Selective binding of carbamate pesticides by self-assembled monolayers of calix[4]arene lipoic acid: Wettability and impedance dual-signal response

Article abstract of DOI:10.1021/ol201143z

A calix[4]arene lipoic acid (C4LA) was synthesized by click chemistry in 62% yield. It was immobilized on Au surfaces via self-assembly to offer C4LA Self-Assembled Monolayers (SAMs). The SAMs show wettability and electrochemical impedance dual-signal res

Full text of DOI:10.1021/ol201143z

ORGANIC
LETTERS
2011
Vol. 13, No. 13
3392–3395
Selective Binding of Carbamate Pesticides by
Self-Assembled Monolayers of Calix[4]arene
Lipoic Acid: Wettability and Impedance
Dual-signal Response
Gui-Fen Zhang,† Jun-Yan Zhan,† and Hai-Bing Li*
Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education,
College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China
lhbing@mail.ccnu.edu.cn
Received April 29, 2011
ABSTRACT
A calix[4]arene lipoic acid (C4LA) was synthesized by click chemistry in 62% yield. It was immobilized on Au surfaces via self-assembly to offer
C4LA Self-Assembled Monolayers (SAMs). The SAMs show wettability and electrochemical impedance dual-signal response for methomyl with
highly sensitivity and selectivity.
Self-assembly monolayers (SAMs) are an important direc-
tion of smart-functional interfaces.1 Many functional
supramolecular systems, including crown ethers,2
cyclodextrin derivatives3 and calixarenes,4 can be immo-
bilized on substrate surfaces to form self-assembled mono-
layers (SAMs). These studies have the common goal
of demonstrating molecular recognition through hostꢀ
guest interactions. Echegoyen and co-workers have de-
monstrated that the SAMs of crown ethers were em-
ployed to selectively bind Kþ in aqueous solutions.2a
The Kaifer3a and Park groups3b have used β-cyclodextrin
SAMs to study the inclusion of electrochemically active
guests such as ferrocene and quinone derivatives, respec-
tively. Calixarenes are a family of cavity-shaped cyclic
molecules with outstanding complex activity toward
† These authors contributed equally to this manuscript.
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Yang, J. D.; Li, M. R.; Li, H. X.; Yang, Y. L.; Kashimura, Y.; Wang, C.;
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r
10.1021/ol201143z
Published on Web 06/01/2011
2011 American Chemical Society

