Colorimetric macrocyclic anion probes bearing nitrophenylurea and nitrophenylthiourea binding groups

Article abstract of DOI:10.1016/j.tet.2013.04.016

Two novel molecular probes bearing two urea (sensor 1) or thiourea (sensor 2) groups (as anion recognition site) coupled with a nitrophenyl group (chromogenic unit) were synthesized and evaluated according to the binding site-signaling subunit approach. T

Full text of DOI:10.1016/j.tet.2013.04.016

Tetrahedron 69 (2013) 4578e4585
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Colorimetric macrocyclic anion probes bearing nitrophenylurea and
nitrophenylthiourea binding groups
a
a
b
,
a
*
ꢀ
Anxela Aldrey , Veronica García , Carlos Lodeiro , Alejandro Macías ,
c
c
a,
b,d,
*
*
ꢀ
ꢀ~
Paulo Perez-Lourido , Laura Valencia , Rufina Bastida , Cristina Nunez
a Inorganic Chemistry Department, Faculty of Chemistry, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain
b BIOSCOPE Group, REQUIMTE/CQFC, Chemistry Department, FCT-UNL, Universidade Nova de Lisboa, 2829-516 Monte de Caparica, Portugal
c Inorganic Chemistry Department, Faculty of Chemistry, University of Vigo, AS Lagoas, Marcosende, 36310 Vigo, Spain
d Ecology Research Group, Department of Geographical and Life Sciences, Canterbury Christ Church University, CT1 1QU Canterbury, United Kingdom
a r t i c l e i n f o
a b s t r a c t
Article history:
Two novel molecular probes bearing two urea (sensor 1) or thiourea (sensor 2) groups (as anion rec-
ognition site) coupled with a nitrophenyl group (chromogenic unit) were synthesized and evaluated
according to the binding site-signaling subunit approach.
Received 23 January 2013
Received in revised form 15 March 2013
Accepted 4 April 2013
The behavior of these different compounds toward metal ions (Co2þ, Ni2þ, Cu2þ, Zn2þ, and Cd2þ) and
anions (Fꢀ, Clꢀ, Brꢀ, Iꢀ, ClO4ꢀ, NO3ꢀ, CNꢀ, OHꢀ, CH3COOꢀ, and H2PO4ꢀ) was investigated by UVevis
spectroscopy in DMSO.
Available online 9 April 2013
Keywords:
Anion sensor
Cation sensor
Ditopic receptor
Urea
Ó 2013 Elsevier Ltd. All rights reserved.
Thiourea
Azo
NMR
Colorimetric
Naked eye
Macrocycle
Deprotonation
1. Introduction
In recent years, considerable attention has been paid to the
development of colorimetric and fluorescent chemosensors for
The study of new ligands, hosts, or receptors for cations and
anions has been an area of considerable interest in the field of su-
pramolecular chemistry.1 Historically, cation complexation has re-
ceived greater attention, but during recent years, the study of
receptors for anions, such as halides and acid anions has become an
area of vigorous research effort.2
The slower development of anion sensors, compared to cation
sensors, is due in part to the fact that detecting small inorganic
anions is often more difficult than detecting cations.3 Furthermore,
while cations are often monatomic and spherical, polyatomic in-
organic anions exhibit a range of geometries with charges that are
delocalized over a number of atoms. The variety of anions makes
each receptor less general and requires it to incorporate individual
design elements.4
sensing anionic species.5e7 Commonly, such sensors offer many
advantages, such as high sensitivity and simplicity, especially for
real-time and on-line analysis of analytes.8
The design and synthesis of colorimetric neutral chemosensors
for anions9,10 usually involves the covalent linking of a chromogenic
fragment to a neutral receptor capable of establishing selective
interactions with the envisaged anion.11,12 Although various su-
pramolecular interactions have proven to be significant, the most
frequent binding motif is arguably hydrogen bonding.13,14
