Selective colorimetric sensing of anions in aqueous media through reversible covalent bonding

Article abstract of DOI:10.1021/jo900573v

(Chemical Equation Presented) Selective colorimetric sensing of anions in aqueous media has been studied, which involves reversible covalent bonding as key binding interactions. By introducing a simple nitro chromophore into an o-(carboxamido)trifluoroace

Full text of DOI:10.1021/jo900573v

Selective Colorimetric Sensing of Anions in Aqueous Media through
Reversible Covalent Bonding
Dae-Sik Kim, Yun-Mi Chung, Mieun Jun, and Kyo Han Ahn*
Department of Chemistry and Center for Electro-Photo BehaViors in AdVanced Molecular Systems,
POSTECH, San 31 Hyoja-dong, Pohang, 790-784, Republic of Korea
ahn@postech.ac.kr
ReceiVed March 18, 2009
Selective colorimetric sensing of anions in aqueous media has been studied, which involves reversible
covalent bonding as key binding interactions. By introducing a simple nitro chromophore into an
o-(carboxamido)trifluoroacetophenone ionophore that recognizes anions through reversible covalent
bonding, we have realized a complete selectivity in colorimetric sensing of cyanide among competing
anions such as fluoride, acetate, and dihydrogen phosphate in aqueous media. Such selectivity is explained
by dominant reversible covalent bonding over hydrogen bonding, which leads to indirect internal charge
transfer. The sensing system is readily converted into a polymeric analogue, demonstrating its potential
applicability to develop a naked eye detection material for highly toxic cyanide ions.
SCHEME 1. Schematic Diagram of Anion Sensing by
Hydrogen Bonding Interactions
Introduction
The development of molecular probes for anions has been a
subject of intense research interest as anions play important roles
in biological systems and also constitute some pollutants in our
environment. For example, phosphate anions not only play
critical roles in biological processes but also are key pollutants,
and cyanide anions are widely used in industrial processes of
chemicals but are highly toxic. Therefore, easy and affordable
detection methods are in great demand for various situations.
In this regard, fluorescent or colorimetric probes are particularly
attractive,1 and especially colorimetric probes are useful for
naked eye detection.
Typically, a colorimetric anion probe is constructed by
combining a chromophore and an anion binding unit. In many
cases, the anion binding unit is primarily composed of H-bond
donors.2 H-bonding interactions between an anion and the
H-bond donors in a sensing system can induce internal charge
transfer (ICT), which results in a change in the absorption of
the chromophore, thus allowing the colorimetric detection
(Scheme 1).3
Therefore, such chromogenic probes respond to anionic
analytes depending on how much an anion induces ICT through
the H-bonding interactions. The degree of ICT is dependent on
the chemical nature of the binding unit that provides the
H-bonding interactions toward anions. Also, the degree of ICT
is influenced by the nature of analyte itself, that is, the anion’s
H-bonding ability and/or basicity. Therefore, the colorimetric
probes that provide H-bonding interactions as the primary
molecular interactions in general respond in preference to anions
having strong H-bonding ability (F-, AcO-, H2PO4-, etc.) or
strong basicity (CN-) but less efficiently toward weakly
(1) Selected reviews on anion sensing: (a) Beer, P. D.; Gale, P. A. Angew.
Chem., Int. Ed 2001, 40, 486. (b) Mart´ınez-Ma´n˜ez, R.; Sanceno´n, F. Chem. ReV.
2003, 103, 4419. (c) Gunnlaugsson, T.; Glynn, M.; Tocci, G. M.; Kruger, P. E.;
Pfeffer, F. M. Coord. Chem. ReV. 2006, 250, 3094. (d) Mart´ınez-Ma´n˜ez, R.;
Sanceno´n, F. Coord. Chem. ReV. 2006, 250, 3081.
(2) (a) Katayev, E. A.; Ustynyuk, Y. A.; Sessler, J. L. Coord. Chem. ReV.
