A thiourea-based chromoionophore for selective binding and sensing of acetate

Article abstract of DOI:10.1016/S0040-4039(01)00916-9

Highly selective binding and sensing of acetate over various monovalent inorganic anions (MeCO₂^-?H₂PO₄^- >Cl^-, Br^-, I^-, SCN^-, NO₃^-, HSO

Full text of DOI:10.1016/S0040-4039(01)00916-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 5053–5056
A thiourea-based chromoionophore for selective binding and
sensing of acetate
Ryo Kato, Seiichi Nishizawa, Takashi Hayashita and Norio Teramae*
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan
Received 8 May 2001; revised 23 May 2001; accepted 25 May 2001
Abstract—Highly selective binding and sensing of acetate over various monovalent inorganic anions (MeCO2−ꢀH2PO4−>Cl−, Br−,
I−, SCN−, NO3−, HSO4−, ClO4−) are achieved by N,N%-bis(p-nitrophenyl)thiourea as a hydrogen-bonding chromoionophore in 1%
water–99% MeCN (v/v), and acetic acid in vinegar is successfully determined by the complexation-induced chromogenic response
of this chromoionophore. © 2001 Elsevier Science Ltd. All rights reserved.
The design and synthesis of hydrogen-bonding recep-
tors for biologically and/or chemically important
anions are of current interest in host–guest chemistry.1,2
Several applications of hydrogen-bonding receptors in
transports and electrochemical sensors have been
reported. Hydrogen-bonding receptors with redox-
active and/or fluorogenic units have also been reported
for selective anion detection. By contrast, despite their
considerable advantage3–5 over other modes of signal
transduction, there are only a few reports on chro-
mogenic receptors that can recognize anions by a read-
ily observable color change.2h,4,5
trast to many papers describing the complexation prop-
erties of various types of (thio)urea derivatives in 100%
organic media,7 we investigated the complexation prop-
erties of 2 in water-containing medium rather than
100% organic medium. The experiment using water-
containing medium is quite important to show appli-
cability of synthetic molecules for the selective
determination of ions normally exist in aqueous phase.
Indeed, chromoionophore 2 is found to be more highly
selective for acetate than various monovalent inorganic
anions in 1% water–99% MeCN (v/v), making it possi-
ble to determine the concentration of acetic acid in
vinegar.8
We have recently shown that a very simple thiourea
conjugated with one p-nitrophenyl unit (1) binds anions
exclusively via formation of hydrogen bonds in MeCN
and produces a color change with a selectivity of
NO2
NO2
-
MeCO2
MeCO2 >H2PO4 >Cl−ꢀClO4 . We have also shown
that hydrogen bond-mediated complexation of anions
in aqueous media can be achieved by 1 located deep
inside the vesicle.6b From a practical viewpoint, how-
ever, complex strengths, binding selectivity and optical
responses are only moderate for 1 when used in the
colorimetric sensing of anions. We now report on the
synthesis of a thiourea-based chromoionophore with
two p-nitrophenyl units (2) and show that both com-
plex stability and optical responses can be significantly
improved by another introduction of a p-nitrophenyl
group into the (p-nitrophenyl)thiourea moiety. In con-
−
−
− 6a
-
O
O
H N
H N
H N
H N
S
S
R
R
1 R = Me
2 R = p-nitrophenyl
Compound 2 was synthesized analogously to 1 by
reacting p-nitroaniline with p-nitrophenyl isothio-
cyanate in THF–triethylamine, and purified three times
by recrystallization from THF.†
Keywords: hydrogen-bonding; ionophore; anion recognition; chro-
mogenic sensing; thiourea.
* Corresponding author. Tel.: +81 22 217 6549; fax: +81 22 217 6552;
e-mail: tera@anal.chem.tohoku.ac.jp
† Identifying data for 2: 1H NMR (270 MHz, in DMSO-d6): l 10.75
(s, br., 2H, NH), 8.23 (d, J=9.2 Hz, 4H, m-ar), 7.83 (d, J=9.2 Hz,
4H, o-ar). Anal. calcd for C13H10N4O4S (318.31): C, 49.05; H, 3.17;
N, 17.6; S, 10.07%. Found: C, 49.04; H, 3.28; N, 17.55; S, 9.95%.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00916-9

