42, 43, and 44 in 65-91% yield (entries 20-22). The results
show that our amination procedure provides convenient access
to a wide range of N-aryl and N-alkyl anthranilic acids from
readily available, unprotected 2-bromobenzoic acids and aniline
derivatives or primary aliphatic amines. The reaction tolerates
various functionalities and proceeds with remarkable regiose-
lectivity, which is probably due to the accelerating effect of
ortho-carboxylate groups in homogeneous copper-catalyzed
exchange reactions.13
Because N-(1-pyrene)anthranilic acid, 9, has a metal binding
site in close proximity to the fluorescent pyrene ring, we decided
to study its use as a metal ion sensor in aqueous solution. The
increasing demand for new strategies that can be employed in
real-time analysis of alkali, alkaline earth, and transition metals
in aqueous solutions has led to the development of numerous
chemo- and biosensors.14 We have recently reported the use of
highly constrained 1,8-diacridylnaphthalenes for selective
fluorosensing of Cu(II), Fe(II), and Fe(III).15 Although the
construction of molecular sensors exhibiting a fluorophore in
close proximity to a metal-chelating site has resulted in a variety
of useful fluorosensors, high selectivity toward one metal ion
in water has rarely been accomplished. Chang and co-workers
have developed an 8-hydroxyquinoline sensor bearing an
ionophoric boron-dipyrrolemethene group that proved to be
FIGURE 1. Fluorescence spectra of 9 in the absence and presence of
-4
various transition-metal ions in aqueous 3 × 10 M K
3 4
PO solution
-5
(pH ) 8.0). The concentration of 9 was 2.5 × 10 M, and the metal
-
4
ion concentration was 1.0 × 10 M. Excitation wavelength ) 390
nm.
Investigation of the fluorescence properties of pyrene-derived
anthranilic acid 9 revealed one maximum at approximately 470
nm and a quantum yield of 0.12. Fluorescence studies using 25
-4
µM of 9 were performed in aqueous 3 × 10 M K3PO4 solution
at pH ) 8.0. The screening of the fluorescence of 9 in the
-
4
1
6
presence of 10 M main group and transition-metal chlorides
showed selective fluorescence quenching but no shift of the
emission maximum (Figure 1). No quenching was observed in
highly selective for Hg(II) in dioxane-water solutions.
A
water-soluble fluorescent naphthalimide PET sensor exhibiting
an iminodiacetate receptor with high selectivity for Zn(II) and
an azobenzene-derived sensor for naked-eye detection of
+
+
2+
the presence of main group metal ions such as Na , K , Mg ,
3
+
and Al , whereas addition of some transition metals results in
Cu(II) in water have recently been reported by Gunnlaugsson
et al.17 MerR-type metal-regulating proteins have been used to
a considerable decrease of the fluorescence response of 9.
-
4
Increasing the metal ion concentrations above 10 M did not
result in any further quenching. Most importantly, only Hg(II)
exhibits a strong quenching effect which is not diminished in
the presence of equimolar amounts of Zn(II) and Cd(II). The
sensor can thus be employed for selective detection of Hg(II)
in water.
construct metal-ion sensitive biosensors for selective detection
18
of Hg(II) or Cu(I), Ag(I), and Au(I). Spectrophotometric
detection of Hg(II) in aqueous solution has also been ac-
complished using an optically transparent, mesoporous nano-
1
9
crystalline TiO2 film sensitized with a ruthenium dye.
Mercury and its ionic forms are highly toxic environmental
pollutants that can be introduced into the food chain by bacterial
methylation and subsequent bioaccumulation. Mercury salts and
Hg-derived organometallic compounds have serious neurotoxic
effects and cause disruption of the central nervous system, e.g.
Minamata disease. Because mercury ions are often accompanied
by Zn(II) and Cd(II), it is crucial to develop Hg(II)-selective
sensors that are not compromised by the presence of these
(
(
13) Couture, C.; Paine, A. J. Can. J. Chem. 1985, 63, 111-120.
14) (a) Unob, F.; Asfari, Z.; Vicens, J. Tetrahedron Lett. 1998, 39,
2
1
951-2954. (b) Purrello, R.; Gurrieri, S.; Lauceri, R. Coord. Chem. ReV.
999, 192, 683-706. (c) Leray, I.; Valeur, B.; O’Reilly, F.; Jiwan, J.-L.