2006, 250, 3004. (b) Schmidtchen, F. P. Coord. Chem. ReV. 2006, 250, 2918.
(c) Bates, G. W.; Gale, P. A. Struct. Bonding (Berlin, Ger.) 2008, 129, 1.
(3) (a) Miyaji, H.; Sessler, J. L. Angew. Chem., Int. Ed. 2001, 40, 154. (b)
Piatek, P.; Jurczak, J. Chem. Commun. 2002, 2450. (c) Nishiyabu, R.;
Anzenbacher, P., Jr. J. Am. Chem. Soc. 2005, 127, 8270. (d) Anzenbacher, P.,
Jr.; Nishiyabu, R.; Palacios, M. A. Coord. Chem. ReV. 2006, 250, 2929.
10.1021/jo900573v CCC: $40.75  2009 American Chemical Society
Published on Web 05/21/2009
J. Org. Chem. 2009, 74, 4849–4854 4849

Kim et al.
SCHEME 2. Schematic Diagram of Anion Binding with
o-CATFA
SCHEME 3. Binding Interactions Plausible in the Cases of
DNPA 1 and Reference 2
H-bonding or weakly basic anions (Cl-, Br-, I-, ClO4 , HSO4 ,
etc.).3a,b Since H-bonding interactions have been widely used
as the primary molecular interactions in molecular recognition
and sensing studies, it is not surprising to find that many anion
probes reported so far show great selectivity for F-, which has
significant basicity as well as the strongest H-bonding ability.4
Such a trend is inevitable with molecular probes based on
H-bonding donors. Therefore, a new discipline in probe design
through which we can alter such a general trend is in great
demand.
-
-
Herein, we disclose a new approach toward this goal. Our
approach is to use organic molecular probes that interact with
analytes through reversible covalent bonding, rather than
H-bonding, as the primary molecular interaction. By this
approach, the above-mentioned selectivity trend in chromogenic
anion sensing is altered and thus selective sensing of a cyanide
anion in aqueous media is demonstrated.
Results and Discussion
Recently we developed a novel anion recognition motif based
on trifluoroacetophenone that recognizes anions through revers-
ible covalent bonding rather than H-bonding.5 The new anion
recognition motif contains an H-bond donor (-XH) at the ortho
position of trifluoroacetophenone ionophore, which stabilizes
anion-ionophore adducts through intramolecular H-bonding
(Scheme 2). When a carboxamide group (-NHCOR) was
introduced as the H-bonding group, the association constant for
an acetate anion increased more than 100 times compared to
the case where such an H-bond donor was absent. The increase
in association constant was explained by enhanced “charged”
H-bonding in the anionic adduct. On the basis of this intramo-
lecular H-bond stabilization approach, we have developed
several anion receptors and fluorescent probes.6
As a further exploration of the novel binding motif for the
development of colorimetric probes, we focused on several
distinctive factors the o-(carboxamido)trifluoroacetophenone (o-
CATFA) system provides: (1) the intramolecular H-bonding
becomes stronger upon anionic adduct formation because of its
charged nature; (2) the XH (-NHCOR′) proton is already
involved in the intramolecular H-bonding and thus is less
susceptible to “direct” H-bonding by anion analytes; and (3)
certain anionic analytes would interact with the H-bond donor
(XH) “indirectly” through adduct formation rather than direct
H-bonding interaction. These factors seem to be valuable in
altering the general trend of guest selectivity in colorimetric
anion sensing through direct H-bonding.
