A chemosensor for dihydrogenphosphate based on an oxoazamacrocycle possessing three thiourea arms

Article abstract of DOI:10.1039/c2ob25498k

We report a new H-bond macrocyclic chromogenic chemosensor in organic media, H₃L, which displayed drastic changes in its UV-vis spectra revealing selectivity for dihydrogenphosphate over other inorganic anions, such as acetate or fluoride. The X-ray crystal structures of the [H ₄L?NO₃]·(CH₃CN)₄ and [H₄L?CF₃CO₂]·(CH ₃CN)₂ salt complexes are also reported.

Full text of DOI:10.1039/c2ob25498k

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PAPER
A chemosensor for dihydrogenphosphate based on an oxoazamacrocycle
possessing three thiourea arms†
Anxela Aldrey,a Alejandro Macías,a Rufina Bastida,*a Guillermo Zaragoza,b Gustavo Ramac
and Miguel Vázquez López*c
Received 15th October 2011, Accepted 17th May 2012
DOI: 10.1039/c2ob25498k
We report a new H-bond macrocyclic chromogenic chemosensor in organic media, H3L, which displayed
drastic changes in its UV–vis spectra revealing selectivity for dihydrogenphosphate over other inorganic
anions, such as acetate or fluoride. The X-ray crystal structures of the [H4L⋯NO3]·(CH3CN)4 and
[H4L⋯CF3CO2]·(CH3CN)2 salt complexes are also reported.
acceptors, such as fluoride, acetate or dihydrogenphosphate,
Introduction
whose basicity varies in the series F− > CH3CO2 ≥ H2PO4
.
−
− 10
The molecular recognition and sensing of anionic analytes is an
area of increasing research activity, mainly because of the impor-
tance of these species in many biological and chemical pro-
cesses.1 Sensing of phosphates and their derivatives is of special
importance as they compose the backbone of DNA and RNA
and also play crucial roles in signal transduction and energy
storage in biological systems.2 Even though a number of chemo-
sensors for phosphate anions have been reported,1,3 there is still
a need for simple receptors with improved optical response and
selectivity.
Most chemosensors for inorganic anions that work in organic
media are neutral receptors equipped with NH recognition units,
such as ureas,4 thioureas,5 amides,6 sulfonamides7 and pyrroles.8
The NH groups of these devices usually act as H-bond donors,
and the anion as an H-bond acceptor.9 The more acidic the
donor, or the more basic the acceptor, the stronger the hydrogen
bonding interaction. In a limiting situation, exceptionally acidic
donors may be deprotonated on reaction with strongly basic
For fluoride anions, the deprotonation process is also favoured
due to the formation of the highly stable [HF2]− self-complex.11
Acetate and dihydrogenphosphate anions can also promote the
formation of [HX2]− dimers, but their stability is lower.12 This
explains why most of this class of chemosensors display greater
response along the series F− > CH3CO2 ≥ H2PO4
,
although
−
− 13
the selectivity is often poor.14 In this context, we have recently
demonstrated how selectivity for fluoride can be enhanced by
using an imine group as an intramolecular H-bond modulator.15
However, examples of H-bond receptors that show selectivity
for dihydrogenphosphate over acetate or fluoride are very
scarce.12b,16
We present a new thiourea-based oxoazamacrocyclic chemo-
sensor (Scheme 1, H3L) which allows naked-eye detection of
fluoride, acetate and dihydrogenphosphate anions in MeCN solu-
−
tion. This receptor shows high sensitivity for F−, CH3CO2 and
−
−
H2PO4 and, surprisingly, displays selectivity towards H2PO4
over the other two anions. The X-ray crystal structures of the
[H4L⋯NO3]·(CH3CN)4 and [H4L⋯CF3CO2]·(CH3CN)2 salt
complexes are also discussed.
aDepartamento de Química Inorgánica, Facultade de Química,
Universidade de Santiago de Compostela, 15782 Santiago de
Compostela, Spain. E-mail: mrufina.bastida@usc.es
bServicio de Difracción de Rayos X, Edificio CACTUS, Universidade de
Santiago de Compostela, 15782 Santiago de Compostela, Spain
cDepartamento de Química Inorgánica and Centro Singular de
Investigación en Química Biolóxica E Materiais Moleculares (CIQUS),
Universidade de Santiago de Compostela, 15782 Santiago de
Compostela, Spain. E-mail: miguel.vazquez.lopez@usc.es
Experimental section
General information
Chemicals and solvents of the highest commercial grade avail-
able were used as received. Oxoazamacrocycle 1 was synthe-
sized as described in the literature.17
High-Performance Liquid Chromatography (HPLC) was
carried out using an Agilent 1100 series LC/MSD instrument.
