Imidazolium-based catenane host for bromide recognition in aqueous media

Article abstract of DOI:10.1039/d0cc06299e

The synthesis of a novel catenated system which is dense in cationic hydrogen bonding imidazolium units is described. The interlocked host system displays a preference for binding of bromide over other halides, overcoming basicity and Hofmeister trends, u

Full text of DOI:10.1039/d0cc06299e

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Imidazolium-based catenane host for bromide recognition in
aqueous media
Christopher J. Serpell,*a,b Ah Young Park,b Carol V. Robinson,b and Paul D. Beer*b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The synthesis of a novel catenated system which is dense in cationic therefore that rotaxane hosts for both cation and anion guest species
hydrogen bonding imidazolium units is described. The interlocked greatly outnumber their catenane host counterparts.3 We were
host system displays a preference for binding of bromide over other therefore interested in combining the topological contraints of
halides, overcoming basicity and Hofmeister trends, under aqueous catenated hosts with a high density of imidazolium C-H hydrogen
conditions. This is the first example of an imidazolium-based bond donors. Herein we report the first imidazolium-based catenane
catenane acting as an anion host through C-H hydrogen bonding.
6, which has a dense core of four imidazolium hydrogen bonding
units (Fig. 1) and displays a rare unconventional preference for
bromide over other halides in aqueous media.
The achievement of selective anion recognition in aqueous media is
challenging due to the competitive nature of the solvent and
Hofmeister-biased selectivity preferences.1 Inspired by the creation
of solvent-excluded binding pockets in anion-binding proteins,2 we
are pursuing the creation of precise cavities within interlocked
architectures (catenanes and rotaxanes) as a strategy for selective
anion binding.3 The imidazolium unit combines a positive charge and
directional hydrogen bonding with chemical stability and synthetic
versatility - factors which have led to its use in many anion binding
systems,4–6 stretching back over many years.7 These properties make
imidazolium a promising candidate for selective anion binding under
aqueous conditions, and indeed usage of multiple imidazolium units
permits binding of anions in competitive media including water.8–10
It is also possible to obtain a high density of imidazolium units within
a molecular structure, separating them by only a methylene unit.11,12
These observations highlight an opportunity for creation of
imidazolium-rich interlocked molecules for binding anions, and while
a handful of imidazolium rotaxanes have been constructed for anion
binding13–15 (and also for other purposes8,16–19), there is currently
only one example of an imidazolium-based catenane, and that uses
halogen bonding rather than direct C-H hydrogen bonds.20 Because
of the additional cyclisation in catenanes as compared to rotaxanes,
the binding cavity in a catenane host structure is potentially both
better defined (due to loss of conformational freedom), and more
shielded from solvent (due to mutual encircling). It is suprising
Figure 1. (a) Formation of an anion-binding cavity in an imidazolium-rich catenane.
(b) Catenane 6.
I
-
2PF6
Cs2CO3, Cu2
O
N
N
I
Salicylaldoxime
Ascorbic acid
71%
K2CO3
KI
N
O
O
O
O
i) CH2I2, MW
ii) NH4PF6
N
N
98%
O
O
2
4
O
O
OH
3
H
N
19%
N
O
OTs
N
1
TBACl
1:1
-
-
-
PF6
2PF6
PF6
N
N
O
O
O
O
N
O
O
O
O
O
O
O
O
N
H
N
N
NH4PF6
21%
Grubbs II
N
N
H
Cl-
Cl-
H
5
H
H
N
H
N
N
N
1:2
-
-
-
4PF6
3PF6
3PF6
N
N
O
O
N
O
O
O
Grubbs
II
O
N
N
O
N
N
O
N
N
O
NH4PF6
33%
O
N
O
O
N
O
H
H
H
N
N
N
N
H
H
Cl-
H
H
N
N
Cl-
H
6
H
H
H
H
O
O
O
O
O
N
N
N
N
O
O
O
O
O
N
N
O
N
Scheme 1. Synthesis of macrocycle 5 and catenane 6.
