Awkwardly-Shaped Dimers, Capsules and Tetramers: Molecular and Supramolecular Motifs in C5-Arylated Chiral Calixsalens

Article abstract of DOI:10.1002/ejoc.201800314

A series of novel C-5 arylated calixsalens synthesized via [3+3] cyclocondensation of trans-(R,R)-1,2-diaminocyclohexane with 2-hydroxyisophthalaldehyde derivatives are presented. The nonsymmetrical aryl substituents of the 1-naphthyl type may act as swit

Full text of DOI:10.1002/ejoc.201800314

A Journal of
Accepted Article
Title: Awkwardly-shaped dimers, capsules and tetramers: molecular
and supramolecular motifs in C5-arylated chiral calixsalens
Authors: Małgorzata Petryk, Agnieszka Janiak, Leonard J. Barbour,
and Marcin Kwit
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800314
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10.1002/ejoc.201800314
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Awkwardly-shaped dimers, capsules and tetramers: molecular
and supramolecular motifs in C5-arylated chiral calixsalens
Małgorzata Petryk,[a],[b] Agnieszka Janiak,*[a],[c] Leonard J. Barbour,[c] and Marcin Kwit*[a],[b]
Dedicated to Prof. Urszula Rychlewska on the occasion of her anniversary
Abstract: A series of novel C-5 arylated calixsalens synthesized via
[3+3] cyclocondensation of trans-(R,R)-1,2-diaminocyclohexane with
2-hydroxyisophthalaldehyde derivatives are presented. The non-
symmetrical aryl substituents of the 1-naphthyl type may act as
switches opening (ON conformation) or closing (OFF conformation)
the macrocycle cavity. This group of macrocycles, depending on the
kind of aryl substituent, is characterized by a large variety of
supramolecular architectures. While the substitution of the calixsalen
skeleton by 2,5-dimethoxybenzene groups promotes the formation of
head-to-head capsules, the presence of 3,5-dimethylbenzene group
favors the tail-to-tail dimers. Introduction of 2-naphthyl substituents,
in turn, results in the formation of a supermolecule consisting of four
monomers that exists only in the solid state. Such arrangements of
macrocycles generate a truncated tetrahedron shaped cavity never
previously observed for this type of macrocyclic compounds.
of the reaction is not a sufficient prerequisite for macrocycle
formation. The structural predisposition of substrates to form
higher-order constructs of various shapes is the most important,
however.[15-17]
The products of [3+3] cyclocondensation between vicinal
chiral diamines of the trans-1,2-diaminecyclohexane (DACH)
type and 2-hydroxyisopthalaldehyde derivatives, dubbed
calixsalens,[18] are particularly attractive.[19] Calixsalens and their
reduced congeners, calixsalans, are prone to form multi-metal
complexes with and without contraction of the macrocycle ring,
and are used in asymmetric synthesis, as receptors, and as
porous materials.[14,19,20]
The general structure of the calixsalen macrocycle may be
split into two parts. The upper-rim of the macrocycle (head)
contains all polar imine and OH groups (see Figure 1a), and the
latter have a profound effect on the macrocycle structure. The
intramolecular OH•••N=C hydrogen bond cascade involving
phenolic hydrogen and nitrogen imine atoms strongly stabilize
the s-trans conformation of the aromatic linker.[18b] The lower-rim
(tail) contains substituents attached to the macrocycle skeleton.
The type and size of the substituent on the lower-rim controls
the ability of calixsalens to form supramolecules.
Introduction
Since their initial discoveries by Ruzicka, chiral macrocyclic
structures of various kinds have become common synthetic
targets in supramolecular, materials and medicinal chemistry.[1-4]
The presence of different functionalities that may form binding
domains within chiral macrocycle skeletons, together with
specific combinations of conformational flexibility and bias,
makes macrocycles attractive as ligands, catalysts and highly
selective receptors.[5-11] Enantiopure, symmetrical, polyimine and
polyamine macrocycles of triangular, rectangular or rhombic
shapes constitute
a
subclass of chiral macrocyclic
compounds.[12,13] These compounds are versatile ligands in
stereoselective synthesis and efficient enantio-discriminating
agents.[14] Among methods developed so far for chiral polyimine
macrocycle synthesis, those based on the concept of Dynamic
Covalent
Chemistry
provide
molecules
that
are
thermodynamically favored over acyclic oligomer(s). Reversibility
[a]
M. Petryk, Dr. A. Janiak, Dr. M. Kwit
Department of Chemistry, Adam Mickiewicz University
Umultowska 89B, 61 614 Poznan, Poland.