Analytical HPLC was run using a Phenomenex Luna C18
(250 × 4.60 mm) analytical reverse phase column using an
Agilent 1100 HPLC equipped with a Mass Spectrometry detec-
tor Agilent LC/MSD VL. The purification of H3L was
†Electronic supplementary information (ESI) available: Crystallographic
data for [H4L⋯NO3]·(CH3CN)4 and [H4L⋯CF3CO2]·(CH3CN)2.
Selected bond distances and angles for [H4L⋯NO3]·(CH3CN)4 and
[H4L⋯CF3CO2]·(CH3CN)2. 1H NMR spectra of H3L. 1H NMR titra-
tions of H3L with F−, CH3CO2 and H2PO4−. Spectrophotometric titra-
−
tions of H3L with OH−, F−, CH3CO2− and NO3−. Fit of the equilibrium
−
constants calculated for F−, CH3CO2 and H2PO4−. CCDC 833635
(nitrate salt) and 863706 (TFA salt). For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c2ob25498k
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 5379–5384 | 5379

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corrections were also applied.18 The structures were solved by
direct methods using SIR-97,19 and finally refined by full-
matrix, least-squares based on F2 by SHELXL.20 All non hydro-
gen atoms were anisotropically refined and the hydrogen atoms
positions geometrically calculated and refined using a riding
model, except the hydrogen atoms of N–H groups involved in
H-Bonds that were located in a difference map and their position
refined isotropically [Uiso(H) = 1.2Ueq(O)].
Synthesis
Synthesis of receptor H3L (Scheme 1). A solution of 4-nitro-
phenylisothiocyanate (0.5 g, 3 mmol) in dry CH2Cl2 (25 mL)
was added dropwise to a refluxing solution of the oxoazamacro-
cycle 1 (0.38 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 deio-
nized water. The organic phase was dried with MgSO4, filtered
and concentrated to dryness in a rotatory evaporator. The yellow
solid residue was purified by HPLC using MeOH–H2O 0.1%
TFA as eluent. Collected fractions were partly concentrated
under reduced pressure at 30 °C to eliminate the MeOH, then
frozen and freeze dried, using a Thermo ModulyoD drier from
Thermo Scientific, to give the desired product as a TFA salt. This
salt was dissolved in water, neutralized with NaOH 1M and
extracted with dichloromethane. The organic phases were dried
(MgSO4), filtered and concentrated to dryness under reduced
pressure to give the desired pure product, confirmed by ESI+-MS
(see ESI†).
Scheme 1 Synthesis and hydrogen labelling scheme of receptor H3L.
performed on a Phenomenex Luna C18 (250 × 10 mm) semi-
preparative reverse phase column. Standard conditions for
analytical RP-HPLC consisted of an isocratic regime during the
first 5 min, followed by a linear gradient from 15 to 95% of
solvent B for 30 min at a flow of 1 mL min−1 with a Retention
Time (RT) for the ligand of 27.2 min and a m/z ratio of 925.1
corresponding to the quasi-molecular ion [M + H]+. For the
purification in the semi-preparative scale, we used a gradient
from 50–85% of solvent B for 30 min at a flow of 3 mL min−1, in
this conditions the RT reduced to 19.0 min. A: water with 0.1%
Trifluoroacetic acid; B: Acetonitrile with 0.1% Trifluoroacetic acid.
FAB mass spectrometry (FAB-MS) was performed on a
Micromass Autospec spectrometer employing m-nitrobenzyl
alcohol as matrix. Electrospray ionization mass spectrometry
(ESI-MS) was performed on an Agilent 1100 Series LC/MSD
instrument in positive scan mode using direct injection. Elemen-
tal analyses were performed on a Carlo Erba EA 1108 analyzer.