A unique chromogenic probe is thus designed by introducing
a simple chromophore such as 3,4-dinitrophenyl to the XH
(-NHCOR) group in o-CATFA. This new CATFA analogue,
DNPA 1 (Scheme 3), would interact with anions by reversible
covalent bonding to form adduct Ia and less efficiently by direct
H-bonding to form species Ib. Thus, the degree of ICT upon
anion binding is expected to be dependent less on the anion’s
H-bonding ability but may be dependent on the anion’s carbonyl
carbon affinity; hence, the usual guest selectivity pattern
dependent on the anion’s H-bonding ability and/or basicity may
be altered. An anion that is a weak H-bonding acceptor but has
strong carbonyl carbon affinity is expected to be differentiated
from other anions that are strong H-bonding acceptors, particu-
larly in aqueous media, because weak solvation is expected in
the former case. It is thus expected that DNPA 1 behaves
differently from a simple model compound 2 that has no
trifluoroacetyl group, which belongs to typical chromogenic
probes that interact with anions mainly through H-bonding.3a
Anions can interact with dinitrobenzamide 2 in two ways:
H-bonding interactions or an acid-base equilibrium involving
the amide NH. In both cases, different degrees of ICT dependent
on anions would result, leading to absorption and thus color
changes. Thus, among commonly tested anions such as F-, Cl-,
(4) (a) Mizuno, T.; Wei, W.-H.; Eller, L. R.; Sessler, J. L. J. Am. Chem.
Soc. 2002, 124, 1134. (b) Boiocchi, M.; Del Boca, L.; Go´mez, D. E.; Fabbrizzi,
L.; Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004, 126, 16507. (c) Lin,
Z.-h.; Ou, S.-j.; Zhang, B.-g.; Bai, Z.-p. Chem. Commun. 2006, 624. (d) He, X.;
Hu, S.; Liu, K.; Guo, Y.; Xu, J.; Shao, S. Org. Lett. 2006, 8, 333. (e) Quinlan,
E.; Matthews, S. E.; Gunnlaugsson, T. J. Org. Chem. 2007, 72, 7497.
(5) Kim, Y. K.; Lee, Y.-H.; Lee, H.-Y.; Kim, M. K.; Cha, G. S.; Ahn, K. H.
Org. Lett. 2003, 5, 4003.
(6) (a) Chung, Y. M.; Balamurali, R.; Kim, D. S.; Ahn, K. H. Chem. Commun.
2006, 186. (b) Kim, D. S.; Miyaji, H.; Chang, B.-Y.; Park, S.-M.; Ahn, K. H.
Chem. Commun. 2006, 3314. (c) Kim, D. S.; Ahn, K. H. J. Org. Chem. 2008,
73, 6831. (d) Ryu, D.; Park, E.; Kim, D.-S.; Yan, S.; Lee, J. Y.; Chang, B.-Y.;
Ahn, K. H. J. Am. Chem. Soc. 2008, 130, 2394. (e) Lee, H.; Chung, Y. M.;
Ahn, K. H. Tetrahedron Lett. 2008, 49, 5544. (f) Chatterjee, A.; Oh, D. J.; Kim,
K. M.; Youk, K.-S.; Ahn, K. H. Chem. Asian J. 2008, 3, 1962.
Br-, I-, SO42-, H2PO4 , AcO-, and CN-, a strongly H-bonding
-
F- (pKa ) 3.15) or a relatively basic CN- (pKa ) 9.2-9.4)
can shift the equilibrium to the right side, forming species IIa
or IIb, respectively, showing the most significant color change,
as already observed in the literature.3a The color change may
be reduced or negligible if the same experiment is carried out
in aqueous media, due to the strong hydration.
4850 J. Org. Chem. Vol. 74, No. 13, 2009

Colorimetric Sensing of Cyanide
FIGURE 1. Color change of dinitrobenzamide 2 (5.0 × 10-5 M) upon
addition of an equimolar amount of each anion (from the left: 2, CN-, F-,
AcO-, and H2PO42-) (a) in CH3CN and (b) in MeOH-water (10:1).
Indeed, when dinitrobenzamide 2 was treated with selected
anions such as CN-, F-, AcO-, and H2PO4 in acetonitrile,
2-
both cyanide and fluoride anions exhibited color change from
colorless to light purple (orchid color) and to light yellow,
respectively (Figure 1a). In the cases of AcO- and H2PO4-, a
color change resulted when 10 equiv of the anions was added
(Figure S1, Supporting Information). However, there was no
color change when the organic solvent was changed to aqueous
media (Figure 1b), even with 250 equiv of anions (Figure S2,
Supporting Information).
