Selective recognition of fumarate from maleate with a gold nanoparticle-based colorimetric sensing system

Article abstract of DOI:10.1016/j.tetlet.2008.03.142

A colorimetric sensing system of gold nanoparticles functionalized with carboxylate-binding units of o-(trifluoroacetyl)carboxanilide is described, which selectively recognizes a trans-dicarboxylate (fumarate) from its cis-isomer (maleate) and several dic

Full text of DOI:10.1016/j.tetlet.2008.03.142

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 3652–3655
Selective recognition of fumarate from maleate with a
gold nanoparticle-based colorimetric sensing system
Kyung-Seog Youk, Kyung Mi Kim, Amrita Chatterjee, Kyo Han Ahn *
Department of Chemistry and Center for Integrated Molecular Systems, POSTECH, San 31, Hyoja-dong, Pohang, 790-784, Republic of Korea
Received 25 February 2008; revised 25 March 2008; accepted 31 March 2008
Available online 8 April 2008
Abstract
A colorimetric sensing system of gold nanoparticles functionalized with carboxylate-binding units of o-(trifluoroacetyl)carboxanilide
is described, which selectively recognizes a trans-dicarboxylate (fumarate) from its cis-isomer (maleate) and several dicarboxylates
through inter-particle cross-linking, resulting in an apparent color change from red to purple.
Ó 2008 Published by Elsevier Ltd.
Keywords: o-(Trifluoroacetyl)carboxanilides; Gold nanoparticles; Colorimetric sensing; Fumarate; Dicarboxylates
Design and synthesis of functionalized gold nanoparti-
cles (AuNPs) are of current interest due to its potential
applications as a colorimetric sensing system for chemical
and biological sciences.1 The visual sensing ability of AuN-
Ps relies on the changes in color, arising from the surface
plasmon resonance phenomenon,2 from red to blue
through analyte triggered aggregation.1h–j,2 The impor-
tance of the anions in a wide range of biological and chem-
ical processes3 has fostered the development of sensing
systems, which can selectively recognize and sense specific
anion through macroscopic physical response.1c,l,4
Recently, considerable efforts have been made in the devel-
opment of selective sensing systems for carboxylates and
dicarboxylates anions, which are present in a variety of bio-
molecules.4c,m–p AlthoughAuNP-based optical sensing sys-
tems have been extensively utilized for the detection of
biological macromolecules such as DNA and proteins,1o,5
there are only a few AuNP-based systems for biologically
important small molecular anions.1c,n,l,4b,d–h For the last
few years our research has been directed toward the utiliza-
tion of a novel anion recognition motif, o-(trifluoroace-
tyl)carboxanilide (TFACA),6 which shows significant
binding affinity toward carboxylates6c,e to a practically use-
ful level. TFACAs are neutral yet recognize anions by
forming a reversible covalent adduct, which properties
seem to be useful for the development of a nanoparticle-
based sensing system. We report herein the synthesis of a
TFACA derivative of thioctic acid (1), which can be
attached on AuNP surface to produce a novel optical sens-
ing system 2 that operates in aqueous media. The sensing
ability was investigated by UV–vis titration for several
dicarboxylates. Noticeably this system shows sensitivity
selective to the analytes that can bind to the TFACA bind-
ing motif on AuNPs in the inter-particle way (Scheme 1).
Hence, a trans -dicarboxylate such as fumarate, one of
the key components generated in the Krebs cycle,7 can be
sensed readily over its cis-isomer, maleate. Selective
Fumarate
Water
Carboxylate
binding motif
Functionalized
AuNPs
"Aggregation"
*
Scheme 1. Schematic diagram for the aggregation of functionalized
AuNPs by molecular recognition event.
Corresponding author. Tel.: +82 54 279 2105; fax: +82 54 279 3399.
E-mail address: ahn@postech.ac.kr (K. H. Ahn).
0040-4039/$ - see front matter Ó 2008 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2008.03.142

