Modulation of Bambusuril Anion Affinity in Water

Article abstract of DOI:10.1002/chem.201701316

Neutral and negatively charged anion receptors functioning in pure water are rare in supramolecular chemistry. Moreover, studies on adjusting the affinity of such receptors toward anions in water are absent from the literature. Two new bambusurils, 1 a and 2 a, were prepared to demonstrate that the affinity of bambusurils towards anions can be altered by the length of carboxyalkyl groups attached to the macrocycles. The stability of the bambusuril complexes was further controlled by the pH value. The crystal structure of bambusuril 1 a was described, in which two carboxyalkyl arms fold into the macrocycle cavity, thus forming the intramolecular self-inclusion complex.

Full text of DOI:10.1002/chem.201701316

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Title: Modulation of Bambusuril Anion Affinity in Water
Authors: Václav Havel, Michal Babiak, and Vladimir Sindelar
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Modulation of Bambusuril Anion Affinity in Water
Vaclav Havel,[a, b] Michal Babiak,[a, c] and Vladimir Sindelar*[a, b]
Abstract: Neutral and negatively charged anion receptors
functioning in pure water are rare in supramolecular chemistry.
Moreover, studies on adjusting the affinity of such receptors toward
anions in water are absent from the literature. We prepared two
novel bambusurils, 1a and 2a, to demonstrate that the affinity of
bambusurils towards anions can be altered by the length of
carboxyalkyl groups attached to the macrocycles. The stability of
bambusuril complexes was further controlled by the pH. The crystal
structure of bambusuril 1a is described in which two carboxyalkyl
arms fold into the macrocycle cavity, forming the intramolecular self-
inclusion complex.
potent anion receptors functioning in water, there are almost no
reports dealing with tuning of the stability of such host–guest
complexes in the same medium. The ability to adjust the
association between host and guest is however crucial for the
applicability of these systems in the fields of biology and
medicine. Miller and co-workers reported
a receptor that
displays moderate anion affinity in a narrow pH window and no
binding outside of this pH range due to a disruption of hydrogen
bonds that stabilize the conformation of this system.[19] Gibb et al.
-
have recently shown that the apparent stability of ClO4 inside
octa-acid macrocycles in water can be varied by the addition of
different salts into a solution of the complex.[20]
Introduction
Binding of anions in water using synthetic receptors is one of the
most urgent topics in supramolecular chemistry.[1–4] Despite
recent progress in the field of synthetic anion receptors, the
majority of binding studies were performed in organic solvent
while similar studies in water are less reported. Lack of
receptors functioning in water is caused by the high energy of
solvation of anions by water molecules, which successfully
compete with the receptors. Thus most receptors bind anions in
water due to the presence of positive charges or metals in their
Figure 1. Structures of studied and discussed bambusuril derivatives.
structure.[5,6] However, these receptors function only in
a
restricted pH window and their anion selectivity is rather low.
The first examples of receptors featuring of neutral binding
pocket with modest affinity and selectivity towards anions in
water were reported only recently. These examples include
Kubik’s peptide macrocycle,[7] Jeong’s foldamer,[8] Beer’s
rotaxanes,[9,10] and Pittelkow’s biotin[6]uril.[11,12] These receptors
benefit from multiple N-H···A-, C-H···A-, and C-X···A- hydrogen
bonding interactions and classical combined with non-classical
hydrophobic effects.[13–16]
Here we report new water soluble bambusuril derivatives 1a and
2a and demonstrate that the binding affinity of these
macrocycles to inorganic anions in water can be modulated not
only by the type of substitution on the macrocycle but also by
changing the pH of their water solutions.
Results and Discussion
Our contribution lies in the preparation of bambusuril 3, which is
soluble in neutral and basic water due to the presence of
multiple carboxylate groups.[17] We showed that this negatively
charged macrocycle binds inorganic anions with affinities of up
Macrocycle 1a was prepared by a synthetic route resembling the
one used for derivative 3,[17] but with a major difference in the
macrocyclization conditions. The glycoluril monomer was used
directly in the form of carboxylic acid instead of its ester.