FIGURE 2. UV-vis absorption change of DNPA 1 (2.0 × 10-5 M in
CH3CN) upon addition of 1.0 equiv of the anions and color change of
DNPA 1 (5.0 × 10-5 M) in CH3CN upon addition of an equimolar
amount of anions (from the left: 1, CN-, F-, AcO-, H2PO42-, HSO4
,
-
SCN-, Cl-, Br-).
In contrast, DNPA 1 is expected to recognize anions mainly
through the formation of adduct Ia. A direct H-bonding
interaction such as in the Ib species is less feasible because the
amide NH is already involved in the intramolecular H-bonding
as discussed above. Therefore, ICT via direct H-bonding is
minimal, whereas enhanced intramolecular H-bonding upon
adduct formation may lead to indirect ICT and thus a color
change. As a result, the anion’s carbonyl carbon affinity can be
a determining factor for the color change. In fact, when DNPA
1 was treated with CN- in acetonitrile, two new peaks at λmax
) 433 and 533 nm appeared and increased dramatically with
apparent color change, from colorless to orange (cinnamon
color) (Figure 2). This result can be explained by the addition
of cyanide to the trifluoroacetyl carbonyl carbon, because
cyanide is a very weak H-bonding acceptor but has a strong
affinity toward the carbonyl carbon.6 Anions such as F-, AcO-,
2-
and H2PO4 showed diminished absorption change compared
to CN- and showed light orange, and other anions such as
HSO4-, SCN-, Cl-, and Br- did not show any color change.
An even more striking feature results when the sensing
experiment is carried out in aqueous media. Only CN- shows
a color change with DNPA 1 in a mixed solvent system of
MeOH-water (10/1), whereas other competing anions such as
F-, AcO-, and H2PO42- are completely nonresponsive (Figure
3). The result indicates that, in aqueous media, anions with
strong or significant H-bonding ability such as F-, AcO-, and
H2PO42- are stabilized by solvation through H-bonding and thus
unable to form the corresponding adduct. Only CN-, which is
a poor H-bond acceptor, can add to DNPA 1 because it has
strong affinity toward the carbonyl carbon, of which solution
showed a dramatic change in the absorption spectrum and thus
a color change from colorless to yellow (cinnamon color). Other
anions did not show any color change even though an excess
amount (50 equiv) was used (Figure S3, Supporting Informa-
tion). We also checked whether OH- species (K+ salt) would
respond to DNPA 1. When DNPA 1 was treated with OH- in
acetonitrile (under the same conditions described in Figure 2),
a color change similar to that of AcO- was observed; however,
FIGURE 3. UV-vis absorption change of DNPA 1 (5.0 × 10-5 M)
upon addition of 2.0 equiv of each anion in MeOH-H2O (10/1) and
color change of probe 1 (1.0 × 10-4 M) upon addition of 2.0 equiv of
each anion in MeOH-H2O (10/1) (from the left: 1, CN-, F-, AcO-,
H2PO42-, HSO4-, SCN-, Cl-, and Br-).
again there was no color change when the same experiment
was carried out in MeOH-H2O (10/1) (Figure S4, Supporting
Information). Thus, a structurally very simple and easy-to-make
DNPA 1 constitutes a specific probe for the naked eye detection
of CN- in aqueous media.7
The critical role of the intramolecular H-bond stabilization
in DNPA 1 is evident from the sensing behavior observed with
its para-analogue 3 (Figure 4). A solution of compound 3 in
acetonitrile turned yellow (canaria color) upon addition of F-
and AcO- as well as CN-, because direct H-bond interactions
at the amide NH and/or acid-base equilibria are possible, in
addition to the trifluoroacetyl carbonyl addition. In the case of
J. Org. Chem. Vol. 74, No. 13, 2009 4851

Kim et al.
FIGURE 6. 19F NMR spectra of (a) DNPA 1 and (b) an equimolar
mixture of DNPA 1 and CN- (as Bu4N+ salt) in CDCl3.
