A R T I C L E S
Yamaguchi et al.
Scheme 1. Synthesis of Bis-DPA-Zn Complexes
converted to fluorescent chemosensors, as shown in the typical
examples of receptors 3 and 4. Thus, the various phosphate
derivatives, such as phosphate, phospho-tyrosine, phenyl phos-
phate, and ATP, can be sensed and discriminated from each
other on the basis of the combination of the several parameters
yielded by the present MR chip, that is, the fluorescence
wavelength shift and ratiometric fluorescence change, as well
as the simple fluorescence intensity change. Recently, supramo-
lecular organo- or hydrogels have been actively developed as a
new class of self-assembled materials.9 In contrast to the well-
studied structural analysis, novel functions originating from the
supramolecular gels have not yet been sufficiently developed.
It is expected that the present results will inspire function-
directed research into these promising soft materials.
Experimental Section
Generals. Mass spectra were recorded on PB Biosystems Voyager
DE-RP MALDI-TOF mass spectrometer. Fluorescence spectra of the
hydrogel chips were recorded using an Otsuka Electronics high
sensitivity Spectro multichannel photodetector, MCPD-7000. Fluores-
cence spectra for the aqueous solution were collected on a Hitachi
F-4500 instrument. Confocal laser scanning microscopy observation
was carried out with a Carl Zeiss LSM 510 device.
Synthesis. The gelator 110 and the chemosensor 23b were prepared
according to the method reported previously by us. The receptors 3
and 4 were prepared as shown in Scheme 1. 3,5-Bis(bromomethyl)-
benzyl alcohol was prepared from trimethyl 1,3,5-benzenetricarboxylate
following a procedure described in a literature.11
3,5-Bis(2,2′-dipicolylaminomethyl)benzyl Alcohol (5). A mixture
of 3,5-bis(bromomethyl)benzyl alcohol (570 mg, 1.9 mmol), 2,2′-
dipicolylamine (860 mg, 4.3 mmol), and potassium carbonate (1.1 g,
7.9 mmol) in DMF (25 mL) was stirred at room temperature for 50
min under a nitrogen atmosphere, and then ethyl acetate and water
were added to the mixture. The organic layer was collected, and the
aqueous layer was extracted with ethyl acetate. The initial organic layer
and eluant were combined, washed (brine), dried (MgSO4), and filtered.
The filtrate was concentrated to dryness, and the residue was purified
by column chromatography (SiO2, dichloromethane/methanol/aqueous
ammonia ) 100:10:1), affording a yellow oil (870 mg, 84%): 1H NMR
(400 MHz, CDCl3) δ 3.68 (s, 4H), 3.79 (s, 8H), 4.68 (s, 2H), 7.05-
7.15 (m, 4H), 7.29 (s, 2H), 7.40 (s, 1H), 7.54-7.64 (m, 8H), 8.46-
8.51 (m, 4H); FAB-MS obsd 531.3 [M + H]+, calcd 530.3 (C33H34N6O).
3,5-Bis(2,2′-dipicolylaminomethyl)benzylmethylamine (6). A solu-
tion of 3,5-bis(2,2′-dipicolylaminomethyl)benzyl alcohol 5 (380 mg,
0.72 mmol) in 47 wt % of aqueous HBr (40 mL) was refluxed for 3 h.
The solution was neutralized with aqueous sodium bicarbonate, and
the resulting solution was extracted with ethyl acetate. To the organic
layer was added 40 wt % of methylamine in methanol (21 mL), and
the mixture was stirred at room temperature for 2 h and then
concentrated to dryness. The residue was dissolved in ethyl acetate,
and the organic layer was washed (water), dried (MgSO4), and
concentrated to dryness. The residue was purified by column chroma-
tography (SiO2, dichloromethane/methanol/aqueous ammonia ) 100:
10:2), affording a colorless oil (870 mg, 84%): 1H NMR (400 MHz,
CDCl3) δ 2.44 (s, 3H), 3.69 (s, 4H), 3.73 (s, 2H), 3.81 (s, 8H), 7.13-
7.16 (m, 4H), 7.22 (s, 2H), 7.42 (s, 1H), 7.59-7.65 (m, 8H), 8.52 (d,
J ) 5.2 Hz, 4H); FAB-MS obsd 534.3 [M + H]+, calcd 543.3
(C34H37N7).
