Dimeric molecular clips based on glycoluril

Article abstract of DOI:10.1039/c7nj00969k

Glycoluril dimers 4a and 4b were prepared and successfully transformed to glycoluril dimeric clips 7a and 7b. ¹H NMR spectroscopy was used to reveal that the dimeric clip 7b with methyl substituents in its structure exists as a mixture of two distinct conformers in D₂O at ambient temperature, while 7a possesses only one stable conformer under the same conditions due to its bulky phenyl substituents. The coalescence temperatures for 7b and its precursor 5b were determined. Both dimeric clips 7a and 7b formed complexes with methylviologen in D₂O in which each of two clip-binding sites was occupied by one molecule of the guest. Thus, this study uncovers possible use of glycoluril dimers 4a and 4b as general building blocks for glycoluril-based supramolecular host molecules with two binding sites in their structure.

Full text of DOI:10.1039/c7nj00969k

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Dimeric molecular clips based on glycoluril†
Jan Sokolov, Tomas Lizal and Vladimir Sindelar
*
Cite this:DOI: 10.1039/c7nj00969k
Glycoluril dimers 4a and 4b were prepared and successfully transformed to glycoluril dimeric clips 7a
1
and 7b. H NMR spectroscopy was used to reveal that the dimeric clip 7b with methyl substituents in its
structure exists as a mixture of two distinct conformers in D2O at ambient temperature, while 7a
possesses only one stable conformer under the same conditions due to its bulky phenyl substituents.
The coalescence temperatures for 7b and its precursor 5b were determined. Both dimeric clips 7a and
7b formed complexes with methylviologen in D2O in which each of two clip-binding sites was occupied
by one molecule of the guest. Thus, this study uncovers possible use of glycoluril dimers 4a and 4b as
general building blocks for glycoluril-based supramolecular host molecules with two binding sites in
their structure.
Received 23rd March 2017,
Accepted 24th May 2017
DOI: 10.1039/c7nj00969k
rsc.li/njc
investigate whether this structural motif could be suitable for
the construction of cucurbituril-based compounds. As a first
Introduction
Cucurbiturils are an important class of supramolecular host approximation of a cucurbituril derivative, we selected to prepare
molecules that are prized for their ability to strongly and dimeric clip 7a. The successful preparation of this compound
selectively bind organic molecules in water.1–6 These macro- should uncover the possibility of attaching methylene bridges to
cycles consist of glycoluril units connected by methylene nitrogen atoms of sterically hindered glycoluril units of 4a.
bridges. Recent progress in the chemistry of cucurbiturils
enables the preparation of their functionalized derivatives,7–13
which can be covalently attached to various substrates and thus
can be used for real applications. Along with the synthesis of
Results and discussion
cucurbituril derivatives, other supramolecular hosts based on The starting building block 4a for this dimeric clip has already
glycoluril have been prepared, including anionic receptors – been reported.26,27 According to the literature, compound 4a
bambusurils14–16 – and acyclic glycoluril oligomers.17–19 The can be prepared by condensation of urea or urea derivative 8
latter group of compounds features high affinities toward (Fig. 1) with compound 3a in refluxing formic or acetic acid
anaesthetics, nitrosamines and various drugs.20–22 Despite with a catalytic amount of sulfuric acid. However, when the
recent progress in cucurbituril synthesis, there have been only two synthesis was repeated in our laboratory under these condi-
reported approaches dealing with the preparation of cucurbituril tions, only compound 9 with one glycoluril moiety was formed.
dimers. The first is based on the condensation of acyclic glycoluril
Fortunately, the reaction of urea with 3a in toluene in the
hexamers with tetraaldehydes;23,24 the second relies on the conjuga- presence of TFA provided dimer 4a in 95% yield. Compound 4a
tion of two monofunctionalized cucurbiturils.25 These cucurbituril was then transformed to cyclic ether 5a by its reaction with
dimers have been used as building blocks for the construction of paraformaldehyde in aqueous HCl (Scheme 1). Compound 5a
supramolecular polymers and oligomers.