To prepare the target catenane 6, an anion-template synthetic
strategy21 was adopted (Scheme 1). Tosylated allyloxyethanol 1
was attached to 3-iodophenol in the presence of potassium
carbonate and catalytic potassium iodide in DMF with the
product 2 being obtained almost quantitatively. Hetero-
Ullmann coupling was used to substitute the iodine, giving the
a. School of Physical Sciences, Ingram Building, University of Kent, Canterbury, CT2
7NH, UK.
b. Chemistry Research Laboratory, Department of Chemistry, University of Oxford,
Mansfield Road, Oxford, OX1 3TA, UK.
Electronic Supplementary Information (ESI) available: synthesis and
characterisation,
crystallography,
and
mass
spectrometry.
See
DOI: 10.1039/x0xx00000x
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imidazole compound 3 in 71 % yield. This was then reacted with the PF6- salts as white precipitates after removal of the organic
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DOI: 10.1039/D0CC06299E
diiodomethane under microwave irradiation in a sealed vial in solvent. These results confirm the expected effect of the
acetonitrile to afford, after anion exchange with aqueous chloride anion template stoichiometry on the selectivity of the
NH4PF6, 4 as a pure white crystalline solid in 19 % yield.
cyclisation reaction to form either the macrocycle or catenane
Crystals of 4 suitable for X-ray diffraction were obtained for product.
both its 2PF6 (see Supplementary Information) and PF6 .Cl- salts Both 5 and 6 were characterised by H and 13C NMR and HR-
-
-
1
1
by slow diffusion of diisopropyl ether into acetonitrile solutions. ESMS. In the catenane H NMR spectrum the imidazolium and
In the latter case, chloride was administered as one equivalent methylene bridge peaks are shifted downfield compared to the
of its tetrabutylammonium (TBA) salt. The structure of the macrocycle (Fig. 3a), probably due to their enforced proximity
monochloride salt of 4 (Fig. 2) reveals the chloride anion to the polyether oxygen atoms. The alkene peak (H12) is not
bridging two imidazolium molecules, via hydrogen bonds from split, indicating the formation of just one isomer – most likely
the 2- and 4-positions, of which the C2 interaction is the shorter. the trans olefin.
-
In this structure the PF6 anion sits close to the imidazolium
groups and takes part in weak hydrogen-bonding and anion-π
interactions. Although the expectation was that the mono-
chloride salt would form a chelate with the halide, this structure
was not observed. Such a result does not preclude the
formation of the chelating structure in solution, since
crystallisation requires the formation of networks of
supramolecular forces, a condition which promotes divergent
hydrogen bonding motifs. The chelating structure has been
observed in the solid state by groups using the methylene-
bisimidazolium unit for other purposes.22–24
Figure 2. X-ray crystal structure of the asymmetric unit of 4. Anisotropic
displacement parameters shown at 50 % probability.
Macrocyclisation and catenation of 4 was performed using 5
wt% Grubbs’ II ring-closing metathesis (RCM) catalyst in
-
dichloromethane. In the absence of any anion other than PF6 ,
only oligomeric products were formed. The introduction of one
equivalent of TBA chloride before the addition of Grubbs’ II
resulted in the formation of the macrocycle 5, in an isolated
yield of 21% after chromatographic purification, as the most
abundant product. Conversely, when the ratio of 4 to chloride
was two, the catenane 6 was the major product, isolated in a
yield of 33 %, together with the macrocycle in 16 % yield.
(Scheme 1). The difference in product distributions according to
presence and stoichiometry of chloride supports the chelating
binding shown in Scheme 1. Separation of the cyclic and
interlocked products was achieved through preparative thin
Figure 3. (a) 1H NMR spectra of macrocycle 5 and catenane 6 (MeCN-d3, 293 K) (b)
X-ray crystal structure of 5 showing: space-filling representation, omitting anions
and disorder; and packing diagram. Thermal ellipsoids shown at 50 % probability.
(c) Mass spectrum of 6 under high energy conditions.
