containing receptor 1 and 1 molar
equivalent of NaPF6 with acetate provides Ka E 50 000 which
indicates that the sodium cation lowers the acetate affinity of 1.
Since in the presence of Na+ some perturbation of the acetate
binding isotherm was observed, an analogous titration was
conducted in the presence of 5 molar equivalents of NaPF6
(Fig. 2). Addition of the first equivalent of acetate only slightly
reduced anion binding affinity. After this point, the binding
isotherm initially decreases before rising to a maximum. This
clearly indicates that the sodium cation is able to sequester the
acetate anion from the receptor which prevents anion–receptor
binding.12 There are likely two factors that contribute to this
effect. First, the affinity of receptor 1 for Na+ is low and hence
resulting titration curves suggests 1 : 1 complex stoichiometry
and the experimental stability constants are listed in Table 1.
Table 1 clearly shows that receptor 1 can effectively bind a
potassium cation, whereas binding of a sodium cation is much
weaker. No perturbation of the 1H NMR spectra was observed
upon addition of TBA+PF6À. Interestingly, alkali cation
addition to the solution of 1 leads to significant downfield
shifts of both thiourea NH signals (Dd r 0.3). This effect may
be attributed to breaking of the intermolecular hydrogen
bonds between thiourea NH’s and ether oxygens of the macro-
cycle. This may be tentatively attributed to a conformational
change of the pendant group upon cation complexation,
allowing interaction of the cation with the sulfur lone pair
(Fig. 1).
The addition of tetra-n-butylammonium acetate or benzoate
to a solution of 1 causes dramatic upfield shifts of the thiourea
NH signals (Dd 4 4 ppm) indicating strong interaction
between the receptor and the anions. The anion binding of 1
1
is too strong to allow quantitative analysis of the H NMR
spectroscopic titration binding isotherms to be determined.8
However, after addition of carboxylate anions to a solution of
receptor 1, the solution changes from colorless to yellow.
Thus, anion-binding properties of 1 could be probed by
UV-vis spectroscopic analysis.
Upon addition of anions to the 4.8 Â 10À5 M solution of 1,
the band centered at 344 nm undergoes a distinct red-shift to
367 nm. This shift is attributed to the hydrogen bond formation
between the two thiourea NH groups and the two oxygen atoms
of the carboxylate ion. Importantly, no additional absorption
band at a longer wavelength is observed. The presence of an
Fig. 2 Titration binding profiles for recÀeptor 1 with acetate (TBA salt)
in the presence of various cations (PF6 salts). [1] = 5.8 Â 10À5 M,
CH3CN, T = 295 K, l = 367 nm.
c
4746 Chem. Commun., 2011, 47, 4745–4747
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the concentration of uncomplexed sodium cations is high.
Second, the ion-pair association constants for sodium salts
in most organic solvents are relatively high (e.g. for sodium
benzoate Ka = 200 in DMSO), therefore formation of the
sodium acetate salt in solution is favored.13 Similar effects
were observed for a benzoate anion whereas dihydrogen-
phosphate addition resulted in the rapid formation of a
precipitate.
anion are coordinated to the receptor in a cooperative fashion.
In contrast, a sodium cation can sequester a carboxylate
anion away from receptor 1. These different modes of
cation and anion binding are accompanied by specific color
changes of solutions of sensor 1. Thus, sensor 1 allows for the
chromogenic detection and discrimination of tetra-n-butyl,
sodium and potassium acetates.
Financial support from The State Committee for Scientic
Research (project T09A-012-030) is gratefully acknowledged.
In contrast, titration experiments of 1 with acetate and
benzoate in the presence of potassium cation showed enhance-
ment of carboxylate affinities (Table 2).14 The metal-induced
enhancement factors (KK+/KTBA+) for acetate and benzoate
are 2.7 and 3.2 respectively. Such cooperative effects could be
rationalized considering the formation of ligand-separated ion
pairs where the interactions between the anion and the cation
occur through a thiourea group (Fig. 1). On the other hand,
such cooperative effects are in agreement with a trend that
metal-induced enhancements are moderate for the more basic
anions such as carboxylates.15
Notes and references
1 B. D. Smith and J. M. Mahoney, in Encyclopedia of
Supramolecular Chemistry, ed. J. L. Atwood and J. W. Steed,
Pergamon, New York, 2004, pp. 1291–1294; J. W. Steed and
J. L. Atwood, Supramolecular Chemistry, John Wiley & Sons,
2009, pp. 286–298; G. J. Kirkovits, J. A. Shriver, P. A. Gale and
J. L. Sessler, J. Inclusion Phenom. Macrocyclic Chem., 2001,
41, 69–75; S. K. Kim and J. L. Sessler, Chem. Soc. Rev.,
2010, 39, 3784–3809; J. M. Mahoney, G. U. Nawaratna,
A. M. Beatty, P. J. Duggan and B. D. Smith, Inorg. Chem.,
2004, 43, 5902–5907.
Unfortunately, the addition of alkali cations to the solution
of dihydrogenphosphate led to the formation of a precipitate.
Finally, Fig. 3 displays the visual aspects of acetate ion
recognition and sensing in the presence of alkali metal cations.
Each vial contains a 7.7 Â 10À4 M solution of 1 in CH3CN.
The addition of five equivalents of TBAAcO induces the
appearance of a bright yellow color (vial b). Subsequent
addition of five equivalents of sodium ions to this solution
causes disappearance of the yellow color (vial c). As mentioned
above, this phenomenon is caused by sequestration of the
acetate anion from the receptor to form a more stable ion-pair
in solution. Upon addition of potassium cations, however, the
initial yellow color substantially fades to a pale yellow color
(vial d).16 This observation supports the proposed salt binding
mode illustrated in Fig. 1. The cation interaction with the
sulfur lone pair promotes electron density transfer from the
anion–1 complex to the cation, which alters the intensity of the
UV-vis spectra.
2 V. Amendola, D. Esteban-Gomez, L. Fabbrizzi, M. Licchelli,
E. Monzani and F. Sancenon, Inorg. Chem., 2005, 44,
8690–8698; J. C. Gong and B. C. Gibb, Chem. Commun., 2005,
1393–1395; C. Suksai, P. Leeladee, D. Jainuknan, T. Tuntulani,
N. Muangsin, O. Chailapakul, P. Kongsaeree and C. Pakavatchai,
Tetrahedron Lett., 2005, 46, 2765–2769; P. R. A. Webber and
P. D. Beer, J. Chem. Soc., Dalton Trans., 2003, 2249–2252;
P. D. Beer, P. K. Hopkins and J. D. McKinney, Chem. Commun.,
1999, 1253–1254.
3 A. W. Czarnik, Chem. Biol., 1995, 2, 423–428; R. C. Helgeson,
B. P. Czech, E. Chapoteau, C. R. Gebauer, A. Kumar and
D. J. Cram, J. Am. Chem. Soc., 1989, 111, 6339–6350;
H. G. Loehr and F. Vogtle, Acc. Chem. Res., 1985, 18, 65–72.
4 Y. H. Kim and J. I. Hong, Chem. Commun., 2002, 512–513.
5 H. Miyaji, S. R. Collinson, I. Prokes and J. H. Tucker, Chem.
Commun., 2003, 64–65.
6 Y. P. Yen, C. L. Chen, T. M. Fu, C. Y. Wu and C. Y. Lin, Aust. J.
Chem., 2006, 59, 805–811.
7 C. M. Browne, G. Ferguson, A. M. McKervey, L. D. Mulholland,
T. O’Connor and M. Parvez, J. Am. Chem. Soc., 1985, 107,
2703–2712.
8 L. Fielding, Tetrahedron, 2000, 56, 6151–6170.
9 M. Boiocchi, L. Del Boca, D. E. Gomez, L. Fabbrizzi, M. Licchelli
´
In conclusion, we have succeeded in preparing a hetero-
ditopic chromogenic ion-pair sensor 1 that is able to bind and
optically detect acetate as well as benzoate anions. In the
presence of a potassium cation the affinity of 1 for both acetate
and benzoate increases, which indicates that the cation and
and E. Monzani, J. Am. Chem. Soc., 2004, 126, 16507–16514.
10 According to referee’s comment, in order to maintain constant
ionic strength, analogous titrations have been performed in the
presence of 100 eq. of TBAPF6. The Ka values for complexes of 1
with acetate and acetate in the presence of 5 eq. KPF6 are 114 000
and 255 000, respectively. These values are in agreement with the
Ka’s determined in the absence of TBAPF6.
11 V. Amendola, L. Fabbrizzi and L. Mosca, Chem. Soc. Rev., 2010,
39, 3889–3915.
12 G. Tumcharern, T. Tuntulani, S. J. Coles, M. B. Hursthouse and
J. D. Kilburn, Org. Lett., 2003, 5, 4971–4974.
13 W. N. Olmstead and F. G. Bordwell, J. Org. Chem., 1980, 45,
3299–3305.
14 1-n-Butyl-3-(4-nitrophenyl)thiourea, a monotopic analogue of 1,
binds benzoate with a Ka value of 85 600. However, in the presence
of 5 eq. of KPF6 the binding constant decreases to 66 000. Thus
ion-pairing with a competing cation diminishes anion basicity,
which results in Ka decrease (see ref. 15).
15 R. Shukla, T. Kida and B. D. Smith, Org. Lett., 2000, 2,
3099–3102.
16 In order to obtain distinct color changes in Fig. 3, the receptor
concentration was relatively high (7.7 Â 10À4 M). At this concen-
tration, a substantial amount of KAcO in solution is formed, thus
some sequestering of acetate from the receptor is possible. How-
ever, we did not observe this effect at the concentration where the
UV-vis titration was performed (4.8 Â 10À5 M).
Fig. 3 Changes in the color of 7.7 Â 10À4 M solutions of receptor 1 in
CH3CN. (a) 1; (b) 1 + TBAAcO (5 equiv.); (c) 1 + TBAAcO (5 equiv.) +
NaPF6 (5 equiv.); (d) 1 + TBAAcO (5 equiv.) + KPF6 (5 equiv.).
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 4745–4747 4747