It is well-known that urea/thiourea with a nitrophenyl group as
a signaling unit showed an enhancement in both the hydrogen-
bond donor tendency and acidity.15
Selectivity of receptors containing one or more urea and thio-
urea subunits is related to the energy of the receptoreanion in-
teraction; in this sense, strong H-bond interactions are established
with anions containing the most electronegative atoms as fluo-
ride16 or inorganic oxoanions.17,18 Solvent cannot be water or any
other hydrogen bond-forming medium (e.g., alcohols) since they
* Corresponding authors. E-mail addresses: cle@fct.unl.pt (C. Lodeiro), mrufi-
na.bastida@usc.es (R. Bastida), cristina.nunez@fct.unl.pt, cristina.nunez@uvigo.es
ꢀ~
(C. Nunez).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.016

A. Aldrey et al. / Tetrahedron 69 (2013) 4578e4585
4579
would compete successfully with the receptor for the anion. Thus,
aprotic solvents of varying polarity are currently employed in anion
recognition studies based on H-bonds (e.g., CHCl3, MeCN, and
DMSO) in order to preclude the competition of the solvent as
a hydrogen-bond donor.19
In recent years, polyazamacrocycle-based receptors have been
well-studied for anions,20 and some of them have been proven as
effective systems showing high selectivity and affinity for simple
inorganic21 to biological anions.22 Compared to acyclic anion sen-
sors, reports on cyclic anion sensors are quite limited, which often
require complicated synthetic pathways.23
(Scheme 1) with ethyl bromoacetate and subsequent reaction of
the intermediate ester with hydrazine hydrate.25 The infrared
spectrum (KBr disc) of LB shows bands at 769 and 3316 cmꢀ1
assigned to the out-of-plane bending and stretching vibrations of
the hydrazone groups, respectively, together with a band at
1675 cmꢀ1 associated with the
n(C]O) vibration of the carbonyl
groups. The ESI mass spectrum presents an intense peak at
528 amu corresponding to the molecular ion [LBþH]þ. The 1H NMR
spectrum shows signals corresponding to the NH groups (8.9,
8.5 ppm). In the 13C NMR spectrum the signal at 170.3 ppm cor-
responds to a carbonyl group.
With this idea in mind and continuing our efforts in producing
new macrocyclic receptors24 we set out to synthesize two novel
colorimetric anion sensors that comprise two urea (sensor 1) and
thiourea (sensor 2) groups (anion binding site) coupled with
2.2. Synthesis and characterization of the colorimetric probes
1 and 2
a nitrophenyl group (chromogenic unit) (Fig. 1). The behavior of
Therefore, we propose the synthesis of two new potential anion
ꢀ
these different compounds toward anions (Fꢀ, Clꢀ, Brꢀ, Iꢀ, ClO4
,
receptors
1 and 2 containing nitrophenylurea and nitro-
NO3ꢀ, CNꢀ, OHꢀ, CH3COOꢀ, and H2PO4ꢀ) and also toward metal
ions (Co2þ, Ni2þ, Cu2þ, Zn2þ, and Cd2þ) was investigated by UVevis
spectroscopy in DMSO.
phenylthiourea moieties, respectively, outlined in Scheme 1.
In the first step, a solution of 4-nitrophenylisocyanate or 4-
nitrophenylisothiocyanate in dry dichloromethane was added
Fig. 1. Schematic representation of chemosensors 1 and 2.
2. Results and discussion
dropwise to a refluxing solution of the precursor LB in the same
24a,26
solvent.
The resulting solutions were gently refluxed with
2.1. Synthesis and characterization of LB
magnetic stirring for ca. 24 h and then evaporated to dryness.
The residues were extracted with waterechloroform. The organic
layers were dried over anhydrous Na2SO4, and the final solutions
were evaporated to dryness yielding solids, characterized as the
Ligand LB was isolated as an air-stable yellow oil in 72% yield
by using a two-step procedure involving the alkylation of LA
Scheme 1. Synthesis of chemosensors 1 and 2.