H.; Soumillion, J.-P.; Valeur, B. Chem. Commun. 1999, 795-796. (d)
Valeur, B.; Leray, I. Coord. Chem. ReV. 2000, 205, 3-40. (e) de Silva, A.
P.; Fox, D. B.; Huxley, A. J. M.; Moody, T. S. Coord. Chem. ReV. 2000,
2
1
05, 41-57. (f) Deo, S.; Godwin, H. A. J. Am. Chem. Soc. 2000, 122,
74-175. (g) Singh, A.; Yao, Q.; Tong, L.; Still, C. W.; Sames, D.
Tetrahedron Lett. 2000, 41, 9601-9605. (h) Prodi, L.; Montalti, M.;
Zaccheroni, N.; Dallavalle, F.; Folesani, G.; Lanfranchi, M.; Corradini, R.;
Pagliari, S.; Marchelli, R. HelV. Chim. Acta 2001, 84, 690-706. (i) Burdette,
S. C.; Walkup, G. K.; Spingler, B.; Tsien, R. Y.; Lippard, S. J. Am. Chem.
Soc. 2001, 123, 7831-7841. (j) Baxter, P. N. W. Chem.-Eur. J. 2002,
20
transition-metal ions. The remarkable fluorescent response of
water-soluble N-(1-pyrene)anthranilic acid, 9, to mercury chlo-
ride in the presence of both Zn(II) and Cd(II) may open new
entries for a fast quantitative and qualitative analysis of Hg(II)
ions in aqueous samples (Figure 2).
We attempted to grow single crystals of 9 for X-ray analysis
and conducted fluorescence titration experiments to reveal the
three-dimensional structure of the sensor and the stoichiometry
and stability of the corresponding Hg(II) complex. We were
able to grow colorless triclinic crystals of 9 belonging to the
P 1h space group from a DMF solution (Figure 3 and Table 2).
5
250-5264. (k) Collado, D.; Perez-Inestrosa, E.; Suau, R.; Desvergne, J.-
P.; Bouas-Laurent, H. Org. Lett. 2002, 4, 855-858. (l) Chao, C.-T.; Huang,
W.-P. J. Am. Chem. Soc. 2002, 124, 6246-6247. (m) Yang, N. C.; Jeong,
J. K.; Suh, D. H. Chem. Lett. 2003, 32, 40-41. (n) Grabchev, I.; Chovelon,
J.-M.; Qian, X. New J. Chem. 2003, 27, 337-340. (o) Zheng, Y.; Gattas-
Asfura, K. M.; Li, C.; Andreopoulos, F. M.; Pham, S. M.; Leblanc, R. M.
J. Phys. Chem. B 2003, 107, 483-488. (p) Kim, J. S.; Noh, K. H.; Lee, S.
H.; Kim, S. K.; Yoon, J. J. Org. Chem. 2003, 68, 597-600. (q) Clark, M.
A.; Duffy, K.; Tibrewala, J.; Lippard, S. J. Org. Lett. 2003, 5, 2051-2054.
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15) (a) Wolf, C.; Mei, X. J. Am. Chem. Soc. 2003, 125, 10651-10658.
(
7
2
b) Wolf, C.; Mei, X.; Rokadia, H. K. Tetrahedron Lett. 2004, 45, 7867-
871. (c) Tumambac, G. E.; Rosencrance, C. M.; Wolf, C. Tetrahedron
004, 60, 11293-11297.
(19) Palomares, E.; Vilar, R.; Durrant, J. R. Chem. Commun. 2004, 362-
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(16) Moon, S. Y.; Cha, N. R.; Kim, Y. H.; Chang, S.-K. J. Org. Chem.
(20) (a) Yoon, J.; Ohler, N. E.; Vance, D. H.; Aumiller, W. D.; Czarnik,
A. W. Tetrahedron Lett. 1997, 38, 3845-3848. (b) Hennrich, G.; Sonn-
enschein, H.; Resch-Genger, U. J. Am. Chem. Soc. 1999, 121, 5073-5074.
(c) Prodi, L.; Bargossi, C.; Montalti, M.; Zaccheroni, N.; Su, N.; Bradshaw,
J. S.; Izatt, R. M.; Savage, P. B. J. Am. Chem. Soc. 2000, 122, 6769-
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2
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004, 69, 181-183.
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003, 1, 3265-3267. (b) Gunnlaugsson, T.; Leonard, J. P.; Murray, N. S.
(
Org. Lett. 2004, 6, 1557-1560.
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(
3
272 J. Org. Chem., Vol. 71, No. 8, 2006