Cooperative and receptor for ion-pairs

Article abstract of DOI:10.1039/b515634c

A novel heteroditopic calix[4]diquinone receptor capable of binding an anion and cation simultaneously in a cooperative fashion is shown only to recognise halide anions in the presence of a suitable cobound cationic guest species, and displays affinity for certain ion-pairs where no affinity for either of the free ions is observed. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b515634c

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COMMUNICATION
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Cooperative AND receptor for ion-pairs{
Michael D. Lankshear, Andrew R. Cowley and Paul D. Beer*
Received (in Cambridge, UK) 3rd November 2005, Accepted 8th December 2005
First published as an Advance Article on the web 13th January 2006
DOI: 10.1039/b515634c
A novel heteroditopic calix[4]diquinone receptor capable of
binding an anion and cation simultaneously in a cooperative
fashion is shown only to recognise halide anions in the presence
of a suitable cobound cationic guest species, and displays
affinity for certain ion-pairs where no affinity for either of the
free ions is observed.
The design and application of new heteroditopic receptor systems
capable of simultaneous coordination of both anionic and cationic
guest species has recently attracted a great deal of interest, as these
systems have the potential to act as salt solubilisation, extraction,
and membrane transport agents.1 A number of receptors whereby
Fig. 1 Ditopic calix[4]diquinone receptor 1.
oxygens were included in the macrocycle design to provide extra
stabilising units for the cation binding site. The resulting model of
the host–guest complex is illustrated in Fig. 2.
an anion and cation are bound separately within the receptor have
been reported previously.2 In these systems, the cation may be
bound using a number of common motifs, while the anion is
coordinated using Lewis acidic, electrostatic, or hydrogen bonding
interactions.3 Interest in a contact ion-pair binding approach,
wherein the anion and cation are bound essentially as one moiety, is
particularly noteworthy as this avoids the energetically unfavour-
able separation of the two ions.4 Importantly, the geometry of the
ditopic receptor must be optimised so that the anion and cation
binding sites are located in proximity so as to enhance this
interaction, as incorrect orientation could lead to the ion pair
associating outside of the receptor, or solvent-separated ion binding.
Herein we describe the design, synthesis and binding properties of
one such rare system, which demonstrates a dramatic enhancement
of anion binding by a cobound cation and, in some cases, strong
binding with associated ion pairs where no affinity for the free ions
is observed, which to our knowledge is without precedent.
The synthesis of the target receptor was accomplished by a four-
step synthetic procedure (Scheme 1).7 This route provides a simple,
high yielding pathway to the possible preparation of a number of
calixarene species with macrocyclic function at the lower rim. The
single crystal X-ray diffraction determined structure of 1 (Fig. 3)
reveals the calixquinone species in a partial cone conformation,
with one of the quinone oxygens hydrogen bonding to the
isophthalamide amide protons.{
1
The anion binding properties of 1 were assessed by H NMR
spectroscopic titration methods in deuterated acetonitrile solution.
One equivalent of tetrabutylammonium (TBA) chloride was found
to induce only very small downfield shifts in the signals arising
from the amide (d, 0.057 ppm) and isophthalyl C-H (c, 0.012 ppm)
protons of receptor 1 (Fig. 4). The change in chemical shift as a
function of concentration revealed a linear relationship (Fig. 5),
indicating that no anion binding was occurring; the change in
chemical shift was attributed to an increase in the ionic strength of
the solution.
Analogous 1H NMR titration experiments were then carried out
in the presence of one equivalent of various cationic guest species.
Remarkably, the signals arising from the amide, d, and
isophthalyl, c, protons were found to broaden and shift downfield
considerably on the addition of one equivalent of TBA chloride
The calix[4]diquinone unit has well-documented cation binding
properties which may be readily probed by electrochemical and
UV-visible spectroscopic methods.5 The isophthalamide cleft has
been widely utilised as an anion binding unit in a variety of
systems.6 By using a combination of these two moieties, it was
hoped that a considerable enhancement of anion recognition
would take place in the presence of a bound cationic guest species.
The design of this system was assisted by using the CAChe
modelling program. MM3 and PM3 calculations indicated that the
target receptor 1 (Fig. 1) provided an optimal spatial arrangement
for the binding of a KCl ion pair within the macrocyclic cavity,
with the calix[4]diquinone unit coordinating the cation, and the
isophthalamide amide motif binding the anion. In addition, ether
Department of Chemistry, Inorganic Chemistry Laboratory, University
of Oxford, South Parks Road, Oxford, UK OX1 3QR.
