A nanoparticle based chromogenic chemosensor for the simultaneous detection of multiple analytes

Article abstract of DOI:10.1039/b813423e

Quantum Dot-Schiff base conjugate 2 displays selectivity for Cu ²⁺ and Fe³⁺ enabling the simultaneous detection of these ions in semi-aqueous solution; in contrast, the Schiff base itself displayed no selectivity. The Royal Society of Chemistry.

Full text of DOI:10.1039/b813423e

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A nanoparticle based chromogenic chemosensor for the simultaneous
detection of multiple analytesw
Narinder Singh, Ray C. Mulrooney, Navneet Kaur and John F. Callan*
Received (in Cambridge, UK) 4th August 2008, Accepted 3rd September 2008
First published as an Advance Article on the web 15th September 2008
DOI: 10.1039/b813423e
Quantum Dot–Schiff base conjugate 2 displays selectivity for
Cu2+ and Fe3+ enabling the simultaneous detection of these ions
in semi-aqueous solution; in contrast, the Schiff base itself
displayed no selectivity.
pod is inserted into a framework of tripodal receptors, the final
sensors (4, 5) display selectivity for a particular metal ion,
meaning receptor binding ability is reduced.7 Thus, the
platform (either aliphatic or aromatic) of these tripodal
receptors provides a framework with divergent pods. The
cation binding sites present on different pods are not easily
accessible simultaneously to make an effective complex with
various types of metal ions and hence selectivity is improved.
For differential sensing the receptor should be semi-selective.
The present design may provide some steric organization to
pods and thus will not allow interaction with every metal ion.
Nevertheless, the system should have enough binding sites
from adjacent pods to complete the coordination sphere of
some metal ions. As 1 has a thiol group present in its structure,
it is an ideal candidate for attachment to a QD. To the best of
our knowledge, this is the first reported example of a nano-
crystal chemosensor for the simultaneous estimation of two
metal ions.
Designing functional chemosensors for the identification and
quantification of important physiological and environmental
analytes is of considerable importance.1 High sensitivity and
selectivity of these chemosensors are pre-requisites for their
effective operational usage.2 Within this context, the develop-
ment of sensors for multianalyte detection in real time is a
challenge. Some examples of such sensors have been reported
and tend to use either: the insertion of multichromogenic units
combined in a single receptor,3 a variety of detection methods
(i.e. fluorescence and electrochemical)4 or require detailed
mathematical tools to help process the data.5 But these
methods can be tedious either from a receptor synthesis or
operational viewpoint. More recently, a move from selective to
differential receptors has enabled the detection of two analytes
simultaneously by a single chromophore.6
Receptor 1, 2-[(2-mercaptophenylimino)methyl]phenol, was
synthesized in one step from 2-mercaptoaniline and salicyl-
aldehyde following a literature procedure.8 CdSe/ZnS QDs
were then surface functionalized with 1 after refluxing in
chloroform for 18 h. Following removal of the solvent by
rotary evaporation the product was precipitated from aceto-
nitrile and centrifuged to yield 2 as a yellow solid.
1H NMR spectroscopy (Fig. 1) confirmed an almost com-
plete ligand exchange with signals at 0.85–1.80 ppm, present in
the parent QD and reflecting the methyl and methylene
protons of the native trioctylphosphine oxide (TOPO) groups,
being absent in the spectrum of 2. In addition, there were
significant changes in the spectra of the free receptor before
In this study, we adopt an alternative strategy to enable
differential receptor behaviour. The incorporation of an or-
ganic receptor onto the surface of a preformed CdSe/ZnS
Quantum Dot (QD) results in a nanocrystal hybrid (2) with
selectivity for both Cu(II) and Fe(III) ions. Thus, the nano-
particle surface appears to provide a framework for the self-
organization of the receptors. The rationale behind the present
design is based upon the fact that both 1 and its disulfide
analogue 3 have effective binding affinity toward many transi-
tion metal ions (Fig. S1 and S2w). But when the same receptor
School of Pharmacy, The Robert Gordon University, Aberdeen,
Scotland, UK AB10 1FR. E-mail: j.callan@rgu.ac.uk;
Fax: +44 1224 262555; Tel: +44 1224 262555
w Electronic supplementary information (ESI) available: Experimental
details and relevant spectra. See DOI: 10.1039/b813423e
Fig. 1 Stacked 1H NMR spectra of CdSe/ZnS QDs (A), 1 (B) and 2
(C). All spectra recorded in CDCl3 at ambient temperature.