NMR spectra were recorded on a Bruker AMX-500 spec-
trometer, using deuterated CD3CN as solvent. UV–vis spectra
were performed on a JASCO V-630 spectrophotometer equipped
with a Peltier thermostat. All the UV–vis titrations experiments
were performed on 2 mL samples of solutions of the receptor
(20 μM) in CH3CN, by addition of CH3CN stock solutions of
appropriate anion in the form of tetrabutylammonium salts. The
UV–vis titration data were fitted using the SPECTFIT/32 and the
HYPERCHEM programmes.
Yield: 65%. Anal. Found: C, 53.5; H, 5.1; N, 14.5; S, 10.2;
Calc. for C43H44N10O8S3·2H2O: C, 53.7; H, 5.0; N, 14.6;
S, 10.0 Mass spectrometry (FAB): m/z = 925 [H3L + H]+.
1
Mass spectrometry (ESI): m/z = 925.3 [H3L + H]+. H NMR
(500 MHz, CD3CN, 25 °C, ppm): 8.86 (hydrogen 15 in
Scheme 1, bs), 8.03 (2 + 8, m, 6H), 7.61 (1, d, 2H), 7.49
(7, d, 4H), 7.27 (5 + 6, m, 4H), 7.02 (4 + 3, m, 4H), 5.14
(14, bm, 4H), 4.38 (13, s, 4H), 3.96 (12, bm, 4H), 3.66
(9, bm, 2H), 2.88 (10 + 11, m, 6H). λmax (ε, CH3CN) = 345
(36 250 M−1 cm−1) nm.
Results and discussion
Synthesis of H3L
Oxoazamacrocycle 1 was prepared following a previously
reported method.20 Reaction of primary and secondary amines of
1 with 4-nitrophenylisothiocyanate in dry CH2Cl2 resulted in
free receptor H3L (Scheme 1). This compound was purified by
semi-preparative HPLC and characterized by a variety of tech-
niques, including FAB and ESI mass spectrometry, UV–vis and
1H NMR spectroscopy and elemental analysis (see ESI†).
H3L is composed of a 17-membered oxoazamacrocycle skele-
ton equipped with three thiourea arms, two of them directly
attached to the macrocycle body, with which they share a nitro-
gen atom, and the other one linked to the remaining nitrogen
atom of the macrocycle through an alkyl spacer.
Crystal structure determinations were performed at low temp-
erature (100 K) with a Bruker APEXII CCD diffractometer,
using graphite-monochromated Mo-Kα radiation from a fine
focus sealed tube source. All computing data and reduction was
made with the APPEX II software. Empirical absorption
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Fig. 1 Spectrophotometric titration of a CH3CN solution 20 μM in
H3L with a standard solution of dihydrogenphosphate ions. Inset: absor-
bance at 470 nm vs. concentration of dihydrogenphosphate ions.
Fig. 2 1H NMR spectra taken over the course of the titration of a
CD3CN solution of H3L (0.6 mM) with a standard CD3CN solution of
[NBu4]H2PO4.
Anion binding studies
bathochromic shift after the addition of the corresponding anion.
In the case of F− and CH3CO2−, the formation of the 470 nm
band is observed even at very low concentration, indicating that
the deprotonation process is always competing with the adduct
The interaction of H3L with a variety of inorganic anions was
studied by UV–vis titrations, which were performed in MeCN
by addition of a standard solution of the corresponding tetraalkyl-
ammonium salt of the corresponding anion to a 20 μM solution
of the receptor.
formation. However, the formation of this new band is not
−
observed during the titration experiment with H2PO4
.
Fig. 1 displays the family of absorption spectra obtained
during titration of H3L with dihydrogenphosphate. The absorp-
tion spectrum of H3L in acetonitrile has one band with a
maximum at 345 nm, assigned to the charge transfer transition
A linear response was observed when the detection was
carried out for H2PO4 concentration in the range of 5–50 ppm
(see ESI†). The limit of detection (LOD) of the method, defined
as the concentration equivalent to a signal of blank plus five
times the standard deviation of the blank, is calculated to be
37.6 ppm.