4580
A. Aldrey et al. / Tetrahedron 69 (2013) 4578e4585
pure chemosensors
respectively).
1
and 2, in good yields (65 and 70%,
systems 1 and 2 and we explored their interaction with cations
ꢀ
(Co2þ, Ni2þ, Cu2þ, Zn2þꢀ, and Cd2þ) and anions (OHꢀ, CNꢀ, H2PO4
,
In the infrared spectra (KBr disc) of 1 and 2 the stretching vi-
brations of the pendant groups appear in their expected position.
The ESI mass spectra of 1 and 2 present intense peaks at m/z 856
(100%) and m/z 887 (100%) corresponding to the molecular ions
[1þH]þ and [2þH]þ, further confirming the presence of 1 and 2
receptors. The 1H and 13C NMR data have been recorded using
DMSO-d6 as a solvent, and they confirm the integrity of the ligands
and its stability in solution.
CH3COOꢀ, NO3ꢀ, ClO4 , Fꢀ, Clꢀ, Brꢀ, Iꢀ) by spectrophotometric and
spectrofluorimetric titrations. To do so, a standard solution of the
corresponding salts in DMSO was added to a solution of com-
pounds 1 and 2 at room temperature in the same solvent.
Upon adding anions, such as OHꢀ or Fꢀ to a solution of 1 and 2 in
DMSO (Fig. 2), the absorption maxima at ca. 345 and 375 nm de-
creased gradually, and new absorption maxima at ca. 463 and
496 nm increased, respectively. These results suggested a pertur-
bation in the ICT character of the sensor, due to the recognition of
the anions at the amidourea and amidothiourea moieties. This
enhances the pushepull character of the ICT state, and conse-
quently a red-shift is observed, upon deprotonation of the receptor
by the anion.28
2.3. UVevis spectral responses of sensors 1 and 2
Probes 1 and 2 show very low solubility in water; and in
watereDMSO solutions (50:50, v/v) those ligands precipitated. For
Fig. 2. Changes in UVevis spectra for compound 1 with addition of [(Bu)4N]OH (a), compound 2 with addition of [(Bu)4N]OH (b), compound 1 with addition of [(Bu)4N]F (c), and
compound 2 with addition of [(Bu)4N]F in DMSO. Absorptions read at 345 and 463 nm (compound 1); and 376 and 496 nm (compound 2), [1]¼[2]¼1.00ꢁ10ꢀ5 M.
the aforementioned reasons all the spectroscopic studies have been
done in a non-protic solvent, DMSO.
In the absence of anions, the UVevis absorption spectra of 1 and
2 showed an absorption maximum peak at ca. 345 and 371 nm,
The presence of the other anions with weaker basicity (CNꢀ,
H2PO4ꢀ, CH3COOꢀ) also resulted in negligible changes in UVevis
spectra of probes 1 and 2 (data not shown). No change occurred
ꢀ
upon interaction with NO3ꢀ, ClO4 , Clꢀ, Brꢀ, and Iꢀ anions. This
respectively, which could be attributed to
p
e
p
* transition in the
result suggests the absence of interaction between these anions
and receptors 1 and 2.
Both nitrophenylurea and nitrophenylthiourea-based receptors
1 and 2, respectively,ꢀallow naked-eye detection of Fꢀ, OHꢀ, CNꢀ,
CH3COOꢀ, and H2PO4 anions, showing more intense colors in the
case of compound 2 (see Fig. 3).
Is very important to remark that probe 1 showed better che-
mosensor properties than 2, because it gave different response and
color changes in the presence of Fꢀ, OHꢀ, CNꢀ, CH3COOꢀ, and
ligand.27 Both systems show very low fluorescence emission,
showing bands centered at ca. 437 (probe 1) and 462 nm (probe 2)
(data not shown).
Probes 1 and 2 were developed to give a highly ordered hy-
drogen donating cavity, which could give rise to colorimetric
changes upon anion recognition.
