Selective chromogenic response via regioselective binding of cations: A novel approach in chemosensor design

Article abstract of DOI:10.1016/S0040-4039(02)00725-6

A calixdiquinone bis-indoaniline derivative with two kinds of potential binding sites, discriminates cations according to their charge/size ratio. Harder and highly oxophilic Eu(III) preferentially interacts with the lower rim quinone oxygens; whereas Na(

Full text of DOI:10.1016/S0040-4039(02)00725-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3981–3983
Selective chromogenic response via regioselective binding of
cations: a novel approach in chemosensor design
Demet Ataman and Engin U. Akkaya*
Department of Chemistry, Middle East Technical University, TR 06531 Ankara, Turkey
Received 13 March 2002; revised 2 April 2002; accepted 12 April 2002
Abstract—A calixdiquinone bis-indoaniline derivative with two kinds of potential binding sites, discriminates cations according to
their charge/size ratio. Harder and highly oxophilic Eu(III) preferentially interacts with the lower rim quinone oxygens; whereas
Na(I) binds to the azacrown moieties. As a consequence of the chromogenic sensor’s design, these two binding events result in
two different responses, Eu(III) causes a remarkable auxochromic change, but Na(I) produces a significant anti-auxochromic
effect. © 2002 Elsevier Science Ltd. All rights reserved.
The construction of ion selective molecular sensors
continues to attract attention due to potential applica-
tions and as a testing ground for molecular recognition
and signal transduction schemes. Progress in the field
has been reviewed in recent years.1–3 In conjugated
donor–acceptor chromophores or fluorophores (inter-
nal charge transfer-ICT sensors), if the receptor is a
part of the donor moiety, cation binding induces a
blue-shift with a decrease in the extinction coefficient
(anti-auxochromic effect); however, if the acceptor
group is part of the receptor then there is a red-shift
with an increase in extinction coefficient results (auxo-
chromic effect) on cation binding.4
fluoroionophore with D1-A-D2 constitution was
reported,7 but both of the receptor units were donor
substituents. Consequently, the receptors displayed dif-
ferential affinity for cations, but the spectral shifts were
in the same direction. de Silva’s quinoline–BAPTA
conjugate8 is particularly relevant, because Ca(II) and
H+ ions were shown to produce blue and red shifts,
respectively, interacting with either the donor or the
acceptor part of the push–pull system. Thus, it is clear
that judicious choice of receptors would yield
chemosensors of broad spectral response range.
Indoaniline derivatives have been used9,10 as chro-
mogenic sensors for some time. These intense blue dyes
can be easily prepared by the reaction of (N,N-dialkyl-
amino)anilines with phenols under oxidative condi-
tions.11 In recent studies on chromogenic sensors, calix-
arenes, which proved themselves to be very useful
scaffolds for sensor design, were coupled with indoani-
line structures to yield remarkable chromogenic
chemosensors.12–15 In these studies, lower rim diquinone
binding is strengthened by further functionalization of
the other two hydroxyls. Pronounced red shifts in the
absorption spectrum were observed when the calix-
diquinone carbonyls coordinate to a number of alkaline
and alkaline-earth cations, especially the high charge
density Ca(II) cation.
Selective response is one of the most important issues
for all chemosensors. This issue has been addressed, at
least in part, by designing selective receptor units with
varying degrees of success.1 In our own attempts in
achieving selective chemosensor response, we reasoned
that the selectivity would be drastically improved if
there were not one, but two competing potential recep-
tor sites, one with donor and one with acceptor charac-
teristics. If the cation shows a preference for the
donor–receptor, it will cause a blue shift, whereas if the
preference is for the acceptor–receptor, there will be a
red shift. In recent years, there have been reports of
ditopic (bifunctional) fluorophores acting as molecular
equivalents of logic gates.5–8 In one case, a bifunctional
In this study, we targeted a calixdiquinone derivative
with an azacrown modification on the N,N-dialkyl-
aminostructure. To that end, our synthesis started with
4-fluoronitrobenzene. In analogy to a recently reported
method,16 we simply carried out an SNAr reaction of
Keywords: chromogenic sensors; chemosensors; indoaniline dyes; cal-
ixarene derivatives.
* Corresponding author. E-mail: akkayaeu@metu.edu.tr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00725-6