−
−
from thiourea to nitrobenzene. Titration with H2PO4 resulted in
an initial red shift of the band at 345 nm and the formation of a
new intense CT band at 470 nm, with an isosbestic point at
380 nm. A titration profile, obtained by plotting the molar absor-
−
bance at 470 nm vs. the concentration of H2PO4 in the media,
NMR studies
is shown in the inset. This new band at 470 nm matches well
with the absorption band generated when H3L reacts with tetra-
butylammonium hydroxide, and can be assigned to the deproto-
nated receptor L3− (see ESI†). Moreover, the addition of
dihydrogenphosphate or hydroxide induced a change in the color
of the solution from pale to bright yellow (see ESI†).
The 1H NMR spectra of H3L in CD3CN (see ESI†) show drastic
changes upon addition of dihydrogenphosphate anions (Fig. 2).
The thioamide signal (8.86 ppm for free H3L, hydrogen 15 in
Scheme 1) rapidly shifts downfield when the concentration of
anion is low, but it disappears in an excess of H2PO4−. On the
other hand, the nitrobenzene proton signals [8.03 (2 + 8),
7.61 (1) and 7.49 (7) ppm] shift appreciably when anions are
added, whereas the phenol protons [7.27 (5 + 6), 7.02 (4 + 3)
ppm] move very little. The aliphatic signals change little during
the titration experiment. This NMR behaviour is very similar to
that observed in the case of fluoride and acetate anions (see ESI†).
It has to be noted that only one thioamide N–H signal has
been observed in the 1H NMR spectrum of the free receptor and,
unfortunately, we have not been able to perform 13C NMR
experiments with receptor H3L in CD3CN due to solubility pro-
blems. All these drawbacks prevent us from determining exactly
which thioamide groups are involved in the adduct formation.
Analogous titration experiments were also carried out with F−,
−
CH3CO2−, HSO4−, Cl−, Br−, I− and NO3 (see ESI†). We
−
observed that only CH3CO2 and F− were able to deprotonate
H3L in a similar way to H2PO4−. However, spectral modifi-
−
cations on titration with HSO4−, Cl−, Br−, I− and NO3 were
very moderate, even after the addition of a large excess of
anions. It has to be noted that detection of acetate, fluoride or
dihydrogenphosphate by H3L does not suffer interferences from
the other anions used in this study. On the contrary, the receptor
−
remains sensitive to the addition of F− or CH3CO2 in the pres-
−
ence of H2PO4
.
The initial red shift of the bands at 345 nm suggests that the
−
−
receptor H3L forms H-bonded adducts with H2PO4−, CH3CO2
At this point, we decided to study the H2PO4 binding by
and F−, when the anion concentration in the media is low.4b,21
In order to gain some insight about these processes, we decided
to carry out further UV–vis titration experiments in the range
between 0–10 eq. of the corresponding anion (see ESI†). In the
three experiments, the 345 nm band of H3L undergoes a
31P NMR spectroscopy (Fig. 3). The spectrum of NaH2PO4 in
CD3CN solution (10 mM) shows a unique signal at −3.6 ppm.
An aliquot containing 0.5 eq of the receptor H3L was added to
this solution. The new 31P spectrum shows a dramatic increase
in the chemical shift of the phosphate signal (+4.5 ppm), which
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Fig. 3 31P NMR spectra of CD3CN solutions of (1) H3PO4 (10 mM),
(2) NaH2PO4 (10 mM) and (3) H3L + 2 eq. NaH2PO4 (10 mM).
Fig. 5 Stick representation of part of the crystal cell of the salt
complex [H4L⋯CF3CO2]·(CH3CN)2, showing the inter and intramole-
cular H-bonds established.
protonation site is the amine group N1), a nitrate counterion and
four molecules of acetonitrile: [H4L⋯NO3]·(CH3CN)4 (Fig. 4).
Two of the three thiourea arms of the receptor point their N–H
−
fragments towards the NO3 ion. The only thiourea group
equipped with two N–H units establishes with the nitrate a bifur-
cate interaction [H5A⋯O9 1.98(3) Å; H6A⋯O10 2.12(2) Å].
