In the past decade, a wide range of efficient and selective
artificial hosts for DA which afford stable complexes in
concentration range, stability, simplicity and speed, low
hazard, and low cost, we now report on two novel 1H-
pyrazole diazatetraester crown receptors containing appended
N-(9H-fluoren-9-yl) and N-(naphth-2-ylmethyl) fluorophoric
functions (1 and 2 in Figure 1B) that interact with AMPH,
METH, MDMA, and DA and can permit their fluorescence
sensing and discrimination in aqueous solution.
7
8
organic or aqueous media have been prepared. Some of
them are able to act directly as selective chemosensors or
9
fluorescent sensors of DA. Others act as selective detectors
of DA when embedded in chromatic polydiacetylene
1
0
11
vesicles or when immobilized in fluorescent films.
However, the design of artificial hosts for the selective
binding of amphetamines is more difficult. In this respect,
several 18C6 derivatives were obtained with the aim of
1
2
solving racemic mixtures. Conventional methods for
amphetamine detection are not based on artificial receptors.
They are separation techniques some of which are based on
1
3
capillary electrophoresis with laser-induced fluorescence
or reversed-phase HPLC in combination with fluorescence
1
4,15
detection.
However, such techniques often require de-
rivatization of the amines and expensive equipments. Re-
cently, several strategies for optical sensing of amphetamines
based either on a chromoreactant or on the analysis of charge-
transfer and ion-pair complexation with some acceptors have
1
6
been described. On the other hand, different immunosen-
sors for amphetamine detection in blood, urine, or saliva have
1
7
also been reported.
In the search of receptors for abuse drugs, we previously
reported on a series of dioxa- and diaza-substituted ester
crowns, which behave as efficient hosts for AMPH and
1
8
METH in DMSO solution. On the other hand, it was
recently proven that the sodium salt of the diethyl 1H-
pyrazole-3,5-dicarboxylate behaves as an efficient am-
phiphilic receptor for dopamine and amphetamines in both
DMSO and aqueous solution. Taking into account that
fluorescence detection offers a number of important advan-
tages over other methods as high sensitivity, specificity, wide
1
9
Figure 1. Compound drawings and synthetic procedure.
The synthesis of 1 and 2 was achieved as depicted in
Figure 1C. The starting N,N-bis(2-hydroxyethyl)-9H-fluoren-
9-ylamine and N,N-bis(2-hydroxyethyl)(naphth-2ylmethy-
l)amine were previously prepared by reaction of 9-bromof-
luorene or 2-(bromomethyl)naphthalene with diethanolamine
(
7) (a) Rodr ´ı guez-Franco, M. I.; San Lorenzo, P.; Mart ´ı nez, A.; Navarro,
P. Tetrahedron 1999, 55, 2763–2772. (b) R u¨ beling, D.; Schrader, T. J. Am.
Chem. Soc. 2003, 125, 12086–12087.
(
8) (a) Lamarque, L.; Navarro, P.; Miranda, C.; Ar a´ n, V. J.; Ochoa, C.;
Escart ´ı , F.; Garc ´ı a-Espa n˜ a, E.; Latorre, J.; Luis, S. V.; Miravet, J. F. J. Am.
Chem. Soc. 2001, 123, 10560–10570. (b) Herm, M.; Molt, O.; Schrader, T.
Chem.sEur. J. 2002, 8, 1485–1499. (c) Escuder, B.; Rowan, A. E.; Feiters,
M. C.; Nolte, R. J. M. Tetrahedron 2004, 60, 291–300.
2
0
following a previously reported method.
The above aminodiols were then heated to reflux in toluene
with butyltin oxide to give a mixture of stannoxanes, which
were later reacted with 1H-pyrazole-3,5-dicarbonyl dichloride
in dry dimethoxyethane at 60 °C. The corresponding reaction
mixtures were then purified as indicated in the experimental
part to yield compunds 1 and 2 as crystalline solids (see the
Supporting Information).
(
(
9) Secor, K. E.; Glass, T. E. Org. Lett. 2004, 6, 3727–3730.
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(
(
1
(
8
(
Steady-state fluorometric titrations recorded in a water/
.
+
ethanol 70:30 v/v mixture at variable pH (pH ) -log [H ])
(
show different behaviors for 1 and 2. Compound 1 displays
below pH ) 6, where both tertiary amines are protonated,
an intense fluorescence due to the fluorene fragments and
does not fluoresce at higher pH values. In a first approach,
the quenching observed above pH ) 6 can be attributed to
a photoinduced electron transfer from the lone pair of a
nonprotonated tertiary amine to the fluorophore as reported
.
(
Bioanal. Chem. 2002, 374, 399–402. (b) Shahdousti, P.; Aghamohammadi,
M.; Alizadeh, N. Spectrochim. Acta A 2008, 69, 1195–1200.
(
17) (a) Butler, D.; Pravda, M.; Guilbault, G. G. Anal. Chim. Acta 2006,
5
56, 333–339. (b) Woodworth, A.; Saunders, A. N.; Koening, J. W.; Mayer,
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(
18) Reviriego, F.; Navarro, P.; Dom e` nech, A.; Garc ´ı a-Espa n˜ a, E. J.
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(
(20) Fletcher, T. Ll.; Wetzel, W. H. J. Org. Chem. 1960, 25, 1348–
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1
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Org. Lett., Vol. 10, No. 22, 2008