Furthermore, the reaction was performed in 1,4-dioxane in the
presence of sulfuric acid. The acid acted as a catalyst but also
to 107 M-1 (for I- and ClO4 ) and exceptional selectivity, for
-
example, 60,000 for ClO4- over Cl-. Bambusuril 3 was also used
1
for recognition of multiple anion mixtures in conjunction with H
NMR.[18]
-
generated HSO4 anions, which drove macrocyclization towards
While great scientific efforts have been devoted to the design of
a six-membered bambusuril. There is one major advantage in
the use of the HSO4 template compared to the halides
-
previously used in bambusuril synthesis. Bambusuril complexes
with halides are very stable in organic solvents as well as water.
This complicates the release of the halide template from the
bambusuril cavity after the reaction.[17,21,22] On the other hand,
[a]
[b]
[c]
V. Havel, M. Babiak, Assoc. Prof. V. Sindelar
Department of Chemistry, Masaryk University, Faculty of Science
Kamenice 5, 625 00 Brno, Czech Republic
E-mail: sindelar@chemi.muni.cz
V. Havel, Assoc. Prof. V. Sindelar
-
while stability of the bambusuril–HSO4 complex in low polar
RECETOX – Research Centre for Toxic Compounds in the
Environment, Masaryk University, Faculty of Science
Kamenice 5, 625 00 Brno, Czech Republic
M. Babiak
CEITEC – Central European Institute of Technology and National
Centre for Biomolecular Research, Masaryk University
Kamenice 5, 625 00 Brno, Czech Republic
solvent is high (Ka ≈ 107 in CHCl3)[22], it is almost negligible in
-
2-
water due to conversion of HSO4 into highly hydrated SO4
anion. Thus the anion-free 1a was obtained by dissolving the
complex in basic water and subsequent precipitation of the
macrocycle by the addition of milder acid. This procedure
allowed gram-scale synthesis (3.8 g) of 1a in yields of up to 62%
without any column separations.
Supporting information for this article is given via a link at the end of
the document.
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Scheme 1. Synthesis of carboxyalkyl bambusuril macrocycles 1 and 2, best isolated yields are indicated in brackets.
1H NMR was used to evaluate the supramolecular properties of
1a in water. The experiments were conducted in D2O at pD 7.5,
which guaranteed good solubility of the macrocycles due to a
partial deprotonation of carboxyl groups on the portals.
Phosphate buffer was selected, as bambusuril macrocycles
have no affinity towards highly hydrated phosphate anion. We
selected Br- and I- as model anions to study the binding affinity
of 1a toward inorganic anions. 1H NMR experiments revealed
that the kinetics of binding differs between these two anions.
Gradual addition of Br- to 1a solution resulted in a continuous
shift of bambusuril proton resonances, indicating that the anion
inclusion is fast on the NMR time scale. In contrast, in the
presence of 0.5 equiv. of I-, signals of free and bound
macrocycles were present, showing the slower kinetics of
binding (see Figures S31-S35). Bambusuril 1a is, after 3,[17] the
only bambusuril with a good solubility in water that allows
comparison of supramolecular properties of these two
macrocycles in this environment. Surprisingly, anion complexes
of bambusuril 3 were 10 times stronger compared to those of
bambusuril 1a under similar experimental conditions (Table 1).
We decided to rationalize these differences in binding affinities.
complexes of bambusurils stabilized by hydrogen bonding
between anions and water were published previously.[23,24]
Table 1. Comparison of association constants (Ka [M-1]) obtained from NMR
for the formation of 1a, 2a and 3 (1 mM) Br- and I- complexes in D2O
(K2DPO4 20 mM, pH*= 7.1, pD = 7.5) at 30°C.
Ka [M-1]
Anion
1a
2a
3
Br-
I-
(1.7 ± 0.2)·103
(1.1 ± 0.1)·106 [a]
(2.4 ± 0.1)·102
(2.1 ± 0.1)·105
(1.4 ± 0.1)·105 [a]
(1.0 ± 0.1)·107 [a]
[a] Association constant was determined by a competition experiment in the
presence of an excess of competing anion (TMABr for 1a and NaCl for 3).