TABLE 1. Thermodynamic Data for the Complexation between
DNPA 1 and Selected Anions, Determined by ITCa
c
c
c
d
entry
guestb
∆Ho
-T∆So
∆Go
Kass
ne
1
2
3
4
CN-
-9.7
-15.2
-5.7
-3.3
1.3
51
-38
1.9
7.4
0.3
-7.8
-7.8
-5.4
-6.2
-6.1
-2.9
-3.6
3.7 × 105
1.5 × 105
7.0 × 103
2.8 × 104
1.2 × 104
1.2 × 102
3.5 × 102
1.02
1.00
1.27
AcO-
-
H2PO4
f
F-
-2.9
-6.9
-54
381
-
FIGURE 4. Color change of reference compound 3 (5.0 × 10-5 M)
upon addition of 0.5 equiv of each anion (from the left: 3, CN-, F-,
AcO-, and H2PO42-) (a) in CH3CN and (b) in MeOH-water (10:1).
a Determined in CH3CN at 303 K. As Bu4N+ salts. c In kcal/mol.
b
d In M-1 e Binding stoichiometry. f Sequential binding.
.
netic shielding caused by increased electron density as the
anionic adduct forms. The amide NH peak disappeared as adduct
formed, probably buried in the solvent peak.
The adduct formation was also clearly observed in the 19F
NMR spectra taken in the same solvent for both DNPA 1 and
its equimolar mixture with CN-: The trifluoromethyl peak,
appearing as a singlet in both cases, showed a large upfield shift,
from -67.2 to -79.8 ppm, as the adduct formed (Figure 6).
As expected, the adduct peak intensity decreased in the order
of CN- > F- > AcO- > H2PO42-, which is in agreement with
the data of absorption spectral change depending on the anions.
The formation of the alkoxide adduct was also supported by
IR spectroscopy. The NH stretching band in DNPA 1 appearing
at 3271 cm-1 as a sharp peak changed into a strong and broad
peak at 3447 cm-1 when 1 equiv of cyanide was added,
supporting the enhanced charged H-bonding character as the
alkoxide adduct forms.
To obtain thermodynamic parameters for the binding process
between DNPA 1 and selected anions, we carried out isothermal
titration calorimetry (ITC),8 the results of which are summarized
in Table 1. To a calorimetry cell containing DNPA 1 (0.2 mM,
1.5 mL) at 303 K was injected a solution of each anion (3-10
mM, depending on anions, 5 µL × 40 times) and the resulting
heat transfer was measured (Figure 7). The binding isotherms
were analyzed by nonlinear least-squares fit to give the
thermodynamic data. The data suggest that all the binding
processes are governed by major favorable enthalpy change
accompanied by minor unfavorable entropy change, conforming
FIGURE 5. 1H NMR spectra of (a) DNPA 1 and (b) an equimolar
mixture of DNPA 1 and CN- (as Bu4N+ salt) in CDCl3 at -40 °C.
H2PO4-, similar color change occurred when 10 equiv was
added (Figure S5, Supporting Information). However, in aqueous
media, compound 3 shows no color change even in the case of
CN-, even though an excess amount was added (250 equiv)
(Figure S6, Supporting Information). The results clearly high-
light the key feature of our indirect charge transfer approach.
The adduct formation between DNPA 1 and each of the
anions can be followed by 1H NMR spectroscopy. Upon addition
of an equimolar amount of CN- (as Bu4N+ salt) to DNPA 1 in
CD3Cl3, all the aromatic protons of the trifluoroacetophenone
moiety and even the aromatic proton between the two nitro
groups shifted significantly to the upfield region (Figure 5).