E-mail: agnieszk@amu.edu.pl, marcin.kwit@amu.edu.pl
M. Petryk, Dr. M. Kwit
Center for Advanced Technologies, AMU
Umultowska 89C, 61 614 Poznan, Poland.
Dr. A.Janiak, Prof. L. J. Barbour
[b]
[c]
Figure 1. General structure of the calixsalen molecule a). Known types of host
packing in calixsalen crystals: tail-to-tail dimer b) capsule c) and “a hourglass”
d).
Department of Chemistry and Polymer Science
University of Stellenbosch
7602, Stellenbosch, South Africa.
Supporting information for this article is given via a link at the end of
the document.
Macrocycles substituted at the C-5 position by small and/or
polar groups such as halogens form mostly tail-to-tail dimers
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10.1002/ejoc.201800314
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(Figure 1b) by mutual insertion of one aromatic moiety of each
monomer into the cavity of a partner. The formation of the tail-to-
tail dimers is highly stereoselective and is driven solely by non-
covalent interactions, such as dipole-dipole and π-π
stacking.[21,22] Calixsalens having bulky groups of spherical
symmetry at the C-5 position crystallize as capsules (head-to-
head dimers) capable of solvent molecule entrapment (Figure
1c). The capsules are only stable in the solid state and
decompose immediately after dissolution.[21]
C-5 Functionalization of the calixsalen skeleton by small
OH groups increases hydrophilicity of the macrocycle lower rim
and favors the formation of supramolecular organic frameworks,
which consists of both the hourglass-like (Figure 1d) and
capsule assemblies stabilized by hydrogen bonding networks.
These coexist in the same crystal.[23]
The results reported so far clearly indicate that the
possibilities for creating supramolecular systems from
calixsalens are still unexplored. Thus, continuing our work on
chiral functionalized macrocycles, we have extended our study
to systems having aromatic units at the periphery of the
calixsalen skeleton. The presence of a π-electron hydrophobic
part may influence molecular conformation and solid-state
supramolecular architecture of the given macrocycle. This in turn
has helped to further our understanding of which structural
factors control the processes of calixsalen assembly.
50% (entries 4 and 7, Table S1 in the SI). Prolonging the
reaction time and altering the conditions (change of catalyst,
base and/or solvent) did not improve the results (all details
regarding synthesis are given in the Experimental Section in the
SI).
The macrocycles 4a-4i were obtained by the reaction of
equimolar amounts of the respective dialdehyde 3a-3i and
optically pure (1R,2R)-DACH, in dichloromethane solutions and
under an inert atmosphere. The concentration of each substrate
did not exceed 0.05 mol dm-3 and the reaction time was 24
hours. The products 4a-4i were isolated and purified by dilution
of the reaction mixture with methanol, filtration of the precipitate
and crystallization from
a
dichloromethane-methanol or
dichloromethane-acetonitrile mixture of solvents. This approach
provided analytically pure 4a-4c and 4g-4i as yellow
microcrystalline powders with yields ranging from 40 to 85%
(see Table S1 in SI). The abovementioned procedure failed for
calixsalens 4d-4f and our attempts to purify the crude products
either by precipitation or by crystallization were unsuccessful.
For 4d-4f, the yields of the trimeric products were estimated
based on the 1H NMR data only.
Taking the cyclocondensation as
a turning point in
synthesis, modification of the calixsalen structure is possible in
two ways: either by modification of substrates (pre-cyclization
approach) or by modification of the product (post-cyclization
approach). However, the latter has limited applicability due to
the instability of the imine bonds under harsh reaction conditions.
We decided to synthesize a series of 2-hydroxyisophthalic
aldehydes, having various aryl substituents at the C-5 position[24]
that were further used as substrates in cyclocondensation
reactions with (R,R)-DACH. Representative calixsalens obtained
in this way were further investigated by means of experimental
and theoretical methods. Special emphasis was placed on
single-crystal X-ray diffraction for the characterization of
supramolecular assemblies in the solid state.
Scheme 1. The general procedure of synthesis of calixsalens 4a-4i from C-5-
aryl substituted aldehydes 3a-3i.