With the aim to compare the influence of the oxygen and the
sulfur atoms in the colorimetric properties, we synthesized these

A. Aldrey et al. / Tetrahedron 69 (2013) 4578e4585
4581
Fig. 3. Colorimetric effect in systems 1 and 2 after interaction with 1 equiv of different ions in DMSO solution.
ꢀ
H2PO4 anions, as a result, 1 could discriminate between these
of Ni(BF4)2 dissolved in DMSO. Upon addition of 1 equiv of this
metal ion to a DMSO solution of probe 1, the absorption maxima at
ca. 345 decreased gradually, and new absorption band at ca. 463
increased. In the case of chemosensor 2, the band centered at ca.
376 nm decreased with the addition of 1 equiv of this metal ion (see
Fig. 4B). Similar results were obtained after the titration of molec-
ular probes 1 and 2 with the other metal ions explored. In respect to
different anions.
Moreover, in order to explore the sensorial ability of receptors
1 and 2 in DMSO solution, the effect of metal cations, such as Co2þ
,
Ni2þ, Cu2þ, Zn2þ, and Cd2þ on the absorption, was studied.
As an example, Fig. 4A and B depicts the absorption spectra of
a solution of probes 1 and 2 in the presence of increasing amounts
Fig. 4. Changes in UVevis spectra for compound 1 (A) and 2 (B) (1.00ꢁ10ꢀ5 M) in DMSO with addition of NiBF4. Absorptions read at 345 and 463 nm (compound 1); and 376 nm
(compound 2).

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A. Aldrey et al. / Tetrahedron 69 (2013) 4578e4585
the colorimetric detection, although addition of nickel(II) develop
a new band at ca. 463 nm (yellow color), the naked-eye detection
was not observed due to the previous colored 1 solution. However,
addition of copper(II) produces a change from yellow to green.
The stability constants for the interaction of receptors 1 and 2 in
the presence of the different ions were calculated using the spec-
trophotometric data and the HypSpec software.29 For all cases very
good mathematical fits were obtained.
The stability constants for the interaction of receptors 1ꢀand 2 in
the presence of the Fꢀ, OHꢀ, CNꢀ, CH3COOꢀ, and H2PO4 anions
and Co2þ, Ni2þ, Cu2þ, Zn2þ, and Cd2þ metal ions are summarized in
Table 1.
performed in order to obtain the LOQ. The LOD was obtained by the
formula:
ydl ¼ yblank þ 3 std
where, ydl¼signal detection limit and std¼standard deviation.
Therefore, the study of the limit of detection (LOD) and the limit
of quantification (LOQ) for the explored anions and metal ions was
performed for probes 1 and 2 bearing in mind their use for real
anion and metal-ion detection for analytical applications.
For these measurements, ten different analyses for each receptor
were performed to obtain the LOQ, and a calibration fit was applied
to determine the LOD. Table 2 includes the LOD and the LOQ in our
experimental conditions, at room temperature, in DMSO.