One of the two remaining thiourea groups of H3L interacts with
one of the nitrate oxygens using its single N–H group
[H9A⋯O9 2.59(10) Å; H9A⋯O11 2.41(4) Å], and the N–H
group of the third thiourea arm is turned to the outside to allow
an N–H⋯O interaction with one of the oxygen atoms of a nitro
group of a neighboring H3L molecule [H3⋯O6i 2.10(2) Å; sym-
metry code: (i) x, y, z + 1]. Then, two of the oxygen atoms of
NO3− form H-bonds with the N–H groups of two of the thiourea
arms of H3L, whereas its third oxygen atom remains unbonded.
The four molecules of acetonitrile present in the crystal cell of
H3L, which have been omitted for clarity in the figures, do not
interact with the salt complex.
Fig. 4 Stick representation of part of the crystal cell of the salt
complex [H4L⋯NO3]·(CH3CN)4, showing the inter and intramolecular
H-bonds established.
can be ascribed to a deshielding effect due to the adduct for-
mation,22 as it cannot be ascribed to the formation of H3PO4.
Taking into account all these observations, we suggest that the
receptor H3L forms H-bonded adducts at low concentrations of
dihydrogenphosphate anion in acetonitrile solution, and that the
−
excess of H2PO4 causes the deprotonation of the thiourea
The crystalization of H3L with TFA in acetonitrile was also
successful. In this case the crystal cell consists of the proto-
groups of H3L.
−
nated receptor, one CF3CO2 counterion and two acetonitrile
molecules: [H4L⋯CF3CO2]·(CH3CN)2 (Fig. 5). This crystal
structure is very similar to that described above for nitrate.
Only two of the three thiourea arms of the receptor interact
with the TFA anion. The thiourea group equipped with two
X-Ray studies
Attempts were made to obtain crystals suitable for X-ray diffrac-
tion studies for all the H-bonded complexes of H3L investigated
in solution. As a general procedure, a CH3CN solution contain-
ing H3L plus an excess of the selected anion was allowed to
slowly evaporate at room temperature. At first, we used their
tetrabutylammonium salts as the anion source but, after several
failures, we decided to use the corresponding acids (1% of con-
centrated acid). Suitable crystals were obtained with this last
method in the case of the nitrate and trifluoroacetate anions. The
main crystallographic data and bond distances are listed in the
ESI.† Fig. 4 and 5 exhibit the stick representations of part of
their crystal cells.
−
N–H units establishes a bifurcate interaction with the CF3CO2
[H5N⋯O9ii 2.02(4) Å; H6N⋯O10ii 2.11(4) Å; symmetry code:
(ii) –x + 2, −y + 1, −z + 1]. Moreover, another thiourea group
interacts with one of the oxygens of TFA using its single N–H
group [H9N⋯O9ii 2.19(5) Å]. The N–H group of the remain-
ing thiourea arm is turned to the outside of the receptor cavity
to allow an N–H⋯N interaction with one acetonitrile molecule
[H3N⋯N11iii 2.14(4) Å; symmetry code: (iii) −x + 1, −y + 1,
−z + 1]. We believe this crystal structure could be useful to
speculate about the possible structural rearrangement of the
−
−
H3L:acetate adduct, as CH3CO2 and CF3CO2 have almost
The colourless crystalline product resulting from the crystaliz-
ation of H3L with HNO3 consists of the protonated receptor (the
identical structures.
5382 | Org. Biomol. Chem., 2012, 10, 5379–5384
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Equilibrium constants
The data collected suggest that changes in the UV–vis and NMR
spectra of H3L in MeCN in the presence of an excess of
fluoride, acetate or dihydrogenphosphate anions are the conse-
quence of the deprotonation of the chemosensor and the for-
mation of the anionic specie L3−. Best fitting curves of the UV–
vis titration data were obtained when assuming that the deproto-
nation process follows the acid–base reaction equilibrium
below:14b,15
H3L þ 3Xꢀ ¼ L3ꢀ þ 3HX ðβDÞ
This equilibrium is progressively displaced to the right on
addition of an excess of X− and the formation of [HX2]−
dimers:23
ð1Þ
Fig. 6 Optimized structure for the [H3L⋯H2PO4]− adduct, as calcu-
lated with a semi-empirical method (AM1) with SPARTAN software,
showing the hydrogen-bonding interactions of the dihydrogenphosphate
anion with the three thiourea arms of the receptor.
HX þ Xꢀ ¼ HX2
ð2Þ
ꢀ
anion recognition, is the property determining anion sensing in
this system.