The [3+3] trimeric structure of the pure 4a-4c and 4g-4i
was confirmed by MS and HR MS analyses. The molecular ion
peaks correspond to the (M+H)+ ions of the [3+3]
cyclocondensation products and no other products were
1
detected. The H NMR spectra of 4a-4c and 4g-4i measured in
Results and Discussion
CDCl3 showed the complete disappearance of aldehyde CHO
signals, and two characteristic peaks for the imine CHN protons
appeared at around 8.8 and 8.3±0.1 ppm (see Table S1 in SI), in
agreement with the preferred s-trans conformation of the bis-
imine system.[18b,21] The spectral regions between 8.1 and 6.5
ppm cover all C-H aromatic protons. These signals are slightly
broadened at ambient temperature, apparently due to the
hindered rotation around the aryl-aryl bond. The number of
signals appearing in the aromatic region confirmed the C3-
symmetrical structure of the given macrocycle. Another
characteristic feature found in the 1H NMR spectra of the
macrocycles under study is the position of OH signals, which
appear at around 14.35±0.15 ppm (see Table S1 in SI),
depending on the substituent at the C-5 position.
Synthesis
The general route to C-5 arylated calixsalens (4a-4i) is shown in
Scheme 1. As the method of choice for synthesis of aldehydes
3a-3i we employed palladium-catalyzed Suzuki reactions
between 5-bromo-2-hydroxyisopthalaldehyde (1) and the
respective boronic acids (2a-2i). In the majority of the cases, the
isolated yields did not exceed 50% after column chromatography.
The best result (64% yield) was obtained for the simplest 2-
hydroxy-5-phenylisopthaldehyde (2a) (see Supplementary
information, Table S1, entry 1). Either the boronic acids
substituted by electron-withdrawing (2d) or electron-donating
(2g) groups gave similar yields of the respective products, ca
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The reaction between DACH and aldehyde 3d is a special
case. We expected diverse reactivity of the formyl groups due to
their different chemical surroundings. Two of the formyl groups
are ortho with respect to the OH group; thus, one of the newly
formed imine bonds will be stabilized by OH•••N hydrogen
bonding. The third formyl group is the most accessible; however,
there is no possibility for stabilization of the imine bond by
hydrogen bonding. The cyclocondensation between equimolar
amounts of (1R,2R)-DACH and 3d provided a [3+3] macrocycle
as the major product, as confirmed by MS analysis. The 1H NMR
spectrum of crude 4d did not show the CHO signals from the
formyl groups surrounding the OH group. The two peaks of the
CH=N imine protons appeared at around 8.76 and 8.34 ppm,
whereas CHO signal (δ = 9.98) of the formyl group attached to
aryl substituent at C-5 remains unchanged. Unfortunately, at the
same time, the 1H NMR spectrum of crude 4d shows the
presence of small amounts of contaminants (see Supplementary
Information) and our attempts to purify the product have been
unsuccessful thus far.
For the non-symmetrical aryl substituents, such as 1-naphthyl,
their relative orientations either opens the macrocycle cavity (ON
state, open) or closes it (OFF state, closed), as presented in
Scheme 2. The ON and OFF conformers represent the extreme
cases characterized by C3 symmetry and may exist in
equilibrium with a number of conformers having C1 symmetry,
where one or two substituents is in either the closed or the open
conformation.
The thermally-accessible structures of 4h were obtained
through a multi-steps computational procedure, involving (i) a
systematic conformational search at the PM6 semi-empirical
level;[26] (ii) geometry optimization of the first 100 low-energy
conformers at the B3LYP/6-31G(d) level; (iii) re-optimization of
the structures thus obtained at the B3LYP/6-311G(d,p) level
employing the IEFPCM solvent model of chloroform;[27] (iv)
calculations of the ECD spectra for the thermally-accessible
structures, by employing CAM-B3LYP[28] and M06–2X[29] hybrid
functionals, all in conjunction with the 6-311G(2d,2p) basis set
and IEFPCM solvent model.[27] For each conformer the 150
electronic transitions were calculated. The calculated ECD
spectra were Boltzmann averaged by taking into account
conformers ranging from 0 to 2.0 kcal mol-1 in relative ΔΔG
energies, following a generally accepted protocol.[25] The ECD
spectra were simulated by overlapping Gaussian functions for
each transition, with 0.4 eV at a half-height, according to the
procedure previously described by Harada and Stephens.[30]
Since the difference between ECD spectra calculated by means
of both DFT methods were negligible, we only discuss the
results obtained employing the CAM-B3LYP hybrid functional.