Table 1
Stability constants for chemosensors 1 and 2 in the presence of some anions and the
metal ions Co2þ, Ni2þ, Cu2þ, Zn2þ, and Cd2þ in DMSO for an interaction 1:1 (X:L), (X:
metal ion or cation; L¼receptor 1 or 2)
Table 2
Limits of detection (LOD) and quantification (LOQ) (ppm) for, Fꢀ, OHꢀ, CNꢀ,
CH3COOꢀ, H2PO4ꢀ, Co2þ, Ni2þ, Cu2þ, Zn2þ, and Cd2þ with compounds 1 and 2
Compound
Interaction (Aꢀ:L)
S log b (abs) (emission)
Compound
Anions
LOD (ppm)
LOQ (ppm)
1
OHꢀ (1:1)
4.30ꢂ4.77ꢁ10ꢀ3
4.23ꢂ2.22ꢁ10ꢀ3
4.46ꢂ2.04ꢁ10ꢀ3
3.29ꢂ1.99ꢁ10ꢀ3
4.72ꢂ1.95ꢁ10ꢀ3
10.45ꢂ3.31ꢁ10ꢀ3
9.96ꢂ3.79ꢁ10ꢀ3
10.69ꢂ4.37ꢁ10ꢀ3
8.89ꢂ5.41ꢁ10ꢀ3
10.76ꢂ3.49ꢁ10ꢀ3
Fꢀ (1:1)
1
Fꢀ
12.23ꢂ0.01
5.91ꢂ0.01
6.09ꢂ0.01
4.38ꢂ0.01
6.86ꢂ0.01
3.59ꢂ0.01
2.73ꢂ0.01
4.01ꢂ0.01
3.62ꢂ0.01
2.06ꢂ0.01
59.63ꢂ0.01
19.93ꢂ0.01
21.63ꢂ0.01
14.02ꢂ0.01
18.56ꢂ0.01
5.68ꢂ0.01
6.18ꢂ0.01
6.19ꢂ0.01
4.42ꢂ0.01
4.87ꢂ0.01
CNꢀ (1ꢀ:1)
OHꢀ
CNꢀ
H2PO4 ð1 : 1Þ
CH3COOꢀ (1:1)
OHꢀ (1:1)
CH3COꢀOꢀ
H2PO4
Fꢀ
2
Fꢀ (1:1)
2
CNꢀ (1ꢀ:1)
OHꢀ
CNꢀ
H2PO4 ð1 : 1Þ
CH3COOꢀ (1:1)
CH3COꢀOꢀ
H2PO4
Compound
Interaction (M:L)
S log b (abs) (emission)
Co2þ (1:1)
Ni2þ (1:1)
Cu2þ (1:1)
Zn2þ (1:1)
Cd2þ (1:1)
Co2þ (1:1)
Ni2þ (1:1)
Cu2þ (1:1)
Zn2þ (1:1)
Cd2þ (1:1)
6.80ꢂ1.50ꢁ10ꢀ3
5.76ꢂ1.51ꢁ10ꢀ3
5.86ꢂ1.75ꢁ10ꢀ3
6.41ꢂ1.39ꢁ10ꢀ3
4.54ꢂ1.21ꢁ10ꢀ3
5.93ꢂ2.30ꢁ10ꢀ3
5.20ꢂ1.45ꢁ10ꢀ3
5.20ꢂ2.74ꢁ10ꢀ3
5.30ꢂ2.30ꢁ10ꢀ3
4.23ꢂ2.87ꢁ10ꢀ3
Compound
Metal ion
LOD (ppm)
LOQ (ppm)
1
1
Co2þ
Ni2þ
Cu2þ
Zn2þ
Cd2þ
Co2þ
Ni2þ
Cu2þ
Zn2þ
Cd2þ
3.09ꢂ0.01
5.51ꢂ0.01
2.54ꢂ0.01
3.69ꢂ0.01
5.48ꢂ0.01
0.96ꢂ0.01
1.08ꢂ0.01
0.74ꢂ0.01
0.88ꢂ0.01
1.24ꢂ0.01
5.34ꢂ0.01
8.80ꢂ0.01
5.96ꢂ0.01
6.49ꢂ0.01
8.37ꢂ0.01
2.16ꢂ0.01
4.16ꢂ0.01
3.32ꢂ0.01
2.98ꢂ0.01
5.16ꢂ0.01
2
2
Although the naked-eye anion detection is better developed in
compound 1, taking into account the values reported in Table 1,
the strongest interaction with anions was observed for chemo-
sensor 2. This fact, it is probably due to the presence of sulfur
atoms in the thiourea groups. In previously similar reported sys-
tems,16a sulfur atoms form weaker intramolecular hydrogen
bonds than oxygen, and hence the intermolecular interactions
(hosteguest) were more favorable allowing the alignment of the
thiourea functionality for the interaction with fluoride ions, being
much easier that it was compared with the urea receptor. It would
be expected that probe 2 acts as better anion receptors at room
temperature in comparison with probe 1. These results are in
agreement with the more intense color changes observed in
sensor 2 in the presence of the different anions. The sequence of
the strongest interaction observed for probes 1 and 2 with the
anions studied in decreasing order is:
As previously stated, in comparison with the other anions
and metal ions explored, the stability constants were higher for
the interaction of probes 1 and 2 with CH3COOꢀ and Co2þ
z
Zn2þ>Cu2þzNi2þ
.