Figure 2. Crystal structure of macrocycle 1a. Carboxyalkyl substituents other
than those forming a self-inclusion complex are shown as thin lines. Solvent
molecules except the water molecule inside the macrocycle are omitted for
clarity. Color coding: C, gray; H, white; O, red; N, blue.
The first hint of the explanation came from the crystal structure
of 1a (Figure 2). Crystals were obtained from CH3CN/H2O
solution by slow evaporation of solvent in the absence of anions.
In the structure, two aliphatic arms, each located on one of two
opposed portals, are folded into the 1a cavity, forming an
intramolecular inclusion complex. The folding is probably caused
by terminal carboxylates of these two arms, which are attracted
by the cavity interior with low electron density. One molecule of
water located in the cavity center further stabilizes this
intramolecular complex by formation of a bridge between two
carboxylates based on O- H···O- hydrogen bonding with an
average distance between oxygen atoms of 2.82 Å. Similar
While folding of flexible aliphatic arms of 1a is documented by
the X-ray structure obtained, the similar folding in the case of
bambusuril 3 is unlikely to be due to the rigidity and bulkiness of
p-carboxybenzyl groups. Carboxylate groups of folded arms in
the intramolecular complex of 1a can compete with the anions of
interest, resulting in lower apparent binding of 1a compared to 3.
To verify this hypothesis, we prepared the derivative 2a bearing
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3-carboxypropyl substituents that are too short to bend. This
precludes the formation of an intramolecular complex for
derivative 2a. However, we found that the receptor 2a displayed
even lower anion affinity than 1a (Table 1 and 2), which
Clearly there must be a reason for the different binding affinities
of 1a, 2a, and 3 besides the intramolecular complex formation.
The most likely hypothesis at this stage is that carboxyalkyl
derivatives (1a and 2a), decorated with flexible negatively
charged groups, are more effective at repulsing the anionic
guests compared to the rigid p-carboxybenzyl groups in the case
of 3. The same explanation can be applied for different affinities
of 1a and 2a, as shorter alkyl chains with carboxylates at a
closer distance to the central binding site of 2a are more
effective in the repulsion of anions.
To discover the influence of negatively charged carboxylates on
bambusuril binding, we performed a series of experiments in
which values of Ka for the complexes of I- and receptors 1a and
2a were measured at different deprotonation states of the
macrocycles. As the macrocycles are poorly soluble in water at
low pH (when the majority of carboxylates are protonated), we
performed our experiments in 1:1 CH3CN/H2O solutions.
Additions of TMAOH into the solution of 1a and 2a receptors
were used to study their anion affinity at varying degrees of
deprotonation. We also performed pH titrations of 1a and 2a to
see whether it is possible to correlate the equivalents of added
base to the amount of deprotonated groups. As expected, the
contradicted our expectation. We selected Br-, NO3 , I- and ClO4
-
-
as model anions to further study the binding affinity of 1a and 2a
toward inorganic anions by isothermal titration calorimetry (ITC)
in water at pH 7.2. We found that the supramolecular properties
of both bambusurils are very similar, e.g. the complex formation
is driven by enthalpy and display a 1:1 stoichiometry, likewise
macrocycles selectivities for studied anions follows similar
trends (Table 2). The observed trends in thermodynamic
parameters can be rationalized as a combination of two driving
forces that were recently described in literature. The chaotropic
effect aims to explain the enthalpically driven inclusion of water
bond breaking guests (chaotropes, e.g. iodide and perchlorate)
into a host cavity.[14] It is also expected that a non-classical
hydrophobic effect influences the observed thermodynamic
parameters, as before the inclusion of a studied guest the cavity
contains high energy water molecules.[15]
Please note that given the presence of twelve carboxylic groups
on the studied receptors it is difficult to ensure identical
conditions in H2O (pH) and D2O (pH*/pD) while maintaining the
same cation and anion concentration. Moreover, the necessity to
employ competition experiments for the NMR determination of
binding constants for several anions create a large disparity in
ionic strengths for NMR and ITC experiments. We suspect this is
the reason for the observed difference between NMR and ITC
experiments. In light of the fact that this system is highly
influenced by variation in experimental conditions (ionic strength,
pH, concentration of macrocycle, etc.) the observed association
constants are apparent and valid only under the exactly same
measurement conditions.
macrocycles behaves as
a weak polybasic acid with an
equilibrium point observed at 12 or 14 equiv. of added base
(Figure 3). The equivalence point depends on the studied
derivative and also the solvent system used. Please note, that
the equivalence point could also mean that after the addition of
12 (14) equivalents of base the most deprotonable form of 1a
(2a) is formed. This form does not have to necessarily
correspond to the 1a12- (2a12-) form. Titration curves for 2a
suggests that deprotonation of 2a macrocycle is even more
difficult than 1a derivative, especially in pure water.
