The anion binding properties bearing neutral cycle amine recognition sites

Article abstract of DOI:10.1002/jhet.260

(Chemical Equation Presented) O-phenylene-diamine derivative containing colorimetric dinitroquinoxaline has been synthesized. Its UV-vis spectroscopy and ¹H NMR investigation reveal that the receptor shows the strong binding ability for AcO^-, F^-, and H₂PO ₄^-, moderate binding abilities for OH^- and almost no binding abilities for Cl^-, Br^-, and I ^-. The interaction of the receptor with studied anions achieving the recognition of anions is proposed to come from the N - H. . .F and potential C - H. . .F hydrogen bonding in its neutral form. The results indicate that it is well suitable for the anion complexation, which is presumably contributed to its ring topology possessing a rigidity conjugation system. Moreover, the molecular orbital level of this receptor and its tautomer were further determined by means of theoretical investigations.

Full text of DOI:10.1002/jhet.260

7
2
The Anion Binding Properties Bearing Neutral Cycle Amine
Recognition Sites
Vol 47
a
Xuefang Shang * and Xiufang Xu
b
a
Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan 453003, China
b
Department of Chemistry, Nankai University, Tianjin 300071, China
*
E-mail: xuefangshang@126.com
Received April 8, 2009
DOI 10.1002/jhet.260
Published online 29 December 2009 in Wiley InterScience (www.interscience.wiley.com).
O-phenylene-diamine derivative containing colorimetric dinitroquinoxaline has been synthesized. Its
UV-vis spectroscopy and H NMR investigation reveal that the receptor shows the strong binding ability
1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
for AcO , F , and H PO , moderate binding abilities for OH and almost no binding abilities for Cl ,
2
4
ꢀ
ꢀ
Br , and I . The interaction of the receptor with studied anions achieving the recognition of anions is
proposed to come from the NAH. . .F and potential CAH. . .F hydrogen bonding in its neutral form. The
results indicate that it is well suitable for the anion complexation, which is presumably contributed to
its ring topology possessing a rigidity conjugation system. Moreover, the molecular orbital level of this
receptor and its tautomer were further determined by means of theoretical investigations.
J. Heterocyclic Chem., 47, 72 (2010).
INTRODUCTION
polyamines with anions, the polyamines were in the
form of protonated polyamines too. However, the neu-
tral amine receptors which can interact with various
anions have not yet been reported, and even more for
achieving the possibility of the naked-eye detection about
the bonding of anions. In the previous work, we studied
the recognition property of 16-membered or 14-membered
amide macrocycle (Scheme 1, 1–3) with various anions
Host-guest systems for recognition of anionic guest
species play an important role in the development of
supramolecular chemistry [1]. The molecular recognition
of anionic guests by synthetic hosts is an area of ever
increasing research activity [2]. Study of anion receptors
has special potential applications in the synthesis of
anion sensors [3], membrane transmit carriers [4], and
mimic enzyme catalysts, etc. [5,6]. Particularly there is
a current interest in the synthesis of colorimetric neutral
chemosensors for detection of anions. Synthetic nitro-
gen-based receptors designed for the selective binding
of anions are usually either the positively charged
ammonium salts, i.e., protonated polyamines and/or qua-
ternary ammonium salts, or some of the neutral species,
such as, amides, sulfonamides, pyrroles, ureas, and thio-
ureas [7–9]. For example, in 1968, Park and Simmons
[17,18]. In this article, we synthesized and studied the
anion binding abilities of six-membered cycle, a neutral
diamine receptor containing dinitroquinoxaline (Scheme 1,
4) in order to find the difference of anion binding ability
between macro and microcycle. The anion recognition
ꢀ
ꢀ
properties of receptor 4 with different anions (F , Cl ,
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Br , I , AcO , H PO , and OH ) has been studied by
2
4
UV-vis and H NMR experiment and the results indicate
1
ꢀ
that the receptor shows higher binding abilities for AcO ,
ꢀ
ꢀ
F , and H PO and the interaction of receptor 4 with vari-
2
4
[
10] synthesized a series of dicyclopolyamines com-
ous anions is in the form of a neutral diamine. This work
is one of the progressive steps in pushing the development
of an anion recognition method based upon the neutral
amine recognition sites.