In order to explore these systems as potential ditopic receptors,
addition of increasing amounts of CuF2 and ZnF2 to a DMSO solu-
tion of probes 1 and 2 (1.00ꢁ10ꢀ5 M), at 298 K, was carried out.
Changes in the absorption spectra were only observed after the
addition of CuF2 to a DMSO solution of probe 1. A moderate de-
crease in the absorption band centered at 345 nm, and an increase
in the band centered at 373 nm was observed, suggesting a simul-
taneous interaction of this receptor with the anion Fꢀ and the Cu2þ
metal ion (see Fig. 5A and B).
2.4. NMR responses of sensors 1 and 2
ꢀ
CH3COOꢀ > CNꢀ > OHꢀ > Fꢀ > H2PO4
1H NMR titration of receptors 1 and 2 with tetrabutylammo-
nium fluoride was performed in order to understand the effect of
this compound on the NH protons of receptors 1 and 2.30
1H NMR spectra were registered in DMSO-d6e0.5% water solu-
tion. The urea NH signals in compound 1 appear at 9.85, 9.55, and
8.43 ppm (Fig. 6). Addition of 0.5 equiv of tetrabutylammonium
fluoride to the solution of receptor 1 in DMSO-d6 is enough to
initialize deprotonation processes.31 In that case, the deprotonation
of the urea subunits in the receptor does not induce effects on the
aromatic substituents. Similar results were obtained in the case of
sensor 2 (data not shown).
For the interaction of probes 1 and 2 with the metal ions, the
sequence obtained was Co2þzZn2þ>Cu2þzNi2þ>Cd2þ. In that
case, the results were similar for both probes. It could probably be
explained as the cavity size of both macrocyclic ligands and the
structure flexibility is the same in both guests, making the in-
teraction of 1 and 2 with the metal ions very similar.
The limit of detection (LOD) and the limit of quantification (LOQ)
for metal ions were performed having in mind their use for real
anion detection and for analytical applications. For these mea-
surements, ten different analyses for the selected receptor were

A. Aldrey et al. / Tetrahedron 69 (2013) 4578e4585
4583
Fig. 5. Changes in UVevis spectra for compound 1 (1.00ꢁ10ꢀ5 M) in DMSO with addition of [CuF2]. Absorptions read at 345 and 373 nm (compound 1).
Fig. 6. 1H NMR spectra taken in the course of the titration of a DMSO-d6 solution of 1 (4.00ꢁ10ꢀ2 M) with a standard solution of [Bu4N]F. Key: no [Bu4N]F addition (bottom);
addition of 1 equiv of [Bu4N]F (top).
3. Conclusions
similar. It could probably be explained because the cavity size of
both macrocyclic ligands and the structure flexibility is similar in
both cases.
In summary, two novel nitrophenylurea and nitrophenylthiourea-
based receptors 1 and 2 were designed and synthesized. Both systems
allow the naked-eye detection of Fꢀ, OHꢀ, CNꢀ, CH3COOꢀ, and
ꢀ
H2PO4 anions. Strongest interaction with anions and more intense
4. Experimental
color changes were observed for chemosensor 2. It would be
explained by the fact that sulfur atoms form weaker intramolecular
hydrogen bonds, and hence, chemosensors containing this atom
should act as better anion receptors at room temperature.