K.-S. Youk et al. / Tetrahedron Letters 49 (2008) 3652–3655
3653
sensing of cis/trans-geometrical isomers is rather challeng-
a
ing, and, to the best of our knowledge, only a handful of
examples are known so far.4n,8 Also, AuNP-based sensing
of dicarboxylates has not been reported yet.
2.0
1.5
1.0
0.5
0.0
AuNPs with an average diameter of about 13 nm were
capped with the TFACA derivative 1 and then stabilized
with poly(vinyl alcohol) (PVA)1d,9 to give the sensing com-
plex 2 (Scheme 2). The functional unit 1 was prepared by
the condensation reaction of 2-(trifluoroacetyl)aniline (3)
and thioctic acid (4) as its acid chloride.10 The AuNPs used
were obtained from the chemical reduction of tetrachloro-
auric acid (HAuCl4) by sodium citrate.5c,d
(only AuNP solution)
(fumarate 0.497 mM)
(fumarate 0.990 mM)
(fumarate 4.76 mM)
For the functionalization of AuNPs, 80 lL of 2.0 mM
solution of 1 in acetonitrile was added to an aqueous solu-
tion of the PVA-stabilized AuNPs (ꢀ3 nM, 20 mL) and
stirred for 12 h at room temperature.11 The solution was
directly used for the sensing study.
The resulting sensing system was characterized by TEM
and FT-IR spectroscopy. The TEM image shows that the
average diameter of the particles is about 13 nm and
remains almost in the same size after the functionalization.
A comparison of FT-IR spectra taken for the AuNP solu-
tions before and after functionalization with the TFACA
derivative 1 showed the characteristic peaks for C–H
stretching peaks at 2865 and 2929 cmÀ1 and aC@O stretch-
ing peak at 1675 cmÀ1, which supports that 1 is attached on
the surface of AuNP.
300
400
500
600
700
800
Wavelength (nm)
b
2.0
1.5
1.0
0.5
0.0
(only AuNP solution)
(maleate 3.0 mM)
(oxalate 3.0 mM)
(malonate 3.0 mM)
(succinate 3.0 mM)
(glutarate 3.0 mM)
(propionate 3.0 mM)
(4-pentenoate 3.0 mM)
300
400
500
600
700
800
The anion sensing properties of the TFACA-functional-
ized AuNPs were investigated by UV–vis titrations with
aqueous solutions of various di- and mono-carboxylate
anions such as fumarate, maleate, oxalate, malonate, succi-
nate, glutarate, propanoate, and 4-pentenoate as their
sodium salts. UV–vis spectra were recorded by using
2.0 mL of the functionalized AuNP solution of 2 and add-
ing an analyte solution (0.1 M aqueous sodium salt) into it
(Fig. 1).12 The aggregation of nanoparticles by the molecu-
lar recognition event in the inter-particle way was not fast
under the conditions, giving a complete color change after
10 min; therefore, the spectrum was measured after 10 min
of each addition. In the case of fumarate the spectrum
shifted from 520 nm to 550 nm (Fig. 1a), indicating a color
change due to the aggregation of AuNPs. Under higher
Wavelength (nm)
Fig. 1. Changes in the UV–vis spectra of 2 upon addition of (a) fumarate
(10, 20, and 100 lL of 0.1 M aqueous sodium salt, respectively); (b) other
di- and mono-carboxylate anions such as maleate, oxalate, malonate,
succinate, glutarate, propionate, and 4-pentenoate (60 lL of 0.1 M
aqueous sodium salt).
concentration of fumarate, the color of the particle solu-
tion became more intense and the peak of the UV–vis spec-
tra showed more red-shift. But in case of other analytes,
the system shows little spectral changes even at the higher
concentration of 3.0 mM (Fig. 1b).
Fig. 2 shows the color changes after addition of different
analytes (20 lL, 0.1 M) to the functionalized AuNPs solu-
tion (400 lL). The color changed from red to purple only in
the case of fumarate. Whereas the other dicarboxylates do
not show any color change. These results can be explained
by assuming that selective aggregation of AuNPs through
COCF3
i. oxalyl chloride,
CH2Cl2, 3 h
NH2
COOH
3
+
S
S
S
ii.THF, K2CO3
2 d, RT
4
3
COCF3
H
N
S
3
O
(PVA-stabilized
AuNP)
1
AuNP sensor 2
Fig. 2. Color changes of an aqueous solution of 2 (400 lL) upon addition
of various analytes (as sodium salt, 20 lL, 0.1 M). From the left: without
analyte, fumarate, maleate, oxalate, malonate, succinate, glutarate,
propionate, and 4-pentenoic acid.
ligand
PVA
Scheme 2. Synthesis of the functionalized AuNP 2.