neutral molecules, including pesticides and other biologi-
cally important molecules such as amino acids and
peptides.5 The potential of calix[n]arenes applied to form
SAMs for neutral molecules has been given considerable
attention. The SAMs of calix[4, 6, 8]arenes derivatives
exhibited selective binding of polyamines,4d aromatic
amines4b and fullerenes,4c respectively.
Scheme 1. Synthesis of the C4LA and Reference Compound 3
via Click Chemistry
In general, molecular recognition of SAMs focuses on
electrochemistry, while the wettability is an important
property of functional interface.6 The control of the hydro-
philic/hydrophobic properties of surfaces attracts growing
interest due to its implementation in practical applications
in antiadhesive coatings, biosensors, and so forth.7 However,
by applying wettability to realize molecular recognition of
SAMs and switch the transition between hydrophobicity and
hydrophilicity has seldom been reported. In this article,
SAMs of calix[4]arene lipoic acid (C4LA), which is synthe-
sized by click chemistry, was constructed. The C4LA SAMs
show wettability and impedance dual-signal response for
methomyl with excellent selectivity and sensitivity, which
may be developed as pesticide-detecting chips.
The synthetic procedure toprepare the target compound
C4LA is depicted in Scheme 1. Azide-functionalized calix-
[4]arene 1 was synthesized according to the literature.8
Then, treatment of thioctic acid with propargyl alcohol in
the presence of DCC and DMAP in dry dichloromethane
afforded thioctic-propyne 2. Further reactions of 2 with 1
were carried out in refluxing toluene using CuI as catalyst
for 24 h to afford calix[4]arene lipoic acid C4LA in 62%
yield.9 Reference compound 3 wassynthesizedin 69%yield
using a method similar to that of C4LA. The structure and
conformation of C4LA were confirmed by EI(þ)MS spec-
tra, elemental analyses, and NMR studies. The 1H NMR
spectrum shows two single peaks for the aromatic protons,
two doublets for the bridging methylene groups and two
singlets for the tert-butyl groups indicating a cone confor-
mation. The 13C NMRspectrum datafurthercorroborated
the cone conformation by the presence of a peak for the
methylene resonances.10
appeared at 170.7 eV due to the S atoms in the C4LA,
which confirmed the presence of C4LA on the electrode.
The properties of functional interface were studied by
CA and impedance spectroscopy. As shown in Figure 1,
the CA of C4LA SAMs was 97.2 ( 3°, which was
comparatively hydrophobic in comparison with bare
Au surface (52.6 ( 3°). Also, impedance spectroscopy
of C4LA SAMs (4.97 KΩ) was greatly increased com-
pared to the bare Au electrode (0.21 KΩ). The results
indicated that the calix[4]arene lipoic acid was modified
on the gold surface successfully.
C4LA SAMs were constructed according to ref 11. The
SAMs were characterized by X-ray photoelectron spectra
(XPS), contact angle (CA), and impedance spectroscopy.
XPS of C4LA modified Au electrode is shown in Figure S1
(see Support Information). A characteristic peak of S (2p)
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2005, 38, 644–652. (b) Sun, T. L.; Feng, L.; Gao, X. F.; Jiang, L. Acc.
Chem. Res. 2006, 39, 487.
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L.; Zhu, D. B. Angew. Chem., Int. Ed. 2004, 43, 357–360. (b) Wang, J. X.;
Hu, J. P.; Wen, Y. Q.; Song, Y. L.; Jiang, L. Chem. Mater. 2006, 18,
4984–4986. (c) Guo, Y.; Xia, F.; Xu, L.; Li, J.; Yang, W. S.; Jiang, L.
Langmuir 2010, 26, 1024–1028. (d) Wang, L. M.; Peng, B.; Su, Z. H.
Langmuir 2010, 26, 12203–12208.
Figure 1. (A) Water-drop profiles on bare Au surface and C4LA/
SAMs. (B) Impedance spectroscopy of 5.0 mM Fe(CN)63-/4- in
0.10 M KNO3 aqueous solution on bare Au and C4LA SAMs
electrode with the frequency ranging from 10 kHz to 1.0 kHz,
scan rate: 0.10 v/s, indicating that C4LA successfully modified
on gold surface.
(8) Saiki, T.; Iwabuchi, J.; Akine, S. J. Am. Chem. Soc. 2005, 127,
5507–5511.
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(10) Jaime, C.; Mendoza, J.; Prados, P.; Nieto, P. M.; Shched, C. J.
Org. Chem. 1991, 56, 3372–3376.
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717–722. (b) Zhang, S.; Echegoyen, L. Tetrahedron Lett. 2003, 44, 9079–
9082. (c) Bandyopadhyay, K.; Liu, H.; Liu, S. G.; Echegoyen, L. Chem.
Commun. 2000, 141–142. (d) Liu, H.; Liu, S. G.; Echegoyen, L. Chem.
Commun. 1999, 1493–1494.
Considering the special structure of C4LA, the carbamate
pesticides (methomyl, san leafhopper, carbosulfan, carbo-
furan and carbaryl) were selected as guest molecules. The
wettability and impedance of C4LA SAMs toward carba-
mates were investigated. As shown in Figure 2, after adding
Org. Lett., Vol. 13, No. 13, 2011
3393