4.1. Synthesis of chemosensors 1 and 2
Chemicals and solvents of the highest commercial grade avail-
able were used as received. Oxaazamacrocycle LA was synthesized
as described in the literature.32
Hosteguest ability of receptors 1 and 2 in solution towards the
metal ions Co2þ, Ni2þ, Cu2þ, Zn2þ, and Cd2þ in DMSO was very

4584
A. Aldrey et al. / Tetrahedron 69 (2013) 4578e4585
4.1.1. Synthesis of macrocycle LB. LA (0.766 g, 2 mmol) was dis-
solved in acetonitrile (50 mL) and Na2CO3 (1.27 g; 12 mmol) was
added. The mixture was refluxed and ethyl bromoacetate (2.1 g;
12 mmol) dissolved in acetonitrile (10 mL) was added dropwise to
the refluxing solution. The mixture was refluxed for 24 h, filtered
off and evaporated to dryness. The residue was then extracted with
waterechloroform. The organic layer was dried over anhydrous
Na2SO4 and evaporated to yield a yellow oil. This was dissolved in
absolute ethanol (10 mL) and hydrazine hydrate (2.6 g; 80 mmol)
was added. The solution was slowly stirred for one night and
concentrated to dryness under reduced pressure. The crude solid
was extracted with waterechloroform. The organic phases were
dried (Na2SO4), filtered and concentrated to dryness under reduced
pressure to give the desired pure product, characterized as the li-
gand LB.
Author contributions
R.B., A.M., C.N., C.L., L.V., and P.P.-L. conceived and design the
experiments, analyzed the data, contributed to discussion, and co-
wrote the manuscript. A.A. and V.G. performed the synthesis and
characterization of both probes. C.N. performed the UVevis spec-
troscopy measurements. A.A. and C.N. performed and discuss the
NMR studies. R.B., C.N., A.M., and C.L. coordinated the project. All
authors have revised the manuscript.
Acknowledgements
We are grateful to the Xunta de Galicia (Spain) for the project
PGIDI10PXIB209028PR, IN845B-2010/057, and 10CSA383009PR
(Biomedicine) for financial support. The authors thank the Sci-
entific Association Proteomass (Spain) for financial support. C.N.
thanks Xunta de Galicia for the I2C program postdoctoral
contract.
Yield: 72% (0.76 g). Anal. Calcd for C27H41N7O4$4H2O: C, 54.1; H,
8.2; N, 16.4. Found: C, 54.1; H, 8.1.; N, 16.6%. IR (KBr, cmꢀ1): 3316
[
[
n(NeH)st], 1675 [n(C]O)], 1526 [d(NeH)ip], 1242 [n(CeN)], 769
d
(NeH)oop]. (ESI, m/z): 528 [LBþH]þ. Color: yellow. 1H NMR
(400 MHz, DMSO-d6): 8.9e8.5 (m, 6H, NH); 7.5e6.88 (m, 8H); 4.5 (s,
4H); 3.6 (s, 4H); 3.14 (s, 4H); 2.4 (t, 4H), 2.2 (t, 4H); 1.99 (s, 3H); 1.5
(t, 4H). 13C NMR (100 MHz, DMSO): 24.5, 43.7, 49.7, 54.1, 59.8, 63.3,
119.2e155.0, 170.3.
Supplementary data
Proton and carbon NMR spectra of reported compounds. This
material is available free of charge via the internet at http://pub-
s.acs.org. Supplementary data related to this article can be found
online at http://dx.doi.org/10.1016/j.tet.2013.04.016.
4.1.2. Synthesis of colorimetric probe 1. A solution of 4-
nitrophenylisocyanate (0.5 g, 3 mmol) in dry CH2Cl2 (25 mL)
was added dropwise to a refluxing solution of the oxaazamacro-
cycle LB (0.599 g, 1 mmol) in the same solvent (25 mL). The
resulting solution was refluxed with magnetic stirring for 24 h,
and then evaporated to dryness under reduced pressure. The solid
residue was dissolved in CHCl3 and extracted with deionized
water. The organic phase was dried with Na2SO4, filtered, and
concentrated to dryness in a rotary evaporator and dried under
vacuum, to give the desired pure product, characterized as the
ligand 1.