The overall equilibrium, with a stoichiometry of 1 : 6 for H3L–X
interactions, can be obtained by combining eqn (1) and (2):14b,15
H3L þ 6Xꢀ ¼ L3ꢀ þ 3HX2
ð3Þ
ꢀ
Molecular modelling studies
We carried out molecular modelling studies in order to gain
some insight into the structural features of the [H3L⋯H2PO4]−
supramolecular adduct. Fig. 6 shows the structure of this adduct,
as calculated by a semi-empirical method (AM1) by using the
SPARTAN software. It shows that H3L adopts a cone confor-
mation reminiscent of those of calixarenes, with the NH donor
groups facing the inside. Noticeably, the dihydrogenphosphate
ion interacts with all the thioamide NH groups of the H3L recep-
tor. It has to be noted that examples of tripodal receptors such as
H3L suitable for accommodating phosphate anions have been
previously reported.26
This two-step equilibrium can be applied to the deprotonation
processes promoted by the anions F−, CH3CO2− and H2PO4−, as
−
all of them can form HX2 dimers.11,12,14b,15,22 Unfortunately,
we do not have experimental evidence of the formation of these
dimer species in our system.
−
Interestingly, the value of log βD [eqn (1)] for H2PO4
[13.32(3)] is higher than those calculated for F− [11.95(12)] and
−
CH3CO2 [11.94(1)] (see ESI†). The value of log βD for OH−,
which could be used as reference, is of 14.48(6). Since the basi-
−
city of these anions decreases in the series F− > CH3CO2
≥
H2PO4−, the observed anomalous tendency in the value of βD
for this system could be explained on the basis of the influence
of the molecular properties of the H-bonded adduct formation on
the sensing properties of H3L.19,21 As βD is a global deprotona-
tion constant of a stepwise equilibrium which leads to the depro-
tonated form of the receptor, it is reasonable that the stability of
the intermediates formed during this process could affect its final
value. In this context, spectrophotometric studies in CH3CN sol-
Conclusions
In summary, we have developed a new colorimetric H-bond
chemosensor based on the deprotonation of its three thiourea
donor fragments in the presence of basic inorganic anions such
as fluoride, acetate or dihydrogenphosphate. The H-bond
complexation/deprotonation mechanism has been demonstrated
by spectrophotometric titrations and by NMR spectroscopy. The
deprotonation constants, calculated using the UV–vis titration
ution showed that F−, CH3CO2 and H2PO4 form 1 : 1 adducts
with receptor H3L at low concentration of the corresponding
anion following the reaction equilibrium:
−
−
−
data, for H2PO4 are two order of magnitude larger than those
H3L þ Xꢀ ¼ ½H3L ꢁ ꢁ ꢁ XꢂꢀðKÞ
ð4Þ
−
for CH3CO2 and F−, making this receptor selective for this
−
We have found that the value of log K [eqn (4)] for H2PO4
anion.
1
[4.31(14)] is higher than that calculated for F− [2.21(4)] and
The UV–vis and H and 31P NMR titration experiments, as
−
only slightly higher than that founded for CH3CO2 [3.89(6),
well as the X-ray crystal structures of the [H4L⋯NO3]·
(CH3CN)4 and [H4L⋯CF3CO2]·(CH3CN)2 salt complexes,24
suggest that the receptor forms H-bonded complexes of the type
[H3L⋯A]− when the concentration of anion in the media is low
see ESI†).24 This suggests that, at low concentrations, the tetra-
−
hedral H2PO4 ion forms a more stable H-bonded complex with
H3L than the spherical F− does,25 and a complex more or less as
stable than that with the triangular planar CH3CO2−. Thus, it
seems that the formation of the [H3L⋯H2PO4]− and
[H3L⋯CH3CO2]− adducts can, in some grade, out-balance the
higher basicity of the fluoride ion, as well as the higher stability
of [HF2]− dimer in comparison to [H(H2PO4)2]− and [H
(CH3CO2)2]−,12b but it can’t explain by itself the difference in
−
(in the case of F−, CH3CO2 and H2PO4−), or at high concen-
trations of the other inorganic anions studied. From the equili-
brium constants it seems that the receptor H3L forms much more
−
stable H-bonded intermediate complexes with H2PO4 or
−
CH3CO2 than with F−. The experimental and theoretical data
collected suggest that anion basicity is the property determining
anion sensing, although anion recognition is also influencing the
deprotonation process.