Table 2. Experimental data obtained from ITC for the formation of 1a and 2a
(1 mM) anion complexes in aqueous phosphate buffer (30 mM, pH = 7.2) at
30°C.
ΔH°
TΔS°
Complex
Ka [M-1]
[kJ·mol-1]
[kJ·mol-1]
[a]
1a·Br-
(2.8 ± 0.2)·103
(2.7 ± 0.2)·103
(4.5 ± 0.1)·103
(3.7 ± 0.3)·105
(8.1 ± 0.4)·105
(3.6 ± 0.1)·102
(1.0 ± 0.2)·103
(7.4 ± 0.7)·104
(1.1 ± 0.1)·105
-27.7 ± 2.1
-32.2 ± 2.8
-41.0 ± 3.8
-57.3 ± 3.9
-68.0 ± 2.5
-40.9 ± 0.6
-46.5 ± 0.6
-63.5 ± 1.5
-64.6 ± 3.4
-7.7
1a·Br- [b]
-12.3
-19.8
-25.0
-33.7
-26.1
-29.1
-35.3
-35.4
-
1a·NO3
1a·I-
-
1a·ClO4
2a·Br-
-
2a·NO3
2a·I-
Figure 3. Acid-base titration of macrocycles 1a and 2a (0.5 mM) in 50%
CH3CN/H2O and macrocycle 2a (0.1 mM) in H2O with TMAOH solution,
equivalence point was indicated by pH measurement. Important points are
highlighted (1:1 CH3CN/H2O in red and H2O in blue).
-
2a·ClO4
[a] Experimental data suffer
a higher uncertainty, not reflected by the
reproducibility, due to a poor fit of the titration curve to a 1:1 binding model
when the stoichiometry is constrained. [b] Measured by a single injection
method at a concentration of 1a (5 mM) and phosphate buffer (0.15 M), titration The obtained results summarized in Table 3 confirmed the
curve displays
performed in duplicate.
a good fit to a 1:1 binding model. All experiments were
expected trend that a higher number of negative carboxylate
groups results in lower anion affinity of the receptors. Please
note that Ka obtained after the addition of 28 equiv. is higher
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compared to the Ka measured after the addition of 14 equiv.
This is the result of increasing cation (TMA) concentration. The
cations interact with carboxylates of bambusurils and
compensate overall negative charge of the macrocycles.[20] This
also proves that the hydroxide anion which is a very hydrophilic
anion has only negligible affinity for bambusuril under the
experimental conditions and is not primarily responsible for the
decrease in affinity.
After defining the effect of substitution on the binding of anions
in CH3CN/H2O, we pursued the modulation of bambusuril
affinity by a change of pH in pure water. 2a with moderate
solubility in neutral water (1.5·10-4 M) was selected for this study,
as 1a is only sparingly soluble (>4·10-5 M) at the same media.
The solution of 2a at 0.1 mM concentration was prepared,
resulting in pH of 4.0. The pH change to 7.2 and 10 was
achieved by addition of TMAOH. Stability of the complexes
between 2a and anions was found to be the highest at pH 4.0
and decreased when the pH was adjusted to 7.2 and 10.0
(Table 4). Thus, the stability of the 2a complex can be tuned in
water in the same manner as it was shown in the CH3CN/H2O
mixture.
Table 3. Experimental data obtained from ITC for complexes of 1a,b and 2a,b
with tetramethylammonium iodide (TMAI) in 1:1 CH3CN/H2O solution at
various concentrations of TMAOH at 30°C.
