10438
J. Am. Chem. Soc. 1999, 121, 10438-10439
Dipyrrolylquinoxalines: Efficient Sensors for
Fluoride Anion in Organic Solution
Christopher B. Black, Bruno Andrioletti, Andrew C. Try,
Cristina Ruiperez, and Jonathan L. Sessler*
Figure 1. Proposed mode of anion binding and sensing. Recognition
of, for instance, fluoride anion, is expected to perturb the orbital overlap
between the pyrrole and quinoxaline subunits, thereby changing the optical
characteristics of the latter.
Department of Chemistry and Biochemistry
The UniVersity of Texas at Austin
Austin, Texas 78712-1167
ReceiVed July 21, 1999
ReVised Manuscript ReceiVed September 16, 1999
Scheme 1
In recent decades, supramolecular chemists have devoted
considerable effort to developing systems capable of recognizing,
sensing, and transporting negatively charged species.1 Among the
range of biologically important anions, fluoride is of particular
interest due to its established role in preventing dental caries.2
Fluoride anion is also being explored extensively as a treatment
for osteoporosis3,4 and, on a less salubrious level, can lead to
fluorosis,5-7 a type of fluoride toxicity that generally manifests
itself clinically in terms of increasing bone density. This diversity
of function, both beneficial and otherwise, makes the problem of
fluoride anion detection one of considerable current interest. While
traditional methods of fluoride anion analysis such as ion selective
electrodes and 19F NMR spectroscopy remain important, there is
mounting incentive to find alternative means of analysis, including
those based on the use of specific chemosensors.8 Particularly
useful would be systems that can recognize fluoride anion in
solution and signal its presence via an easy-to-detect optical
signature.
In the past few years, we and others have proposed a wide
range of anion sensors (sapphyrins,9 calixpyrroles,10,11 poly-
amines,12-15 guanidinium,16,17 etc.) that present varying degrees
of affinity (and selectivity) toward anions such as F-, Cl-,
H2PO4-, and carboxylates. Unfortunately, and despite considerable
effort, a need for good anion sensors remains. This is particularly
true in the case of fluoride anion where few, if any, easy-to-use
signaling agents exist.18 Our recent experience with polypyrrole-
based anion binding agents led us to consider that pyrrolic systems
containing a built-in chromophore might give rise to useful anion
sensors.
Our current investigations utilize the easy-to-prepare 2,3-
dipyrrol-2′-ylquinoxaline 1. While known in the literature since
1911,19 to the best of our knowledge, this particular entity has
never been considered as being a possible colorimetric anion
sensor. It contains two pyrrole NH groups that could function as
anion binding moeities and a built-in quinoxaline ring that might
serve as a colorimetric reporter of any binding events. As
illustrated in Figure 1, this putative sensing system is expected
to operate through a combination of electronic and conformational
effects.
The preparation of 1 involves condensing oxalyl chloride with
pyrrole at -80 °C as described first by Oddo19 and later refined
by Behr.20 Subsequent reaction between the resulting 2,3-dipyrrol-
2′-ylethanedione 2 with o-phenylenediamine in acetic acid at
reflux leads to 2,3-dipyrrol-2′-ylquinoxaline 1 in excellent yield
(Scheme 1). By modifying this procedure and using other 1,2-
diaminobenzenes, a wide range of 2,3-dipyrrol-2′-ylquinoxaline
derivatives, possessing various electron-withdrawing or -donating
groups, may, in principle, be prepared. In this paper we describe
the synthesis of 2,3-dipyrrol-2′-yl-6-nitroquinoxaline 3 and the
anion binding properties of it, its “parent” 1, and the control
systems, quinoxaline, 2,3-dipyrrol-2′-ylethanedione 2, and the
monotrimethylsilylethoxymethyl (SEM)-protected species 4.
(1) Dietrich, B.; Hosseini, M. W. In Supramolecular Chemistry of Anions;
Bianchi, A., Bowman-James, K., Garc´ıa-Espan˜a, E., Eds.; Wiley-VCH: New
York, 1997; pp 45-62.