The same protocol was applied to model compounds composed
of one third of the parent macrocycle 4h (the remaining results
are deposited as supplementary material).
ON-OFF conformation of 4h from 1H NMR and ECD
measurements and DFT calculations
While the conformation of the macrocycle core is essentially
invariant, the aryl substituents at the periphery may adopt
different orientations to minimize steric repulsion between
hydrogen atoms and/or substituents in ortho positions. The
representative example for discussion of molecular conformation
of those compounds is calixsalen 4h.
Temperature-dependent 1H NMR spectra of 4h, shown in
Figure 2, confirm the preference of non-symmetrical over
symmetrical conformers. At room temperature all signals in the
diagnostic, aromatic region of the spectrum are averaged, which
suggests rather unrestricted rotation of the aryl substituents. The
most indicative CH=N peaks appear as a pair of singlets, which
correspond to the s-trans conformation of bis-imine system and
the overall C3-symmetry of the molecule. Upon gradual cooling
of the sample to -70 °C, broadening occurs at first, followed by
signal splitting. The total number of CH=N signals increases to
14 and some of them are partially overlapped. A similar situation
is observed for peaks originating from CH aromatic protons and
from labile OH protons. The latter at the lower temperature are
downfield shifted and split into five overlapped signals. The data
obtained from 1H NMR measurements suggest a rather complex
conformational equilibrium rather than the existence a single
conformer characterized by trivial C1 symmetry.
Scheme 2. ON-OFF conformational change in 4h. The green boxes at the top
of the vases represent non-symmetrical aryl substituents, red balls represent
hydroxyl groups.
To shed light on the structural preference of calixsalen 4h
we performed in depth experimental and theoretical studies.
Since X-ray diffraction data were unavailable for this particular
case, the conformational dynamics of 4h were determined
primarily by comparison of experimental and calculated
electronic circular dichroism (ECD) spectra and variable-
temperature 1H NMR measurements. It has been shown that
agreement between experimental and calculated chiroptical
properties unequivocally confirms not only the postulated
favored structure of the given compound but also shed light on
its conformational dynamics.[25]
This conclusion remains in agreement with theoretical
results. As expected, calixsalen 4h is not characterized by one
low-energy structure in particular. The number of thermally
accessible low-energy conformers reached 10. From them the
ΔΔG-based lowest energy conformer is also the most abundant
(see Table 1 and Figures 3 and S1 in SI).
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10.1002/ejoc.201800314
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steric repulsions between the naphthalene groups. As a result,
in the thermally accessible conformers of 4h at least one of the
naphthyl groups retains in open conformation.
At the final stage of the analysis we compared the
experimental, the ΔΔG-based and the Boltzmann averaged
calculated ECD spectra of 4h (see Figure 3 and Figures S3-S6
in SI). It worth noting that the calculated ECD spectrum of 4h is
dominated by the most abundant the lowest-energy conformer
no. 29 (see Figure S7 in SI).
Figure 2. Traces of variable-temperature 1H NMR spectra [CD2Cl2, 400 MHz]
of calixsalen 4h.
The characteristic feature of this and its related structures
is the presence of O-H•••N intramolecular hydrogen bonds
between hydroxyl groups and the imine nitrogen atoms in syn
conformation that stabilize the macrocycle skeleton.[21] The
conformation of the aryl substituent in each fragment of the
molecule can be conveniently described in terms of P and M
helicity, if we prioritize the imino group involved in hydrogen
bonding over the non-hydrogen bonded one.[31] P Helicity is
defined for 0° < ω < 180° and M is defined for twist angle ω
adapting values between -180° and 0°, where ω is the angle
defined by the sequence of C6-C5-C1'-C9' carbon atoms. The
overall structure of the lowest energy conformer of 4h is
characterized by P,P,M-helicity of the biaryl moieties that
correspond to ω values of 59, 124 and -120 degrees. It is more
illustrative to describe this particular conformer as partially
closed, since two of the three naphthyl groups are directed away
from the centre of the macrocycle, whereas the third one closes
the macrocycle cavity. This particular conformation is the
superposition of a few opposing factors. First, conformers
characterized by values of the ω angle equal to ±60° and ±120°
represent the energetic minima. When one or more naphthyl
groups adopt the closed conformation, the calculated dipole
moment decreases. Additionally, the conformers having at least
two groups closing the macrocycle cavity might be stabilized by
CH•••π interactions between adjacent aromatic rings. However,
the C3-symmetrical OFF conformer is neither the energy
minimum nor a stable structure, which is apparently due to the
Figure 3. UV (upper panel) and ECD spectra (lower panel) of calixsalen 4h
measured in chloroform (black lines) and calculated at the IEFPCM/TD-CAM-
B3LYP/6-311G(2d,2p) level and ΔΔG-based Boltzmann averaged (red lines).