E-mail: paul.beer@chem.ox.ac.uk; Fax: +44 1865 272960;
Tel: +44 1865 285142
{ Electronic supplementary information (ESI) available: Synthesis and
characterisation data for compounds 1–4, general procedures used for 1H
NMR and UV-visible spectroscopic titration experiments, single X-ray
crystal data for 1. See DOI: 10.1039/b515634c
Fig. 2 Optimised CAChe model of 1?KCl recognition. Potassium is in
purple, chloride in green.
612 | Chem. Commun., 2006, 612–614
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Fig. 4 Changes in the aromatic region of the 1H NMR spectrum
(CD3CN, 298 K) of 1 : 1 mixtures of 1?TBACl, 1, 1?KPF6 and
1?KPF6?TBACl (1?KCl).
Scheme 1 Formation of compound 1. Abbreviations used: Tos =
tosylate, Phth = phthalimide.
Fig. 5 Plot of chemical shift of the NH protons of 1?M+ as a
function of added chloride concentration (CD3CN, 298 K)§. [1?M]+
=
0.0015 mol dm23
.
Fig. 3 ORTEP thermal ellipsoid plot of 1 at 40% probability. Selected
The cation binding properties of this system were probed in
CH3CN solution by UV-visible spectroscopic analysis of the
quinone n–p* absorption band. The free receptor was found to
bind only with potassium cations, as could be demonstrated by
SPECFIT9 analysis of the titration spectra obtained, but in the
presence of one equivalent of a coordinating anion (chloride) the
binding constants obtained from all the cations studied were
enhanced, suggesting a dramatic positive cooperativity effect
whereby chloride binding can enhance the cation binding in these
systems (Table 2). This effect is most noteworthy for ammonium
and sodium binding, as in these cases cation binding can only be
detected in the presence of chloride anion. No significant changes
in the absorption spectra of 1 were induced on addition of TBA
chloride. Thus, chloride can be said to ‘switch on’ sodium and
ammonium cation recognition by the quinone groups of 1; indeed
it seems that 1 will, in some cases, bind the ion-pair strongly where
no affinity for the discrete ions is observed (e.g. NH4Cl, NaCl). To
the best of our knowledge, this is the first such example of a system
…
…
distances: N(1) O(4) 3.171(3), N(2) O(4) 3.237(3) A.
˚
(y1.51 and y1.135 ppm, respectively, in the case of potassium,
see Fig. 4). Job Plot analysis indicated that the host–guest
interaction demonstrated 1 : 1 complex stoichiometry, but the
interaction was too strong to allow accurate stability constant
determination through WinEQNMR8 analysis of the titration
binding curves (Fig. 5). This was found to be the case for a number
of cationic guest species (Table 1), although importantly no
chloride recognition was observed in the presence of one
equivalent of a non-coordinating cationic species such as TBA
or tetramethylammonium. These results illustrate a ‘switching on’
of chloride recognition in receptor 1, which appears to display
absolutely no affinity for chloride in the absence of
a
suitable cationic guest, but which binds very strongly when this
species is present. This is a very dramatic enhancement of anion
binding effected by a cobound cation, one of the largest yet
reported.
Furthermore, it was demonstrated that this effect is not confined
to chloride recognition, as a similar enhancement in binding is
induced by one equivalent of KPF6 in the cases of bromide and
iodide anions in CD3CN solution. Neither anion binds to the free
receptor, but, as with chloride, the stability constant for bromide in
the presence of potassium is >104 M21. With iodide, as may be
expected, the enhancement is weaker, with KI = 380 M21.§
Table 1 Switching on of chloride recognition by coordinating cations
+
+
Cation
TBA
NMe4
Li+
Na+
K+
NH4
NH Dda
logKCl
a
0.057
—
0.101
—
0.881
3.79c
y0.99
.4
y1.51
.4
1.106
.4
b
b
Change in amide chemical shift (ppm) on addition of 1 equivalent
b
c
chloride anion. No binding interaction observed. Error , 10%.