Figure 3. (A) Impendance response of Fe(CV)63-/4- at C4LA SAMs
electrode in the presence of the five carbamates (1 ꢁ 10ꢀ4 M),
including blank as control, methomyl, san leafhopper, carbosulfan,
carbofuran, carbaryl. (B) Histogram showed the impedance value
of A.
To substantiate the role of the calix[4]arene platform in
the recognition process, the control experiments were
carried out. Reference compound 3 without calix[4]arene
platform was synthesized and 3 SAMs was also success-
fully constructed which adopted the same method as
C4LA. The contact angle of 3 SAMs in the presence of
methomyl, san leafhopper, carbosulfan, carbofuran and
carbaryl were studied. As can be seen from Figure S2
(Supporting Information), the wettability of 3 SAMs
shows only a little change upon addition of the carbamates
(<20°). Moreover, impedance response with no obvious
selectivity was observed after the addition of the five
carbamates in the redox probe solution (Figure S3, Sup-
porting Information). Thus, the control experiment results
indicated that the calix[4]arene cavity played an important
role in the efficient recognition process of methomyl.
Compared the wettability and impedance dual-signal
responsive results of the reference compound 3 to that of
C4LA molecules modified the self-assembly monolayer,
the C4LA SAMs expressed well selective to methomyl,
indicating that the special C4LA cavities played a critical
role in binding methomyl guest which caused the interface
wettability change. The contact angle for C4LA SAMs is
97.2 ( 3°, indicating a hydrophobic surface, which agrees
with the fact that calix[4]arene has four hydrophobic tert-
butyl groups at the upper rim. After methomyl is encapsu-
lated by the C4LA SAMs on the Au substrates, the CA
value decreases significantly to 30.7 ( 3°, indicating the
transformation from the hydrophobic surface to the hy-
drophilic surface.
Figure 2. (A) CAs relationship images of C4LA SAMs with dif-
ferent guests: methomyl, san leafhopper, carbosulfan, carbofuran,
carbaryl. (B) Contact angle variation (ΔCA = CAcontrol ꢀ CA)
histogram of C4LA SAMs in the presence of different carbamates,
indicating that the selectively wettability responsive of C4LA
toward methomyl. (C) Structure of the five guests.
mehtomyl solution, CA of C4LA SAMs was 30.7 ( 3°,
which was greatly decreased compared to that of C4LA
SAMs (97.2 ( 3°). However, the other four carbamates
including san leafhopper, carbosulfan, carbofuran, and
carbaryl did not show any distinct CA change, indicating
that the excellent wettability was responsive for C4LA
toward methomyl.
Simultaneously, the C4LA SAMs were further investigated
by electrochemical impedance spectroscopy. Figure 3 shows
3-/4-
impedance response of the redox couple Fe(CN)6
in the
presence of the five carbamates (0.1 mM). A simple Randles
equivalent circuit12 to describe the impedance consists of a
charge-transfer resistance, Rct, in series with a Warburg
impedance and in parallel with a total interfacial capacitance.
Addition of 0.1 mM methomyl to the electrolyte, Rct value was
increased from 4.97 KΩ to 9.82 KΩ while the Rct value was
seldom affected by other four carbamates. The results indi-
cated that the C4LA SAMs exhibited a remarkably sensitive
response to methomyl due to a hostꢀguest interaction be-
tween methomyl and C4LA SAMs.13 The impedance results
were consistent with the selectivity of contact angles which
indicated that the SAMs show wettability and electro-chemi-
cal impedance dual-signal response for methomyl with high
selectivity.
To further study the binding model and stoichiometry
between the C4LA host and methomyl guest, UV and
NMR spectra in solution were carried out. As shown in
Figure S4 (Supporting Information), upon addition of
methomyl to the C4LA in CH3CN, a new peak appeared
around 360.5 nm while the other four carbamates gave no
changes, which indeed indicates the formation of the
(12) Finklea, H. O.; Snider, D. A.; Fedyk, J.; Sabatani, E.; Gafni, Y.;
Rubinstein, I. Langmuir 1993, 9, 3660–3667.
(13) Xiong, D. J.; Li, H. B. Nanotechnology 2008, 19, 465502–465508.
3394
Org. Lett., Vol. 13, No. 13, 2011