When a subequimolar amount of CN- was added, both peaks
from DNPA 1 and its adduct were observed, indicating that the
equilibrium of adduct formation is slow compared to the NMR
time scale. The upfield shifts can be explained by the diamag-
to the formation of covalent adducts under the conditions. The
-
association constants of DNPA 1 toward the anions (H2PO4
,
AcO-, and CN-) increased 2-5 times compared with the
original (N-propionyl)trifluoroacetophenone,5 which can be
attributed to the increased electrophilicity owing to the electron-
withdrawing dinitrobenzoyl group. The data clearly show that
(7) (a) Garc´ıa, F.; Garc´ıa, J. M.; Garc´ıa -Acosta, B.; Mart´ınez-Ma´n˜ez, R.;
Soto, J. Chem. Commun. 2005, 2790. (b) Tomasulo, M.; Sortino, S.; White,
A. J. P.; Raymo, F. M. J. Org. Chem. 2005, 70, 8180. (c) Tomasulo, M.; Raymo,
F. M. Org. Lett. 2005, 7, 1109. (d) Ros-Lis, J.; Mart´ınez-Ma´n˜ez, R.; Soto, J.
Chem. Commun. 2005, 5260. (e) Tomasulo, M.; Sortino, S.; White, A. J. P.;
Raymo, F. M. J. Org. Chem. 2006, 71, 744. (f) Yang, Y.-K.; Tae, J. Org. Lett.
2006, 8, 5721. (g) Sessler, J. L.; Cho, D.-G. Org. Lett. 2008, 10, 73. (h) Cho,
D.-G.; Kim, J. H.; Sessler, J. L. J. Am. Chem. Soc. 2008, 130, 12163.
(8) (a) Christensen, J. J.; Wrathall, D. P.; Oscarson, J. O.; Izatt, R. M. Anal.
Chem. 1968, 40, 1713. (b) Smithrud, D. B.; Wyman, T. B.; Diederich, F. J. Am.
Chem. Soc. 1991, 113, 5420.
4852 J. Org. Chem. Vol. 74, No. 13, 2009

Colorimetric Sensing of Cyanide
FIGURE 7. Binding isotherms and their integration plots obtained from the ITC titrations of DNPA 1 (0.2 mM, 1.5 mL) in CH3CN at 303 K: from
the left, with (a) CN-, (b) AcO-, and (c) F- (as Bu4N+ salts, 3.0 mM, 0.2 mL).
DNPA 1 binds CN- or AcO- with a 1:1 stoichiometry, as their
n values, the binding stoichiometry, are close to unity. This 1:1
binding stoichiometry is also indicative of a predominant binding
mode, the carbonyl addition mode in these cases. However, in
the case of H2PO42-, the n value is a little deviated from unity
(n ) 1.3), suggesting that another binding mode, plausibly direct
H-bonding, is competing with the adduct formation. Interest-
ingly, in the case of F-, more complex binding modes are
inferred from the titration isotherms: A sequential binding mode
best fit the titration isotherms, of which two dominant processes
at early stages are similar in their association constants (entry
4, Table 1). The complex binding mode may be explained by
evoking the facts that both the direct H-bonding at the amide
FIGURE 8. UV-vis titration of DNPA 1 (5.0 × 10-5 M) with CN-
(0-3.0 equiv) in MeOH-H2O (10/1) at 25 °C.
NH and the carbonyl addition by F- are possible, and also once
initially formed these binary complexes may further interact with
additional fluoride to give the corresponding ternary complexes,
respectively.
use a solution of DNPA 1 in CH2Cl2 (10-4 M) in the presence
of a phase transfer catalyst such as Bu4N+Br- (Figure S9,
Supporting Information). Thus, DNPA 1 can be used for
colorimetric sensing of CN- present in aqueous samples.
Finally, a water-soluble analogue of DNPA 1 was synthesized
and its sensing behavior was evaluated. We introduced a
poly(ethyleneglycol) unit to DNPA 1 to give peg-DNPA 4,
which is soluble both in usual organic solvents and also in sole
water. peg-DNPA 4 also showed a significant change in the
UV-vis absorption spectra only toward CN- and very little
change toward other anions in a buffered aqueous solution (pH
8.2, Tris buffer) (Figure 9). Accordingly, a solution of peg-
DNPA 4 (1.0 × 10-4 M) became yellow (egg color) when 30
equiv of CN- was added, and there was no change for the other
anions.
