which inevitably hinders their applications in vivo. Among
various fluorescent sensors, 6-methoxy-(8-p-toluenesulfon-
amido) quinoline (TSQ) and its derivatives are the first class
of fluorescent probes to be developed for Zn2+.14 They exhibit
high selectivity for Zn2+ as compared to Ca2+, Mg2+ and
other metal ions. In order to improve the water solubility of
TSQ, several attempts have been made, such as introducing
carboxylic acid groups or ester groups to extend the
6-methoxyl group15,16 and replacing the methyl group on the
benzene ring with a carboxylic acid group.17 However, an
inherent disadvantage of these probes is their sparing
solubility in neutral aqueous solution.
the reaction of mono[6-O-(p-toluenesulfonyl)]-â-CD with
HQAS did not give the desired product, presumably because
of the relatively weak nucleophilic reactivity of the amino
group in HQAS. In contrast, the reaction of 6-deoxy-6-
formyl-â-CD with HQAS followed by the reduction of the
imino group was observed to give the target product in
moderate yield. Owing to the good solubilizing properties
of the â-CD unit, the solubility limit of 1 in water is about
0.6 mM.
The mode of coordination of 1 with Zn2+ was investigated
by spectrophotometric titration at 25 °C in aqueous buffer
solution. Figure 1 illustrated a typical UV-vis titration
Possessing a hydrophobic cavity and numerous hydroxyl
groups, cyclodextrins (CDs), cyclic oligosaccharides with
6-8 D-glucose units linked by R-1,4-glucose bonds, are
widely used as drug carriers and solubilizers.18,19 In a
preliminary study, we attempted to solubilize TSQ by
forming CD/TSQ inclusion complexes, but neither native
CDs nor methylated CDs were observed to markedly increase
the water solubility of TSQ. Therefore, we covalently linked
an analogue of TSQ, i.e., N-(8-quinolyl)-p-aminobenzene-
sulfonamide (HQAS), to â-CD. The resulting water-soluble
HQAS-modified â-CD 1 showed satisfactory water solubilty,
a high binding affinity and good fluorescence sensing ability
to Zn2+. Simultaneously, 1 also possesses the ability to
include various organic and biological substrates within its
hydrophobic cavity.20 This property may enable it to adhere
to the surface of tissues or cells by including accessible
surface molecules in the cavity.13c-e
HQAS was prepared according to a procedure similar to
that reported by Kojima et al.,21 where N-(8-quinolyl)-p-
acetylaminobenzenesulfonamide (QAS) was obtained by the
reaction of 4-acetamidobenzene-1-sulfonyl chloride with
8-aminoquinoline, followed by hydrolysis in either an acidic
or a basic environment to cleave the acetylamino bond. In
order to prevent the TSQ framework bound to zinc from
being destroyed, the methyl group on the benzene ring was
replaced by an amino group. It has been reported that both
mono[6-O-(p-toluenesulfonyl)]-â-CD and 6-deoxy-6-formyl-
â-CD can react with amino group nucleophiles.22 However,
Figure 1. (a) UV-vis spectral changes of 1 upon the addition of
Zn2+ in buffer solution (pH 7.2, I ) 0.1 M NaNO3) at 25 °C ([1]
) 50 µM, [Zn2+] ) 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 µM
from a to k). (b) Absorption changes of 1 at 362 nm upon the
addition of Zn2+
.
curve of 1 with Zn2+. As can be seen in Figure 1, the
absorption intensity of 1 at 271 nm gradually increased,
accompanied by the obvious hypsochromic shift of the
absorption peak (from 271 to 259 nm), as the concentration
of Zn2+ was increased stepwise. Moreover, a new absorption
peak appeared at 362 nm in the UV-vis spectrum of 1/Zn2+
system, and its intensity also gradually increased with the
addition of Zn2+. This absorption peak is expected to
correspond to the coordination of HQAS unit in 1 with Zn2+.
That is, two nitrogen atoms in the HQAS unit coordinated
with Zn2+ to form a five-membered chelate ring, which
consequently extended the conjugated system and resulted
in the appearance of the new absorption in the long
wavelength region. The spectra obtained during the stepwise
addition showed the appearance of two isobestic points at
ca. 272 and 332 nm. In the control experiment, the UV-vis
spectrum of Zn2+ within the appropriate concentration range
displayed no appreciable absorption between 200 and 450
nm under comparable experimental conditions. Taken to-
gether, these phenomena illustrated the transformation from
free 1 to the Zn2+-coordinated species. Moreover, the
coordination stoichiometry between 1 and Zn2+ was obtained
by the molar ratio method using UV-vis spectrometry. As
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