TMAOH
(equiv)
ΔH°
TΔS°
Host
Ka [M-1]
[kJ·mol-1]
[kJ·mol-1]
Table 4. Association constants obtained from ITC for the formation of 2a
complexes in acidic, neutral and basic water at 30°C.
1a
1a
1a
1a
2a
2a
2a
2a
1b
2b
0
(4.2 ± 0.4) × 105
(3.1 ± 0.4) × 104
(1.5 ± 0.1) × 104
(3.0 ± 0.4) × 104
(2.0 ± 0.1) × 105
(3.5 ± 0.1) × 103
(2.4 ± 0.1) × 103
(4.4 ± 0.1) × 103
(1.4 ± 0.1) × 106
(1.0 ± 0.1) × 106
–35.2 ± 0.9
–45.7 ± 1.8
–57.5 ± 2.5
–56.1 ± 1.5
–35.7 ± 0.7
–49.5 ± 1.4
–52.9 ± 1.3
–53.5 ± 0.5
–45.4 ± 1.0
–39.6 ± 0.8
–2.5
6
–19.6
–33.2
–30.1
–5.0
Complex stability Ka [M-1]
pH
-
-
14
28
0
NO3
I-
ClO4
4.0
(9.6 ± 0.6) × 103
≈100[a]
(3.0 ± 0.2) × 105
(1.8 ± 0.4) × 104
(1.3 ± 0.3) × 104
(1.2 ± 0.1) × 106
(4.1 ± 0.5) × 104
(1.1 ± 0.2) × 104
7.2
---[b]
6
–28.9
–33.3
–32.3
–9.8
10.0
14
28
0
[a] Due to a small difference between the titration and a blank experiment, the
association constant was only estimated. [b] No appreciable binding was
detected after the subtraction of dilution heats from the experimental data (Ka <
10 M-1). All experiments were performed in duplicate.
0
–4.8
All experiments were performed in duplicate.
Conclusions
The importance of the distance of carboxylate groups from
bambusuril portals for anion binding can be documented when
Ka for the iodide complexes of 1a and 2a in the presence of 14
equiv. of TMAOH is compared (Table 3). Under these conditions
both macrocycles are deprotonated. The affinity of 1a to iodide
was found to be six times higher compared to the complex of 2a
with the same anion. Similar difference in the iodine binding for
both macrocycles was realized also in pure water (Table 1 and
2). Lower stability of the 2a·I- complex can be rationalized by
smaller distance of carboxylate groups from its portal compared
to that one in 1a. Thus carboxylates in 2a are more effective in
anion repelling than in 1a. Finally, values of Ka for both ester
derivatives, 1b and 2b, are nearly identical (Table 3). This
further proves that the observed differences in affinity of both
macrocycles are indeed the result of electrostatic repulsion of
the macrocycles and anions.
In summary, we reported the high-yield preparation of two
bambusuril derivatives, 1a and 2a, with different carboxyalkyl
substituents on their macrocyclic portals. NMR and ITC were
used to evaluate their supramolecular properties in water. Our
study revealed that the affinity of bambusuril receptors bearing
carboxylic groups towards anions can be modulated by the pH
of water solution. Moreover, a change in the stability of
bambusuril complexes with anions of more than two orders of
magnitude was achieved through the choice of spacer between
the glycoluril nitrogen atoms and the carboxylic groups within the
macrocycle. Thus our work has demonstrated that not only can
bambusurils bind inorganic anions with unprecedentedly high
affinities in water but also the affinity can be tuned by the choice
of substituents on macrocycle portals and external conditions
such as pH.
We investigated the affinity of 1b towards carboxylates, but no
binding was observed in 1:1 CH3CN/H2O (see Figure S72-S73).
The formation of self-inclusion complex in solution was
investigated by measuring 2D NMR experiments (ROESY). Two
pairs of experiments were conducted. Spectra for 1a and 1a∙NaI
complex were recorded in DMSO-d6 and for 1a and 1b in 1:1
CH3CN/H2O (S15 and S16). In both cases however, no
significant difference was observed between the two spectra.
