An isothiouronium-derived organized monolayer at the air-water interface: Design of film-based anion sensor systems for H2PO4 -

Article abstract of DOI:10.1246/cl.2004.1118

We have prepared for the first time an organized monolayer with long-chain amphiphiles possessing an isothiouronium segment. Interactions between the monolayer and anions in aqueous subphase have been investigated and show a significant selectivity of H

Full text of DOI:10.1246/cl.2004.1118

1118
Chemistry Letters Vol.33, No.9 (2004)
An Isothiouronium-derived Organized Monolayer at the Air–Water Interface:
À
Design of Film-based Anion Sensor Systems for H2PO4
Yoshihiro Misawa, Yuji Kubo,ꢀ Sumio Tokita, Hirokazu Ohkuma,y and Hiroo Nakaharaꢀy
Department of Applied Chemistry, Faculty of Engineering, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama, 338-8570
yDepartment of Chemistry, Faculty of Science, Saitama University, 255 Shimo-ohkubo, Sakura-ku, Saitama, 338-8570
(Received June 7, 2004; CL-040647)
We have prepared for the first time an organized monolayer
with long-chain amphiphiles possessing an isothiouronium seg-
ment. Interactions between the monolayer and anions in aqueous
subphase have been investigated and show a significant selectiv-
ity of H2PO4ꢁ. Also, by fabricating the Langmuir–Blodgett (LB)
films under competitive conditions of thꢁe anions used and picrate
as an indicator, we can read out H2PO4 recognition using UV–
vis spectroscopy, providing a potential application for the design
of film-based anion sensor systems.
tadecane in DMF at 70 ꢂC in the presence of K2CO3 to give di-
alkoxybenzyl alcohol (3), and then bromination of 3 with PBr3 in
THF yielded dialkoxybenzyl bromide (4); reaction with dime-
thylthiourea in EtOH at 60 ꢂC then gave 1.7
Figure 1A shows the surface pressure versus area per mole-
cule (ꢀ-A) isotherms for the monolayers of 1 on pure water (Mil-
li-Q, pH 5.8) and the aqueous subphases containing NaH2PO4
(1, 10, and 100 ꢁM) at 20 ꢂC. The monolayer at 20 ꢂC on pure
water has a clearly condensed phase with the molecular limiting
area of ca. 0.52 nm2ꢁmoleculeꢁ1. By adding to these incremental
amounts of H2PO4 as a possible oxoanion in the subphase, the
monolayer showed an expansion of up to ca. 0.55 nm2 mole-
culeꢁ1 above 10 ꢁM of H2PO4ꢁ. This suggests that H2PO4ꢁ in-
teracted with the isothiouronium-containing monolayers at the
air–water interface.8 In contrast, other anions (AcOꢁ and Clꢁ)
did not induce any expansion even with excess amounts of these
anions (Figure 1B). The absence of expansion with AcOꢁ, hav-
ing pKa value higher than that of H2PO4ꢁ, may be because the
highly ordered isothiouronium units at the air–water interface
can participate in multiple hydrogen bondings with tetrahedral
H2PO4ꢁ. This is due to the fact that tripodal isothiouronium re-
ceptors significantly bind tetrahedral oxoanions.1a On the other
hand, we discovered that when hydrophobic picrate is added to
the aqueous subphase the monolayer of 1 expanded remarkably
below 10 mN mꢁ1; the large expansion of molecular area at
0.95 nm2 moleculeꢁ1 reflects the fact that the monolayer inter-
acts with a bulky picrate. Therefore, picrate could act as an indi-
The family of isothiouronium salts has great potential for
use as an anion-binding site in supramolecular chemistry,1 be-
cause 1) it has a similar structure to guanidinium; 2) it enhances
NH acidity compared to the corresponding thiourea; 3) the
chemical modification is easy using synthetic methods to make
several types of functional molecular systems. Here, taking ad-
vantage of these properties, we have synthesized cationic iso-
thiouronium amphiphiles with long alkyl-chains, and then fabri-
cated organized monolayers at the air–water interface. We
thereby develop film-based anion receptors enabling to recog-
nize the anions in water, since hydrogen bonding at the air–water
interface is not only stronger than that in bulk water,2 but also at
the interface a highly ordered structure could be oriented3 to give
rise to an effective host/guest complexation. In this work, it has
been interestingly found that the orgꢁanized molecular film shows
a signifiꢁcant selectivity for H2PO4 over AcOꢁ, even though
H2PO4 is less basic than AcOꢁ (pKa: 2ꢁ.16 for H2PO4ꢁ, 4.76
for AcOꢁ in water at 25 ꢂC)4 and H2PO4 is more hydrophilic
than AcOꢁ (Hofmeister series). This phenomenon might be use-
ful in the design of H2PO4ꢁ-selective receptors,5 which have po-
tential applications in chemical, biological, and environmental
research.6 Further, we tried to read out the H2PO4ꢁ-recognition
over AcOꢁ and Clꢁ by fabricating the LB films in the presence
of picrate as an indicator; the result is also reported here.