Chem. Commun., 2006, 612–614 | 613
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Table 2 Enhancement of cation recognition by cobound chloride
aniona
logKNa
logKK
logKNH
4
b
b
1
1?TBACl
—
3.13
3.08
4.13
—
4.65
a
Measurements carried out at 298
analysed using the SPECFIT computer program. Errors , 15%. In
K in dry CH3CN, spectra
the case of lithium, SPECFIT analysis of the titration data failed to
give an association constant value. Insufficient changes in the
absorption spectrum to infer binding.
b
where the receptor displays no discernible affinity for either one of
the free ions, but which binds the associated ion pair species
strongly (for summary of potential solution equilibria, see
Scheme 210). This behaviour can be treated through Boolean logic
to show that this receptor behaves in a manner consistent with an
AND gate; that is, it only demonstrates binding in the presence of
both a suitable anion and cation.11 A possible reason for this
phenomenon could be the self-inhibition of the cation and anion
binding sites of the molecule by intramolecular hydrogen bonding
of the quinone unit with the isophthalamide, as illustrated in the
solid state structure of 1 (Fig. 3), which is disrupted only by a
suitable ion-pair.
Fig. 6 Changes in aliphatic region of 1H NMR spectrum (CD3CN,
298 K) of 1, 1?KPF6 and 1?KPF6?TBACl (1?KCl).
based on the calix[4]diquinone unit, which furthermore displays
unprecedented properties consistent with the cooperative AND
recognition of ion-pairs.
The authors wish to thank the EPSRC and GE Healthcare
(Amersham) for a CASE supported studentship.
Notes and references
In order to gain more insight into the cooperative enhancement
of cation recognition by the presence of an anion, 1H NMR
spectroscopic analysis of the aliphatic region of 1?KPF6 was carried
out. This suggests a conformational change of the calix[4]diquinone
unit on binding chloride anion. Binding one equivalent of
potassium ion leads to a widening of the splitting between the
peaks arising from the bridging methylene protons i, an effect
which is magnified when anions are added (Fig. 6). Changes are
also seen in the signals arising from the alkyl protons e–h. These
changes definitely imply a conformational change in the calixarene
unit on cation-induced anion binding, and may indicate an
enhancement of cation binding strength as the anion is added;
certainly the complex 1?KCl is solely in the cone conformation with
little in the way of conformational lability. Similar conformational
changes are seen for LiCl, NaCl and NH4Cl recognition. These
observations reinforce the suggestion of cooperative binding
behaviour obtained from the UV-visible spectroscopic experiments.
These results lead us to propose that the new ditopic receptor 1
behaves in a manner consistent with the model calculations
outlined above, that is it binds appropriate group 1 metal and
ammonium chlorides as contact ion-pair species. This would
account for the remarkable enhancement of both cation and anion
recognition observed in the presence of an appropriate cobound
guest. To the best of our knowledge, this system provides the first
evidence of a neutral macrocyclic contact ion-pair binding system
{ Crystal data for 1: Chemical formula C54H59N3O10; M = 910.08;
¯
T = 150 K; triclinic; space group P1; a = 10.0261(3), b = 12.5372(4), c =
˚
˚
20.4416(6) A; a = 102.137(3), b = 94.601(3), c = 20.4416(6)u; V =
3
2442.24(14) A ; Z = 2.00; m = 0.085 mm21; 22 001 reflections measured;
11 760 unique reflections; Rint = 0.030; R (wR) = 0.0447 (0.0514) for the
5735 unique data with I > 3s(I) and 612 parameters. CCDC 289857. For
crystallographic data in CIF or other electronic format see DOI: 10.1039/
b515634c
§ All titrations conducted in CD3CN solution at 298 K. Halide added as
TBAX. Metal cations added as MPF6 salt except for Li+ and Na+, where
the ClO42 salts were used. At >1 equivalent of added Cl2 in the cases of K,
Li and NH4 vs. TBACl titrations peak broadness led to significant errors in
the chemical shift plotted. For Na the broadening was so severe only an
extrapolation of dNH was possible (see Fig. 5).
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Scheme 2 Summary of potential CH3CN solution equilibria for e.g.,
M = NH4, X = Cl. For M = potassium, K39 and, by implication, K3,
are >0. L = 1 in this case. N.B. equilibrium M+
+ X2
= MX(sol) is
(sol)
(sol)
also possible.10
614 | Chem. Commun., 2006, 612–614
This journal is ß The Royal Society of Chemistry 2006