−
the values of log βD between CH3CO2 and H2PO4. Therefore,
in the light of these data, it seems that anion basicity, instead of
This journal is © The Royal Society of Chemistry 2012
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5 T. Gunnlaugsson, A. P. Davis, G. M. Hussey, J. Tierney and M. Glynn,
Org. Biomol. Chem., 2004, 2, 1856.
6 P. A. Gale, Chem. Commun., 2005, 37.
We are currently modifying the structure of H3L in order to
modulate its affinity and selectivity.
7 (a) M. A. Hossain, S. O. Kang, J. M. Llinares, D. Powelland and
K. Bowman-James, Inorg. Chem., 2003, 42, 5043.
8 J. L. Sessler, M. J. Cyr, V. Lynch, E. McGhee and J. A. Ibers, J. Am.
Chem. Soc., 1990, 112, 2810.
Acknowledgements
9 T. Steiner, Angew. Chem., Int. Ed., 2002, 41, 48.
10 R. M. Duke, J. E. O’Brien, T. McCabe and T. Gunnlaugsson, Org.
Biomol. Chem., 2008, 6, 4089.
R. B. thanks the Xunta de Galicia (Spain), Projects PGIDI10P-
XIB209028PR and INCITE09E1R209058ES. M. V. L. thanks
the Directorate-General for Research and Development of the
Xunta of Galicia (INCITE09 209 084 PR) and the Ministry for
Science and Innovation of Spain (CTQ2009-14431/BQU) for
financial support. M. V. L. also thanks M. Eugenio Vázquez
(CIQUS) for his help in the molecular modeling studies. G. R.
thanks the International Iberian Nanotechnology Laboratory
(INL) for a PhD grant.
11 S. Gronert, J. Am. Chem. Soc., 1993, 115, 10258.
12 (a) M. J. Barrow, M. Currie, K. W. Muir, J. C. Speakman and
D. N. J. White, J. Chem. Soc., Perkin Trans. 2, 1975, 15; (b) D. Esteban-
Gómez, L. Fabbrizzi, M. Licchelli and E. Monzani, Org. Biomol. Chem.,
2005, 3, 1495.
13 M. Vázquez, L. Fabbrizzi, A. Taglietti, R. M. Pedrido, A. M. González-
Noya and M. R. Bermejo, Angew. Chem., Int. Ed., 2004, 43, 1962.
14 (a) T. Gunnlaugsson, A. P. Davis, J. E. O’Brien and M. Glynn, Org.
Biomol. Chem., 2005, 3, 48; (b) Y. Wu, X. Peng, J. Fan, S. Gao, M. Tian,
J. Zhao and S. Sun, J. Org. Chem., 2007, 72, 62.
15 M. Vázquez López, M. R. Bermejo, M. E. Vázquez, A. Taglietti,
G. Zaragoza, R. Pedrido and M. Martínez-Calvo, Org. Biomol. Chem.,
2010, 8, 357–362.
References
1 (a) Supramolecular Chemistry of Anions, ed. A. Bianchi, K. Bowman-
James and E. García-España, Wiley-VCH, New York, 1997;
(b) P. D. Beer, Acc. Chem. Res., 1998, 31, 71; (c) C. R. Bondy and S.