The calculated spectra were wavelength-corrected to match the experimental
short-wavelength UV maximum. Insert shows structure of ΔΔG-based the
lowest-energy conformer of 4h, calculated at the IEFPCM/B3LYP/6-311G(d,p)
level. For clarity some hydrogen atoms were omitted and naphthalene
substituents were green-colored.
The experimental ECD spectrum of 4h is rather complex
and characterized by the presence of a negative exciton couplet
corresponding to the UV absorption band around 350 nm, and
by partially overlapping CD bands originating from the higher-
energy electronic transitions. In the interpretation of the
experimental ECD spectrum, calculations carried out for model
compounds have become useful (see Supporting Information for
details). In general, the ECD spectrum constitutes of two parts.
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The lowest-energy exciton couplet and the negative Cotton
effect at around 300 nm originate from electronic transitions
within the macrocycle core (macrocycle 4h without naphthalene
subtituents). The low-energy electronic transitions involve imine
chromophores. Since these transitions are polarized along the
line connecting the nitrogen atoms, the negative sign of the low-
energy exciton couplet is in agreement with the negative helicity
of the N-C*-C*-N torsion angle (see Figure S8 in SI).
even at low temperature, the quality of the X-ray data recorded
was poor. Consequently, it was not possible to reliably
determine all positions of solvent molecules for most of the
crystals. Therefore, their unresolved electron densities were
treated with SQUEEZE, as implemented in Platon.[32] All details
regarding SQUEEZE treatment are provided in the SI.
The higher-energy region of the ECD spectrum is
dominated by the exciton interactions between the napthalene
substituents. The negative exciton couplet originating from these
interactions partially overlaps the Cotton effects from the
macrocycle core. As a result, the higher energy region of the
ECD spectrum displays the -/-/+ sequence of the Cotton effect.
To summarize this paragraph, we may conclude that the
calculated at the IEFPCM/CAM-B3LYP/6-311G(2d,2p) level and
the Boltzmann averaged the ECD spectrum remains in very
good agreement with the experimental one, by this way we
confirmed the postulated preferred structure of the macrocycle
4h.
Table 1. Relative energies (ΔE, ΔΔG in kcal mol-1), percentage populations
(Pop), values of ω angles (in degrees) and helicities calculated for individual
conformersa of 4h at the IEFPCM/B3LYP/6-311G(d,p) level of theory.
Conformer
no
ΔE
Pop
ΔΔG
Pop
ω
Helicity
4
0.28
0.60
0.53
0.23
0.00
0.39
0.65
0.38
0.47
0.28
12
7
1.10
0.00
1.31
1.10
1.62
0.71
1.38
1.02
1.05
1.37
7
-120
-120
-127
-59
-122
124
-65
123
-60
59
61
MMP
MPP
MMP
MPP
MMP
MPP
MMM
MMP
MPP
MPP
29
31
34
50
69
64
89
94
100
43
5
60
7
123
126
125
60
13
18
9
7
3
-57
13
4
-119
-58
6
-63
-62
61
-128
57
10
8
8
-59
7
-58
124
123
Figure 4. Orientation of the C-5 peripheral substituents in the symmetry-
independent molecules of 4c (a), 4g (b) and 4i (c). The disordered moieties of
molecule 2 in crystals 4c and 4g are shown in red and green.
