1
1,12
-5
3
3
sensing of saccharides.
interesting intra-
Shinkai has also developed several
(w/w) and 2 (1.57 × 10 mol/dm ) in 0.05 mol/dm NaCl
52.1:47.9 methanol/water (w/w) were followed using a UV-
vis spectrometer. The experiments were then repeated with
1
3,14
15
and intermolecular color sensors for
saccharides utilizing the boronic acid-amine interaction.
Previously, we reported our findings with azo dye mol-
ecule compound 1. This compound shows a large color
change, from purple to red. However, the color change was
only observed at pH 11.32, so the system will not be useful
for the detection of saccharides in biological systems.
Since we reported our work with compound 1, we have
been searching for systems capable of producing a large
visible color change with saccharides at neutral pH. We
screened a number of azo dyes without success; then by
3
0.05 mol/dm D-fructose also present. Because the titrations
are carried out in a methanol-water mixture rather than
simply water, the measurement of pH using a standard
electrode is not strictly applicable. However, De Ligny and
Rehbach have shown that for solutions in 50% methanol the
pH is changed by only 0.1 pH unit compared to a 100%
water solution. Therefore, the pH values used are those
recorded using a Hanna Instruments HI 9321 Microprocessor
pH meter calibrated using Fisher Chemicals standard buffer
solutions (pH 4.0 phthalate, 7.0 phosphate, and 10.0 borate).
16
1
9
2
0
17,18
serendipity, we discovered the tricyanovinylarylamine dyes.
a
The pK of compounds 1 and 2 calculated from the
4,21
absorption-pH titration were 10.19 and 7.81, respectively,
and in the presence of 0.05 M fructose, the values drop to
7
a
.04 and 6.46, respectively. The observed shift in pK on
saccharide binding is in agreement with previous work and
can be explained by the decrease in oxygen-boron-oxygen
bond angle upon saccharide binding, which increases the
3
acidity of the boron center.
Compound 2 was synthesized from readily available
starting materials as outlined in Scheme 1.
Scheme 1a
Figure 1. Absorption spectral changes of dye molecule 2 (3.14 ×
-
5
3
10
mol/dm ) with increasing concentration of D-fructose at pH
8.21.
With compound 1 we proposed that deprotonation of the
anilinic nitrogen was the cause of the observed color change
from purple to red with added saccharides at pH 11.32. With
compound 2 the pK without saccharide was 7.81, which is
a
a
Reagents and conditions: (i) EtOH-PhMe, ∆; (ii) MeOH,
4
NaBH , 83% (2 steps); (iii) tetracyanoethylene, DMF, 55 °C, 63%.
significantly less than the value of 10.2 with compound 1.
Therefore, with compound 2 we were able to observe a color
change with added saccharide from purple to pink at a pH
Absorption-pH titrations, from pH 2 to 12, of 1 (5.66 ×
0 mol/dm ) in 0.05 mol/dm NaCl 33:67 methanol/water
-
5
3
3
1
(
11) Davis, C. J.; Lewis, P. T.; McCarroll, M. E.; Read, M. W.; Cueto,
R.; Strongin, R. M. Org. Lett. 1999, 1, 331-334.
12) Lewis, P. T.; Davis, C. J.; Cabell, L. A.; He, M.; Read, M. W.;
McCarroll, M. E.; Strongin, R. M. Org. Lett. 2000, 2, 589-592.
13) Sandanayake, K. R. A. S.; Shinkai, S. J. Chem. Soc., Chem.
(17) McKusick, B. C.; Heckert, R. E.; Cairns, T. L.; Coffman, D. D.;
Mower, H. F. J. Am. Chem. Soc. 1958, 80, 2806-2815.
(18) Roland, J. R.; McKusick, B. C. J. Am. Chem. Soc. 1961, 83, 1652-
1657.
(19) Bates, R. G. Determination of pH, Theory and Practice; John Wiley
& Sons: New York, 1964.
(
(
Commun. 1994, 1083-1084.
(
14) Koumoto, K.; Shinkai, S. Chem. Lett. 2000, 856-857.
(20) De Ligny, C. S.; Rehbach, M. Recl. TraV. Chim. Pays-Bas 1960,
(15) Koumoto, K.; Takeuchi, M.; Shinkai, S. Supramol. Chem. 1998, 9,
79, 727-730.
2
(21) The pKa and K values were analyzed in KaleidaGraph using
nonlinear (Levenberg-Marquardt algorithm) curve fitting. The errors
reported are the standard errors obtained from the best fit.
2
000, 229-230.
478
Org. Lett., Vol. 4, No. 4, 2002