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and after conjugation to the QD surface. Most notable was the
large downfield shift for the imine proton from 7.25 ppm in the
free receptor to 8.70 ppm in 2. The UV spectrum of 2 showed
peaks in both the UV and visible regions, the former originat-
ing from the bound receptor and the latter due to the first
exciton peak of the QD (Fig. S4w). The mean particle size of 2,
measured by dynamic light scattering (Fig. S5w), was found to
be 15 Æ 2 nm, slightly larger than the parent QD (12 Æ 2 nm),
most likely due to the presence of the more rigid 1 on the
surface of the QD compared to flexible TOPO groups.
However, when 2 was excited at 370 nm there was no evidence
of QD emission. This suggests that the electron rich receptor
quenches QD fluorescence, most likely by electron transfer, as
has been observed when other electron rich entities have been
added to solutions of QDs.9
Fig. 3 Photograph illustrating the naked eye identification by 2 of
Cu(II) and Fe(III). [2] = 4.0 Â 10À8 M; [ion] = 100 mM; in an 80%
THF–20% 0.01 M HEPES buffer solution at pH = 7.0.
metals produced any significant interference for Fe(III) at
325 nm.
The UV profile of 2 was also observed to be strongly
dependent on solution pH (Fig. S7w). At low pH (B3.5) 2
displayed a prominent UV band with lmax 325 nm. Upon
increasing the pH, this absorbance gradually decreased while a
new red shifted band appeared with lmax 382 nm. This band
most likely reflects the deprotonation of the phenolic group of
the receptor and from a plot of absorbance against pH the pKa
was calculated as 8.92.10 Thus, operating at pH 7.0 enables the
clear observation of Cu(II) induced changes at 410 nm.
The titration of 2 with Cu(II) and Fe(III) is shown in Fig. 4.
Both ions displayed good linearity up to a concentration of
40 mM with their binding constants (log b) being determined as
4.86 and 4.69 respectively.11 Importantly, Fig. 4c shows that 2
is also capable of measuring Cu(II) in the presence of Fe(III)
and of measuring Fe(III) in the presence of Cu(II) up to a
concentration of 20 mM. Although it was possible to monitor
Fe(III) concentrations in the presence of equimolar Cu(II) it
was only possible to monitor Cu(II) in 0.25 molar equivalents
of Fe(III). To the best of our knowledge this is the first reported
Nonetheless, 2 shows remarkable chromogenic selectivity
for Cu(II) and Fe(III) ions when tested against a range of other
physiologically and environmentally important cations in a
buffered THF–H2O (80 : 20) solvent system. As shown in
Fig. 2a, 2 is characterized by two UV bands, one centered at
275 nm and the other at 355 nm. Addition of Fe(III) resulted in
a substantial increase in absorbance of these bands while the
addition of Cu(II) caused a substantial bathochromic shift of
both bands to 295 and 410 nm respectively. In fact these
changes were so significant they could be detected by the
naked eye (Fig. 3) with Fe(III) causing a change from colour-
less to orange and Cu(II) from colourless to green. In contrast,
the addition of the other ions had a negligible effect on the UV
profile of 2. Fig. 2b shows the selectivity of 2 for various metal
ions when measured at 325 and 410 nm. These particular
wavelengths were chosen as 325 nm represents an isosbestic
point for all ions except Fe(III) while 410 nm was the lmax for
Cu(II) induced changes. As is evident from Fig. 2b, only Fe(III)
causes significant inference with Cu(II) at 410 nm while no
Fig. 4 UV spectra of 2 in the presence of (a) increasing Cu(II)
concentration and (b) increasing Fe(III) concentration. (c) Plot of
absorbance intensity of 2 against metal ion concentration for Fe(III)
(blue diamonds), for Fe(III) in the presence of equimolar Cu(II) (purple
squares), for Cu(II) (blue triangles) and Cu(II) in the presence of 0.25
molar equivalents of Fe(III) (red circles). Fe(III) and Cu(II) measurements
were recorded at 325 and 410 nm respectively. [2] = 4.0 Â 10À8 M.