11
3
-64
59
[a] conformers are number according to their appearance in conformational
search
The single-crystal X-ray diffraction analyses revealed that
C-5 arylated calixsalens 4c and 4g crystallize in the
orthorhombic space group P212121 while 4i crystallizes in the
trigonal space group R32. The asymmetric units of 4c and 4g
each consist of two symmetry-independent macrocycles that
occupy general positions. While one molecule in both structures
is completely ordered, the other displays disorder that involves
one of the three peripheral substituents. The disordered model
considers that atoms of the C-5 aryl substituent can be split over
two equivalent positions. Despite the fact that calixsalens 4c and
4g formally have C3 symmetry, they remain unsymmetrical in the
solid state. On the other hand, 4i, crystallizes with one molecule
in a general position and the other molecule situated on a three-
Solid-state supramolecular architectures of 4c, 4g and 4i
Crystallization experiments were carried out using common
organic solvents; however, it was not possible to obtain crystals
in most cases. However, after many attempts, we were able to
grow the crystals of 4c, 4g and 4i by slow evaporation from
acetone (4i), acetonitrile (4g) and a mixture of acetonitrile and
dichloromethane (4c) solutions at room temperature.
Calixsalens 4c, 4g and 4i form inclusion crystals with the solvent
used for crystallization. Since all of the crystals investigated
were unstable under ambient conditions and easily lose solvent,
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10.1002/ejoc.201800314
European Journal of Organic Chemistry
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fold axis. Hence, its asymmetric unit contains one and a third
molecules of 4i. In structures 4c and 4g it was possible to locate
some solvent molecules in the asymmetric unit. In both crystals
the solvents occupy two different voids; while in 4c one molecule
of acetonitrille and half a DCM molecule are located in the
extrinsic space. In 4g two acetonitrille molecules occupy the
intrinsic pores of the capsule.
the crystals of chiral calixsalens substituted by bulky tert-butyl
groups and in all racemic crystals having both large and small
groups attached to the calixsalen skeleton.[21,22]
The two symmetry-independent macrocycles in the
structures of 4c, 4g and 4i differ subtly in the orientation of the
biaryl moieties and this effect may be enhanced in the presence
of disorder. In 4c the twist angle ω adopts values of -21, -38
and -53° in molecule 1, which corresponds to the M,M,M helicity
of the biaryl moieties while in molecule 2, due to disorder, the
helicity of the biaryl moieties can be described by sets of ω
values that are either 54, -19 and -30° (P,M,M) for the ON state
or -62, -19 and -30°(M,M,M) for the OFF state. In 4g, the
corresponding twist angle adopts values of 48, 51 and 81° in
molecule 1, and 33, 40 and 61/54° in molecule 2. Thus, both
macrocycles display the same P,P,P-helicity but different states
(ON/OFF). While molecule
1
adopts
a
partially open
conformation, in molecule 2 the peripheral substituents are
directed towards the macrocyclic cavity and thus obscure its
entrance. In turn, molecule 1 of 4i is characterized by P,P,P-
helicity that corresponds to ω values of 32, 33 and 37°, while
molecule 2 displays the opposite M,M,M-helicity with all twist
angle values of -38°. The van der Waals representations of the
4c, 4g and 4i are shown in Figure 4.
In all crystals investigated, calixsalens display a diverse
set of supramolecular architectures. In crystals of 4c two
symmetry-independent molecules self-assemble into a tail-to-tail
dimer by mutual insertion of one of the biaryl moieties of each
molecule into the cavity of the other macrocycle, as shown in
Figure 5a. This dimeric arrangement, commonly observed in the
crystals of calixsalen with small and/or polar groups at the C-5
positions, is stabilized by π•••π stacking interactions with short
centroid-centroid distances of 3.645
Å and supported by
numerous weak C-H•••π and C-H•••N interactions. Within the
dimers, molecules are tilted toward each other by 70°.
Despite similarity in the size of the aryl substitutuents in 4c
and 4g, these macrocycles self-assemble differently. Unlike 4c,
the two symmetry-independent molecules in 4g are situated
above each other in a head-to-head manner and are mutually
twisted by about 60°. This arrangement promotes the formation
of capsules (see Figure 5b). Each capsule thus obtained is
stabilized by five C-H•••O intermolecular interactions (H•••O
distances ranging from 2.34 to 2.68 Å). Symmetry expansion of
the asymmetric unit shows that two neighboring capsules are
mutually tilted by 74° and the intermolecular interactions
between them are limited to the C-H•••π (mean H•••π distance is
2.83Å) and C-H•••O (H•••O distance is 2.64 Å) interactions. The
solvent-accessible space of 212 Å3 inside the capsule is fully
occupied by acetonitrile molecules that can easily be removed
from the cavity under ambient conditions. This tendency is
supported by the open conformation of one of the two
macrocycles constituting the capsules, which, in consequence,
allows the solvent molecules to escape. Our previous studies
show that this type of solid-state arrangement was observed in
Figure 5. Perspective view of the supramolecular assemblies observed in the
crystals investigated: a) The tail-to-tail dimer in 4c, b) head-to-head capsule
containing two solvent molecules in the void of 212 Å3 in 4g and tetramers with
truncated tetrahedron shape voids volume of 732.864 Å3 in 4i c). The solvent
accessible volume is shown as pink Connolly surfaces[33] using a probe radius
of 1.5 Å. The guest molecules are shown as space-filling models.