Cyanides are widely used in industrial processes of organic
chemicals and polymers such as nitriles, nylon, and acrylic
plastics, as well as in the gold-extraction process. However,
cyanides are highly toxic and thus should be strictly regulated.9
The detection of cyanide ions in drinking water by colorimetric,
ion-selective electrode, and ion-exchange chromatography meth-
ods has been established.10 However, still there is a need to
develop versatile molecular sensing systems for cyanide detec-
tion in a variety of settings. To evaluate DNPA 1 as colorimetric
probe for CN-, we carried out UV-vis titrations in
MeOH-H2O (10/1). Upon addition of CN-, the absorption
peaks of DNPA 1 (λmax ) 432 and 520 nm) linearly increased
up to the equivalent point (Figure 8). From a plot for the linear
region, a detection limit of cyanide by DNPA 1 was estimated
to be ∼3 µM, a value close to the maximum permissible level
for drinking water (0.07 mg/L or 2.7 µM in water) set by the
WHO (Figure S7, Supporting Information).10
The results demonstrate that the molecular interactions
involved in DNPA 1 can also be realized in its polymeric
analogue. A further elaboration of DNPA 1 into a heterogeneous
sensing material may lead to a useful cyanide probe for specific
purposes.
A similar color change was observed when CN- was added
to a solution containing all the other anions such as F-, AcO-,
H2PO4-, HSO4-, SCN-, Cl-, and Br- (Figure S8, Supporting
Information). Because DNPA 1 was not soluble in sole water
even at the low concentration level, we used the mixed solvent
system. Furthermore, the colorimetric sensing of CN- can be
carried out for a sample of NaCN in water (∼10-3 M) if we
Conclusions
We have disclosed a selective colorimetric sensing of anions
in aqueous media through reversible covalent bonding between
an ionophore and an anion. By combining a trifluoroacetophe-
none ionophore and a simple nitro chromophore, we have
realized a complete selectivity in colorimetric sensing of cyanide
among competing anions such as fluoride, acetate, and dihy-
drogen phosphate in aqueous media. Such selectivity results
(9) ATSDR 2006. Toxicological Profile for Cyanide: Atlanta, GA; U.S.
Department of Health and Human Services.
(10) Guidelines for Drinking-Water Quality; The World Health Organization:
Geneva, Switzerland, 1996.
J. Org. Chem. Vol. 74, No. 13, 2009 4853

Kim et al.
CDCl3) δ 12.20 (s, 1H), 9.25 (t, J ) 3 Hz, 1H), 9.20 (d, J ) 2 Hz,
2H), 8.97 (d, J ) 8.5 Hz, 1H), 8.14-8.11 (m, 1H), 7.86 (dt, J )
7.9 and 1.3 Hz, 1H), 7.39 (dt, J ) 7.9 and 0.7 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 185.48, 185.00, 184.55, 184.07 (q, J ) 34.7
Hz, -COCF3), 162.0, 149.7, 143.2, 139.0, 138.5, 133.25, 133.20,
133.14, 133.07 [q, J ) 4.79 Hz (coupled with F), an aromatic
carbon], 133.1 128.1, 125.0, 122.5, 122.2, 116.6, 122.5, 119.0 115.2,
111.3 [q, J ) 292.03 Hz (coupled with F), -CF3]; 19F NMR (300
MHz, CDCl3) δ 7.24; HRMS (FAB) m/z for C15H9F3N3O6 (M +
H+) calcd 384.0443, found 384.0443.
1
3,5-Dinitro(N-phenyl)benzamide (2): mp 235.8 °C; H NMR
(300 MHz, CDCl3) δ 9.23 (t, J ) 1.8 Hz, 1H), 9.07 (d, J ) 2.1
Hz, 2H), 7.65 (s, 1H), 7.67 (d, J ) 8.1 Hz, 2H), 7.46 (t, J ) 7.5
Hz, 2H), 7.29 (s, 1H); 19F NMR (300 MHz, CDCl3) δ 4.55; HRMS
(FAB) m/z for C13H10N3O5 (M + H+) calcd 288.0620, found
288.0623.
