dos Santos et al.
anions. The use of such versatile synthetic functionalities has
enabled the design and construction of more sophisticated anion
receptors,16 which facilitates a more effective targeting approach
to anion sensing using arrays of hydrogen bonding donors,
where both the selectivity and the sensitivity of the recognition
process can be tuned.17 We have in the past demonstrated that
such charge neutral functionalities can be employed in both
colorimetric18,19 and fluorescent20,21 anion sensing, either in
organic solvents such as CH3CN and DMSO, or in more
competitive media such as ethanol and buffered aqueous
solution.5 Recently, amidoureas and thioureas11 have been
incorporated into structurally preorganized hosts which gave
rise to both enhanced selectivity and sensitivity for ions such
as phosphate and pyrophosphate. While the ‘amide’ functionality
of these systems has been an integrated part of the main
“receptor moiety”, we demonstrate herein that the introduction
of these functional groups into simple anion based diaryl
(7) (a) Kang, S. O.; Begum, R. A.; Bowman-James, K. Angew. Chem., Int.
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(h) Gunnlaugsson, T.; Pfeffer, F. M.; Buschgens, A. M.; Barnett, N. W.;
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Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.; Glynn, M. Org. Biomol. Chem.
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Go´mez, D. E.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. J. Am. Chem. Soc. 2004,
126, 16507. (l) Kato, R.; Cui, Y.-Y.; Nishizawa, S.; Yokobori, T.; Teramae, N.
Tetrahedron Lett. 2004, 45, 4273. (m) Jose, D. A.; Kumar, D. K.; Ganguly, B.;
Das, A. Org. Lett. 2004, 6, 3445. (n) Gunnlaugsson, T.; Davis, A. P.; O’Brien,
J. E.; Glynn, M. Org. Lett. 2002, 4, 2449. (o) Davis, A. P.; Glynn, M. Chem.
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Chem. B 2008, 112, 5105. (b) Liu, W.-X.; Jiang, Y.-B. Org. Biomol. Chem.
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Chem. Commun. 2006, 965. (e) Wu, F. Y.; Li, Z.; Guo, L.; Wang, X.; Lin,
M. H.; Zhao, Y. F.; Jiang, Y. B. Org. Biomol. Chem. 2006, 4, 624. (f) Nei, L.;
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Biomol. Chem. 2003, 1, 741.
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2007, 5, 1795. (b) Bates, G. W.; Triyanti, Light, M. E.; Albrecht, M.; Gale, P.
A J. Org. Chem., 2007, 72, 8921.
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20, 407.
(22) (a) The field of “Allosteric Supramolecular Receptors and Catalysts”
has recently been reviewed by Kovbasyuk, L.; Kra¨mer, R. Chem. ReV. 2004,
104, 3161. (b) Ercolani has recently reviewed and examined the cause of
cooperatively in self-assembly formations in supramolecular chemistry Ercolani,
G. J. Am. Chem. Soc. 2003, 125, 16097. While our results do not strictly fulfill
the criteria set out in this publication for positiVe cooperatiVity, the results
demonstrate that only after the first binding at the urea moiety is the binding of
the amide activated in compounds 1 and 2. While this is most likely the cause
of enhanced inductive effect as the result of the first anion binding (caused by
enhanced ICT within the molecule), we proposed that this “mechanism” for anion
recognition can be described as an example of positive allosteric effect. (c) Other
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(d) Recently, pyridyl thioureas were developed as switchable anion receptors
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2006, 4578.
receptors as independent components, 1-3 (where the amide
is located at the para, meta and ortho positions, respectively),
gives rise to the recognition of several anions with concomitant
high binding affinities in CH3CN. We also demonstrate that the
substitution pattern in 1-3, has significant effects on both the
sensitivity as well as the stoichiometry of the anion recognition,
which was investigated using both UV-vis absorption and 1H
NMR spectroscopy in organic solvents. We demonstrate, for
the first time that in the case of 1 and 2, the binding of anions
at the urea moiety, enhances, or activates, the recognition ability
of the amide moiety enabling these receptors to bind anions
such as acetate in 1:1 as well as in 1:2 binding stoichiometry.
Here, the second anion binding at the amide site only occurs
after this primary recognition at the urea site takes place. This
phenomenon we like to describe as being an example of a
“positive allosteric effect”22a caused by the first anion binding
event.22b,c In comparison, 3 only gave the 1:1 binding stoichi-
ometry, where the amide moiety cooperatively participated in
the initial anion binding event at the urea site. Hence, this
location prevents any “allosteric activation” caused by the first
anion binding. To the best of our knowledge, this is the first
time that such effects have been employed for the sensing of
anions using urea based receptors.22d Consequently, the results
presented herein open up a new avenue for the design of anion
targeting receptors. Herein, we describe the synthesis and the
characterization of 1-3, which includes the analysis of their
X-ray crystal structures and packing in the solid state, as well
as their ability to bind anions in the manner outlined above.
Results and Discussion
Synthesis and X-Ray Crystallographic Analysis of 1-3.
The synthesis of compounds 1-3 is shown in Scheme 1. Using
the commercially available nitroanilines 4-6 (the para, meta
and ortho isomers, respectively), the amino groups were
converted to the corresponding amides 7-9, by reacting 4-6
in neat acetic anhydride at room temperature overnight. The
resulting off-white colored precipitates were collected by
filtration and each batch washed twice with diethyl ether and
dried under high vacuum, giving 7-9 in 83, 57 and 57% yields,
respectively. Reduction of the nitro groups in 7-9 using
hydrazine monohydrate and 10% Pd/C in ethanol under reflux
for 12 h, gave 10-12 as off-white solids in almost quantitative
9236 J. Org. Chem. Vol. 73, No. 23, 2008