C O M M U N I C A T I O N S
be noticed that practical hurdles including solvent effects and inter-
actions with chiral catalysts and reagents still have to be overcome
before this methodology can become a widely useful tool for HTS.
In conclusion, we have developed a C2-symmetric sensor that
undergoes stereoselective interactions with a variety of chiral
carboxylic acids, resulting in fluorescence quenching. The high
sensitivity inherent to fluorescence spectroscopy, combined with
the considerable stereoselectivity and broad application spectrum
of this chemosensor, provides the potential for real-time analysis
of the enantiomeric composition of chiral carboxylic acids. Further
studies of the chiral recognition mechanism and the usefulness of
1,8-diacridylnaphthalenes for enantioselective fluorosensing of
different classes of chiral compounds are currently underway in
our laboratories.
Acknowledgment. Funding from the National Science Foundation
(CAREER Award, CHE-0347368) and the Petroleum Research Fund
administered by the ACS (PRF40897-G4) is gratefully acknowledged.
We thank Mark Olsen, GlaxoSmithKline Pharmaceuticals, for LC/APCI/
MS analysis of 1 and the Center for Fluorescence Spectroscopy, University
of Maryland at Baltimore, School of Medicine, for fluorescence lifetime
measurements.
Figure 2. Linear Stern-Volmer plots for the enantioselective fluorescence
quenching of (+)-1 in the presence of carboxylic acids 7, 11, and 14. The
concentration of (+)-1 in acetonitrile was 2.6 × 10-6 M. Excitation
(emission) wavelength, 360 nm (550 nm).
Table 1. Enantioselective Fluorescence Quenching of (+)-1 in the
Presence of Carboxylic Acids 7-14
a
a
analyte
ratio 1/analyte
R
K(+
)-1
K(+
)-1
-(R)
-analyte
-(S)-analyte
7
8
9
10
11
12
13
14
1:1
1:1
1:1
1:1
1:2
1:2
1:2
1:2
1.7 (R/S)
1.3 (S/R)
2.2 (S/R)
1.1 (S/R)
2.1 (S/R)
2.2 (R/S)
1.3 (R/S)
4.5 (R/S)
88.5 M-1
56.5 M-1
610.0 M-1
75.6 M-1
840.0 M-1
241.3 M-1
18.4 M-1
20.0 M-1
2100.0 M-2
16000.0 M-2
5300.0 M-2
63000.0 M-2
4900.0 M-2
7100.0 M-2
4700.0 M-2
36000.0 M-2
a Obtained using the Benesi-Hildebrand equation for 1:1 complexes
(7-10) and 1:2 complexes (11-14).
Supporting Information Available: Experimental procedures and
full characterization of 1, Stern-Volmer plots for all fluorescence
titration experiments and actual measurements of the enantiopurity of
different samples of 14 (PDF, CIF). This material is available free of
an enantioselectivity factor, R ) KRSV/KSSV, of 1.7 based on a linear
Stern-Volmer plot for the corresponding diastereomeric 1:1
complexes (Figure 2). By contrast, (+)-1 forms a 1:2 complex with
N-t-Boc-phenylalanine (11), with an enantioselectivity factor KS
/
sv
References
KR of 2.1. The fluorosensor also differentiates between the
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1,1′-Binaphthyl-derived fluorosensors have been designed for
chiral recognition of mandelic acid and its derivatives.3e,5d,9 How-
ever, to the best of our knowledge, diacridylnaphthalene 1 is the
first enantioselective fluorosensor applicable to a broad variety of
carboxylic acids, including amino acids, aliphatic acids, arylalkanoic
acids, and halogenated carboxylic acids. The observed change of
the fluorescence intensity of excited (+)-1 in the presence of
carboxylic acids 7-14 is probably a result of static quenching
through nonradiative relaxation of diastereomeric acid-base ad-
ducts.10 The equilibrium binding constants of the diastereomeric
complexes were obtained using the Benesi-Hildebrand equation
for 1:1 complexes (7-10) and 1:2 complexes (11-14) (Table 1).4d,11
The binding constants vary significantly and indicate that coordina-
tion between the sensor and the carboxylic acids may be attributed
either to O-H‚‚‚N hydrogen bonds or to charge-assisted carbox-
ylate-acridinium O-‚‚‚HsN+ hydrogen bonding involving proton
transfer in some cases.12
Achiral fluorosensors have been used for HTS of combinatorial
libraries,13 but only a few examples of enantioselective analysis
with chiral fluoroprobes have been reported to date.14 Since our re-
sults show that 1,8-diacridylnaphthalene 1 is a fluorosensor with a
broad application spectrum, it may be employed in HTS efforts based
on indicator-displacement assays to evaluate the asymmetric syn-
thesis of chiral carboxylic acids, including non-steroidal anti-inflam-
matory drugs such as naproxen or ibuprofen.2 However, it should
(14) (a) Korbel, G. A.; Lalic, G., Shair, M. D. J. Am. Chem. Soc. 2001, 123,
361-362. (b) Matsushita, M.; Yoshida, K.; Yamamoto, N.; Wirsching,
P.; Lerner, R. A.; Janda, K. Angew. Chem., Int. Ed. 2003, 42, 5984-5987.
JA0459781
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