Dansyl-Appended Bis-DPA Compound (7). A solution of 3,5-bis-
(2,2′-dipicolylaminomethyl)benzylmethylamine 6 (180 mg, 0.33 mmol)
and N,N′-diisopropylethylamine (DIEA, 90 µL, 0.52 mmol) in dichlo-
romethane (10 mL) was treated with dansyl chloride (110 mg, 0.40
mmol) at 0 °C for 50 min under a nitrogen atmosphere, and then
dichloromethane and water were added to the reaction mixture. The
organic layer was collected, and the aqueous layer was extracted with
dichloromethane. The initial organic layer and eluant were combined,
dried (MgSO4), and filtered. The filtrate was concentrated to dryness,
and the residue was purified by column chromatography (SiO2,
dichloromethane/methanol/aqueous ammonia ) 150:10:2), affording
a pale green solid (180 mg, 70%): 1H NMR (400 MHz, CDCl3) δ
2.67 (s, 3H), 2.91 (s, 6H), 3.62 (s, 4H), 3.78 (s, 8H), 7.12-7.15 (m,
4H), 7.20 (s, 1H), 7.22 (s, 2H), 7.39 (s, 1H), 7.53-7.57 (m, 2H), 7.56-
7.68 (m, 8H), 8.24 (d, J ) 6.8 Hz, 1H), 8.47 (d, J ) 8.6 Hz, 1H), 8.51
(d, J ) 4.8 Hz, 4H), 8.57 (d, J ) 8.6 Hz, 1H); FAB-MS obsd 777.4
[M + H]+, calcd 776.4 (C46H48N8O2S).
(9) (a) Estroll, L. A.; Hamilton, A. D. Chem. ReV. 2004, 104, 1202-1217. (b)
Kisiday, J.; Jin, M.; Kurz, B.; Hung, H.; Semino, C.; Zhang, S.; Grodzinsky,
A. J. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 9996-10001. (c) Kobayashi,
H.; Friggeri, A.; Koumoto, K.; Amaike, M.; Shinkai, S.; Reinhoudt, D. N.
Org. Lett. 2002, 4, 1423-1426. (d) Jung, J.-H.; John, G.; Masuda, M.;
Yoshida, K.; Shinkai, S.; Shimizu, T. Langmuir 2001, 17, 7229-7232. (e)
Menger, F. M.; Caran, K. L. J. Am. Chem. Soc. 2000, 122, 11679-11691.
(f) Maitra, U.; Mukhopadhyay, S.; Sarkar, A.; Rao, P.; Indi, S. S. Angew.
Chem., Int. Ed. 2001, 40, 2281-2283. (g) Estroff, L. A.; Hamilton, A. D.
Angew. Chem., Int. Ed. 2000, 39, 3447-3449. (h) Bhattacharya, S.;
Acharya, S. N. G. Chem. Mater. 1999, 11, 3504-3511. (i) Oda, R.; Huc,
I.; Candau, S. J. Angew. Chem., Int. Ed. 1998, 37, 2689-2691. (j)
Makarevic, J.; Jokic, M.; Peric, B.; Tomisic, V.; Kojic-Prodic, B.; Zinic,
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528.
Dansyl-Appended Bis-DPA-Zn Complex (3). To a solution of a
dansyl-appended bis-DPA compound 7 (150 mg, 0.19 mmol) in
methanol (5 mL) was added 0.05 M zinc(II) nitrate in water (7.6 mL,
0.38 mmol), and the mixture was stirred at room temperature for 30
min in the dark. The mixture was concentrated to dryness, and water
was added to the residue. The insoluble material was filtered off and
the filtrate was concentrated to dryness, and then the residue was washed
with ethyl acetate, affording a pale green solid (200 mg, 92%): 1H
NMR (600 MHz, D2O) δ 2.59 (s, 6H), 3.05 (s, 3H), 3.38 (s, 4H), 3.62
(11) D´ıez-Barra, E.; Garc´ıa-Mart´ınez, J. C.; del Rey, R.; Rldr´ıguez-Lo´pez, J.;
Sa´nchez-Verdu´, P.; Tejada, J. J. Org. Chem. 2001, 66, 5664.
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11840 J. AM. CHEM. SOC. VOL. 127, NO. 33, 2005