N-[4-(2,2,2-Trifluoroacetyl)phenyl]-3,5-dinitrobenzamide (3):
1
Rf 0.5 (hexane/EtOAc ) 7/3); mp 168.6 °C; H NMR (300 MHz,
CDCl3) δ 9.26 (t, J ) 2.0 Hz, 1H), 9.12 (d, J ) 2.0 Hz, 2H), 8.56
(s, 1H), 8.17 (d, J ) 8.2 Hz, 2H), 7.95-7.92 (m, 2H); 19F NMR
(300 MHz, CDCl3) δ 4.55; HRMS (FAB) m/z for C15H9F3N3O6
(M + H+) calcd 384.0443, found 384.0443.
peg-DNPA 4. Poly(ethyleneglycol) of molecular weight of about
1100 was used to couple with the 4-carboxy derivative of o-CATFA
to give peg-DNPA 4 in 20% yield after purification by flash column
1
chromatography (DMF/EtOAc ) 6 mL/100 mL). H NMR (300
MHz, CDCl3) δ 9.30 (d, J ) 2.0 Hz, 2H), 9.24 (t, J ) 2.0 Hz,
1H), 8.26 (d, J ) 1.4 Hz, 1H), 8.20 (dd, J ) 8.3, 1.6 Hz, 1H),
87.78 (d, J ) 8.0 Hz, 1H), 4.6 (t, J ) 4.8 Hz, 2H), 3.88 (t, J ) 5.4
Hz, 9H), 3.65 (br s, ∼120H).
ITC Experiments: A Typical Procedure. To a solution of
DNPA 1 (0.2 mM, 1.5 mL) in CH3CN taken in the calorimetry
cell was added 5 µL of guest solution (3.0 mM in CH3CN, except
for Bu4N+H2PO4- in which case 10 mM solution was used) a total
of 40 times at 303 K. In all the titrations, dilution effects were
corrected, which were done by carrying out separate titration
experiments. Thus, the titration result obtained by adding the same
guest solution into the cell in the absence of the probe was
subtracted from the raw titration data to obtain the final binding
curve. The titration data were analyzed by curve-fitting software,
which gave thermodynamic values such as the apparent binding
affinity K and the standard enthalpy change ∆H° as well as the
binding stoichiometry n.
FIGURE 9. Change in the absorption spectra of peg-DNPA 4 (1.0 ×
SCN-, Cl-, Br-: 30 equiv) in a buffered solution (pH 8.2, Tris buffer)
and color change under the same conditions (peg-DNPA 4, CN-, F-,
AcO-, and H2PO42-, from the left).
10-5 M) upon addition of anions (CN-, F-, AcO-, H2PO42-, HSO4
,
-
from the unique binding mode of the o-(trifluoroacetyl)car-
boxanilde group toward the anions, which leads to indirect
internal charge transfer. The sensing system is converted into a
polymeric analogue, demonstrating its potential applicability to
develop a naked eye detection material for highly toxic cyanide
ions.
Acknowledgment. This work was supported by the EPB
center (R11-2008-052-01001) and the Korea Research Founda-
tion Grant funded by the Korean Government (KRF-2008-313-
C00509).
Experimental Section
Characterization data for the compounds 1-4 are given below.
For detailed experimental procedures, see the Supporting Informa-
tion.
Supporting Information Available: Experimental proce-
dures for the synthesis of all the compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
N-[2-(2,2,2-Trifluoroacetyl)phenyl]-3,5-dinitrobenzamide (1):
Rf 0.23 (EtOAc/hexane ) 1/4); mp 153.2 °C; 1H NMR (300 MHz,
JO900573V
4854 J. Org. Chem. Vol. 74, No. 13, 2009