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R. Kato et al. / Tetrahedron Letters 42 (2001) 5053–5056
+
anions, where 2 has a UV–vis spectrum with umax at 343
nm (m=3.1×104 M−1 cm−1), which can be assigned as an
intramolecular charge transfer (CT) absorption band.
As shown in spectrum (b), 2 exhibits negligible pertur-
bation upon addition of 1 equiv. of Cl−. Similarly, 2
does not show any obvious spectral change even in the
The effect of various anions as N(C4H9)4 salt on
absorption spectrum of 2 (2.0×10−5 M) was examined in
1% water–99% MeCN (v/v), and results are shown in
Fig. 1. Spectrum (a) was measured in the absence of
presence of 1 equiv. of Br−, I−, SCN−, NO3 , HSO4
−
−
−
and ClO4 , while a slight response is observed after
−
addition of 1 equiv. of H2PO4 (spectrum c). By con-
trast, significant changes are observed in the presence of
−
1 equiv. of MeCO2 . As shown in spectrum (d), the CT
absorption band appears at 392 nm with a shoulder
absorption at around 450 nm, and the solution color
changes from colorless to yellow (Fig. 2). The changes
in molar extinction coefficient m monitored at 450 nm as
a function of anion concentration are illustrated in the
inset of Fig. 1. It is apparent that 2 has higher selectiv-
ity for acetate than various monovalent inorganic
−
anions under the examination conditions (MeCO2 ꢀ
H2PO4 >Cl−, Br−, I−, SCN−, NO3 , HSO4 , ClO4 ).
−
−
−
−
−
The binding properties of 2 with MeCO2 were further
Figure 1. UV–vis spectra of 2 in 1% water–99% MeCN (v/v)
assessed by UV–vis spectroscopy. Fig. 3A shows the
dependence of UV–vis spectra of 2 in 1% water–99%
(a) in the absence of anions and in the presence of (b) Cl−, (c)
−
H2PO4 and (d) MeCO2−. [2]=[anion]=20 mM. Cell length:
−
MeCN (v/v) on the concentration of MeCO2 . Increas-
1.0 cm. Inset: dependence of molar extinction coefficient m at
−
ing the concentration of MeCO2 produces a significant
450 nm of 2 on the concentrations of (ꢀ) MeCO2−, (")
bathochromic shift in the umax from 343 to 392 nm, and
a clear isosbestic point appears at 364 nm. The changes
in molar extinction coefficient m at 450 nm as a function
of the acetate concentration give a distinct titration
endpoint at a 1:1 ratio of host and guest (cf. inset of
Fig. 1). These observations are good evidence of 1:1
binding stoichiometry. In addition, a dilution of a 1:1
H2PO4 and (ꢁ) other anions (Cl−, Br−, I−, SCN−, NO3
,
−
−
HSO4−, ClO4−).
−
mixture of 2 and MeCO2 in the binary solvent results
in a decrease in m at 450 nm, indicating that the
acetate-induced change in the UV–vis spectrum can be
ascribed not to proton transfer, but to complex forma-
tion through hydrogen bonding.9 The dilution experi-
ment also allowed the determination of the stability of
the acetate complex, which is 3.0×105 M−1. Under
identical conditions, a control chromoionophore 1
shows a much weaker response to acetate as shown in
+
Figure 2. Effect of anions (as N(C4H9)4 salt) on color
changes of 2 in 1% water–99% MeCN (v/v). From left to
right: 2; 2+MeCO2−; 2+H2PO4−; 2+Cl−. [2]=[anion]=20 mM.
Fig. 3B (analysis: 358 nm; K11=5.6×103 M−1; Dumax
=
17 nm). It is evident that another introduction of a
p-nitrophenyl group into the (p-nitrophenyl)thiourea
moiety enhances the hydrogen bonding ability, result-
ing in an extremely strong binding with acetate accom-
panied by more significant changes in the UV–vis
spectrum. It is interesting to note that in MeCN the
stability of the acetate complex of neutral thiourea-
based receptor 2 (K11=1.7×106 M−1) is going to reach
that of the positively charged thiouronium-based recep-
tor (K11>106 M−1),2c in which the favorable electrostatic
attraction between the binding site and acetate, in
addition to the hydrogen bonding interaction, should
have considerable influence on anion binding
events.2c,10 However, the difference in the substituting
groups between these compounds should be mentioned
for the comparison of binding constants. It is well
demonstrated that phenyl substituted thiourea com-
pounds such as chromoionophore 2 exhibit strong
binding ability as compared with that of alkyl substi-
tuted ones.7a All the thiouronium-based receptors
Figure 3. Changes in UV–vis spectra of 1 and 2 titrated with
−
+
MeCO2 (as N(C4H9)4 salt) in 1% water–99% MeCN (v/v).
−
(A) Chromoionophore 2 (21 mM) upon addition of MeCO2
(0, 10, 15, 20, 30 mM). (B) Chromoionophore 1 (50 mM) upon
addition of MeCO2 (0, 50, 100, 200, 300 mM). Cell length:
−
1.0 cm.

