Synthesis of colorimetric receptors for dicarboxylate anions: A unique color change for malonate

Article abstract of DOI:10.1016/j.tetlet.2005.12.009

Three new chromogenic receptors (1, 2, and 3) containing p-nitrophenyl or p-nitronaphthyl or methyl groups appended to the thiourea groups were synthesized and characterized. Upon addition of a series of dicarboxylate anions to receptor 1 in DMSO, only th

Full text of DOI:10.1016/j.tetlet.2005.12.009

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1193–1196
Synthesis of colorimetric receptors for dicarboxylate anions:
a unique color change for malonate
Yao-Pin Yen* and Kao-Wai Ho
Department of Applied Chemistry, Providence University, 200 Chungchi Road, Sha-Lu, Taichung Hsien 433, Taiwan
Received 14 November 2005; revised 30 November 2005; accepted 2 December 2005
Available online 20 December 2005
Abstract—Three new chromogenic receptors (1, 2, and 3) containing p-nitrophenyl or p-nitronaphthyl or methyl groups appended
to the thiourea groups were synthesized and characterized. Upon addition of a series of dicarboxylate anions to receptor 1 in
DMSO, only the appearance of the solution of receptor 1 with malonate showed a color change from blue to yellow which can
be detected by the naked eye at parts per million. With the addition of the series of dicarboxylate anions to receptor 2, the solutions
showed an indistinct intense dark-red color. Whereas the addition of the same dicarboxylate anions to receptor 3, the solutions did
not induce any color change. Thus, for the unique color change, the receptor 1 can act as an optical chemosensor for the malonate
anion even in the presence of other dicarboxylate anions.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The design and synthesis of sensitive chromogenic recep-
tors for detecting biologically important anions and
monitoring environmentally harmful anion pollutants
have attracted considerable attention in the field of
supramolecular chemistry.1 Particularly, dicarboxylates
play an important role in chemical and biological pro-
cesses. Dicarboxylates are critical components of
numerous metabolic processes including, for instance,
the citric acid and glyoxylate cycles.2 They also play
an important role in the generation of high-energy
phosphate bonds and in the biosynthesis of important
intermediates.3 To date, several receptors containing
different functional groups for selective binding of
dicarboxylate anions have been reported.4,5 However,
to our best knowledge, chromogenic sensors selecting
recognizing dicarboxylate anions are still limited.5 Here-
in, we report the synthesis and binding properties of
three new chromogenic receptors (1, 2, and 3) contain-
ing p-nitrophenyl or p-nitronaphthyl or methyl groups
appended to the thiourea groups. The anionic recogni-
tion of receptors has been investigated by UV–vis
ethylamino)-anthraquinone (4) in high yields (Scheme
1
1).6,7 All of these compounds were characterized by H
NMR, IR, and HRMS.
The colorimetric sensing ability of the receptors 1–3 with
a series of dicarboxylate anions ½ꢀO2CðCH2ÞnCO2ꢀꢁ such
as malonate, succinate, glutarate, adipate (n = 1, 2, 3, 4),
terephthalate and isophthalate in DMSO was monitored
by UV–vis absorption and by Ônaked eyeÕ observation.
The anions were added as tetrabutylammonium salts
to the DMSO solutions of the receptors 1–3 (5 ·
10ꢀ5 M). Figure 1 shows that the UV–vis absorption
spectra of a mixture of receptor 1 with different concen-
trations of malonate in DMSO. When increasing the
concentration of malonate, a new absorption band at
480 nm was gradually enhanced, while the intensity of
absorption at 362 nm was decreased correspondingly.
The color of the solution of receptor 1 was changed
from blue to yellow, which could be easily observed by
the naked-eyes. A clear isobestic point was observed at
393 nm. This result demonstrates that a complex forma-
tion of 1 with malonate anion is taking place via hydro-
gen bonding electrostatic interactions. The formation of
these hydrogen bonds affects the electronic properties of
the chromophore, resulting in a color change with a sub-
sequent new charge-transfer interaction between the
malonate-bound thiourea and electron deficient 4-nitro-
phenyl group.8 Judging from the titrations, the strong
binding of malonate allowed the JobÕs plot method9
(as shown in the inset of Fig. 1) to be used in the
1
absorption and H NMR spectroscopy.
The receptors 1–3 were synthesized by the reaction of
p-nitrophenylisothiocyanate or p-nitronaphthylisothio-
cyanate or methylisothiocyanate with 1,4-di-(2-amino-
*
Corresponding author. Tel.: +886 4 2632 8001x15218; fax: +886 4
2632 7554; e-mail: ypyen@pu.edu.tw
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.009