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D. Ataman, E. U. Akkaya / Tetrahedron Letters 43 (2002) 3981–3983
the azacrown (1-aza-15-crown-5) with the fluoroarene in
DMSO. Usual work-up, followed by a silica-gel column
purification yielded compound 2. The reduction of the
nitro group was accomplished using 10% Pd–C in reflux-
ing ethanol with cyclohexene as the hydrogen source.
novel chromophore with a number of cations (perchlo-
rates or nitrates). It was expected that the harder
calixdiquinone site would preferentially bind harder
cations and large alkaline cations would preferentially
interact with the azacrown units. Our experiments
revealed that this is exactly the case. Apparently in aprotic
acetonitrile, further functionalization of the lower rim is
not necessary for binding to take place. The practical
outcome of this sensor design is the broader palette of
colors in response to the binding of different metal ions;
for example, a dilute solution of 4 in acetonitrile is blue,
but the addition of sodium perchlorate to yield a 9 mM
solution creates a pink solution with a blue shift (−30 nm)
in the absorption spectrum (Fig. 1). On the other hand,
Compound 3 obtained in this way, was then coupled with
calix[4]arene under alkaline conditions with potassium
ferricyanide as the oxidizing agent by an adaptation of
the relevant literature procedures.9 The major product
which is 1,3-calixdiquinone bis-indoaniline 4 was col-
lected following chromatography on silica-gel (chloro-
form–acetone, 50:1 v/v) and satisfactory analytical data
were obtained. The calixdiquinone bis-indoaniline deriva-
tive 4 was moderately soluble in acetonitrile and the
absorption spectrum showed a broad peak at 605 nm
(m=31,600 cm−1 M−1). We studied the interaction of this
Figure 2. Absorption spectrum of 1.4 mM 4 in response to
different concentrations of Eu(III) in acetonitrile: (a) 0, (b)1.0
mM, (c) 2.5 mM, (d) 5.0 mM, (e) 12.5 mM, (f) 100 mM, (g)
saturating.
Figure 1. Absorption spectrum of 1.2 mM 4 in response to
different concentrations of Na(I) in acetonitrile: (a) 0, (b) 1.0
mM, (c) 9.0 mM, (d) saturating.

D. Ataman, E. U. Akkaya / Tetrahedron Letters 43 (2002) 3981–3983
3983
adding just 10 equiv. of a europium salt (Eu(NO3)3)
generates a green solution with a strong red shift (+140
nm) in the absorption spectrum (Fig. 2). The lack of a
clean isosbestic point in response to Eu(III) binding may
be an indication of multi-cation or multi-mode binding.
This seems to be more likely with calcium: Ca(II) also
forms a green solution, but the absorption spectrum
shows a very broad peak in the 400–750 nm range,
suggesting a more complex pattern of binding interac-
tions. Nevertheless, the principle of selective chro-
mogenic response via regioselective binding of cations
was shown to be valid. The work described here clearly
points the direction for further development, as the
receptor–ligand structure can be chosen in such a way
that only very soft cations would bind to the donor–
receptor site. In combination with a hard receptor site
like the calixdiquinone unit of this work or others,12,13
very cleanly separated metal ions responses would be
obtained. Our own work to that end is in progress.
A.; Huxley, T. M.; McCoy, C. P.; Rademacher, J. T.; Rice,
T. E. Chem. Rev. 1997, 97, 1515.
2. de Silva, A. P.; Fox, D. B.; Huxley, A. J. M. Coord. Chem.
Rev. 2000, 205, 41.
3. Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3.
4. Fluorescent Chemosensors for Ion and Molecule Recogni-
tion; Czarnik, A. W., Ed.; ACS Books: Washington, 1993.
5. de Silva, A. P.; McClean, G. D.; McClenaghan, N. D.;
Moody, T. S.; Weir, S. M. Nachr. Chem. 2001, 49, 602.
6. de Silva, A. P.; Gunaratne, H. Q. N.; McCoy, C. P. Nature
1993, 364, 42.
7. Rurack, K.; Kovalchuck, A.; Bricks, J. L.; Slominskii, J.
L. J. Am. Chem. Soc. 2001, 123, 6205.
8. de Silva, A. P.; McClenaghan, N. D. J. Am. Chem. Soc.
2000, 122, 3965.
9. Dix, J. P.; Vo¨gtle, F. Chem. Ber. 1980, 113, 457.
10. Dix, J. P.; Vo¨gtle, F. Chem. Ber. 1981, 114, 638.
11. Brown, G. H.; Figueras, J.; Gledhill, R. J.; Kibler, C. J.;
McCrossen, F. C.; Parmerter, S. M.; Vittum, P. W.;
Weissberger, A. J. Am. Chem. Soc. 1957, 79, 2919.
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Acknowledgements
13. Kubo, Y.; Obara, S.; Tokita, S. Chem. Commun. 1999,
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14. Werner, T.; Ku¨rner, J. M.; Krause, C.; Wolfbeis, O. S.
The authors gratefully acknowledge support from
TUBITAK (TBAG-1885) and METU Research Funds.
Anal. Chim. Acta 2000, 421, 199.
15. Choi, M. J.; Kim, M. Y.; Chang, S.-K. Chem. Commun.
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