Hydrogen-bonded molecular capsules: Probing the role of water molecules in capsule formation in modified cyclotricatechylene

Article abstract of DOI:10.1039/c7ce01075c

Two new pyridine moiety-appended cavitands, CTC(Py)₂(OH)₂ and CTC(Py)₃, were synthesized and characterized. The solid state structures of both cavitands were studied by single crystal X-ray diffraction. CTC(Py)₂(OH)₂ resulted in a hydrogen-bonded dimeric molecular capsule, entrapping two molecules of DMSO and intervening water molecules that formed hydrogen bonding to DMSO and CTC(Py)₂(OH)₂. When crystallized in the absence of water, it forms a 2D polymer by hydrogen bonding of pyridine nitrogen and phenolic hydrogen atoms. CTC(Py)₃ forms no such capsule.

Full text of DOI:10.1039/c7ce01075c

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Hydrogen-bonded molecular capsules: probing
the role of water molecules in capsule formation
in modified cyclotricatechylene†
Cite this: DOI: 10.1039/c7ce01075c
*
Giri Teja Illa, Sohan Hazra, Pardhasaradhi Satha and Chandra Shekhar Purohit
Two new pyridine moiety-appended cavitands, CTC(Py)2IJOH)2 and CTC(Py)3, were synthesized and charac-
terized. The solid state structures of both cavitands were studied by single crystal X-ray diffraction.
CTC(Py)2IJOH)2 resulted in a hydrogen-bonded dimeric molecular capsule, entrapping two molecules of
DMSO and intervening water molecules that formed hydrogen bonding to DMSO and CTC(Py)2IJOH)2.
When crystallized in the absence of water, it forms a 2D polymer by hydrogen bonding of pyridine nitrogen
and phenolic hydrogen atoms. CTC(Py)3 forms no such capsule.
Received 8th June 2017,
Accepted 7th July 2017
DOI: 10.1039/c7ce01075c
rsc.li/crystengcomm
Cyclotriveratrylene (CTV) and its analogues have been used
for complexation with different molecules.14 A triscatechol
Introduction
Molecular capsules have attracted much attention of synthetic
chemists and chemical biologists in the past few decades.1
These are macro-molecules or supra-molecules, which have
space inside to conceal other molecules as guests. The first
synthesis of these types of molecules was reported by Cram
et al.2 These were formed by networks of covalent bonds that
sealed-in their guests using mechanical forces rather than
chemical ones. Apart from using covalent bonds for incarcera-
tion of guests (i.e., cryptands), non-covalent interactions like
ionic interactions,3 metal coordination,4 hydrogen bonding,5
hydrophobic interactions,6 or a combination of them1b,7 are
used for entrapping guests. Recently, halogen bonding has
also been utilized for formation of capsular assemblies.8 Guest
molecules can also induce capsule formation.9 Formation of
capsules by non-covalent interactions has the advantage of re-
versibly binding and releasing guest molecules, controlled by
chemical and physical stimuli. One of the widely used non-
covalent interactions for capsule formation is hydrogen-bond-
ing.7 Some motifs like glycolurils1c,5c,10 and resorcinarenes11
have been used in the formation of hydrogen-bonded molecular
capsules. Water molecules also mediate capsule formation
through hydrogen bonding in suitable molecular systems. The
formation of dimeric12 and hexameric13 molecular capsules
assisted by water molecules are known in the literature.
version of CTV, cyclotricatechylene (CTC), has been used for a
few supramolecular complexes utilizing hydrogen-bonded as-
semblies.15 Out of these, only a few examples of CTC forming
capsular assemblies are known. Robson and co-workers have
trapped tetra-alkyl ammonium cations as well as alkali metal
ions by forming hydrogen-bonded capsules in basic me-
dium.16 A recent report from our group has shown that the
same molecule under neutral conditions forms a capsular
structure induced by guest entrapment.9c
Although CTC is used as a scaffold for molecular capsules,
the shallow cavity of CTC is a limitation. Thus, many groups
have adopted methods to extend CTC that will help increase its
cavity size. Mostly, two approaches are implemented. One is to
use CTG, a partially methylated version of CTC, and attach
functionalities (linkers) to phenolic groups.18 The other
method is to attach bridging functionalities to the hydroxyl
group of different catechol units. In 1988, Cram and co-
workers synthesized, for the first-time, a cavitand by bridging
three aryl groups on CTC.19 This gives certain rigidity to the
molecule, along with extending the cavity and allowing
functionalization of the rim of CTC. This strategy was adopted
by Wytko and Weiss, using pyridyl m-xylene bridges.20 Re-
cently, this kind of approach was used by Hardie's group to
synthesize bow-tie metallo-cryptophanes.21 The crystal struc-
tures of these metallo-cryptophanes showed that they have a
pinched-in rim. This creates a bow-tie effect, which Hardie and
co-workers have exploited. This shows that even though the
cavity volume can be increased, the opening of the cavity nar-
rows, preventing the guest molecule from entering the cavity.
In continuation of our research with CTC/CTV,9c,15e,17,22
we assumed that if two pyridine moieties can be appended to
CTC (1, in Chart 1), it will form a donor–acceptor system. In
School of Chemical Sciences, National Institute of Science Education and Research
Bhubaneswar, HBNI, Jatni, Khurda – 752050, Odisha, India.
E-mail: purohit@niser.ac.in
† Electronic supplementary information (ESI) available: NMR spectra, mass spec-
tra and tables of bond angles, and bond lengths for all synthesized complexes.
CCDC 1525712, 1525713 and 1530352. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/c7ce01075c
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slow stirring, the mixture was heated up to 70 °C. After the
mixture became a yellowish paste, heating was stopped. A
highly exothermic reaction resulted in the formation of a yel-
low solid. The mixture was cooled to room temperature, wa-
ter (100 mL) was added, and the yellow suspension was
stirred for 20 minutes at room temperature. The solid was fil-
tered, washed thoroughly with water and placed in a round
bottom flask (100 mL) along with ethanol (50 mL). This was
then refluxed for 15 minutes and cooled to room temperature
with stirring. The solid was filtered and washed thoroughly
with ethanol yielding 3 as a bright yellow solid, which was
dried in a vacuum and used without further purification.
Chart 1 Target molecules.
this molecule, free phenolic hydrogen could act as a H-bond
donor while nitrogen atoms in the pyridine rings could be
H-bond acceptors.23 This kind of molecule would have the po-
tential to form homodimeric capsular complexes. A similar
doubly bridged CTC system was synthesized as a side product
(∼15% yield) by Cram's group, using m-xylylene bridges.19 In
this case, the absence of a third bridge would allow small mole-
cules to enter. It would also be interesting to investigate the ef-
fect of introducing three pyridine bridges (2 in Chart 1) with
methyl groups at the 2,6 positions to increase the steric
crowding between the bridging groups. This may help the cav-
ity to open up for easy passage of guest moleculeIJs) in 2. Thus,
we targeted an optimised synthesis of doubly and triply bridged
CTC pyridine derivatives, 1 and 2, to study their properties.
Synthesis of diethyl 2,6-dimethylpyridine-3,5-dicarboxylate
(4)25
A mixture of 1,4-dihydropyridine 3 (2.53 g, 10.00 mmol), NHPI
(0.160 g, 1.00 mmol) and CoIJOAc)2·4H2O (0.012 g, 0.05 mmol)
in dry acetonitrile (25 mL) was stirred in open air, at room
temperature for 4 h. After removal of the solvent under re-
duced pressure, the residue was purified by column chroma-
tography to afford the corresponding pyridine derivative 4 in
1
quantitative yield. H NMR (400 MHz, CDCl3) δ: 8.66 (s, 1H),
4.37 (q, J = 7.1 Hz, 4H), 2.84 (s, 6H), 1.39 (t, J = 7.1 Hz, 6H).
13C NMR (101 MHz, CDCl3) δ: 165.94, 162.25, 141.20, 123.30,
77.48, 77.16, 76.84, 61.56, 24.89, 14.38.
Synthesis of (2,6-dimethylpyridine-3,5-diyl)dimethanol (5)26
Experimental section
To an ice-cold mixture of lithium aluminium hydride (95%)
(6.7 g, 168 mmol) in dry THF (500 mL) was added a solution
of 4 (31.5 g, 125 mmol) in dry THF (250 mL) under a nitrogen
atmosphere. The mixture was removed from the ice bath and
stirred at room temperature for 3 h. After completion, the re-
action mixture was cooled to 0 °C and a mixture of ethyl ace-
tate : methanol : water (15 : 4 : 1) was added slowly. The
resulting solids were filtered over Celite® 545 and washed
with ethyl acetate (500 mL) and methanol (20 mL). The fil-
trate was concentrated and dried in a vacuum, and the prod-
uct was obtained as a white solid (17.12 g, 82% yield), which
was used without further purification. 1H NMR (400 MHz,
DMSO-d6) δ: 7.63 (s, 1H), 5.22 (s, 2H), 4.47 (s, 4H), 2.35 (s,
6H). 13C NMR (101 MHz, DMSO-d6) δ: 152.36, 133.33, 132.23,
60.14, 39.84, 39.62, 39.31, 20.83.
General
Reagent grade chemicals were acquired from Aldrich and used
as received. All solvents were procured from Merck Limited, In-
dia. The solvents were purified prior to use by following stan-
dard procedures. NMR was recorded with a Bruker Advance-III
400 MHz instrument. Single crystal X-ray diffraction studies
were conducted on a Bruker 4-circle Kappa APEX-II diffractom-
eter equipped with a CCD detector, with the X-ray source being
Mo Kα (wavelength 0.71073 Å) at room temperature. Data col-
lection was monitored with Apex II software, and pre-
processing was performed with SADABS integrated with Apex
II.30 Crystal structure solution and refinement was carried out
using WingX and PLATON software.31 In the case of 1 with a
non-capsular assembly, the sulphur atoms in DMSO molecules
are disordered. They were split over two places and hydrogen
atoms were not added to methyl groups. In the case of 2, peaks
were found in Fourier maps that could be assigned to oxygen
atoms of water. When assigned, they were found to have a high
thermal parameter. Therefore, they were squeezed using the
PLATON SQUEEZE command. HRMS was performed on a
Bruker ESI-MS microTOFQ.
Synthesis of 3,5-bisIJbromomethyl)-2,6-dimethylpyridine (6)
To an ice-cold solution of 5 (2.93 g, 10 mmol) in 1,4-dioxane,
PBr3 (4.75 mL, 50 mmol) was added slowly under stirring. The
solution was brought to room temperature and stirred for 4 h.
After completion, the reaction mixture was quenched with so-
dium bicarbonate solution and extracted with DCM. The aque-
ous layer was washed with DCM (2 × 50 mL), and the com-
bined organic layers were dried over anhy. sodium sulphate.
The solvent was evaporated to obtain a white crystalline solid
Synthesis of diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-
dicarboxylate (3)24
1
Ethyl acetoacetate (6.5 g, 50 mmol), paraformaldehyde (0.75
g, 250 mmol) and ammonium acetate (2.9 g, 375 mmol) were
placed in a 100 mL beaker covered with a watch glass. Under
(6), with 92% yield. H NMR (400 MHz, CDCl3) δ: 7.54 (s, 1H),
4.44 (s, 4H), 2.61 (s, 6H). 13C NMR (101 MHz, CDCl3) δ: 156.96,
139.24, 129.68, 77.48, 77.16, 76.84, 30.04, 21.42.
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Synthesis of cyclotriveratrylene (CTV) (7)28
N2 to a stirred solution of K2CO3 (4.5 g) in dry degassed DMF
(100 mL). The suspension was stirred at 70 °C for 72 hours.
K2CO3 was filtered off and DMF was removed under vacuum.
The residue was purified by column chromatography (silica, 0–
5% MeOH in CH2Cl2) to yield 2 as a white powder, with 49%
Veratryl alcohol (10 g, 0.06 mol) was placed in a 250 mL
round bottom flask and heated in an oil bath up to 80 °C. 3
drops of H3PO4 were added to the solution which was then
stirred for 2 h. Within that time, the reaction mixture became
a white paste. Then the reaction mixture was cooled to room
temperature and methanol (50 mL) was added to the off-
white solid while stirring. The crude solid was collected by fil-
tration and recrystallized from DCM to obtain pure white
crystals of CTV (7) in 40% yield. 1H NMR (400 MHz, CDCl3) δ:
6.83 (s, 2H), 4.72 (d, J = 13.7 Hz, 1H), 3.84 (s, 6H), 3.52 (d, J =
1
yield. H NMR (400 MHz, CDCl3/CD3OD (3 : 1)) δ 7.68 (s, 3H),
6.43 (s, 6H), 4.99 (m, 12H), 4.31 (d, J = 12 Hz, 3H), 3.16 (d, J = 12
Hz, 3H), 2.48 (s, 6H). 13C NMR (101 MHz, CDCl3/CD3OD (3 : 1))
δ 156.85, 145.99, 144.75, 131.63, 126.91, 116.45, 67.36, 35.03,
29.25, 19.71. ESI-HRMS: m/z 760.3378 [M + H]+ (calc. 760.3381).
13.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ: 147.73, 131.85, Results and discussion
113.15, 77.48, 77.16, 76.84, 56.07, 36.47.
We synthesised a Hantzsch pyridine diester, from which the
Synthesis of cyclotricatechylene (CTC) (8)29
required 3,5-dibromomethyl pyridine moiety can be obtained.
The Hantzsch dihydropyridine diester was prepared
according to
Hantzsch dihydropyridine was carried out with cobalt
diacetate and N-hydroxyphthalimide, both used in catalytic
amounts.25 The reduction went smoothly as per literature re-
ports26 to yield 5. Bromination of 5 was carried out using
PBr3 in 1,4-dioxane which gave satisfactory yields of 6 (see
the ESI†). Cyclotricatechylene was synthesised in two steps,
following literature reports28,29 (see the ESI†).
To synthesise the doubly bridged CTC, we adopted a
slightly modified reported procedure.21 The use of caesium
carbonate for bridging gave multiple products, as detected by
TLC. So, we used a milder base, potassium carbonate, for
cyclisation. We were able to isolate the desired product in
29% yield. To improve the yield, we performed the reaction
at varying reaction times. While 24 h of reaction gave the
highest yield of 45%, 12 h, 36 h and 48 h of reactions gave
35%, 32% and 29%, respectively (Scheme 1). The doubly
bridged product, CTC(Py)2IJOH)2 (1), was initially characterised
by ESI-MS, m/z at 629.2644 [M + H]+ (calc. 629.2646). In the 1H
NMR spectra of 1, the characteristic singlet aryl–CTC peak is
split into three peaks, indicating the absence of a three-fold
symmetry, as compared to CTC. Similarly, the two characteris-
tic doublets of CTC methylene protons are split into four dou-
blets, in a 2 : 1 ratio within each pair. Comparison of the inte-
gration values of bridge methylene protons and pyridine
aromatic protons, at 5.11–5.14 ppm and 8.5 ppm, respectively,
with those of the CTC scaffold confirms the formation of the
doubly bridged CTC cavitand, 1.
In a two-neck 100 mL round bottom flask, a solution of CTV
(2.52 g, 5 mmol) in dry DCM was cooled to −40 °C under a
N2 atmosphere. To this stirred solution, BBr3 (3.3 mL, 35
mmol) was added. The solution was removed from the
cooling bath and the purple-coloured reaction mixture was
brought to room temperature and stirred for further 15 min.
Then it was refluxed for 12 h. After this time, the reaction
mixture was slowly cooled to 0 °C. It was then quenched by
slow addition of ice-cold water (50 mL). The resulting slurry
was filtered and the residue was washed with water (200 mL)
and acetonitrile (10 mL). The crude wet solid was
recrystallized from ethanol to obtain brown crystals of CTC
(8) in 87% yield. 1H NMR (400 MHz, DMSO-d6) δ: 8.55 (s,
2H), 6.65 (s, 2H), 4.48 (d, J = 13.4 Hz, 1H), 3.20 (d, J = 13.6
Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ: 143.49, 130.83,
116.74, 40.15, 39.94, 39.73, 39.52, 39.31, 39.10, 38.89, 35.07.
a
literature procedure.24 Oxidation of the
Synthesis of bis-(3,5-bisIJmethyl)-2,6-
dimethylpyridine)cyclotricatechylene (CTC(Py)2IJOH)2) (1)
A solution of CTC (8) (100 mg, 0.271 mmol) and 6 (175 mg,
0.596 mmol) in dry degassed DMF (50 mL) was added under
N2 to a stirred solution of K2CO3 (3.5 g) in dry degassed DMF
(100 mL). The suspension was stirred at 70 °C for 24 hours.
K2CO3 was filtered off and DMF was removed under vacuum.
The residue was purified by column chromatography (silica,
0–5% MeOH in CH2Cl2) to afford 1 as a white powder, with
1
45% yield. H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 8.18
(s, 1H), 6.76 (s, 1H), 6.74 (s, 1H), 6.56 (s, 1H), 5.14 (s, 2H),
5.11 (s, 2H), 4.47 (d, J = 13.0 Hz, 1H), 4.35 (d, J = 13.1 Hz,
1H), 3.33 (d, J = 13.2 Hz, 1H), 3.14 (d, J = 13.5 Hz, 1H), 2.47
(s, 3H), 2.46 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ: 157.54,
157.01, 145.43, 144.80, 144.43, 142.7, 131.39, 130.42, 125.68,
117.06, 116.30, 79.22, 68.15–67.41, 67.23, 40.04, 39.80, 39.73,
39.52, 39.31, 39.10, 38.89, 34.59, 21.42. ESI-HRMS: m/z
629.2644 [M + H]+ (calc. 629.2646).
In the mass spectrum along with a monomer peak (m/z =
629.2644), one more peak appears at m/z = 1257.5093 which
may be assigned to dimer [2M + H]+, possibly indicating the
Synthesis of trisIJ3,5-bisIJmethyl)-2,6-
dimethylpyridine)cyclotricatechylene CTC(Py)3 (2)
A solution of CTC (8) (100 mg, 0.271 mmol) and 6 (262 mg,
0.894 mmol) in dry degassed DMF (50 mL) was added under
Scheme 1 Synthesis of CTC(Py)2IJOH)2 (1).
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formation of a dimeric assembly under mass spectroscopic
conditions. This encouraged us to investigate the assembly in
the solid state by single crystal X-ray diffraction (see the
ESI†).
Owing to the limited solubility of the compound in low
polarity solvents, crystallisation was performed in highly po-
lar solvents. The crystallisation of 1 was tried in various sol-
vent systems and crystals suitable for X-ray diffraction were
obtained in a DMSO–chloroform solvent mixture. Slow evapo-
ration of a very dilute solution of 1 gave reddish-brown rect-
angular crystals in about two weeks. Compound 1 crystallised
in the monoclinic crystal system with the P21/n space group
(no. 14). The asymmetric unit shows a molecule of 1
containing a DMSO molecule near its cavity and one mole-
cule of DMSO along with three molecules of water outside
the cavity. It became evident, during further analysis, that 1
forms a water mediated dimeric self-assembly, encapsulating
two molecules of DMSO (Fig. 1). Similar water mediated di-
meric capsules are reported with resorcinarene.12 However,
to the best of our knowledge, this is the first example of a
CTC-based molecular capsule.
Fig.
2
Stick model of 1, showing hydrogen bonding and DMSO
position in the capsule.
Phenolic –OH and pyridine nitrogen take part in hydrogen
bonding, but they do not interact with each other directly, as
we expected. Instead, four water molecules conveniently me-
diate between two molecules resulting in a molecular capsule
(Fig. 2). Each water molecule forms two hydrogen bonds, one
with a phenolic OH and another with a pyridine nitrogen
atom in two different molecules. The lattice is extended by
π–π interaction and non-classical hydrogen bonding of
CH⋯O. Apart from keeping the dimeric form, each water
molecule also forms a hydrogen bond with the oxygen of
DMSO trapped inside the cavity.
O–H (∼2.7 Å), pyridine nitrogen with water hydrogen (∼2.8
Å) and DMSO oxygen with water hydrogen (∼2.75 Å).‡
The two DMSO molecules are oppositely faced, with the
sulphur atoms in proximity to each other. The sulphur–sul-
phur distance is 3.698(9) Å, slightly above twice the van der
Waal's radius of sulphur (3.6 Å) indicating weak interactions
between them. The solvent accessible volume is 1410 Å3, as
calculated after removing the solvent molecules.
A simplified packing diagram of 1 is shown in Fig. 3. The
dimeric capsular assembly packs itself in a herringbone pat-
tern of 2 : 1 ratio in the (−0.65, 0, −0.75) plane. This pattern is
driven by weak π–π stacking between the pyridine ring of the
monomer of one capsule and the CTC benzene ring at the
base of the monomer of another capsule (shown in blue bro-
ken lines) (see the ESI†). Also, the parallel-displaced arrange-
ment of each dimeric capsule is facilitated by weak π–π stack-
ing between each CTC benzene ring of opposite facing
monomers in two different capsules (shown in red broken
lines) (see the ESI†). CTC benzene rings have π–π stacking
that helps in extending the lattice.‡
In total, four water molecules are involved in twelve hydro-
gen bonds in the capsular assembly, out of which eight
bonds are utilised in forming the dimer. Three kinds of hy-
drogen bonds are present in the lattice: water with phenolic
As 1 forms a water-mediated dimeric capsule, we were cu-
rious to know whether 1 would form a dimeric capsule via
phenol–pyridine hydrogen bonding in the absence water.
Hence, we tried the crystallisation under anhydrous condi-
tions, maintaining the same solvent system (CHCl3/DMSO) as
used previously.
Colourless crystals appeared after almost a month. In this
condition, compound 1 crystallised in the monoclinic system
with the P21 space group (no. 4). The asymmetric unit con-
sists of two molecules of 1 along with three molecules of
DMSO, two of which are in the cavity of 1. Further analysis
revealed that although there exists direct phenol–pyridine hy-
drogen bonding interaction between two molecules of 1, it
Fig. 1 Crystal structure showing a dimeric assembly. Non-hydrogen
bonded hydrogen atoms are omitted for clarity. Encapsulated DMSO
has been shown in a space filling model.
‡ Refer to the ESI† for more details.
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Fig. 3 Packing diagram of 1 showing a capsular assembly arranged in
a 2 : 1 herringbone pattern. Hydrogen atoms and DMSO have been
omitted for clarity.
Fig. 5 Packing diagram of 1 showing a zig-zag chain polymer in the
absence of water.
does not form a dimeric capsular assembly (Fig. 4). In the ab-
sence of water, each molecule of 1 is involved in hydrogen
bonding with two neighbouring molecules. Probably due to
steric strain, they cannot occupy the face to face position and
therefore, no capsular assembly was formed. As a result, 1
forms a 1D zig-zag chain polymer driven by hydrogen bond-
ing interactions between phenol–pyridine (Fig. 5).
Two consecutive linear chains are held together by weak
hydrogen bonding interactions. Each molecule of 1 forms
three hydrogen bonds with another molecule of the same
type in the subsequent chain (Fig. 6). Two of these are be-
tween the methylene protons of the bridge moiety of one
molecule of 1 and the bridged oxygen atoms in the CTC scaf-
fold of another (dC29–O11 = 3.444(5) Å, dC11–O5 = 3.428(3) Å).
The third hydrogen bond is between the methyl proton of
pyridine of one molecule and the bridged oxygen atom of an-
other (dC31–O10 = 3.475(1) Å). Thus, a 2D polymer forms in the
lattice by connecting the 1D zig-zag chain.
Cram et al. have reported CTC triple-bridging with the 2,6-
lutidylene group, where the position of the pyridine nitrogen
is such that it makes itself unavailable for H-bonding with
another molecule.19 In our system, we wanted the nitrogen
atom of the pyridine ring to face outwards and be available
for hydrogen bonding or metal coordination. Therefore, we
attached a 3,5-disubstituted pyridine molecule to synthesize
the desired molecules.
During the synthesis of 1, we isolated this molecule,
CTC(Py)3 (2) in a small amount. This was characterised by
NMR and ESI-MS, m/z 760.3378 [M + H]+ (calc. 760.3381). The
major peak in the mass spectra appearing at m/z 380.6733
corresponds to [M + 2H]2+, while the peak at m/z 628.2552
corresponds to [M − Py]+. The NMR spectra of 2 show the
characteristic singlet aryl–CTC peak at 6.43 ppm, indicating
the retention of the three-fold symmetry similar to CTC.
Comparison of the integration values of bridge methylene
and pyridine aromatic protons at 5 and 7.68 ppm, respec-
tively, with those of the CTC scaffold confirms the formation
After successfully probing 1, in the solid state, we thought
it would be interesting to probe the triply bridged pyridine
molecule, CTC(Py)3. This would have three nitrogen atoms
for hydrogen bonding, and if water molecules would lend as-
sistance like in 1, it might also result in a molecular capsule.
Fig. 4 Crystal structure of 1 showing a non-capsular assembly in the
absence of water. Non-hydrogen bonded hydrogen atoms are re-
moved for clarity.
Fig. 6 Hydrogen bonding between molecules of 1 which are part of
two different chains. Non-hydrogen bonded hydrogen atoms are re-
moved for clarity.
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of the triply bridged CTC cavitand 2. We optimised the syn-
thesis of this molecule by modifying a reported procedure,21
using potassium carbonate instead of caesium carbonate. Af-
ter 72 h, CTC(Py)3 (2) was obtained in 49% yield as a white
solid (Scheme 2).
(CTC(Py)3) pyridine moieties bridging between CTC aryl
rings. CTC(Py)2IJOH)2 was designed to exhibit hydrogen bond
donor–acceptor properties, aiming to form a dimeric capsule.
This doubly bridged cavitand shows dimeric capsular self-
assembly via water molecule-mediated hydrogen bonding,
entrapping two molecules of DMSO, while in the absence of
water, it a forms 2D polymeric assembly. It is expected that
the α,α′ di-substitution might widen the opening in CTC(Py)3.
Our future task is to investigate the effect of different bridg-
ing moieties and the propensity of the resulting cavitands to
form capsules in the solution phase and in doubly and triply
bridged CTC. Also, efforts to obtain metallo-cryptophanes for
both 1 and 2 are underway.
To study the solid-state structure of 2, we crystallised it
using DMSO–THF as solvent. Colourless, needle-like crystals
were obtained within a week, which degraded rapidly upon
exposure to air. Diffraction data was collected by placing
these crystals inside a capillary, in the presence of the
mother liquor. 2 crystallized in the orthorhombic crystal sys-
tem with the Pna21 space group (no. 33). The asymmetric
unit shows a molecule of 2 as can be seen in Fig. 7. The sol-
vent accessible volume, as calculated after removing the sol-
vent molecules, is 1667 Å3. Packing is driven by weak C–H/π
stacking between methyl C–H on the pyridine ring and the
pyridine ring of the adjacent molecule of 2 (Fig. S12†). The
values for d between C and the aromatic ring centroid, θ and
ϕ angles are 3.755(6) Å, 16.5° and 143°, respectively.27 In
Cram's report, the triply m-xylylene bridged CTC had one out
of three rings facing outwards.19 Also, in the case of Hardie's
bow-tie metallo-cryptophane, the bridged aryl groups of the
cavitand exhibit metal coordination and are thus forced into
facing upwards.21 However, it is interesting to note that in
the case of CTC(Py)3 (2), all the bridge groups are facing up-
wards, without any coordination.
Conflicts of interest
There are no conflicts of interest to declare.
Notes and references
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