was further reacted with hydroquinone to provide dimeric
We decided to investigate a different approach for the prepara- molecular clip 6 bearing OH groups on its terminal aromatic
tion of dimeric cucurbiturils and their acyclic analogs. Our work walls in 69% yield. Clip 6 was alkylated using 1,3-propanesultone
was inspired by compound 4a (Scheme 1) previously reported in to give water-soluble clip 7a in 68% yield.
the literature.26,27 This compound contains two glycoluril units
The phenyl substituent present in glycoluril dimer 4a can be
connected through phenylene links. Therefore, we wanted to a source of low reactivity and low solubility of this compound,
as previously reported on the corresponding glycolurils for
cucurbituril syntheses.8 Thus, we decided to prepare dimer 4b in
which two phenyls are replaced by methyl substituents. The
synthesis of 4b required precursor 3b, which was not commercially
available (unlike 3a) and had to be prepared from 1,4-diethynyl-
benzene (1) (Scheme 1). Alkyne 1 was deprotonated with
Department of Chemistry and RECETOX, Masaryk University, Kamenice 5,
62500 Brno, Czech Republic. E-mail: sindelar@chemi.muni.cz
† Electronic supplementary information (ESI) available: 1H NMR spectra of all
compounds, NMR titration data, and DFT calculation details (PDF). See DOI:
10.1039/c7nj00969k
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Scheme 1 Synthesis of molecular clips 7a and 7b. Conditions: (a) urea, PhMe/TFA, reflux, 12 h, 96%; (b) CH2O, 7 M HCl, reflux, 12 h, 91%;
(c) hydroquinone, TFA, reflux, 6 h, 69%; (d) 9, NaOH, water/dioxane, 25 1C, 12 h, 68%; (e) (1) n-BuLi, THF, À78 1C, 1 h, (2) MeI, 0–25 1C, 12 h, 95%; (f) RuCl3,
NaIO4, CCl4/MeCN/water, 25 1C, 2 h, 55%; (g) urea, 0.3 M HCl, 25 1C, 48 h, 77%; (h) CH2O, 7 M HCl, 25 1C, 36 h, 47%; (i) 10, TFA/Ac2O, 95 1C, 3 h, 59%.
Fig. 1 Structures of selected compounds discussed in this work.
n-butyllithium and subsequently treated with methyl iodide to expected one signal for each of their protons. These two sets of
give 2. Compound 2 was oxidized to 3b using an RuCl3/NaIO4 signals can be attributed to two distinct conformers, which
mixture. Having compound 3b in our hands, we performed its were likely enabled by the rotation of two single C–C bonds
reaction with urea in an aqueous HCl/CH2Cl2 emulsion to obtain connecting the central phenylene group to the glycoluril
glycoluril dimer 4b, which was transformed into cyclic ether 5b moieties. The rotation was slow on the NMR timescale at 30 1C;
by its reaction with paraformaldehyde. Each of the glycoluril thus, the conformers were distinguished by their unique NMR
units of 5b bears methyl groups in the methine position, which spectra. Steric hindrance between methyl groups (attached to the
are significantly smaller compared to phenyl groups in 5a. Cyclic methine carbon atoms of the glycoluril units) and the side walls of
ether 5b can react directly with compound 10 yielding molecular glycoluril units were likely the reason why the rotation was
clip 7b in 59% yield. This approach was significantly less restricted. We decided to label the first conformer syn (the methyl
efficient in the case of 5a as bulky phenyl groups lower the groups located on the same side of the central phenylene group)
reactivity of the ether groups towards the aromatic ring. This and second anti (the methyl groups on opposite sides) (Fig. 2).
observation is in agreement with previously reported synthesis.16 Unfortunately, we could not distinguish which set of signals in the
NMR spectra belonged to which conformer. Conformers of 5b, as
Conformational properties
well as of 7b, are present in a ratio of 58: 42, which is based on
When recording the 1H NMR spectra of compounds 5b and 7b the integration of the corresponding signals in the NMR spectra.
at 30 1C in DMSO, we observed two signals instead of the The ratio corresponds to a 0.2 kcal molÀ1 energy difference (DE)
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Table 1 Determined values of the activation Gibbs energy of the inter-
conversion of conformers
Compound
5b
7b
Signals
1
4
1
4
DG‡ (kcal molÀ1
)
Major - minor 18.42 18.95 21.05 21.14
Minor - major 18.20 18.71 20.81 20.89
around which the rotation occurs. Due to this, there is a
possibility of two different kinds of rotational movements:
(i) rotation of phenylene with respect to the glycoluril units
and (ii) rotation of one glycoluril unit with respect to the other.
The signals of protons 1 and 4 were used for the calculation of
Fig. 2 Optimized structures of anti (A) and syn (B) conformers of
compound 5b obtained at the B3LYP/6-311G level of theory.
between the two conformers. The situation is different in the Gibbs activation energies of both rotations (DG‡) using the
case of glycoluril dimer 4b, which shows only one set of signals Eyring equation. The resulting values of DG‡ are shown in
under the same conditions. This indicates that the rotation is Table 1. The whole calculation is described in detail in the ESI.†
fast on the NMR timescale as it is not restricted, due to the
In contrast to 5b, dimeric molecular clip 7b showed only a
absence of the methylene side-groups featuring in 5b and 7b. single coalescence temperature, 110 1C. The values of DG‡ of 7b
Glycoluril dimer 4a and its derivatives 5a and 7a also showed calculated using singlets 1 and 4 were greater than those of 5b
only one set of signals in their NMR spectra. However, these (Table 1). This means that the xylylene side walls of the clip 7b
compounds distinguish themselves from 4b, 5b, and 7b by the are a source of more significant steric hindrance than the cyclic
presence of phenyl instead of methyl groups in the two methine ether groups of 5b. In the case of compound 4b, the DG‡ might
positions of the glycoluril dimer core. We assume that two be determined by measurement of the NMR spectra at low
phenyl groups are too bulky to be fitted in the syn conformation. temperature. However, compound 4b was insoluble in common
This is why 4a and its derivatives adopt only the sterically organic solvents including DMF. The only suitable NMR solvent
favorable anti conformation.
for this compound was DCOOD. The melting point of formic
In order to gain information on the energy characteristics of acid is 8.4 1C and therefore we could not measure the low-
the conformational changes in 5b, the 1H NMR spectra in temperature spectra and determine the DG‡ of compound 4b.
DMSO-d6 with temperature rising to 130 1C were recorded
Supramolecular properties
(Fig. 3). It was discovered that some signals in the NMR spectra
show coalescence at a different temperature from the others. The ability of dimeric clips 7a and 7b to act as supramolecular
The coalescence temperature of signals 2b and 4 was 90 1C, hosts was investigated by 1H NMR spectroscopy. Inclusion
while 1, 2a and 3b had already coalesced at 60 1C. The reason complexes between viologens with cucurbiturils as well as their
why there are two coalescence temperatures observed instead of acyclic versions have been previously described. However,
one may be that compound 5b possesses two C–C bonds interactions of molecular clips resembling those present in
dimeric clips 7a and 7b with viologen have not been reported.
Thus, methylviologen 11 was selected as a suitable guest for
supramolecular studies with dimeric clips 7a and 7b and their
interactions in D2O (Fig. 4).
The aromatic signals of 11 underwent an upfield shift after
addition of clips 7a and 7b to the guest solution. This indicates
the formation of an inclusion complex between the clips and
methylviologen. Since compounds 7a and 7b have two sites that
could encapsulate guest 11, it was expected that these compounds
would form 1:2 complexes, in which each clip arm holds one
guest molecule 11. To prove the expected binding mode, the
stoichiometry of the complex was determined by the continuous
variation method (Job’s plot). The maximum of Job’s curve
appeared approximately at x-coordinate = 0.66 which proves that
1:2 complexation is predominant at equilibrium (Fig. S19 and
S20, ESI†). This binding mode was further visualized by a model
obtained by quantum chemical calculations (Fig. 5).
A plot of the chemical shifts of signals 1 and 2 of the guest
was fitted to the binding isotherm of the 1 : 2 binding model to
Fig. 3 1H NMR spectra (500 MHz, DMSO-d6) of compound 5b recorded
at 30 1C (A), 60 1C (B), 90 1C (C), and 130 1C (D). * denotes the signals of
#
major conformers. denotes the signals of minor conformers.
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Table 2 Association constants of complexes of hosts 7a and 7b with 11
determined by NMR titrations in D2O at 30 1C
Host b (MÀ2
)
K1 (MÀ1
)
K2 (MÀ1
)
4 K2/K1
7a (2.11 Æ 0.41) Â 107 (1.28 Æ 0.25) Â 104 (1.66 Æ 0.34) Â 103 0.52
7b (1.31 Æ 0.42) Â 107 (2.15 Æ 0.19) Â 104 (6.3 Æ 1.4) Â 102 0.12
can be rationalized by the inclusion of the guest molecule in
the first binding side of the dimeric clip which causes con-
formational changes at the second binding site of the host.
However, in our case the binding sites are separated by a rigid
phenylene moiety. Therefore, we do not expect that the negative
cooperativity is a result of conformational changes. We pre-
sume that binding of the first cation 11 affects the distribution
of electron density in the host molecule, which makes it less
attractive for another guest 11. Thus, electronic effects, rather
than conformational changes, are the reason for the negative
cooperativity. Finally, we determined the binding between 11
and model compound 12 to be (8.82 Æ 0.77) Â 103 MÀ1 which is
in good agreement with the values obtained for binding sites in
dimeric clips.
Fig. 4 1H NMR (300 MHz, D2O) spectra of 11 in the absence (A) and in
the presence of 0.13 equiv. (B), 0.25 equiv. (C), 0.38 equiv. (D), 0.50 equiv. (E),
0.63 equiv. (F), 0.75 equiv. (G), 1.00 equiv. (H), 1.50 equiv. (I), 2.00 equiv. (J),
and 3.00 equiv. (K) of 7b. * denotes the signals of 7b.
Conclusion
We prepared compounds 7a and 7b as the first examples of
glycoluril-based dimeric molecular clips. Clip 7b, as well as
other compounds derived from glycoluril dimer 4b, can adopt
two different conformations, which can be distinguished by
means of NMR. On the other hand, free rotation is forbidden
in compounds based on 4a due to the presence of the bulky
phenyl substituent. Both dimeric clips 7a and 7b form complexes
with methylviologen in a 1 : 2 ratio and with submillimolar
stability in water. Our work demonstrated that structural motifs
represented by compounds 4a and 4b can be converted to
supramolecular hosts with two binding sites. Thus, a similar
strategy should be applicable to the synthesis of dimers of acyclic
Fig. 5 Optimized structures of the 7aÁ112 complex obtained using the
PM6 method.
obtain the corresponding association constants (Table 2). glycoluril oligomers or cucurbituril dimers. The syntheses of
Unlike clip 7a, the situation in the case of clip 7b was complicated these compounds are under development in our laboratory.
by its ability to adopt two different conformers. In aqueous
solution, the conformers were always in a ratio of 58 : 42; the
equilibrium was not affected by the presence of guest 11. We were
not able to determine the association constants for separate
conformers due to the presence of four binding sites (each
conformer has two indistinguishable binding sites) during
Experimental section
General methods
titration with 11. However, if the concentration of 11 was kept Starting materials were purchased from commercial suppliers
constant during the titration and the concentration of 7b was and used without further purification. NMR spectra were
varied, it was possible to use the signals of guest 11 to establish recorded using a Bruker Avance 500 spectrometer operating
the association constants describing the affinity of 11 towards at frequencies of 500.13 MHz (1H) and 125.77 MHz (13C), and a
an equilibrium mixture of both conformers of 7b. The associa- Bruker Avance 300 spectrometer operating at frequencies of
tion constants determined for complexes 7aÁ112 and 7bÁ112 are 300.13 MHz (1H) and 75.48 MHz (13C). Both spectrometers were
summarized in Table 2.
equipped with a BBFO probe. High-resolution mass spectra
Hosts 7a and 7b bind methylviologen 11 with a very similar were recorded on an Agilent 6224 Accurate-Mass TOF LC-MS
overall affinity and in both cases the binding is associated with spectrometer using a multimode ESI/APCI ion source and a
a negative cooperativity. The observed negative cooperativity KDS Model 100 Series manual pump for sampling.
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Synthetic procedures and characterization
in vacuo to afford 7a as a yellowish powder (0.728 g, 68%).
1H NMR (300 MHz, D2O) d 7.22 (m, 10H), 7.09 (s, 4H), 7.03
(s, 4H), 6.99 (s, 4H), 5.42 (d, J = 15.9 Hz, 4H), 5.38 (d, J = 15.9 Hz, 4H),
4.18 (m, 16H), 4.00 (d, J = 15.9 Hz, 4H), 3.66 (d, J = 15.9 Hz, 4H),
3.22 (m, 16H), 2.31 (m, 16H). 13C NMR (126 MHz, D2O,
1,4-dioxane as internal reference) d 159.82, 150.70,150.68, 134.62,
133.57, 129.51, 129.36, 129.03, 128.28, 127.93, 115.86, 115.72, 86.45,
86.12, 69.48, 69.43, 48.72, 48.65, 37.27, 25.18, 25.10. HR-MS
(ESI+): m/z [C82H86N8Na8O36S8 + 2Na]2+ observed: 1122.5939,
m/z [C82H86N8Na8O36S8 + 2Na]2+ calculated: 1122.5953.
Glycoluril dimer (4a). Compound 3a (2.480 g, 7.43 mmol)
was dissolved in toluene (150 mL); urea (8.91 g, 0.149 mol) and
trifluoroacetic acid (7.5 mL) were added and the mixture was
heated to reflux in a flask equipped with a Dean–Stark trap for
12 h. A precipitate was formed at the bottom of the flask during
the reaction. Toluene was then removed by decantation and the
precipitate was treated with methanol (200 mL) and sonicated
for 30 min. The suspension was filtered and the solid was
washed with acetone and dried in vacuo to give 4a as a white
powder (3.605 g, 95%). 1H NMR (300 MHz, 96% D2SO4, DMSO-d6
as external reference) d 6.72 (t, J = 7.2 Hz, 2H), 6.59 (t, J = 7.2 Hz,
4H), 6.53 (s, 4 H), 6.24 (d, J = 7.8 Hz, 4H). 13C NMR (126 MHz,
96% D2SO4, DMSO-d6 as external reference) d 161.86, 131.69,
130.92, 128.44, 126.85, 126.45, 124.68, 87.26, 85.82.
Cyclic ether (5a). Compound 4a (3.01 g, 5.89 mmol) was
mixed with paraformaldehyde (5.30 g, 0.177 mol); water (48 mL)
and 35% HCl (72 mL) were added and the suspension was
heated to reflux for 16 h. The suspension was cooled to RT and
filtered. The solid material was washed with water and dried
in vacuo to give 5a as a white powder (3.64, 91%). 1H NMR
(300 MHz, DMSO-d6) d 7.14 (m, 6H), 7.09 (m, 4H), 6.93 (s 4H),
5.43 (m, 8H), 4.56 (d, J = 11.4 Hz, 4H), 4.04 (d, J = 11.4 Hz, 4H).
13C NMR (126 MHz, DMSO-d6) d 157.67, 133.50, 132.45, 128.79,
128.38, 128.08, 127.86, 78.79, 78.46, 71.60, 71.54. HR-MS
(APCIÀ): m/z [C32H28N8O7 + Cl]À observed: 713.1884, m/z
[C32H28N8O7 + Cl]À calculated: 713.1881.
Dimeric clip (6). Compound 5a (1.20 g, 1.77 mmol) was
dissolved in TFA (15 ml); hydroquinone was added (4.21 g,
38 mmol) and the mixture was heated to reflux for 6 h and then
allowed to cool to RT. The product was precipitated with
methanol (100 ml) and the precipitate was collected by filtra-
tion. The crude product was dissolved in DMSO (15 ml) at
80 1C. Methanol (80 ml) was added to the solution and the
mixture was cooled to RT. The precipitate was collected by
filtration and washed with methanol and diethyl ether to give 6
as a white powder (1.29 g, 69%). 1H NMR (300 MHz, DMSO-d6) d
8.76 (s, 4H), 8.67 (s, 4H), 7.00 (t, J = 7.9 Hz, 4H), 6.92 (d, J =
7.4 Hz, 4H), 6.79 (t, J = 7.1 Hz, 2H), 6.75 (s, 4H), 6.52 (s, 4H), 6.45
(s, 4H), 5.32 (d, J = 15.9 Hz, 4H), 5.30 (d, J = 15.7 Hz, 4H), 3.53
(d, J = 15.9 Hz, 4H) 3.21 (d, J = 15.7 Hz, 4H). 13C NMR (126 MHz,
DMSO-d6) d 156.50, 146.93,134.01, 133.83, 128.25, 127.95,
124.89, 124.82, 115.32, 115.19, 84.32, 84.14, 36.48, 36.29.
Dimeric clip (7a). Compound 6 (0.510 g, 0.49 mmol) was
dissolved in 2.5 M NaOH (3.5 mL). The solution was treated
with 1,3-propanesultone (0.911 g, 7.46 mmol) in dioxane (3.5 mL).
The reaction mixture was stirred at RT for 8 h. The resulting
precipitate was collected by filtration, washed with methanol and
suspended in 2.5 M NaOH (7 mL). The suspension was again
treated with 1,3-propanesultone (2.139 g, 17.51 mmol) in dioxane
(9 mL). The reaction mixture was stirred at RT for 8 h. The
resulting precipitate was collected by filtration and washed with
methanol. The crude product was dissolved in water (20 mL) and
precipitated with acetone (120 mL). The precipitate was collected
by filtration, washed with methanol and diethyl ether and dried
1,4-Bis(1,2-dioxopropane-1-yl)benzene (3b). Compound 228
(0.771 g, 5.00 mmol) was dissolved in a mixture of CCl4
(15.5 mL) and CH3CN (15.5 mL). A mixture of NaIO4 (6.42 g,
30.02 mmol), NaHCO3 (67.3 mg, 0.80 mmol) and MgSO4 (308.0 mg,
2.56 mmol) in water (20 mL) was added to the solution. Aqueous
0.01 M RuCl3 (4 mL, 0.04 mmol) was added and the reaction
mixture was stirred at RT for 1.5 h. The mixture was diluted with
ethyl acetate (100 ml) and the organic phase was separated from
the precipitated salts by decantation. The organic phase was dried
over MgSO4 and the solvents were removed by rotary evaporation.
The crude product was dissolved in ethyl acetate and filtered
through a plug of silica gel. The solvent was removed by rotary
evaporation to give compound 3b as a yellow solid (0.605 g, 55%).
1H NMR (500 MHz, CDCl3): d 8.13 (s, 4H), 2.55 (s, 6H). 13C NMR
(126 MHz, CDCl3): d 199.30, 189.93, 136.15, 130.64, 26.22.
Glycoluril dimer (4b). Compound 3b (1.42 g, 6.51 mmol) was
dissolved in CH2Cl2 (20 mL). Urea (5.06 g, 92.7 mmol) was
dissolved in 0.3 M HCl (20 mL). The solutions were mixed and
stirred together at RT for 2 days. The resulting precipitate was
collected by filtration, washed with water and acetone and dried
1
in vacuo to give 4b as a white powder (1.95 g, 77%). H NMR
(500 MHz, 95% DCOOD) d 7.80 (s, 4H), 1.22 (s, 6H). 13C NMR
(126 MHz, 95% DCOOD) d 162.24, 137.44, 127.58, 81.68, 79.21, 22.70.
Cyclic ether (5b). Paraformaldehyde (1.60 g, 53.3 mmol) was
dissolved in 9 M HCl (20 mL) at 60 1C, the solution was cooled
to RT and compound 4b (0.690 g, 1.78 mmol) was added and
the solution was stirred for 24 h. Water was added to the
mixture (11 mL) and stirred for another 12 h. The resulting
precipitate was filtered, washed with water and dried in vacuo to
give ether 5b as a white powder (0.465 g, 47%). Compound 5b
was obtained as a mixture of two conformers in a 58 : 42 ratio.
1H NMR (500 MHz, DMSO-d6) major conformer: d 7.63 (s, 4H), 5.40
(d, J = 11.3 Hz, 4H), 5.32 (d, J = 11.2 Hz. 4H) 5.01 (d, J = 11.2 Hz, 4H),
4.62 (d, J = 11.3 Hz, 4H), 1.18 (s, 6H). Minor conformer: d 7.62
(s, 4H), 5.39 (d, J = 11.3 Hz, 4H), 5.32 (d, J = 11.2 Hz, 4H), 5.03
(d, J = 11.2 Hz, 4H), 4.57 (d, J = 11.3 Hz, 4H), 1.27 (s, 6H). 13C NMR
(126 MHz, DMSO-d6) major conformer: d 157.56, 134.84, 128.73,
77.87, 73.96, 71.30, 70.57, 18.77. Minor conformer: d 157.56, 134.59,
128.73, 77.89, 73.89, 71.30, 70.57, 19.14. HR-MS (APCIÀ): m/z
[C24H26N8O7 + Cl]À observed: 589.1570, m/z [C24H26N8O7 + Cl]À
calculated: 589.1568.
Dimeric clip (7b). Compound 5b (0.460 g, 0.83 mmol) and
compound 10 (2.31 g, 5.83 mmol) were dissolved in a mixture
of TFA (12 mL) and acetic anhydride (12 mL). The solution
was heated to 95 1C for 4 h. The solvents were removed by
rotary evaporation and the resulting solid was washed with
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methanol (200 mL). The crude product was dissolved in Competing financial interest
water (15 mL) and precipitated with acetone (120 mL). The
The authors declare no competing financial interest.
precipitate was filtered and dissolved in water (20 mL);
the pH of the solution was adjusted to 7 using 1 M NaOH
and the water was removed by rotary evaporation. The result-
ing solid was washed with methanol and diethyl ether and
dried in vacuo to afford 7b as a yellowish solid (1.01 g, 59%).
1H NMR (500 MHz, D2O) major conformer: d 7.71 (s, 4H), 7.03
(s, 4H), 6.94 (s, 4H), 5.41 (d, J = 16.3 Hz, 4H), 5.23 (d, J = 15.7
Hz, 4H), 4.25 (m, 4H), 4.15 (m, 20H), 3.18 (m, 16H), 2.28
(m, 16H), 1.31 (s, 6H). Minor conformer: d 7.74, (s, 4H), 7.03
(s, 4H), 6.91(s, 4H), 5.41 (d, J = 16.3 Hz, 4H), 5.29 (d, J =
15.7 Hz, 4H), 4.25 (m, 4H), 4.15 (m, 20H), 3.18 (m, 16H),
2.28 (m, 16H), 1.36 (s, 6H). 13C NMR (126 MHz, D2O,
1,4-dioxane as internal reference) major conformer: d 159.30,
150.82, 135.96, 129.49, 128.92, 127.84, 115.92, 115.83, 85.04,
80.64, 69.66, 69.51, 48.64, 37.41, 35.97, 25.10, 18.95. Minor
conformer: d 159.30, 150.72, 135.92, 129.67, 128.92, 127.84,
115.92, 115.63, 85.11, 80.36, 69.66, 69.44, 48.64, 37.38, 35.97,
25.10, 18.69. HR-MS (ESI+): m/z [C72H82N8Na8O36S8 + 2Na]2+
observed: 1060.5797, m/z [C72H82N8Na8O36S8 + 2Na]2+ calculated:
1060.5796.
Acknowledgements
This work was supported by the Czech Science Foundation
(13-15576S) and the MEYS CR (projects LM2011028 and LO1214).
Jan Sokolov acknowledges the Brno PhD Talent Scholarship program
´
funded by the Brno City Municipality. We thank Dr Robert Vıcha
´
(Tomas Bata University in Zlın) for helpful discussion.
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