pounds and the results indicated that it is the protonated
polyamines that interacted with anions. Lehn and co-
workers [11–16] reported that during the interaction of
V
C
2009 HeteroCorporation

January 2010
The Anion Binding Properties Bearing Neutral Cycle Amine Recognition Sites
73
Scheme 1. The structure of receptors.
Figure 1. UV-vis spectrum of receptor 4 changes upon the addition of
fluoride anion; [4] ¼ 4.0 ꢁ 10ꢀ mol/L, [F ] ¼ 0–160 ꢁ 10 mol/L.
5
ꢀ
ꢀ5
Arrows indicate the direction of increasing anion concentration.
RESULTS AND DISCUSSION
Figure 1 shows the changes in the absorption
spectrum of receptor 4 observed upon the addition of
fluoride anion. In the absence of anion, the spectrum of
receptor 4 is characterized by the presence of one peak
at 315 nm. The addition of fluoride anion results in the
development of a new band at 409 nm, changing the
The interaction of receptor 4 with anions was investi-
gated through the spectrophotometric titration by the
addition of a standard dimethyl sulfoxide (DMSO) solu-
tion of the tetrabutyl ammonium salt (TBA) of the
investigated anion to a DMSO solution of 4.
1
Figure 2. Plots of H NMR spectra of receptor 4 in DMSO-d
the additions of Bu NF are 0, 0.5, 1, 2, 5, 10 equiv., respectively.
6
upon the addition of various quantities of Bu
4
NF. The arrows’ direction represent
4
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

7
4
X. Shang and X. Xu
Vol 47
Table 1
anion, detailed analysis reveals the significant upfield
Affinity constants of receptor 4 with various anions.
shifts of H , except H , which exhibits a downfield shift
c
b
from 7.1 to 7.3 ppm, indicating the formation of poten-
tial C—H. . .F H-bonding during the titration [22].
ꢀ
1
Anion
K (M )
s
ꢀ
4
4
4
3
AcO
ꢀ
(3.20 6 0.35) ꢁ 10
(1.32 6 0.33) ꢁ 10
(1.12 6 0.12) ꢁ 10
(2.99 6 0.41) ꢁ 10
Job plots for receptor 4 at 298 K with anions as guest
in DMSO solution show the maxima at a mole fraction
of 0.5, which signifies that the host binds the anionic
guest in a 1:1 ratio. Affinity constants of receptor 4 for
anionic species are calculated according to the eq. (1),
F
ꢀ
H
OH
2
PO
ꢀ
4
color of the solution from colorless to pale-yellow. The
ꢀ
1
:1 host-guest complexation [23–25].
ꢀ
ꢀ
addition of AcO , H PO , and OH , respectively, indu-
2
4
ces a similar color change. On the other hand, exposure
X ¼ X0 þ 0:5DefcH þ cG þ 1=Ks
½ðcH þ cG þ 1=KsÞ ꢀ 4cHcGꢂ
ꢀ
ꢀ
ꢀ
to Cl , Br or I , i.e., species that do not bind to recep-
tor 4 appreciably, do not lead to any noticeable change
in the solution color. This phenomenon makes this sys-
tem an effective anion sensor under these solution
conditions.
2
1=2
ꢀ
g ð1Þ
where cG and cH are the concentration of guest and
host, respectively. X is the intensity of absorbance at
certain concentration of host and guest. X is the inten-
Very recently, a number of fluorogenic and/or chro-
mogenic anion sensors comprising recognition moieties,
such as, urea, thiourea, or amide have been reported to
undergo an anion-induced deprotonation [19–21].