Experimental Section
Dodeca(5-carboxypentyl)bambus[6]uril 1a
2,4-Bis(5-carboxypentyl) glycoluril (6 g, 16.2 mmol) paraformaldehyde
(0.61 g, 20.3 mmol) were stirred in 1,4-dioxane (24 ml) at 80 °C
(temperature of DrySyn™ heating block). After 10 min 96 % H2SO4 (0.7
ml) was added into the warm mixture. The reaction was further heated
and stirred for 2.5 h. After cooling to RT the mixture was diluted with 1 M
KOH (12 ml) and concentrated on rotavap. Oily material was dissolved in
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1 M KOH (100ml), diluted with water to volume 300 ml and precipitated
with 1 M H3PO4 (~100ml to pH 1-2). The solid material was collected by
filtration and washed with water (3x50 ml). The KOH/H3PO4 precipitation
was repeated one more time. After second filtration the solid was washed
with water (3x50 ml) and after air drying it was washed with diethyl ether
(25 ml) to prevent conglutination during vacuum drying. After drying this
mixture (5.6 g) of 1a with R8BU[4] (10 %) was stirred in acetone (60 ml)
for one day. Solid material at first becomes gum like substance, but later
solidifies (large pieces of material were disintegrated by ultrasound and
crushed with spatula). The solid was collected by filtration and washed
with acetone (2x10ml) and Et2O (20 ml). After vacuum drying white solid
(4.4 g) still contained 1a with R8BU[4] (4%). Material was homogenized
by mixing it with acetonitrile (50 ml) and adding water until complete
dissolution. Solution was filtered and evaporated to dryness. After drying
in vacuum the solid material was further stirred in acetone (60 ml) and
next day it was collected by filtration. After filtration it was washed with
acetone (2x10 ml) and with diethyl ether (20 ml). After vacuum drying the
product was obtained as an off white solid in yield (3.84 g, 62 %). The
purity of the product was estimated by 1H NMR in DMSO-d6 (integration
with internal standards hydroquione and TBAI) to be >95 %, this
corresponds to a molecular weight ~ 2395 g·mol-1.
collected and the solids were combined. Solid material was dried from
water on air, washed with Et2O (2x10 ml) and dried in vacuum.
Derivative 2a was obtained as a white solid (127 mg, 41%). This batch
molecular weight corresponded to the theoretical value within
experimental error ≈2%.
Please note that it is sometimes more difficult to force 2a to solidify from
its gum like form, even when the crude mixture appears to contain only
2a macrocycle and the corresponding R8BU[4] derivative.
1H NMR (500 MHz, DMSO-d6) δ 11.88 (s, 12H), 5.35 (s, 12H), 4.83 (s,
12H), 3.49 (s, 12H), 3.39 (s, 12H), 2.21 (s, 24H), 1.88 (s, 12H), 1.74 (s,
12H). 13C NMR (126 MHz, DMSO) δ 174.1, 158.9, 158.5, 68.4, 47.6, 43.0,
31.0, 23.4. MALDI-TOF MS: for [C78H108N24O36
+
K]+ theoretical:
1995.700, experimental: 1995.699 ± 0.007. Melting point: 202 - 206 °C.
Dodeca(methyl-3-propylcarboxylate)bambus[6]uril 2b
2a (0.1 g, 0.051 mmol) was dissolved in MeOH (10 ml) with PTSA (9.3
mg, 0.049 mmol) and the solution was left standing in sealed reaction
vessel for 8 days. MeOH was evaporated and the residue was dissolved
in DCM (20 ml). Solution was washed with 5 % NaHCO3 (2x50 ml) and
water (50 ml). Centrifugation was used to speed up the phase separation.
DCM was evaporated and product was dissolved in CH3CN and
evaporated again. After drying in vacuum the ester was obtained as a
slightly sticky solid (92 mg, 84%). After esterification the molecular weight
corresponds to theoretical value. The ester derivative 2b is not stable in
chloroform solution and hydrolyzes more readily than 1b (see figure S29).