(2) Kirk, K. L. Biochemistry of the Halogens and Inorganic Halides;
Plenum Press: New York, 1991; p 58.
(3) Riggs, B. L. Bone and Mineral Research, Annual 2; Elsevier:
Amsterdam, 1984; pp 366-393.
(4) Kleerekoper, M. Endocrinol. Metab. Clin. North Am. 1998, 27, 441.
(5) Wiseman, A. Handbook of Experimental Pharmacology XX/2, Part 2;
Springer-Verlag: Berlin, 1970; pp 48-97.
(6) Weatherall, J. A. Pharmacology of Fluorides. In Handbook of Experi-
mental Pharmacology XX/1, Part 1; Springer-Verlag: Berlin, 1969; pp 141-
172.
The ability of the dipyrrole systems 1 and 3 to coordinate to
F-, Cl-, and H2PO4 (as tetrabutylammonium salts) was inves-
-
(7) Dreisbuch, R. H. Handbook of Poisoning; Lange Medical Publishers:
Los Altos, CA, 1980.
(8) Chemosensors of Ion and Molecular Recognition; Desvergne, J.-P.,
Czarnik, A. W., Eds., NATO ASI Series, Series C; Kluwer Academic Press:
Dordrecht, the Netherlands, 1997; Vol. 492.
(9) Sessler, J. L.; Andrievsky, A.; Genge, J. W. In AdVances in Supramo-
lecular Chemistry; Lehn, J. M., Ed.; JAI Press Inc.: Greenwich, CT, 1997;
Vol. 4, pp 97-142.
(10) Gale, P. A.; Sessler, J. L.; Kra´l, V. K.; Lynch, V. M. J. Am. Chem.
Soc. 1996, 118, 5140.
(11) Sessler, J. L.; Gale, P. A.; Genge, J. W. Chem. Eur. J. 1998, 4, 1095.
(12) Dietrich, B.; Hosseini, M. W.; Lehn, J. M.; Sessions, R. B. J. Am.
Chem. Soc. 1981, 103, 1282.
(13) Hosseini, M. W.; Lehn, J. M. HelV. Chim. Acta 1988, 71, 749.
(14) Huston, M. E.; Akkaya, E. U.; Czarnik, A. W. J. Am. Chem. Soc.
1989, 111, 8735.
(15) Czarnik, A. W. Acc. Chem. Res. 1994, 27, 302.
(16) Dietrich, B.; Fyles, D. L.; Fyles, T. M.; Lehn, J.-M. HelV. Chim. Acta
1979, 62, 2763.
(17) Metzger, A.; Lynch, V. M.; Anslyn, E. V. Angew. Chem., Int. Ed.
Engl. 1997, 36, 862.
(18) For a recent report of fluorescence-based F- detection using boronic
acids, see: Cooper, C. R.; Spencer, N.; James, T. D. Chem. Commun. 1998,
1365.
(19) Oddo, B. Gazz. Chim. Ital. 1911, 41, 248.
(20) Behr, D.; Branda¨nge, S.; Lindstro¨m, B. Acta Chem. Scand. 1973, 27,
2411.
(21) UV/vis titrations: All stock solutions were prepared in dichlo-
romethane. Spectra were collected on a Beckman DU-640 UV/vis spectro-
photometer. Since 2 does not fluoresce significantly, yet maintains a relatively
large extinction coefficient, anion binding titrations were carried out by
monitoring changes in the UV band at 341 nm as a function of added anion
concentration. The resulting decrease in intensity was fit using eq 1, as
described by Connors.23
∆A/b ) (QtK∆ꢀ[L])/(1 + K[L])
(1)
Here, ∆A refers to the change in absorbance from the initial value, Qt is the
total concentration of 1, K is the binding constant, ∆ꢀ is the change in
extinction coefficient between the bound and unbound species, and L is the
concentration of anion titrated.
10.1021/ja992579a CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/23/1999