Single molecular multianalyte sensor: Jewel pendant ligand

Article abstract of DOI:10.1021/ol0507219

(Chemical Equation Presented) The jewel pendant ligand has multiple chromogenic units combined in a single molecule with the dyes linked to a semiselective binding site by three heteroatoms (O, N, S) having different HSAB characteristics, to indicate dive

Full text of DOI:10.1021/ol0507219

ORGANIC
LETTERS
2005
Vol. 7, No. 14
2857-2859
Single Molecular Multianalyte Sensor:
Jewel Pendant Ligand
Hirokazu Komatsu,† Daniel Citterio,† Yukio Fujiwara,† Katsuya Minamihashi,†
Yoshio Araki,‡ Masafumi Hagiwara,‡ and Koji Suzuki*,†,§
Department of Applied Chemistry and Department of Information and Computer
Science, Keio UniVersity, Yokohama 223-8522, Japan, and JST-CREST,
Saitama 332-0012, Japan
suzuki@applc.keio.ac.jp
Received April 5, 2005
ABSTRACT
The jewel pendant ligand has multiple chromogenic units combined in a single molecule with the dyes linked to a semiselective binding site
by three heteroatoms (O, N, S) having different HSAB characteristics, to indicate diverse response to individual transition metal ions. Using
a single-molecular multianalyte sensor, multiple analytes could be determined with a minimal sensing system.
A number of molecular optical sensors (chromoionophores,
fluoroionophores) have been developed that focus on the
selective binding to an analyte.1 Those molecules are used
in many fields, such as bioimaging,2 and clinical and
environmental analysis with fiber-optic sensors.3 They are
composed mainly of a binding site and a transducer site
(chromophore) combined in one molecule. The molecular
design of the sensor molecules that show selective binding
to an analyte has been well established especially for
alkaline4,5 (NaI, KI, etc.) and alkaline-earth metals6,7 (CaII,
MgII etc.). Since the selective ion-ligand complexes for those
ions are charge-interaction dominated, the search for selective
binding sites has focused on the ion-size recognition proper-
ties of the ligands. These selectivities have been investigated
in our laboratories for the molecular design of ionophores
and fluorescent probes.8 Recently, optical molecular sensors
with specific response to heavy- and transition-metal ions9
such as HgII, CuII, and ZnII have been reported. However,
for ionophore design,10 the selective binding to these metals
is a challenging issue; thus, not only the selective binding
† Department of Applied Chemistry, Keio University.
‡ Department of Information and Computer Science, Keio University.
§ JST-CREST.
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Tusa, J. K. Anal. Chem. 2003, 75, 549-555.
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10.1021/ol0507219 CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/02/2005