1H NMR (500 MHz, CD3CN) δ 5.34 (s, 12H), 4.88 (s, 12H), 3.63 – 3.54
(m, 48H), 3.50 – 3.41 (m, 12H), 2.37 – 2.28 (m, 24H), 2.01 – 1.95 (m,
12H), 1.88 – 1.79 (m, 12H). 13C NMR (126 MHz, CD3CN) δ 174.4, 160.3,
160.1, 69.6, 52.1, 49.5, 44.2, 31.9, 24.6. MALDI-TOF MS: for
[C90H132N24O36 + Na]+ theoretical: 2147.913, experimental: 2147.912 ±
0.002. Melting point: 66 - 69 °C.
The preparation was performed two times at lower scale (3 g of starting
glycoluril) under same reaction and similar isolation conditions. The
yields were (1.87, 58%) and (1.67, 52%). All batches displayed same
supramolecular behaviour after their corresponding molecular weight was
determined.
The acetone washing fractions contain 1a and R8BU[4] in approximately
1:1 ratio and this mixture can be separated by column chromatography
(MF - THF). After complete elution of R8BU[4] 1a is eluted by MeOH
(partial ester formation – must be hydrolyzed).
1H NMR (500 MHz, DMSO-d6) δ 11.95 (s, 12H), 5.26 (s, 12H), 4.80 (s,
12H), 3.62 – 3.43 (m, 12H), 3.43 – 3.20 (m, 12H), 2.18 (t, J = 7.3 Hz,
24H), 1.70 (s, 12H), 1.50 (d, J = 6.6 Hz, 36H), 1.39 – 1.15 (m, 24H). 13
C
NMR (126 MHz, DMSO) δ 174.3, 158.8, 158.5, 68.2, 47.8, 43.4, 33.6,
27.8, 25.8, 24.1. MALDI-TOF MS: for [C102H156N24O36 +Na]+ theoretical:
2316.101, experimental: 2316.103 ± 0.018. Melting point: 163°C collapse
of particles to amorphous (gum like) solid 169-174 °C liquid.
Acknowledgements
This work was supported by the Czech Science Foundation (13-
15576S) and MEYS CR (projects LM2011028 and LO1214). We
acknowledge the CEITEC Core Facilities supported by the
CIISB research infrastructure (LM2015043, funded by MEYS
CR) for their support in obtaining the scientific data presented in
this paper.
Dodeca(5-methoxy-5-oxopentyl)bambus[6]uril 1b
1a (0.2 g, 0.087 mmol) was dissolved in MeOH (20 ml) with PTSA (16.6
mg, 0.087 mmol) and the solution was left standing in sealed reaction
vessel for 3 days. MeOH was evaporated and the residue was dissolved
in DCM (15 ml). Solution was washed with 10 % NaHCO3 (20 ml) and
water (3x20 ml). Centrifugation was used to speed up the phase
separation. DCM was evaporated and product was dissolved in CH3CN
and evaporated again. After drying in vacuum the ester was obtained as
viscous oil that slowly crystalize to sticky solid (0.19 g, 87%). After
esterification the molecular weight corresponds to theoretical. The ester
derivative 1b is not stable in chloroform solution and slowly hydrolyzes
(see figure S19).
1H NMR (500 MHz, CDCl3) δ 5.47 (s, 12H), 4.76 (s, 12H), 3.63 (s, 48H),
3.44 – 3.34 (m, 12H), 2.30 (t, J = 7.4 Hz, 24H), 1.82 – 1.76 (m, 12H),
1.68 – 1.52 (m, 36H), 1.38 – 1.27 (m, 24H). 13C NMR (126 MHz, CDCl3)
δ 173.9, 159.4, 159.1, 77.4, 77.4, 77.2, 76.9, 69.3, 51.6, 48.7, 44.1, 34.0,
28.0, 26.4, 24.6. MALDI-TOF MS: for [C114H180N24O36 +Na]+ theoretical:
2484.289, experimental: 2484.290 ± 0.003. Melting point: liquid > 100 °C.
Keywords: anion recognition • macrocycles • bambusurils • self-
assembly • supramolecular chemistry
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Bambusuril affinity towards
inorganic anions in water is tuned by
the pH of their solutions and
distances of solubilizing carboxylates
functions from the macrocycle
portals.
Vaclav Havel, Michal Babiak, and
Vladimir Sindelar*
Page No. – Page No.
Modulation of Bambusuril Anion
Affinity in Water
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