complex between the methomyl and C4LA. Simulta-
neously, the corresponding complex constant (Ks) was
evaluated using the BenesiꢀHildebrand equation and was
found to be 2.58 ꢁ 103 Mꢀ1 (Figure S4). Meanwhile, a Job
plot shown in Figure S5 (Supporting Information) has a
peak at a molar fraction of 0.5 in 360.5 nm and gave the
binding stoichiometry, implying that a 1:1 inclusion com-
plex was formed.
On the basis of the above analysis and for further study,
1
the binding model between the C4LA and methomyl, H
NMR spectra of C4LA, methomyl, mixed C4LA with
methomyl were characterized. As shown in Figure S6
(Supporting Information), protons of SCH3 groups in
methomyl changed significantly from the two doublet peaks
and underwent upfield shifting (Ha, ꢀ0.139 ppm; Hb,
ꢀ0.303 ppm); however, the proton of NH in methomyl
(Hc) almost had no shifting. The above results indicated
that the SCH3 end of methomyl would interact with the
C4LA cavities and its upper; the NH end does not associate
with the C4LA. In summary, the model of inclusion com-
plex between the C4LA and methomyl could be constructed
in Figure 4, and it also explained the wettability and
impedance change before and after C4LA SAMs exposing
in methomyl solution well.
It was noted that methomyl was a linear molecular
containing the amide groups as the hydrophilic side and
two methyl groups as the hydrophobic side. The amide
groups were exposed to the outside of C4LA cavities and
interacted with water through a hydrogen bond interaction,
which caused the great changes of wettability from hydro-
phobic to hydrophilic. At the same time, the impedance of
C4LA SAMs dramatically increased due to mutual inclu-
sion interaction between methomyl and C4LA.
Figure 4. Schematic representation of the possible recognition
process for C4LA toward methomyl on the surface of a self-
assembled calix[4]arene monolayer via hostꢀguest interaction.
concentration of methomyl increased. Once the concentra-
tion of the methomyl reaches 1.0 ꢁ 10ꢀ3 M, CA was down
to 30.7 ( 3° compared to that of C4LA SAMs (97.2 ( 3°),
which suggested the wettability transition from hydropho-
bicity to hydrophilicity.
In summary, the SAMs of calix[4]arene lipoic acid were
successfully constructed and showed remarkable sensitiv-
ity for methomyl by a wettability and impedance dual-
signal response. The high selectivity and sensitivity with
methomyl is attributed to the inclusion complex form
between C4LA and methomyl through the host and guest
inclusion. The dual-signal response for methomyl would
develop to a chip or microelectrode and is of potential
application.
For quantitative analysis of methomyl, impedance spec-
troscopies of C4LA SAMs in the presence of different
concentrations of methomyl were carried out. A plot of
the Rct versus concentrations of methomyl over the range of
1.0 ꢁ 10ꢀ12 to 1.0 ꢁ 10ꢀ4 M is shown in Figure S7
Acknowledgment. This work was financially supported
by the National Natural Science Foundation of China
(21072072), Program for Excellent Research Group of
Hubei Province (2009CDA048), Self-determined research
funds of CCNU from the colleges’ basic research, and
operation of MOE (CCNU09AO200) and PCSIRT (NO.
IRTO953).
(Supporting Information). The linear equation is Rct
=
4835 þ 502.7 ꢁ [C] with a linearity coefficient of 0.991. The
limit of detection (3σ) for methomyl is 1 pM. Meanwhile, a
plot of the contact angle (CA) versus concentrations of
Supporting Information Available. Experimental de-
tails, NMR spectra of C4LA, XPS, and UV spectra. This
material is available free of charge via the Internet at
http://pubs.acs.org.
methomyl over the range of 1.0 ꢁ 10ꢀ6 to 1.0 ꢁ 10ꢀ2
M
is shown in Figure S8 (Supporting Information). The
monolayers show an initially steep decrease in CA as the
Org. Lett., Vol. 13, No. 13, 2011
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