References and notes
1. (a) Hiraoka, M. Crown Compounds: Their Characteristics and Applications;
Kodanisha-Elsevier: Tokyo, Japan, 1982; (b) Balzani, V.; Scandola, F. Supramolec-
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Yield: 65% (0.56 g). Anal. Calcd for C41H49N11
O10$H2O: C, 56.3; H,
5.9; N, 17.6. Found: C, 56.5; H, 5.7; N, 17.6; IR (KBr, cmꢀ1): 3300
[n(NeH)st], 1714 [n(C]O)], 1559 [n(NO2)as], 1303, 1329 [n(NO2)sim],
~
2. (a) Bianchi, A.; Bowman-James, K.; García-Espana, E. Supramolecular Chemistry
1111 [
n
(CeN)]. (ESI, m/z): 856 [1þH]þ. Color: yellow. 1H NMR
of Anions; Wiley-VCH: New York, NY, 1997; (b) Sessler, J. L.; Gale, P.; Cho, W.-S.
Anion Receptor Chemistry; Royal Society of Chemistry: Cambridge, UK, 2006.
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Soc. 2009, 131, 8703e8707.
(400 MHz, DMSO-d6): 9.85 (s, 2H, NH); 9.55 (s, 2H, NH); 8.4 (s, 2H,
NH); 8.15 (d, 4H); 7.66 (d, 4H); 7.37e6.88 (m, 8H); 4.36 (s, 4H); 3.71
(s, 4H); 3.14 (s, 4H); 2.27e2.12 (m, 8H); 1.99 (s, 3H); 1.62e1.45 (m,
4H). 13C NMR (400 MHz, DMSO): 25.0, 43.4, 48.7, 51.4, 54.7, 59.0,
67.8, 115.0e158.1, 168.5, 170.5.
4.1.3. Synthesis of colorimetric probe 2. A solution of 4-nitro-
phenylisothiocyanate (0.54 g, 3 mmol) in dry CH2Cl2 (25 mL)
was added dropwise to a refluxing solution of the oxaazama-
crocycle LB (0.599 g, 1 mmol) in the same solvent (25 mL). The
resulting solution was refluxed with magnetic stirring for 24 h,
and then evaporated to dryness under reduced pressure. The
solid residue was dissolved in CHCl3 and extracted with deion-
ized water. The organic phase was dried with Na2SO4, filtered,
and concentrated to dryness in a rotary evaporator and dried
under vacuum, to give the desired pure product, characterized as
the ligand 2.
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Yield: 70% (0.62 g). Anal. Calcd for C41H49N11O8S2$H2O: C, 54.4;
H, 5.7; N, 17.1; S, 7.1 Found. C, 54.1; H, 5.8; N, 17.2; S, 7.4. IR (KBr,
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cmꢀ1): 3292 [
(NO2)sim], 1330 [
n
(NeH)st], 1590 [
n(C]O)], 1559 [n(NO2)as], 1303, 1329
n
[
n
n
(CS)], 1111 [
(CeN)]. (ESI, m/z): 887 [2þH]þ.
Color: orange. 1H NMR (400 MHz, DMSO-d6): 10.26 (s, 2H, NH); 9.15
(s, 2H, NH); 8.26 (d, 4H); 8.07 (s, 2H, NH); 7.36 (d, 2H); 7.25e7.11 (m,
6H); 7.05e6.79 (m, 4H); 5.29 (s, 4H); 4.34 (s, 4H); 4.09 (s, 4H);
3.49e3.20 (m, 8H); 2.88e2.55 (m, 3H); 1.31e1.06 (m, 4H). 13C NMR
(400 MHz, DMSO): 24.7, 43.4, 50.1, 51.4, 55.0, 59.6, 67.3,
114.2e156.1, 169.6, 182.0.
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