R. Kato et al. / Tetrahedron Letters 42 (2001) 5053–5056
5055
reported by Yeo et al.10 and Kubo et al.2c are alkyl
substituted compounds. Thus, it seems likely that
hydrogen-bonding interaction between the reported
thiouronium compound and anion is much weaker than
that between our compound and anion, although elec-
trostatic interaction is strong for thiouronium group.
Chem. Rev. 1997, 97, 1609; (b) Beer, P. D. Acc. Chem.
Res. 1998, 31, 71; (c) Antonisse, M. M. G.; Reinhoudt,
D. N. Chem. Commun. 1998, 443; (d) Snowden, T. S.;
Anslyn, E. V. Curr. Opin. Chem. Biol. 1999, 3, 740; (e)
Antonisse, M. M. G.; Reinhoudt, D. N. Electroanalysis
1999, 11, 1035; (f) Beer, P. D.; Gale, P. A. Angew.
Chem., Int. Ed. 2001, 40, 486.
Chromoionophore 2 was then applied to the colorimet-
ric determination of acetic acid in a commercially avail-
able brand of vinegar. The analysis was carried out in
1% water–99% MeCN (v/v) by a standard addition
method using the complexation-induced absorption
change at 450 nm.‡ The acetic acid concentration in the
vinegar sample was determined to be 4.14 0.06 g/100
mL, which agrees with the specification provided by the
supplier (4.2 g/100 mL). As compared with standard
enzymatic methods that require use of three enzymes,8b
use of hydrogen-bonding chromoionophores8d is a
much simpler method to detect acetate (or acetic acid)
in solution.
2. For recent topics, see: (a) Nishizawa, S.; Kato, Y.;
Teramae, N. J. Am. Chem. Soc. 1999, 121, 9463; (b)
Berrocal, M. J.; Cruz, A.; Badr, I. H. A.; Bachas, L.
G. Anal. Chem. 2000, 72, 5295; (c) Kubo, Y.; Tsuka-
hara, M.; Ishihara, S.; Tokita, S. Chem. Commun. 2000,
653; (d) Sun, S.-S.; Lees, A. J. Chem. Commun. 2000,
1687; (e) Anzenbacher, Jr., P.; Jurs´ıkova´, K.; Sessler, J.
L. J. Am. Chem. Soc. 2000, 122, 9350; (f) Chamberlain,
II, R. V.; Slowinska, K.; Majda, M.; Bu¨hlmann, P.;
Aoki, H.; Umezawa, Y. Langmuir 2000, 16, 1388; (g)
Watanabe, S.; Higashi, N.; Kobayashi, M.; Hamanaka,
K.; Takata, Y.; Yoshida, K. Tetrahedron Lett. 2000, 41,
4583; (h) Lu¨cking, U.; Rudkevich, D. M.; Rebek, Jr., J.
Tetrahedron Lett. 2000, 41, 9547.
In summary, we have shown that highly selective, col-
orimetric sensing of acetate can be achieved by 2 in a
binary mixture of water and MeCN. Although further
improvements of the acetate selectivity over higher
charged inorganic anions as well as other carboxylates
may be necessary for the analysis of acetate in other
types of samples, the concentration of acetic acid in the
vinegar was successfully determined with 2. Due to its
very strong ability to form complexes with anions that
act as hydrogen bond acceptors, receptor 2 might also
be a promising candidate for various applications such
as anion transports and/or electrochemical sensors,1,8c
which are now underway in our laboratory.
3. (a) Bell, T. W.; Hou, Z.; Luo, Y.; Drew, M. G. B.;
Chapoteau, E.; Czech, B. P.; Kumar, A. Science 1995,
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5. For competition methods for chromogenic anion sens-
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Acknowledgements
We thank Dr. Hinako Ando, Instrumental Analysis
Center for Chemistry, Faculty of Science, Tohoku Uni-
versity, for microanalysis. This work was supported by
Grants-in-Aid for Scientific Research (A), No.
11304054, Encouragement of Young Scientist, No.
13740417, from the Ministry of Education, Science,
Sports and Culture, Japan, and RFTF of Japan Society
for the Promotion of Science.
6. (a) Nishizawa, S.; Kato, R.; Hayashita, T.; Teramae,
N. Anal. Sci. 1998, 14, 595; (b) Hayashita, T.;
Onodera, T.; Kato, R.; Nishizawa, S.; Teramae, N.
Chem. Commun. 2000, 755.
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‡ Sample preparation: To eliminate interfering cations, 0.1 mL of
vinegar was first passed through
a cation exchange column
(DOWEX-50-X8, H+-form) with deionized water as an eluting
solvent. The pH of the eluent collected was adjusted to ca. 6.0 with
N(C4H9)4OH, followed by making up the volume to 100 mL with
deionized water. An aliquot (0.1 mL) out of 100 mL was then
−
diluted to 10 mL with MeCN containing 2 (20 mM) and MeCO2
(as N(C4H9)4 salt, 0–10 mM).
+

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