According to these reports, there appears one new triplet
resonance at 16.1 ppm, the characteristic resonance of
bifluoride (FAHAF) and the chemical shifts of noninter-
acted sites’ proton signals occur up-field. To look into
the anion binding properties of receptor for fluoride on
0
sity of absorbance of host when the anion is not added.
K is the affinity constant of host-guest complexation.
s
De is the change in molar extinction coefficient.
Affinity constants of receptor 4 for anionic species
are summarized in Table 1. The affinity constants of
ꢀ
ꢀ
ꢀ
receptor with Cl , Br , and I cannot be determined
because the anions almost have no binding abilities with
receptor. From Table 1, the anion affinity of receptor 4
ꢀ
ꢀ
ꢀ
1
is decreased in the order of AcO > F > H PO4 >
2
anion recognition, H NMR titration experiments in
DMSO-d were performed (Fig. 2). From Figure 2, dif-
ferent patterns are observed in the titration ranges of 0–
ꢀ
ꢀ
ꢀ
ꢀ
OH >> Cl , Br , and I . Among the anions investi-
gated, the highest affinity is observed with acetate. The
reason may be that only the acetate matches perfectly
with receptor 4 geometrically and thus has the highest
affinity with receptor 4.
6
1 and 1–2 equiv. ranges. The NH signal (11.9 ppm)
becomes broadened and the chemical shift of the phenyl
signal H upfield after the addition of 1 quantities of
a
As is well-known, neutral amines almost have no
binding ability with anions. However, receptor 4 we
synthesized has high affinity with some anions. We
speculate that the electron density of diamine moieties
is decreased due to the very strong electron-withdrawing
TBAF. During this process, the chemical shifts of Hb
and H do not change. After the addition of 2 equiv of
c
TBAF, the NH signal completely disappears and the
shift of H is stopped, only peak-shape change occur
a
(
from broad to sharp). The state of affairs can be
accounted by hypothesizing that the first added fluoride
anion establishes H-bonding interaction with the NH of
receptor 4. Due to the strong electron-withdrawing
effect of NO . Theoretical investigation on molecular
2
orbital level using density functional theory at B3LYP/
3-21G level with Gaussion03 program [26] can prove
this (Fig. 3). In receptor 4, the charges of the nitrogen
atoms interacted with anion (N11, N12) are ꢀ0.569624
and ꢀ0.569623, respectively. The charges of N11 and
effect of NO , the shielding effect induced by H-bond-
2
ing is more sensitive to H than H and H . Therefore,
a
b
c
the signal of H upfield and the signal of H , H almost
a
b
c
occurs no changes. On addition of 2 equiv. fluoride
N12 interacted with anions in non-containing NO
2
Figure 3. Molecular orbital level of receptor 4, its tautomer and compound 5. [Color figure can be viewed in the online issue, which is available at
www.interscience.wiley.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2010
The Anion Binding Properties Bearing Neutral Cycle Amine Recognition Sites
75
Scheme 2. The synthesis route of 4.
Figure 4. The structure of receptor 4 and tautomer.
In previous papers, 16-membered and 14-membered am-
ide macrocycle (receptor 1-3) show high selectivity for
certain anion. So, we may be further modify the recep-
tor by tuning the size of the ring in receptor 4 (for
example, altered to a 16-membered or a 18-membered
ring, etc.) in order to find a receptor containing amine
compound (5) are both ꢀ0.581427. The stronger the
binding ability, the smaller the charge of N11 and N12.
Thus, the ability of forming the hydrogen bond between
diamine and anion is appeared in receptor 4. In addition,
receptor 4 exists as tautomer (Fig. 4). Whether does
receptor 4 or its tautomer interact with various anions?
The molecular orbital level of its tautomer was opti-
mized (Fig. 3). The charges of N11 and N12 in tautomer
are both ꢀ0.655013. Therefore, receptor 4 may interact
with anions rather than its tautomer.