3654
K.-S. Youk et al. / Tetrahedron Letters 49 (2008) 3652–3655
Fig. 3. TEM images of the TFACA-functionalized AuNPs 2: (a) before and (b) after fumarate addition.
inter-particle cross-linking results from a molecular recog-
nition event. The trans-isomer, fumarate, seems to provide
a favorable geometry required for the inter-particle cross-
linking of AuNPs. Obviously, the inter-particle cross-link-
ing is not possible in the cases of monocarboxylates such as
propionate and 4-pentenoic acid. Also, maleate, the cis-iso-
mer of fumarate, is geometrically unfavorable to form the
inter-particle cross-linking.
Fig. 4. Color changes of an aqueous solution of 2 (400 lL) upon addition
of a larger amount of analyte (as sodium salt, 70 lL, 0.1 M). From the left:
fumarate, maleate, oxalate, malonate, succinate, glutarate, propionate,
and 4-pentenoic acid.
In the cases of other dicarboxylate analytes, their two
carboxylate groups can add to the trifluoroacetyl binding
sites on different AuNPs; however, under the sensing con-
ditions, the inter-particle cross-linking seems to be unfavor-
able for the dicarboxylates that are conformationally
flexible. In this case, rather than the inter-particle intra-
particle cross-linking, that is, the molecular interaction
between the two carboxylate functions of an analyte and
two nearby trifluoroacetyl binding sites on the same nano-
particle seems to be favored. Therefore, the results suggest
that analyte-triggered aggregation of AuNPs is a useful
approach to selectively sense analytes containing the same
functional groups but with different conformational flexi-
bility. Our AuNP-based sensing system also shows that
we can discriminate a trans-isomer, fumarate, from its
cis-isomer, maleate, through geometry-driven inter-particle
cross-linking.
are unfavorable factors for the effective inter-particle
cross-linking. Surely, monocarboxylates did not show the
aggregation behavior observed by the dicarboxylates even
at the high concentration.
In conclusion, we have demonstrated that a TFACA-
functionalized AuNP-based sensing system can differenti-
ate geometrical isomers, such as fumarate, a trans-dicar-
boxylate, from its
cis-isomer and also from
conformationally flexible dicarboxylates, through analyte-
triggered aggregation caused by inter-particle cross-linking.
Current efforts are directed toward the structural modifica-
tion of the binding sites and applications to other analytes.
Acknowledgments
Aggregation of the nanoparticles was confirmed by tak-
ing a TEM image of the resulting solution in the case of
fumarate. An extensive aggregation change is shown after
addition of the fumarate ion to the solution of AuNPs 2
(Fig. 3).
This work was supported by grants from the Center for
Integrated Molecular Systems (R11-2000-070-070010),
Korea Health Industry Development Institute (A05-0426-
B20616-05N1-00010A), and Korea Research Foundation
Grant (MOEHRD, Basic Research Promotion Fund:
KRF-2005-070-C00078).
Interestingly, the competition between the inter- and
intra-particle binding processes seems to be affected by
the analyte concentration. When we increased the analyte
concentration to a higher concentration (15 mM), the
dicarboxylates such as malonate, succinate, and glutarate
showed color changes in addition to fumarate, plausibly
due to the inter-particle aggregation (Fig. 4). Under the
higher concentration of analytes, we can expect that the
probability of inter-particle cross-linking will increase and
thus the nanoparticle aggregation seems to be effective as
the sensing process. Under the condition the oxalate did
not show any change, plausibly owing to its short distance
between the dicarboxylate groups and/or its decreased
binding affinity toward the trifluoroacetyl group. Both
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deionized water (100 mL, purified by using
a
Milli-QTM water
purification system) under reflux was added quickly a solution of
sodium citrate dihydrate (130 mg, 0.44 mmol) in deionized water
(5 mL). The resulting solution became deep red within minutes,
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12. As the titration proceeds, the pH of the solution became a little basic
(pH 7.8 when 20 lL of 0.10 M aqueous fumarate solution was added
to 2.0 mL of the AuNP solution) because of added dicarboxylate
anions; however, this direct sensing scheme is preferred over that of
using a buffer solution. At lower pH such as pH 6, there was no color
change for the given time because some of the dicarboxylate dianions
become monocarboxylate, which is unable to cross-link the nanopar-
ticles. In the case of a more basic solution such as at pH 8 (HEPES
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media). When necessary, it is recommended to use a buffer solution of
neutral pH or slightly basic one (pH 6 8).