COMMUNICATIONS
study are commercially available or can be easily synthesized.
They spontaneously self-assemble in neutral water giving rise
to an assembly that displays some of the most important
features of a sensor, such as sensitivity and selectivity. This
modular approach allows for the easy variation of the
components, which makes the process of system optimization
very simple. Work is in progress to extend such a concept to
ligands selective towards other metal ions and to widen its
scope to the sensing of neutral molecules.
N,N-Diethanolaminomethyl Polystyrene:
An Efficient Solid Support to
Immobilize Boronic Acids**
Dennis G. Hall,* Jyoti Tailor, and Michel Gravel
Insoluble resins that selectively couple to a functional
group are vital in combinatorial chemistry to immobilize
substrates to be derivatized by solid-phase synthesis.[1] They
are also employed as scavenger or ªfishing outº resins in the
solution-phase parallel synthesis of small molecule libraries.[2]
Despite the use of boronic acids as intermediates in reactions
such as the Suzuki cross-coupling[3] and in biological applica-
tions including sugar recognition[4] and inhibition of serine
proteases,[5] there are currently no solid supports available
that couple to the boronic acid functionality. Herein we report
on the preparation of N,N-diethanolaminomethyl polystyrene
(DEAM-PS), the first resin capable of immobilizing boronic
acids, along with a preliminary assessment of its usefulness
toward combinatorial chemistry applications. DEAM-PS
resin can immobilize aryl, alkenyl, and alkyl boronic acids
almost quantitatively in a wide range of organic solvents.
Moreover, it is easily synthesized at low cost and can be
recycled.
Diethanolamine boronate adducts have long been em-
ployed to stabilize, purify, and characterize boronic acids.[6]
We looked at several ways to derivatize polystyrene resin to
include such a diethanolamine anchor. We have best achieved
this goal through the reaction of aminomethylated polystyr-
ene (AM-PS) with excess ethylene oxide at 508C in a THF/
water solvent mixture in a sealed, pressure-resistant tube
(Scheme 1). Under these conditions, quaternization to give
the triethanolalkylammonium hydroxide salt and oxirane
Experimental Section
N-Decylglycylglycine (1) was synthesized following a reported proce-
dure[13] and was isolated as the CF3COOH salt. All spectral and analytical
data were in agreement with the proposed structure. Representative data
for 1: m.p. 109 ± 1108C; elemental analysis calcd for C16H29N2O5F3: C 49.7,
H 7.56, N 7.25; found: C 50.1, H 7.51, N 7.27; 1H NMR (250 MHz, CD3OD,
258C, TMS): d 0.94 (t, J 6.5 Hz, 3H), 1.38 (m, 14H), 1.74 (m, 2H), 3.07
(t, J 6.7 Hz, 2H), 3.88 (s, 2H), 4.03 (s, 2H).
Critical micellar concentrations were obtained from surface tension
measurements using a Krüss K6 apparatus. Ultrafiltrations were performed
with a 8010 Amicon cell equipped with a regenerated cellulose Millipore
filter with a cut-off of 104 Daltons. Emission spectra were recorded on a
Perkin ± Elmer LS-50B spectrofluorimeter. Titrations were performed in a
4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid (HEPES) buffer
0.01m, pH 7, and 258C. Excitation and emission wavelengths (nm) were,
respectively: 375 and 500 for ANS; 286 and 360 for 1-NAFOSF; 362 and
415 for 9-anthracenecarboxylic acid (ACA); 325 and 530 for dansylamide
(DANSA).
Received: May 10, 1999 [Z13396IE]
German version: Angew. Chem. 1999, 111, 3247 ± 3250
Keywords: copper ´ fluorescent sensor ´ micelles ´ self
assembly ´ supramolecular chemistry
[1] a) ªFluorescent Chemosensors for Ion and Molecule Recognitionº:
ACS Symp. Ser. 1993, 538; b) A. P. de Silva, H. Q. N. Gunaratne, T.
Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher, T. E.
Rice, Chem. Rev. 1997, 97, 1515 ± 1566.
[2] R. Krämer, Angew. Chem. 1998, 110, 804 ± 806; Angew. Chem. Int. Ed.
1998, 37, 772 ± 773.
OH
OH
a
CH2NH2
CH2N
PS
1
[3] G. De Santis, L. Fabbrizzi, M. Lichelli, C. Mangano, D. Sacchi, N.
Sardone, Inorg. Chim. Acta 1997, 257, 69 ± 76.
[4] J. Yoon, N. E. Ohler, D. H. Vance, W. D. Aumiller, A. W. Czarnik,
Tetrahedron Lett. 1997, 38, 3845 ± 3848.
[5] A. Torrado, G. K. Walkup, B. Imperiali, J. Am. Chem. Soc. 1998, 120,
609 ± 610.
[6] R. Corradini, A. Dossena, G. Galaverna, R. Marchelli, A. Panagia, G.
Sartori, J. Org. Chem. 1997, 62, 6283 ± 6289.
[7] P. Ghosh, P. K. Bharadwaj, S. Mandal, S. Ghosh, J. Am. Chem. Soc.
1996, 118, 1553 ± 1554.
[8] D. Y. Sasaki, D. R. Shnek, D. W. Pack, F. H. Arnold, Angew. Chem.
1995, 107, 994 ± 996; Angew. Chem. Int. Ed. Engl. 1995, 34, 905 ± 907.
[9] A different approach to a self-assembling sensor is based on the
competition between the target substrate and the dye for the receptor.
For a recent example, see A. Metzger, E. V. Anslyn, Angew. Chem.
1998, 110, 682 ± 684; Angew. Chem. Int. Ed. 1998, 37, 649 ± 651.
[10] For a different strategy to self-assembling systems, see J. W. Canary,
B. C. Gibb, Prog. Inorg. Chem. 1997, 45, 1.
[11] H. Siegel, R. B. Martin, Chem. Rev. 1982, 82, 385 ± 426.
[12] The observed quenching is at least partly due to the absorbance of the
Fe(NO3)2 solution at the wavelength used for the excitation of ANS
(e ꢀ 1000m 1 cm 1 at 375 nm). Experiments performed in the presence
of excess EDTA show that at least 30% of the quenching observed is a
result of the absorbtion of the exciting light.
HO
HO
O
B
c
b
B
R
CH2N
R
HO
HO
O
B
R
2
3
2
Scheme 1. Synthesis of DEAM-PS resin 1. Immobilization and subsequent
release of boronic acids 2. a) Ethylene oxide (excess), THF/H2O 9/1 (sealed
tube), 508C, 24 h; b) boronic acid 2 (see Table 1), solvent, RT, 15 min;
c) THF/H2O/AcOH 90/5/5, RT, 1 h; or THF/H2O 9/1, RT, 2 h.
[*] Prof. D. G. Hall, J. Tailor, M. Gravel
Department of Chemistry, University of Alberta
Edmonton, AB, T6G 2G2 (Canada)
Fax: (1)780-492-8231
[**] Financial support for this research by the Natural Sciences and
Engineering Research Council (NSERC) of Canada and by the
University of Alberta is gratefully acknowledged. D.G.H. also
acknowledges receipt of a Research Innovation Award from the
Research Corporation. M.G. thanks NSERC for a Postgraduate
Scholarship.
[13] M. C. Cleij, P. Scrimin, P. Tecilla, U. Tonellato, J. Org. Chem. 1997, 62,
5592 ± 5599.
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