ꢀ
ꢀ
recognition site that fits well for AcO , F , or other
anions geometrically.
CONCLUSION
These results enable us to assume that the binding of
anion with diamine moieties will induce a spectral
change in the complex (Fig. 5). From Figure 5, the dif-
ference in spacer units are responsible for the anion se-
lectivity. Fluoride anion, a spherical ion, interacts with
diamines through the H-bonding. Both of the two oxy-
gen atoms of acetate anion, forming a ‘‘Y’’ configura-
tion, probably interact with diamines through two H-
bonding. The affinity constant of acetate anion is higher
than that of fluoride anion due to the ‘‘Y’’ configuration,
acetate anion, is better matched with receptor than
spherical configuration, fluoride anion in space. There-
fore, the affinity constant is related on the matched
degree between receptor and anion. Here, it should be
pointed out that the proposed binding mode in Figure 5
as drown is planar structure and does not present its ge-
ometry. According to optimized results, the geometry of
receptor 4 is planar. It may change under the induce-
ment of anions, especially the NH ring may distort [27].
In summary, we have synthesized a neutral cyclic dia-
mine containing phenyl ring and colorimetric dinitroqui-
1
noxaline. The UV-vis titration and H NMR experiments
indicate that receptor 4 shows the strong affinity for
ꢀ
ꢀ
ꢀ
ꢀ
AcO , F , and H PO , moderate affinities for OH ,
2
4
ꢀ
ꢀ
ꢀ
and almost no affinities for Cl , Br , and I . Moreover,
ꢀ
ꢀ
the interaction of the synthetic receptor with F , AcO ,
ꢀ
ꢀ
H PO , and OH results in a visible change of color,
2
4
and the receptor can thus be used as a colorimetric sen-
sor. Receptor 4 interacts with various anions in the form
of a neutral diamine, not protonated polyamines. In
addition, we found that the selectivity of six-membered
amine cycle (4) is not better than that of 16- or 14-
membered amide cycle (1–3). In addition, theoretical
investigations show that receptor 4 may interact with
anions rather than its tautomer.
This work is one of the progressive steps in pushing
the development of an anion recognition method based
upon the neutral amine recognition site. Further studies
on this line are in progress.
ꢀ
ꢀ
However, the selectivity between AcO and F is
unfortunately not large enough for any practical applica-
tion purpose. The selectivity is probably also influenced
by the size complementarity between anions and cavity.
EXPERIMENTAL
Most of the starting materials were obtained commercially
and all reagents and solvents used were of analytical grade.
All anions, in the form of TBAs, were purchased from Sigma-
Aldrich Chemical Co., stored in a desiccator under vacuum
containing self-indicating silica, and used without any further
purification. DMSO was distilled in vacuo after dried with
CaH . Tetra-n-butylammonium salts (such as (n-C H ) NF, (n-
2
4 9 4
C H ) NCl, (n-C H ) NBr, (n-C H ) NI, (n-C H ) NAcO, (n-
4 9 4
4
9 4
4
9 4
4
9 4
C
vacuum with P
4
H
9
)
4
NH
2
PO
4
, and (n-C
O
4 9 4
H ) NOH) were dried for 24 h in
2
5
at 333 K before use. C, H, and N elemental
1
analyses were made on Vanio-EL. H NMR spectra were
recorded on a Varian UNITY Plus-400 MHz Spectrometer.
FAB-MS was made on VG ZAB-HS. UV-vis spectroscopy
titrations were made on Shimadzu UV2450 spectrophotometer.
Figure 5. A proposed hydrogen bond configuration formed between
receptor 4 and anions.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

7
6
X. Shang and X. Xu
Vol 47
0
N,N -(o-phenylene)-6,7-dinitro-2,3-diamino-quinoxaline (4)
was synthesized according to the route shown in Scheme 2.