but also the optical discrimination of the cations is discussed
for the development of new chromoionophores. On the other
hand, the multisensor array approach, consisting of the
combination of multiple nonselective transition-metal chro-
moionophores and mathematical analysis systems11 (such as
PLS, ANNs) has been investigated for the simultaneous
determination of several heavy-metal ions. In these systems,
sensors are not required to indicate high selectivity to a single
analyte but should be semiselective (i.e., selective to several
analytes of interest and no response to analytes out of
interest) and show a discriminating response to many
analytes.
Here, we demonstrate that a minimal multisensor can
consist of one single molecule. The goal of our research is
the development of a single-molecular sensor for multiple
analytes. This concept has to our best knowledge not been
reported to date. For establishing our goal, we propose a
novel molecular design called a “jewel pendant ligand”.
The jewel pendant ligand possesses multiple chromogenic
subunits in one molecule with the dyes linked to a semise-
lective binding site with three heteroatoms (N, O, S) having
different hard-soft acid-base (HSAB) characteristics.12 The
molecule is designed to indicate a diverse response to
individual cations.
units were chosen to have different λmax values. They were
selected from indan or stilbene derivatives, since those dyes
do not have substituents acting as potential binding sites to
metal ions such as phenol, carboxyl, or diazo groups.
Therefore, all chromophore-ion interactions can be assumed
to occur at the heteroatomic binding sites connected to the
different chromophoric units.
The nitrogen-linked dye (N-dye) used for JPL-1 is an aza
analogue of the dicyanovinyl indan derivatives,13 having a
peak of maximum absorbance at 710 nm. The oxygen-linked
dye (O-dye) is a dicyanovinyl indan derivative with a λmax
value at 460 nm. The sulfur-linked dye (S-dye) is stilbene14
with λmax at 380 nm.
The organic synthesis of JPL-1 (refer to Scheme 1 in the
Supporting Information) was performed starting from a
commercially available aniline derivative by first connecting
a part of the S-dye via the tosylate followed by the final
S-dye synthesis via the Heck reaction.15 The next steps were
the connection of a part of the O-dye via the methylate and
the synthesis of the final O-dye by a coupling reaction.
Finally the synthesis of JPL-1 was completed by coupling
of the N-dye (overall 2.4% yield).
The absorbance spectra of JPL-1 measured in acetonitrile
solution are shown in Figure 1. The absorbance peak near
710 nm originates from the N-dye, and the shoulder near
460 nm results from the O-dye overlapping to some extent
with the S-dye. The observed λmax value in the 340 nm region
is composed of the combined peak of the O-dye, S-dye, and
the second absorbance band of the N-dye.
The change in the absorbance spectra of JPL-1 in the
presence of 10 equiv of 12 metal cations (MgII, CaII, MnII,
CoII, NiII, ZnII, AgI, HgII, CuII, FeIII, AlIII, CrIII, and PbII) was
measured in acetonitrile solution. For CuII, FeIII, AlIII, PbII,
and CrIII, the absorbance spectra showed changes compared
to the ion-free solution (Figure 2), where the changes for
the band of the N-dye were most significant and varied with
those ions (see Figure S1 in the Supporting Information).
The response of the absorbance from the O- and S-dyes was
minor, but apparently different for CuII. The apparent binding
constants with those ions calculated by curve fitting are listed
in Table S1 (Supporting Information). The binding constants
K are on the order of 105-106 M-1 and not significantly
different for the metals. Thus, JPL-1 appears to interact
“semiselectively” with a series of metal ions.
Figure 1. Structure and spectra of JPL-1 (10 µM) in MeCN.
An open-shaped ligand was selected for JPL-1 (Figure 1)
to show semiselectivity to cations. The three chromophoric
The relative changes in absorbance of JPL-1 with these
ions are compared at the characteristic wavelengths of the
three chromophores of JPL-1 in Figure 3 (see Table S3 in
the Supporting Information for details). In the presence of
CuII, all dye units showed a change in absorbance, to FeIII,
the N- and O-dyes, to PbII, the N- and S-dyes, and to trivalent
AlIII and CrIII, the N-dye only. The proposed coordination
models, based on the observed spectral changes, are sche-
matically shown in Figure 4.
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Org. Lett., Vol. 7, No. 14, 2005

Figure 4. Proposed model for response of JPL-1. Interacting dyes
are underlined, and interaction is shown as a dashed line.
only be partially accounted for by the HSAB principle. Other
assumed influencing factors are solvent effects and ion size.
With this molecular discrimination ability of JPL-1, the
simultaneous determination of multiple cations was demon-
strated for mixed sample solutions of FeIII and CuII as a first
model of a simple application.
The absorbance spectra of 5 × 5 combinations of
concentrations of FeIII and CuII in the 3-50 µM range in
the mixture with JPL-1 were measured in acetonitrile. The
experimental data was analyzed with a back-propagation
artificial neural network (BP-ANN)16,17 that has already been
reported for the simultaneous determination of metal ions
in mixed solution.11
With the BP-ANNs, the concentrations of CuII and FeIII
in mixtures were simultaneously estimated. For CuII, a root-
mean-square error of prediction (RMSEP) of 4.3 mM was
achieved (R ) 0.94) and for FeIII the RMSEP was found to
be 5.0 µM (R ) 0.90). (Table S2, Supporting Information).
We have proposed a novel strategy to determine heavy-
and transition-metal ions with a single-molecular multianalyte
sensor having a unique molecular design concept. JPL-1 has
the capability of determining multiple metal ions with the
spectral diversity of three heteroatom-linked dyes, based on
the nature of the heteroatoms and their interaction with the
cations. The simultaneous determination of FeIII and CuII was
achieved by analysis with BP-ANNs as an example. By using
this concept of the jewel pendant ligand as a multianalyte
sensor, we have demonstrated a way to determine multiple
analytes with a single-molecular sensor component.
Figure 2. Absorbance spectra of JPL-1 (10 µM) in the presence
of 10 equiv of various metal cations: (a) FeIII, CuII; (b) AlIII, CrIII,
PbII in MeCN (O, free; b, FeIII; 9, CuII; [, AlIII; ], CrIII; 0, PbII).
Supporting Information Available: Experimental de-
tails, figures and tables, and analysis by ANNs. This material
is available free of charge via the Internet at http://pubs.acs.org.
Figure 3. Comparison of the response (A/A0) of JPL-1 (10 µM) at
different wavelengths (380, 460, 710 nm) to 10 equiv of various
metals (PbII, FeIII, AlIII, CuII, CrIII).
OL0507219
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The different optical response reflects different complex
formations in correspondence to the molecular design
concept. However, the differences in response behavior can
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