The synthesis of compound 1 is shown in Scheme 1: 3,5-di-
hydroxybenzyl alcohol (2) was allowed to react with 1-bromooc-
ꢁ
cator to monitor the selective binding of H2PO4 (vide infra).
To investigate the film structure, we fabricated Langmuir–
Blodgett (LB) films by transferring the monolayer on pure water
onto hydrophobic plates at 24 mN mꢁ1 and 20 ꢂC. The molecular
orientation in the film was estimated by polarized FTIR spectra
80
B
A
H2PO4
AcO , Cl , and picrate
60
40
10
100
µ
µ
M
M
water
1 µM
RO
OR
H
37C18
O
OC18H37
picrate 1
0.8
µM
water
20
0
100
µ
100
M AcO
M Cl
(iii)
µ
0.2
0.4
0.6
0.8
0.2
2
X
Br
S
0.4
0.6
1.0
2 : R = H, X = OH
3 : R = C18H37, X = OH
4 : R = C18H37, X = Br
1
(i)
Area / nm molecule
N
H
N
H
(ii)
Figure 1. (A) ꢀ-A Isotherms of the monolayers of 1 on the sub-
phase of water and in the presence of varying concentrations of
NaH2PO4 at 20 ꢂC; (B) ꢀ-A Isotherms of the monolayers of 1 on
the subphase of water, 100 ꢁM of NaOAc and NaCl, and 1 ꢁM
of potassium picrate.
1
Scheme 1. Reagents and conditions: (i) n-C18H37Br, K2CO3,
dry DMF, 44%; (ii) PBr3, dry THF, 94%; (iii) dimethylthiourea,
EtOH, 71%.
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.9 (2004)
1119
for 30-layers on CaF2 plate. The polarized transmission meas-
urements for the inclined CaF2 plate can evaluate the tilt angle
of alkyl chains from the dichroic ratio of the band.9 The CH2
symmetric and antisymmetric stretching vibration bands due to
the hydrocarbon chains appeared at 2850 and 2917 cmꢁ1, re-
spectively. These wavenumbers indicate that the alkyl-chains
are mostly in a trans-zigzag conformation involving a certain
number of gauche states.10 Assuming a uniaxial distribution of
transition dipole moments, the tilt angle of the alkyl chains from
the normal line of the CaF2 plate can be estimated to be ca. 10ꢂ.
Out-of plane XRD patterns obtained for 30-layers of the mono-
layer of 1 showed that the long spacing of the film is 3.2 nm. This
value is similar to that estimated from Chem 3D modeling (not
containing counter anion). The in-plane XRD (Bruker AXS,
MXP-BX) gave single diffraction (d ¼ 0:41 nm), suggesting a
hexagonal packing with 0.41 nm spacing among the hydrocar-
bon chains.11 The polarized IR and XRD profiles indicate the
presence of a highly ordered layer structure (Figure 2).
0.1
0.06
0.02
0
20
40
60
80 100
[anion] / [picrate]
Figure 3. Absorbance at 365 nm of the film of 1 deposited from
different concentrations of anions in the presence of 1 ꢁM of
picrate at 24 mN mꢁ1 and 20 ꢂC: ( ) NaH2PO4, ( ) NaOAc,
( ) NaCl.
to design new types of film-based sensor systems for detecting
anions in water. Further investigation is underway involving
the exploration of a more powerful indicator than picrate.
d1 = d2 = d3 = 0.41nm
ca. 10o
This research is financially supported by Shorai Foundation
of Science and Technology and Izumi Science and Technology
Foundation.
d
1
1
3.2 nm
d
2
References and Notes
d
1
For current reports, see: a) H. R. Seong, D.-S. Kim, S.-G. Kim,
H.-J. Choi, and K. H. Ahn, Tetrahedron Lett., 45, 723 (2004). b)
Y. Kubo, M. Kato, Y. Misawa, and S. Tokita, Tetrahedron Lett.,
45, 3769 (2004). c) R. Kato, Y.-Y. Cui, S. Nishizawa, T.
Yokobori, and N. Teramae, Tetrahedron Lett., 45, 4273 (2004).
K. Ariga and T. Kunitake, Acc. Chem. Res., 31, 371 (1998).
M. Liu, A. Kira, and H. Nakahara, Langmuir, 13, 779 (1997); Y.
Zheng, J. Orbulescu, X. Ji, F. M. Andreopoulos, S. M. Pham,
and R. M. Leblanc, J. Am. Chem. Soc., 125, 2680 (2003).