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Y.-P. Yen, K.-W. Ho / Tetrahedron Letters 47 (2006) 1193–1196
O
O
O
O
HO
O
OH
O
HN
NH
i
ii
HN
NH
NHb
HN
S
H2N
S
NH2
NHa
R
HN
R
4
1. R = p-NO2-phenyl (Yield : 81%)
2. R = p-NO2-naphthyl (Yield : 91%)
3. R = methyl (Yield : 69%)
Scheme 1. Reagents and conditions: (i) ethylenediamine, THF, 50 ꢁC, 2 h, 37.2%; (ii) R-isothiocyanate, THF, reflux, 18 h.
Figure 2. UV–vis changes of 1 operated in DMSO (5 · 10ꢀ5 M) after
the addition of 2 equiv of anion: (a) 1 only, (b) 1 + isophthalate, (c)
1 + terephthalate, (d) 1 + adipate, (e) 1 + glutarate, (f) 1 + succinate,
(g) 1 + malonate.
Figure 1. A family of spectra taken in the course of the titration of a
5 · 10ꢀ5 M DMSO solution in 1 with a standard solution of malonate
at 25 ꢁC titration profiles (insert) indicate the formation of a 1:1
complex.
determination of the binding stoichiometry, which was
found to be a 1:1 host-to-anion complexation.
Figure 3. Effect of anions (as (C4H9)N+ salt) on color changes of 1 in
DMSO: (a) 1 only, (b) 1 + isophthalate, (c) 1 + terephthalate, (d)
1 + adipate, (e) 1 + glutarate, (f) 1 + succinate, (g) 1 + malonate.
Parallel investigations were carried out with a series of
other dicarboxylate anions (succinate, glutarate, adi-
pate, terephthalate, and isophthalate). A similar phe-
nomena of UV–vis absorptions are observed in Figure
2. Spectrum (a) was measured in the absence of anions
where 1 has a UV–vis spectrum with kmax at 396, 596,
and 643 nm. As shown in spectrum (b)–(d), 1 exhibits
negligible perturbations upon addition of 2 equiv of iso-
phthalate, terephthalate, and adipate anions, respec-
tively. By contrast, significant changes are observed in
the presence of glutarate as well as other anions such
as succinate and malonate anions. As shown in spectra
(e)–(g), the CT absorption bands appear at 480 nm
and the solution color changes from blue to yellow color
(Fig. 3). Interestingly, the colors of (e) and (f) stay con-
sistently even at higher concentrations of glutarate or
succinate. It is apparent that 1 has a unique color change
and higher selectivity for malonate anion than other
anions. The selectivity of 1 for recognition of these
anions can be rationalized on the basis of the chain
length of the anionic species. The original blue color in
the host solution might be ascribed to the chromophore
of 1,4-diaminoanthraquinone moiety. The yellow color
(new absorption peak at 480 nm) could be explained
by the charge-transfer interactions between the elec-
tron-rich donor nitrogen of the thiourea units and the
electron-deficient p-nitrophenyl moieties. The receptor
bound anions, hydrogen bonds were constructed to
form stable complexes, and the electron density in the