,4-Quinoxaline-2,3-dione [28]. o-diaminebenzene (10.8 g,
.1 mol), diethyl oxalate (13.5 mL, 0.1 mol), and pyridine
200 mL) were added in 250 mL three-neck. The mixture
refluxed with N for 72 h. After cooled, the mixture was fil-
trated and we obtained colorless solid. The solid was washed
[7] Bianchi, A.; Bowman-James, K.; Garcia-Espana, E., Eds.
Supramolecular Chemistry of Anions; Wiley-VCH: New York, 1997.
[
8] Schneider, H. J.; Yatsimirsky, A. Principles and Methods in
Supramolecular Chemistry; Wiley: New York, 2000.
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004, 6, 3445.
1
0
(
[
2
2
[
10] Park, C. H.; Simmons, H. E. J Am Chem Soc 1968, 90, 2431.
1
[11] Graf, E.; Lehn, J. M. J Am Chem Soc 1976, 98, 6403.
with ethanol, ether, and dried in vacuum. Yield 61.3%.
NMR (400 MHz DMSO-d ) d 11.9 (s, 2H), 7.1 (m, 4H). Anal.
H
[
12] Lehn, J. M.; Sonveaux, E.; Willard, A. K. J Am Chem Soc
978, 100, 4914.
13] Dietrich, B.; Guihem, J. M.; Pascard, C.; Sonveaux, E. Helv
Chim Acta 1984, 67, 91.
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525.
6
1
Calcd. for C H N O : C, 59.26; H, 3.73; N, 17.28; Found: C,
þ
8
6 2 2
[
5
9.73; H 3.58; N, 17.67. FAB-MS (m/z): 163 (M þ H) .
0
N,N -(o-Phenylene)-6,7-dinitro-2,3-diamino-quinoxaline
4). 1,4-quinoxaline-2,3-dione (2.5 mmol, 0.81 g), 4,5-dinitro-
[
(
3
5
o-diaminebenzene (2.5 mmol, 0.49 g), and acetic acid (100
mL) were refluxed for 12 h. After cooled, the mixture was fil-
trated and we obtained brown solid. The solid was washed
with water, ethanol, and recrystallized, respectively, from ace-
tic acid and dried in vacuum. Yield 84.8%. H NMR (400
MHz DMSO-d ) d 11.9 (s, 2H), 8.3 (s, 2H), 7.1 (m, 4H).
[
[
15] Hosseini, M. W.; Lehn, J. M. Helv Chim Acta 1986, 69,
87.
16] Aguilar, J. A.; Garcia-Espana, E.; Guerrero, J. A.; Luis,
S. V.; Linarese, J. M.; Miravet, J. F.; Ramirez, J. A.; Soriano, C. J
Chem Soc Chem Commun 1995, 2237.
1
6
[17] Shang, X.-F.; Cai, Z.-S.; Lin, H.-K.; Lin, H. J Heterocycl
Chem 2008, 45, 1329.
Anal. Calcd. for C28 O
N, 21.87; Found: C, 49.73; H, 3.58; N, 21.77.
H
16
N
12
8
3
ꢃ2CH COOH: C, 50.01; H, 3.15;
[18] Shang, X.-F.; Xu, X.-F.; Lin, H.; Shao, J.; Lin, H.-K. J Mol
Recognit 2007, 20, 39.
[
19] Wu, C. Y.; Chen, M. S.; Lin, C. A.; Lin, C.; Sun, S. S.
Chem Eur J 2006, 12, 2263.
20] Zhang, B. G.; Xu, J.; Zhao, Y. G.; Duan, C. Y.; Cao, X.;
Meng, Q. J. Dalton Trans 2006, 1271.
21] Esteban-Gomez, D.; Fabbrizzi, L.; Licchellic, M. J Org
Chem 2005, 70, 5717.
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P. Dalton Trans 2006, 3678.
Acknowledgments. This work was supported by 20371028 and
20671052 project from the National Natural Science Foundation
of China.
[
[
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet