fluorescent probes for cations have been reported,6 very
few ratiometric fluorescent sensors for F- are known.7
Thus, it still remains a challenge to develop a ratiometric
fluorescence probe for F-.
Scheme 1. Structures of Chemosensors 1 and 2, and a Plausible
Mechanism for the Spectroscopic Changes of 1 in the Presence
of F-
Recently, two-photon microscopy (TPM), utilizing two
photons of lower energy for the excitation, has become a
vital tool in biology. Compared to traditional fluorescence
microscopy, TPM offers intrinsic 3D resolution combined
with reduced phototoxicity, increased specimen penetra-
tion, and negligible background fluorescence. To make
TPM more versatile tool in biology, it is crucial to develop
a variety of two-photon (TP) probes for specific applica-
tions.8 Although some TP probes have been reported, only
a few of them had sufficient selectivity for anions.9 More-
over, TP probes that can selectively detected analyte via
ratiometric measurement are very rare.
To develop a ratiometric TP probe for F-, we utilized
1,8-naphthalimide, a prototype intramolecular charge
transfer (ICT) fluorophore, because of its advantageous
optical properties, such as strong absorption and emission
in the visible region, high photostability, large Stokes’
shift, insensitivity to pH and a significant two-photon
cross section.10 A silyl ether has been introduced as the
reaction site for F-, because of the high affinity of F- for
silicon,11 with the expectation that the reaction of F- with
1 would trigger the cleavage of Si-O bond and release the
green fluorescent 4-aminonaphthalimide (3) as shown in
Scheme 1, thereby inducing the ratiometric changes in both
color and fluorescence.
Herein, we report a new ratiometric TP fluorescent
probe 1, which shows a dramatic color change, remarkable
ratiometric fluorescence enhancement, and significant
ratiometric changes in the TP absorption and emission
spectra upon addition of F- in CH3CN. For comparison,
the photophysical properties of a reference compound 2
are also presented.
The synthesis of 1 is outlined in Scheme S1 (see Support-
ing Information). To synthesize 1, N-butyl-4-amino-1,8-
naphthalimide (3) was reacted with phosgene in the pre-
sence of 4-dimethylaminopyridine (DMAP) to obtain the
carbamoyl chloride as an intermediate. Reaction of the
carbamoyl chloride with [4-(triisopropylsilyoxy) phenyl]
methanol (4) at 0 °C afforded 1 in 41% yield. Compound 2
was obtained in 59% yield by the same procedure except
that methanol was used in place of 4. The detailed experi-
1
mental procedures and H and 13C NMR spectra are
(6) (a) Zhang, J. F.; Zhou, Y.; Yoon, J.; Kim, Y.; Kim, S. J.; Kim, J. S.
Org. Lett. 2010, 12, 3852. (b) Zhang, J. F.; Kim, J. S. Anal. Sci. 2009, 25,
1271. (c) Kim, J. S.; Quang, D. T. Chem. Rev. 2007, 107, 3780. (d) Kim,
H. N.; Lee, M. H.; Kim, H. J.; Kim, J. S.; Yoon, J. Chem. Soc. Rev. 2008,
37, 1465. (e) Xu, Z.; Yoon, J.; Spring, D. R. Chem. Soc. Rev. 2010, 39,
1996. (f) Lee, M. H.; Lee, S. W.; Kim, S. H.; Kang, C.; Kim, J. S. Org.
Lett. 2009, 11, 2101. (g) Lee, M. H.; Kim, H. J.; Yoon, S.; Park, N.; Kim,
J. S. Org. Lett. 2008, 10, 213. (h) Kim, H. J.; Lee, S. J.; Park, S. Y.; Jung,
J. H.; Kim, J. S. Adv. Mater. 2008, 17, 3229.
(7) (a) Kumar, S.; Luxami, V.; Kumar, A. Org. Lett. 2008, 10, 5549.
(b) Qu, Y.; Hua, J.; Tian, H. Org. Lett. 2010, 12, 3320. (c) Hu, R.; Feng,
J.; Hu, D.; Wang, S.; Li, S.; Li, Y.; Yang, G. Angew. Chem., Int. Ed. 2010,
49, 4915. (d) Xu, Z.; Kim, S. K.; Han, S. J.; Lee, C.; Kociok-Kohn, G.;
James, T. D.; Yoon, J. Eur. J. Org. Chem. 2009, 18, 3058.
summarized in Supporting Information.
The reaction of 1 with tetrabutylammonium fluoride
(TBAF) produced N-butyl-4-amino-1,8-naphthalimide (3)
as the only product as revealed by the identical NMR
spectrum of the reaction product compared to that of
authentic 3 (Figure S1). This indicates that the reaction
between 1 and TBAF most probably proceeds by the
proposed mechanism as shown in Scheme 1.
When excess F- (120 μM) was added to 1 in MeCN, the
colorless solution turned jade-green; this was clearly re-
cognizable by naked eyes. At a lower F- concentration
(<40 μM) the absorption band at 365 nm decreased and a
new band with a shoulder at 487 nm appeared (Figure 1).
To assess the origin of this shoulder, we performed a
proton NMR titration (Figure S1). When 3 equiv of F-
was added to 1, the N-H signal of 1 at 7.46 ppm
disappeared, whereas other protons shifted toward up-
field. This indicates that the N-H bond is deprotonated by
(8) Kim, H. M.; Cho, B. R. Acc. Chem. Res. 2009, 42, 863.
(9) (a) Mohan, P. S.; Lim, C. S.; Tian, Y. S.; Roh, W. Y.; Lee, J. H.;
Cho, B. R. Chem. Commun. 2009, 5365. (b) Lee, J. H.; Lim, C. S.; Tian,
Y. S.; Han, J. H.; Cho, B. R. J. Am. Chem. Soc. 2010, 132, 1216. (c)
Zhang, J. F.; Lim, C. S.; Cho, B. R.; Kim, J. S. Talanta 2010, 83, 658.
(10) Qian, X.; Xiao, Y.; Xu, Y.; Guo, X.; Qian, J.; Zhu, W. Chem.
Commun. 2010, 46, 6418.
(11) (a) Kim, S. Y.; Hong, J. I. Org. Lett. 2007, 9, 3109. (b) Kim, S. Y.;
Park, J.; Koh, M.; Park, S. B.; Hong, J. I. Chem. Commun. 2009, 4735. (c)
Yang, X. F.; Ye, S. J.; Bai, Q.; Wang, X. Q. J. Fluoresc. 2007, 17, 81. (d)
Yang, X. F.; Qi, H.; Wang, L.; Su, Z.; Wang, G. Talanta 2009, 80, 92.
Org. Lett., Vol. 13, No. 5, 2011
1191