Y.-P. Yen, K.-W. Ho / Tetrahedron Letters 47 (2006) 1193–1196
1195
tinct (Fig. 5). Judging from the titrations, the JobÕs plot
method (as shown in the inset of Fig. 4) proved the for-
mation of a 1:1 stoichiometry complex of 2 with malon-
ate. The association constants were calculated by the
Benesi–Hildebrand equation9 and listed in Table 1.
The data showed that receptor 1 has higher selectivity
for malonate than other dicarboxylate anions.
In order to gain a clear picture of how p-nitrophenyl or
p-nitronaphthyl unit affects the chromogenic property of
1 or 2, a UV–vis study was conducted on the control
compound 3. In contrast to both 1 and 2, 3 showed
two absorption bands at 596 and 643 nm in DMSO.
Upon gradual increase of the concentration of malon-
ate, the peaks at 596 and 643 nm were gradually de-
creased and no color change was observed. The JobÕs
plot of malonate in DMSO showed a 1:1 binding stoi-
chiometry, and the association constant was calculated
as 1.54 · 103 Mꢀ1 which is smaller than that for receptor
1 or 2. Based on the above results, the receptor 1 pro-
vides a suitable chromophore and a binding site for mal-
onate anion.
Figure 4. A family of spectra taken in the course of the titration of a
5 · 10ꢀ5 M DMSO solution in 2 with a standard solution of malonate
at 25 ꢁC titration profiles (insert) indicate the formation of a 1:1
complex.
1H NMR spectroscopy is of immense value in the under-
standing of receptor–substrate interaction and is capable
of providing a revealing picture of the details of the
interaction between receptor and dicarboxylate anions.
Addition of 1 equiv of the tetrabutylammonium salts
of malonate to 1 or 2 in DMSO-d6 caused remarkable
downfield shifts of the NH resonances in the 1H
NMR. In the case of 1 with malonate, the proton chem-
ical shifts of thiourea (Ha, Hb) changed from 10.26 to
11.00 (Dd = 0.74 ppm), 8.51 to 8.95 (Dd = 0.44 ppm),
respectively (Fig. 6). These larger downfield shifts indi-
cate the formation of two hydrogen bondings between
Ha, Hb and malonate. These results show that receptor
1 and malonate form a 1:1 stoichiometry complex via
Figure 5. Effect of anions (as (C4H9)N+ salt) on color changes of 2 in
DMSO: (a) 2 only, (b) 2 + isophthalate, (c) 2 + terephthalate, (d)
2 + adipate, (e) 2 + glutarate, (f) 2 + succinate, (g) 2 + malonate.
supramolecular system was much increased to enhance
the charge-transfer interactions between the electron-
rich and electron-deficient moieties, which resulted in a
visible color change.10
The UV–vis absorption spectral interactions of receptor
2 with malonate anion were studied by gradual addition
of different concentrations of malonate anion to a solu-
tion of receptor 2 and results are shown as Figure 4. The
initial absorption peak at 384 nm was gradually
decreased and a new absorption band appeared with a
maximum absorption at 523 nm. The color of the solu-
tion of receptor 2 with malonate was changed from blue
to dark-red. The color change can be attributed to the
appearance of a new long wavelength peak. This result
demonstrates that the receptor 2 formed complex with
malonate. Similarly, a dark-red color can be observed
while adding other dicarboxylate anions into the solu-
tion of 2 in DMSO, but the color changes were not dis-
1
Figure 6. Partial H NMR (400 MHz) spectra of sensor 1 (10 mM) in
DMSO-d6 at rt in: (a) sensor 1 only, (b) 1 + 1.0 equiv tetrabutylammo-
nium malonate.
Table 1. Association constants Ka (Mꢀ1) of receptors 1 and 2 with guest anions
Anion
Receptor 1 K (Mꢀ1 a
)
Rb
Receptor 2 K (Mꢀ1 a
)
Rb
Malonatec
Succinatec
Glutaratec
Adipatec
Terepthalatec
Isophthalatec
(1.39 0.03) · 104
(1.00 0.03) · 104
(6.22 0.29) · 103
(3.38 0.29) · 103
(3.21 0.10) · 103
(1.60 0.29) · 103
0.9937
0.9924
0.9957
0.9961
0.9967
0.9901
(1.42 0.02) · 104
(1.38 0.03) · 104
(1.20 0.02) · 104
(1.02 0.01) · 104
(1.17 0.03) · 104
(1.13 0.01) · 104
0.9967
0.9904
0.9976
0.9011
0.9919
0.9973
a The data were calculated from UV–vis titration in DMSO.
b The data values of R were obtained by the results of nonlinear curve fitting.
c The anions were used as their tetrabutylammonium salts.