The two species could also be differentiated by their HR-ESMS
spectra. A singly charged peak at m/z 619.1898 (calc. for [M –
PF6]+ 619.1903) indicated the macrocycle, whereas the same
peak was doubly charged for the catenane, and in addition a
new peak at m/z 1383.3466 (calc. for [M – PF6]+ 1383.3465) was
observed (Fig. S10, S14 ESI).
layer
chromatography
eluted
with
14:2:1
acetonitrile/water/KNO3 (aq, sat.). After removal of the
appropriate bands, the products were extracted using a 98:2
mixture of acetone and saturated aqueous NH4PF6, which gave
Single-crystal X-ray diffraction data were obtained for the
macrocycle 5. The large hexafluorophosphate anions preclude
2 | J. Name., 2012, 00, 1-3
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any inclusion within the macrocyclic annulus. Although the of the mass spectrum of macrocycle 5 respectively, matching
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2
DOI: 10.1039/D0CC06299E
cavity appears small (Fig. 3b), this is due to a contracted the modelled value of 147.08 Å . Examination of the [M - 3H -
conformation controlled by crystal packing requirements. A 4PF6]+ peak of 6 gave a collision cross section of 226.18 Å2,
more open conformation would allow the interpenetration slightly closer to the modelled value for the catenane (204.93
necessary to form 6. One remarkable feature of the crystal Å2) than that of the large [1 + 1] macrocycle (248.26 Å2). The
structure is the contrast between the ordered ionic portions technique is capable of differentiating different components in
and the heavily disordered ethylene glycol chains. These are the same peak, and therefore the possibility of a mixture of the
arranged within the crystal giving alternating layers of rigidity topological isomers was eliminated. In addition to the results of
and flexibility. Given this level of disorder, it is remarkable that the anion templating experiments, these mass spectrometric
crystallisation occurred at all. Such properties may explain why experiments add weight to the proposed catenated topology,
it has not been possible to crystallise the catenane 6.
and in anion binding experiments discussed below we
In characterising the catenane, it was important to consider the continued to seek evidence for or against this model.
possibility of forming a topologically isomeric [1 + 1] macrocycle
10.2
instead of the interlocked product. Such a product could have
very similar NMR spectra, and display the same molecular ion
10.1
peaks in ESMS. To investigate this possibility, mass
10
spectrometric techniques were conducted. Firstly, high energy
9.9
ionisation conditions were used to induce fragmentation. The
[1 + 1] macrocycle would be expected to produce fragments of
9.8
Fluoride
various m/z values up to 1383, whereas the catenane should
result in no fragments with 619 < m/z < 1383, since cleavage of
one bond would result in disassembly into fragments no larger
than macrocycle 5.25 Upon raising the energy to the highest
instrumental level (Synapt 1, TRAP collision energy: 200V and
bias 200 V), new peaks could be observed at m/z 945.46,
1091.44, and 1237.42 (Fig. 3c). It was found that these
corresponded to the sequential loss of HPF6 moieties –
presumably due to deprotonation at the imidazolium C2
position, producing a carbene. No other peaks with significant
intensity were observed with 619 < m/z < 1383, in keeping with
the hypothesised catenane topology. The peak at m/z 473.25 is
consistent with a single macrocycle (identical to 5) arising from
fragmentation, but is mixed with a double charged peak from
the catenane at the same m/z.
Further characterisation was sought using ion mobility mass
spectrometry (IM-MS). In this method, ionised molecules enter
a drift tube, in which they are drawn by an applied electric field.
A carrier buffer gas opposes the motion of the ions, resulting in
longer drift times for species with larger cross sections due to
collisions with the He atoms. At the end of the drift chamber is
a mass spectrometer which can identify the exiting species.
Analysis of the time-of-flight through the drift chamber enables
calculation of the collision cross section, and thus a measure of
the size and shape of the molecules. The collision cross section
is rotationally time-averaged and is consequently larger for
prolate molecular ions than spherical analogues. There is
precedent for use of this technique to distinguish between
macrocyclic and catenated isomers.26–29 Energy minimised
(MMFF94) anion-free models of the macrocycle 5, and the
catenated and macrocyclic topological isomers of 6 were
produced (Figure S16, Supplementary Information). The
catenated and macrocyclic topological isomers of 6 should have
different levels of extension and hence different collision cross-
sections. IM-MS was performed focusing on the peaks
corresponding to the imidazolium species flying in the absence
of any anions. Collision cross sections of 147.13 and 148.86 Å2
were measured from the [M - H - 2PF6]+ and [M – 2PF6]2+ peaks
9.7
9.6
9.5
9.4
Chloride
Bromide
Iodide
0
2
4
6
8
10
Equivalents of anion
Figure 4. 1H NMR titration binding curve for halide binding derived from the
imidazolium C2 proton peak for catenane 6 (5:1 MeCN-d3/H2O, 293 K). Black lines
represent the calculated fit (1:1 host:guest model).