Fig. 2 (a) UV spectra for 2 in the presence of various metal ions and
(b) bar chart revealing the selectivity of 2 for metal ions when
determined at 325 nm (purple) and 410 nm (blue). [2] = 4.0 Â 10À8 M;
[ion] = 50 mM.
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example of a single sensor capable of measuring both Cu(II)
and Fe(III) simultaneously.
3 H. Komatsu, D. Citterio, Y. Fujiwara, K. Minamihashi, Y. Araki,
M. Hagiwara and K. Suziki, Org. Lett., 2005, 7, 2857.
4 (a) M. Schmittel and H. W. Lin, Angew. Chem., Int. Ed., 2007, 46,
We have demonstrated for the first time that the selectivity
of a receptor can be altered by its incorporation onto the
surface of a QD. The organization offered to the receptors by
the three-dimensional surface of the nanoparticle was suffi-
cient to enable the determination of Cu(II) and Fe(III) simulta-
neously, in buffered solution at physiological pH. This offers
the ability to screen for these ions in competitive media by UV
or the naked eye. The principle may also be extended to other
receptors to help improve their selectivity and could poten-
tially lead to a new generation of optical sensors.
893; (b) D. Jimenez, R. Martınez-Manez, F. Sancenon and J. Soto,
´ ´ ´ ´
Tetrahedron Lett., 2004, 45, 1257.
5 (a) D. Mikami, T. Ohki, K. Yamaji, S. Ishihara, D. Citterio, M.
Hagiwara and K. Suzuki, Anal. Chem., 2004, 76, 5726; (b) T. A.
Lee, L. M. Headley and J. K. Hardy, Anal. Chem., 1991,
63, 357.
6 (a) N. Kaur and S. Kumar, Tetrahedron Lett., 2008, 49, 5067;
(b) N. Kaur and S. Kumar, Chem. Commun., 2007, 3069; (c) H.
Komatsu, T. Miki, D. Citterio, T. Kubota, Y. Shindo, K.
Yoshiichiro, K. Oka and K. Suzuki, J. Am. Chem. Soc., 2005,
127, 10798.
7 (a) V. K. Bhardwaj, A. P. S. Pannu, N. Singh, M. S. Hundal and
G. Hundal, Tetrahedron, 2008, 64, 5384; (b) V. K. Bhardwaj, N.
Singh, M. S. Hundal and G. Hundal, Tetrahedron, 2006, 62, 7878;
(c) N. Singh and G. Hundal, J. Inclusion Phenom. Macrocyclic
Chem., 2005, 52, 253.
The authors would like to acknowledge financial assistance
from the EPSRC and RGU. They also thank the EPSRC
national mass spectrometry and TEM services.
8 F. Tisato, F. Refosco, U. Mazzi, G. Bandoli and M. Nicolini,
J. Chem. Soc., Dalton Trans., 1987, 1693.
9 (a) I. Yilidiz, M. Tomasulo and F. M. Raymo, Proc. Natl. Acad.
Sci. U. S. A., 2006, 103, 11457; (b) K. S. A. Palaniappan, S. A.
Hackney and J. Liu, Chem. Commun., 2004, 2704.
Notes and references
1 (a) R. Martınez-Manez and F. Sancenon, Chem. Rev., 2003, 103,
´ ´ ´
4419; (b) J. F. Callan, A. P. de Silva and D. C. Magri, Tetrahedron,
2005, 61, 8551; (c) A. P. de Silva, H. Q. N. Gunaratne, T.
Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. R.
Rademacher and T. E. Rice, Chem. Rev., 1997, 97, 1515.
2 H. He, M. A. Mortellaro, M. J. P. Leiner, R. J. Fraatz and J. K.
Tusa, J. Am. Chem. Soc., 2003, 125, 1468.
10 (a) A. P. de Silva and H. Q. N. Gunaratne, J. Chem. Soc., Chem.
Commun., 1990, 186; (b) A. P. de Silva, H. Q. N. Gunaratne and P.
L. M. Lynch, J. Chem. Soc., Perkin Trans. 2, 1995, 685.
11 D. C. Magri, J. F. Callan, A. P. de Silva, D. B. Fox, N. D.
McClenaghan and K. R. A. S. Sandanayake, J. Fluoresc., 2005,
15, 769.
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