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Y.-P. Yen, K.-W. Ho / Tetrahedron Letters 47 (2006) 1193–1196
Bianchi, A.; Fusi, V.; Garcia-Espana, E.; Giorgi, C.;
Llinares, J. M.; Ramirez, J. A.; Valtancoli, B. Inorg.
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hydrogen-bonding interaction between the thiourea with
carboxyl groups.
In conclusion, the new colorimetric anion receptors 1, 2,
and 3 were synthesized in high yields and can form 1:1
complex with dicarboxylate anions by multiple hydro-
gen bonding interactions. Among them, only the recep-
tor 1 has higher selectivity for the malonate and there is
a distinct color change that can be observed by the
naked-eyes. Thus, the receptor 1 can act as an optical
chemosensor for the malonate anion even in the pres-
ence of other dicarboxylate anions.
5. (a) Sancenon, F.; Martinez-Manez, R.; Miranda, M. A.;
Segui, M.-J.; Soto, J. Angew. Chem., Int. Ed. 2003, 42,
647–650; (b) Lavigne, J. J.; Anslyn, E. V. Angew. Chem.,
Int. Ed. 1999, 38, 3666–3669; (c) Metzger, A.; Anslyn, E.
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6. Data for 1: Yield 81%. Mp 213–214 ꢁC. 1H NMR
(400 MHz, DMSO-d6): d 3.74–3.76 (m, 8H), 7.71 (s, 2H),
7.75–7.77 (m, 4H), 7.80–7.82 (m, 2H), 8.14–8.16 (m, 4H),
8.25–8.27 (m, 2H), 8.49 (br s, 2H), 10.24 (br s, 2H), 10.90
(br s, 2H). 13C NMR (100 MHz, DMSO-d6): d 40.6, 44.1,
109.0, 120.9, 124.7, 125.9, 132.6, 134.0, 142.1, 146.2, 146.3,
180.7, 181.1. IR (KBr): m = 3329, 3067, 2933, 2858, 2356,
2335, 1639, 1598, 1511, 1326 cmꢀ1. UV (DMSO): 362 nm
(e = 3504), 596 nm (e = 9370), 643 nm (e = 8635). HRMS
(FAB): calcd for C32H28N8O6S2 [M+] 684.1576; found
684.1584. Compound 2: Yield 91%. Mp 206–207 ꢁC. 1H
NMR (400 MHz, DMSO-d6): d 3.72–3.75 (m, 8H), 7.67–
7.69 (m, 4H), 7.76–7.83 (m, 6H), 8.10 (d, J = 8.4 Hz, 2H),
8.26–8.31 (m, 6H), 8.41 (d, J = 8.4 Hz, 2H), 10.13 (br s,
2H), 10.92 (br s, 2H). 13C NMR (100 MHz, DMSO-d6): d
30.9, 40.8, 44.3, 108.9, 122.4, 122.9, 123.9, 124.8, 125.6,
125.9, 127.7, 129.5, 130.0, 132.7, 134.0, 141.0, 143.4, 146.4,
181.1, 182.2. IR (KBr): m = 3293, 3068, 2930, 2853, 2330,
Acknowledgements
We thank the National Science Council of the Republic
of China, for financial support (NSC 93-2113-M-126-
004).
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2005.12.009.
1639, 1568, 1506, 1311, 1265, 1168, 1045, 1025, 830 cmꢀ1
.
References and notes
UV (DMSO): 382 nm (e = 2510), 532 nm (e = 7493),
597 nm (e = 2662), 644 nm (e = 1442). HRMS(FAB):
calcd for C40H32N8O6S2 [M+] 784.1890; found 784.1891.
Compound 3: Yield 69%. Mp 219–220 ꢁC. 1H NMR
(400 MHz, DMSO-d6): d 2.66–2.81 (m, 6H), 3.63 (s, 8H),
7.57–7.65 (m, 6H), 7.78–7.80 (m, 2H), 8.23–8.25 (m, 2H),
10.89 (br s, 2H). 13C NMR (100 MHz, DMSO-d6): d
41.3, 108.8, 124.9, 125.9, 132.6, 134.1, 146.4, 181.0. IR
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