J. Loeb, Coord. Chem. Rev., 2003, 240, 77; (d) P. A. Gale and
R. Quesada, Coord. Chem. Rev., 2006, 250, 3219; (e) C. Suksai and
T. Tuntulani, Chem. Soc. Rev., 2003, 32, 192; (f) C. Bowman-James,
Acc. Chem. Res., 2005, 38, 671; (g) T. Gunnlaugsson, M. Glynn,
G. M. Tocci, P. E. Kruger and F. M. Pfeffer, Coord. Chem. Rev.,
2006250, 3094; (h) V. Amendola, D. Esteban Gómez, L. Fabbrizzi
and M. Licchelli, Acc. Chem. Res., 2006, 39, 343; (i) R. Martinez-
Máñez and F. Sancenon, Chem. Rev., 2003, 103, 441; ( j) J. L. Sessler
and J. M. Davis, Acc. Chem. Res., 2001, 34, 989; (k) M. Berger and
F. P. Schmidtchen, Chem. Rev., 1997, 97, 1609.
16 V. Amendola, M. Boiocchi, D. Esteban-Gómez, L. Fabbrizzi and
E. Monzani, Org. Biomol. Chem., 2005, 3, 2632.
17 H. Keypour and F. A. Araey, Asian J. Chem., 2007, 19, 2873.
18 G. M. Sheldrick, SADABS, Program for Empirical Absorption Correction
of Area Detector Data, University of Göttingen, Germany, 1996.
19 A. Altomare, M. C. Burla, M. Camalli, G. L. Cascarano, C. Giacovazzo,
A. Guagliardi, A. G. G. Moliterni, G. Polidori and R. Spagna, J. Appl.
Crystallogr., 1999, 32, 115.
20 G. M. Sheldrick, SHELX-97, An Integrated System for Solving and
Refining Crystal Structures from Diffraction Data, University of Göttin-
gen, Germany, 1997.
21 M. Boiocchi, L. del Boca, D. Esteban-Gómez, L. Fabbrizzi, M. Licchelli
and E. Monzani, J. Am. Chem. Soc., 2004, 126, 16507.
2 (a) The Biochemistry of Nucleic Acids, ed. R. L. P. Adams, J. T. Knower
and D. P. Leader, Chapman and Hall, New York, 10th edn, 1986;
(b) W. Saenger, Principles of Nucleic Acid Structure, Springer,
New York, 1998.
3 (a) M. E. Huston, E. U. Akkaya and A. W. Czarnik, J. Am. Chem. Soc.,
1989, 111, 8735; (b) P. Schiessl and F. P. Schmidtchen, J. Org. Chem.,
1994, 59, 510; (c) L. Fabrizzi, N. Marcotte, F. Stomeo and A. Taglietti,
Angew. Chem., Int. Ed., 2002, 41, 3811; (d) T. Gunnlaugsson,
A. P. Davis, J. E. O’Brien and M. Glynn, Org. Lett., 2002, 4, 2449;
(e) H. Kwan Cho, D. Hoon Lee and J.-I. Hong, Chem. Commun., 2005,
1690.
22 D. M. Rudkevich, W. Verboom, Z. Brzozka, M. J. Palys, W. P. R.
V. Stauthamer, G. J. van Hummel, S. M. Franken, S. Harkema,
J. F. J. Engbersen and D. N. Reinhoudt, J. Am. Chem. Soc., 1994, 116, 4341.
23 (a) V. Amendola, M. Boiocchi, L. Fabbrizzi and A. Palchetti, Chem.–Eur.
J., 2005, 11, 5648; (b) M. Boiocchi, L. del Boca, D. Esteban-Gómez,
L. Fabbrizzi, M. Licchelli and E. Monzani, Chem.–Eur. J., 2005, 11,
3097; (c) R. M. Duke, J. E. O’Brien, T. McCabe and T. Gunnlaugsson,
Org. Biomol. Chem., 2008, 6, 4089.
24 H. Gampp, M. Maeder, C. J. Meyer and A. D. Zuberbuehler, Talanta,
1985, 32, 1133.
25 (a) S. O. Kang, R. A. Begum and K. Bowman-James, Angew. Chem., Int.
Ed., 2006, 45, 7882; (b) E. A. Katayev, J. L. Sessler, V. N. Khrustalev
and Y. A. Ustynyuk, J. Org. Chem., 2007, 72, 7244.
4 (a) A. B. Descalzo, K. Rurack, H. Weisshoff, R. Martinez-Máñez,
M. D. Marcos, P. Amoros, K. Hoffmann and J. Soto, J. Am. Chem. Soc.,
2005, 127, 184; (b) V. Amendola, L. Fabbrizzi and L. Mosca, Chem. Soc.
Rev., 2010, 39, 3889.
26 (a) A. Pramanik and G. Das, Tetrahedron, 2009, 65, 2196; (b) H. Xie,
S. Yi, X. Yang and S. Wu, New J. Chem., 2009, 23, 1105.
5384 | Org. Biomol. Chem., 2012, 10, 5379–5384
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