In contrast, in the crystal structure of 4i, two symmetry
independent molecules display preferences to self-organize in a
head-to-head manner. In this case, however, the arrangement
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does not lead to dimers but rather favors the formation of large
sized supermolecules that are constructed of three molecules of
type 1 and one molecule of type 2 of 4i. Such spherical
cycloimination
between
optically
pure
trans-1,2-
diaminecyclohexane and the respective C-5 aryl substituted 2-
hydroxyisopthaldehyde. The aldehydes are conveniently
synthesized by Suzuki coupling.
arrangement of four neighboring macrocycles generate
a
truncated tetrahedron shaped cavity with a mean diameter of ca
8.5 Å and encloses 733 Å3 of solvent occupied space, as shown
in Figure 5c. Within the tetrameric capsule, the macrocyles are
held together solely by weak C-H•••O and C-H•••π
intermolecular interactions with H•••O distances of 2.65 Å and
H•••π distances of 2.79 Å, respectively. Notably, this is the first
observation of these types of head-to-head tetramers that are
maintained by the weak non-covalent interactions and hence it
represents an important extension to the known self-assembly of
similar types of architecture that are mostly based on covalent
bonds and/or hydrogen bonds. Extension of the crystal packing
reveals interdigitation of the 2-naphthyl tails of the tetrameric
supermolecules. Interestingly, this motif appears only between
symmetry-independent macrocycles in which molecule 2 inserts
one of the three 2-naphthyl substituents into the cavity of
molecule 1 belonging to the neighboring supermolecule. In this
assembly the intermolecular interaction is only observed
between two 2-naphthyl moieties that are not parallel to each
other; the dihedral angle between their planes is 52°. Such
orientation of two moieties leads to formation of C-H•••π
intermolecular interactions with H•••π distances of 2.78 Å that
are responsible for stabilization of this supramolecular motif (see
Figure 6).
Formal C3 symmetry of the macrocycle (e.g. 4h) is not
evidenced in solution, as indicated by ECD spectra, variable-
temperature 1H NMR measurements and theoretical calculations.
The same behavior is observed in the solid-state structures of
4c and 4g, but not in 4i, which maintains formal C3 symmetry in
the crystals. Despite the presence of bulky substituents attached
to the aromatic ring that potentially can prevent interdigitation in
the solid state, this type of assembly is observed in crystals of
4c and 4i. However, in 4i it does not lead to formation of the
high-order structure in the solid state. Calixsalen 4i forms
supermolecules that consist of four monomers arranged in a
head-to-head fashion and gives rise to
a novel type of
supramolecular architecture that has not previously been
observed for this class of compounds.
Experimental Section
For synthetic procedures, full characterization of all new compounds,
calculation details and X-ray diffraction experimental details see the
Supporting Information. CCDC 1819412-1819414 contain the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
The authors thank the National Science Centre in Poland, grants
no
UMO-2012/06/A/ST5/00230
(AJ,
MK)
and
no
2017/24/T/ST5/00121 (MP), and the National Research
Foundation of South Africa (AJ, LJB), for financial support. All
calculations were performed at Poznan Supercomputing and
Networking Centre (grant no 217).
Keywords: supramolecular assemblies • chiral calixsalens •
tetrameric capsules • solid state architecture • egzo-
functionalization
Conflict of interest
The authors declare no conflict of interest.
Figure 6. Packing mode of two neighboring supermolecules and their mutual
interactions in the crystals of 4i.
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Key Topic*
Novel C-5-functionalized calixsalens
show substituent-driven self-
association that can lead to the
formation of supramolecules in the
solid state.
Małgorzata Petryk, Agnieszka Janiak,*
Leonard J. Barbour, and Marcin Kwit *
Page No. – Page No.
Awkwardly-shaped dimers,
capsules and tetramers:
molecular and supramolecular
motifs in C5-arylated chiral
calixsalens
*calixsalen self-assembly
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