D. D. Perrin, Pure Appl. Chem., 20, 133 (1969); S. Nishizawa
and N. Teramae, Anal. Sci., 13, Suppl., 485 (1997).
3
Figure 2. Schematic representation of the film of 1 ( : alkyl
chain, : S-benzyl-N,N0-dimethylisothiouronium segment).
Since significant interaction of the monolayer of 1 and pic-
rate was observed in the ꢀ-A isotherm experiment (Figure 1B),
we tried to read out selective H2PO4ꢁ-binding using LB films
fabricated from the monolayer under competitive conditions
for anions with picrate indicator. The 30-layer LB films were
prepared in the presence of picrate (1 ꢁM) deposited on the
quart plate; the color was light yellow. The UV–vis spectra were
then recorded, showing an absorption band at 365 nm. This
implies that the prepared LB film contained the picrate. When
similar films were prepared with picrate and H2PO4ꢁ in the sub-
phase, the absorption intensity at 36ꢁ5 nm significantly decreased
with increasing amounts of H2PO4 as a result of competitive
binding between picrate and the anion at the air-water interface.
Subsequently there is almost no absorption of the films in the
presence of 20 equiv. of H2PO4ꢁ. In contrast, AcOꢁ and Clꢁ
scarcely induced any change in the absorption spectra. The in-
2
3
4
5
For an example at the electrode surface, see: K. P. Xiao, P.
Buhlmann, and Y. Umezawa, Anal. Chem., 71, 1183 (1999);
¨
For examples at the liquid-liquid interface, see: K. Shigemori,
S. Nishizawa, T. Yokobori, T. Shioya, and N. Teramae, New
J. Chem., 26, 1102 (2002); ref. 1c.
´
´
´
6
7
R. Martınez-Man˜ez and F. Sancenon, Chem. Rev., 103, 4419
(2003); C. Suksai and T. Tuntulani, Chem. Soc. Rev., 32, 192
(2003).
1H NMR (400 MHz, CDCl3, TMS) ꢂ 9.14 (br s, 1H), 8.63 (br s,
1H), 6.52 (s, 2H), 6.39 (t, J ¼ 2:1 Hz, 1H), 4.56 (s, 2H), 3.91 (t,
J ¼ 6:5 Hz, 4H), 3.25 (s, 3H), 3.10 (s, 3H), 1.79–1.72 (m, 4H),
1.47–1.39 (m, 4H), 1.35–1.26 (m, 56H), 0.88 (t, J ¼ 6:8 Hz,
6H). FAB-MS, m=z ¼ 732½M ꢁ Brꢃþ. Anal. Calcd for
ꢁ
tensity change at 365 nm with 50 ꢁM of H2PO4 is larger than
those with other anions under similar conditions by a factor of 8
for AcOꢁ and 25 for Clꢁ, respectively (Figure 3). Clear selectiv-
ity was therefore observed, being consistent with the results of
the ꢀ-A isotherm experiments (Figure 1). Although in this ap-
proach we used 30-layer LB films because of the low color value
of picrate, the obtained result is promising for the design of new
types of sensor films, since recognition and sensing of anion spe-
cies in water has still been a challenge12 due to the fact that the
water molecules surrounding the anion (e.g. phosphates) inter-
fere with the desired host/guest interactions.
.
C46H87BrN2O2S 0.5 H2O: C, 67.28; H, 10.80; N, 3.41. Found:
C, 67.57; H, 10.83; N, 3.32%.
8
9
As a control experiment, S-methyl-N,N0-ꢁdimethylisothiouroni-
um iodide does not interact with H2PO4 in an aqueous solu-
tion, being checked by 1H NMR study in D2O–CD3CN (9:1v/
v) at 23 ꢂC.
H. Akutsu, Y. Kyogoku, H. Nakahara, and K. Fukuda, Chem.
Phys. Lipids, 15, 222 (1975).
10 T. Seki, T. Fukuchi, T. Kobayashi, and K. Ichimura, Bull.
Chem. Soc. Jpn., 76, 2217 (2003).
In conclusion, we have shown that an organized film com-
posed of an isothiouronium-derived amphiphile exhibits signifi-
cant H2PO4ꢁ-selectivity on the surface of aqueous subphases
containing anion species, and we can read out the anion through
a competitive assay with picrate. This provides a promising way
11 A. Fujimori, Y. Sugita, H. Nakahara, E. Ito, M. Hara, N.
Matsuie, K. Kanai, Y. Ouchi, and K. Seki, Chem. Phys. Lett.,
387, 345 (2004).
12 For a current example, see: A. Ojida, Y. Mito-oka, K. Sada, and
I. Hamachi, J. Am. Chem. Soc., 126, 2454 (2004).
Published on the web (Advance View) July 31, 2004; DOI 10.1246/cl.2004.1118