1H NMR anion binding experiments were conducted on 5 and 6
in 9:1 MeCN-d3/H2O (Fig. S17-26), to test the capacity of the
charged systems to compete with water. Although the water
present may not be acting as ‘bulk water’ in this medium, it will
compete for coordination of anions (both the intended guest
and the hexafluorophosphate). In both cases, significant
downfield perturbations of the acidic imidazolium C2 proton
peak (up to +0.64 ppm) were observed (Fig. 3, Fig. S27), and the
methylene spacer proton resonances were also sensitive to
addition of coordinating anions, displaying shifts of up to +0.28
ppm. Further evidence in favour of the catenane structure over
the macrocyclic topological isomer can be seen here – it would
be expected that the larger macrocycle would possess chirality
when twisted around an anion, resulting in diasterotopic
splitting of 1H NMR resonances. No such splitting was observed.
Analysis using WinEQNMR30 of the titration data obtained by
monitoring the imidazolium C2 proton determined 1:1
stoichiometric association constants summarised in Table 1.
Amongst the halides, both the macrocycle 5 and the catenane 6
display the greatest preference for bromide, followed by
chloride. Although these two values are close, their standard
deviations do not overlap, indicating a genuine difference. This
preference is contrary to both halide basicity and the
Hofmeister series, and is demonstrative of a size selective
binding domain. The iodide ion is too large, while water
competes more efficiently for the small and more basic fluoride.
It is possible that water remains in the coordination sphere of
the anion when bound, at least for the macrocycle 5. Notably,
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J. Name., 2013, 00, 1-3 | 3
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the catenane binds anions more strongly than the macrocycle
by factors of up to 3.5. Simplistically, a factor of two would be
expected if the increase in binding was purely electrostatic due
to the doubling of the positive charge. The topology of the
cavity can therefore be said to contribute to the enhanced anion
5
6
7
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DOI: 10.1039/D0CC06299E
binding, again consistent with
a catenane structure.
Geometrically controlled selectivity is illustrated by the basic,
trigonal planar acetate being the weakest bound by catenane 6.
8
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C. J. Serpell, J. Cookson, A. L. Thompson and P. D. Beer,
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Anion
F-
Macrocycle 5
82 (2)
163 (2)
171 (6)
145 (5)
Catenane 6
291 (20)
479 (17)
524 (23)
271 (14)
242 (4)
6/5 ratio
3.5
2.9
3.1
1.9
10
11
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I-
AcO-
119 (10)
2.0
12
13
14
15
16
17
18
19
20
21
Table 1 – Association constants (mol-1 dm3) for titration of 5 and 6 with
tetrabutylammonium salts in 9:1 MeCN-d3/H2O (293 K). Errors are given in
brackets. Stacked spectra of these titrations can be found in the Supplementary
Information Fig. S17-S26
In conclusion, the first hydrogen bonding imidazolium catenane
has been prepared via a chloride anion template Grubbs’
catalysed RCM double cyclisation synthesis. Evidence for the
catenated topology is found in the synthetic outcomes with
respect to templating anion stoichiometry, mass spectrometry
(fragmentation and ion mobility), NMR, and anion binding
trends. The catenane is dense in anion-binding functionality and
displayed improved anion recognition properties in competitive
aqueous solvent mixtures when compared to the macrocyclic
analogue. The geometric demands of the interlocked cavity
results in an unusual halide selectivity preference for bromide.
Further elaboration of imidazolium-dense structures may
permit yet stronger and more selective anion coordination in
competitive aqueous media.
Conflicts of interest
There are no conflicts to declare.
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Acknowledgements
C.J.S. thanks Johnson Matthey and the Engineering and
Physical Sciences Research Council for a CASE Studentship.
25
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4 | J. Name., 2012, 00, 1-3
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A tetracationic imidazolium-based catenane is reported which is selective for bromide over other
halides in aqueous media.