Conformational polymorphism and amphiphilic properties of resorcinarene octapodands

Article abstract of DOI:10.1039/c0ob00602e

o-Nitroaniline functionalized resorcinarene octapodands 1-5 with pendant methyl, ethyl, pentyl, nonyl or 1-decenyl groups, respectively, were synthesized and their structural properties investigated using X-ray crystallography and NMR spectroscopy. The up

Full text of DOI:10.1039/c0ob00602e

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PAPER
Conformational polymorphism and amphiphilic properties of resorcinarene
octapodands†
Kaisa Helttunen,a Elisa Nauha,a Anni Kurronen,a Patrick Shahgaldianb and Maija Nissinen*a
Received 18th August 2010, Accepted 25th October 2010
DOI: 10.1039/c0ob00602e
o-Nitroaniline functionalized resorcinarene octapodands 1–5 with pendant methyl, ethyl, pentyl, nonyl
or 1-decenyl groups, respectively, were synthesized and their structural properties investigated using
X-ray crystallography and NMR spectroscopy. The upper rim of each podand is identical containing
flexible side arms, in which rotation around the -OCH2CH2N- linkers create excellent possibilities for
polymorphism. Two conformational polymorphs of acetone solvate of 2 were identified containing
different side arm orientation and crystal packing. Compound 1 crystallized from acetone and
nitromethane yielding two pseudopolymorphs with different packing motifs. The longer alkyl chains of
3–5 lead to differences in solubility and induce amphiphilic properties, which were studied at the
air–water interface using the Langmuir-film technique. Crystals of amphiphilic compound 5, which has
hydrophobic alkyl tails at the lower rim and hydrophilic nitroaniline groups at the upper rim, showed
an interesting packing motif with alternating aromatic and aliphatic layers. Versatile structures of the
octapodands in solid state and in solution serve as an example of how conformational flexibility can be
utilized in crystal engineering and creating self-assembling monolayer structures.
Resorcinarenes and calixarenes seem to present unlimited
Introduction
possibilities for crystal engineering and creating new supramolec-
ular architectures such as nanotubes,33,34 preorganizing arrays of
Calixarenes and resorcinarenes are widely utilized building blocks
for designing supramolecular hosts and self-assembling struc-
tures since they offer a concave binding cavity and diverse
synthetic pathways for obtaining desired functionalities.1–6 Re-
cently, work in this field has continued to produce increas-
ingly elaborate host molecules for cations,7–12 anions,13,14 ion-
pairs,15,16 neutral guests10,15,16 and biomolecules.17,18 In addition,
unique self-assembling properties of resorcinarenes have been
used to prepare novel nanomaterials with examples ranging from
gold/organic microtubular composites19,20 and coated gold and
cobalt nanoparticles21–24 to dimeric25,26 and hexameric capsules27
and molecular containers.11,12 The design of amphiphilic cal-
ixarenes and resorcinarenes bearing long alkyl chains has provided
interesting applications,26,28 such as templating calcite crystalliza-
tion under monolayers29 and preparation of solid lipid nanoparti-
cles which interact with DNA30,31 or proteins.32
35,36
fullerene C60
and benzil in resorcinarene matrices.37 However,
polymorphism, the existence of two or more different crystal
forms of one compound, which is considered a very important
aspect of crystal engineering,38 has hardly been studied in these
macrocyclic hosts. Resorcinarenes and calixarenes polymorphs
have been found by changing crystallization conditions, such as
solvent, temperature or pressure,39–43 but to our knowledge, there
are not any reported cases where resorcinarenes or calixarenes are
able to form conformational polymorphs44 in identical crystalliza-
tion conditions. However, for calixcrowns,41 a thermally induced
conformational change has been reported, and a case of thermal
polymorphic change for amino acid derivative of calixarene
has been published.39 Investigation of new polymorphs of a
known macrocyclic compound has already provided interesting
applications, such as gas absorption in the crystal lattice of
various calixarenes.45–50 In addition, development of new poten-
tially polymorphic compounds can lead the way to new material
innovations and deeper understanding of the principles directing
the crystallization process.
aDepartment of Chemistry, Nanoscience Center, University of Jyva¨skyla¨,
P.O. Box 35, FIN-40014, University of Jyva¨skyla¨, Finland. E-mail: maija.
nissinen@jyu.fi; Fax: +358 14 260 4756; Tel: +358 14 260 4242
bSchool of Life Sciences, Institute of Chemistry and Bioanalytics, University
of Applied Sciences Northwestern Switzerland, Gru¨ndenstrasse 40, 4132,
Muttenz, Switzerland
Our earlier work with tetramethoxy resorcinarenes has pro-
vided a selection of cation and anion binding receptors by
adding crown ether bridges or pendant groups in upper rim
hydroxyl groups.51–54 A similar synthetic approach has now
been applied to resorcinarenes with the objective of creat-
ing novel self-assembling properties for supramolecular hosts.
† Electronic supplementary information (ESI) available: Synthetic pro-
cedures and NMR spectra for each podand; details of X-ray structure
analysis and crystallographic data. CCDC reference numbers 781919–
781925. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c0ob00602e
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Indeed, a selection of structurally flexible resorcinarene oc-
tapodands were obtained, which exhibit conformational poly-
morphism and in the case of long alkyl chain compounds,
amphiphilic properties, which were demonstrated by preparing
Langmuir-films at the air–water interface, as well as formation
of a crystal structure with alternating aromatic and aliphatic
layers.
long chain podands to produce amorphous powders at 44–54%
yield.‡
Single crystal X-ray crystallography
The octapodands 1, 2 and 5 provided single crystals suitable for X-
ray analysis from nitromethane–CH2Cl2 solution (structures 1A,
2C and 5A respectively). Crystallization from nitromethane was
a slow process, and took several months for all the investigated
compounds providing a selection of yellow needles, blocks, plates
and rods. 1A and 5A were crystallized without nitromethane in
the lattice but 2C, using acetone solvate as a starting material
incorporated two disordered nitromethane molecules per unit
cell. Structure 2D, which crystallized from acetonitrile–CH2Cl2
solution has an isomorphous unit cell and packing with 2C.
Compounds 1 and 2 crystallized from acetone and acetone–
CH2Cl2 solutions as acetone solvates (structures 1B, 2A and
2B), which were only poorly soluble in acetone. Interestingly,
2A and 2B formed simultaneously in the same test tube and
are conformational polymorphs of each other.§ Structure 2A was
obtained from a plate and structure 2B from a needle shaped
crystal. Obtaining several polymorphs simultaneously under the
same crystallization conditions is quite rare; an example of such
a macrocyclic compound is furanotribenzo-21-crown-7 in which
the conformation of the macrocycle is however unchanged.56
Crystallographic data of all structures are presented in Table 1.
The resorcinarene core of all octapodands is in a boat con-
formation since all phenolic hydroxyl groups are alkylated.4 The
angle of the upright resorcinol rings C1–C6 and C15–C20 against
Results and Discussion
Synthesis
Octapodands 3–5 bearing long alkyl chains were prepared by
attaching eight o-nitro-N-(2-hydroxyethyl)aniline units into a
resorcinarene platform using Cs2CO3 or K2CO3 as a base and
dibenzo-18-crown-6 as a phase transfer catalyst in refluxing
acetonitrile (Scheme 1).54 The octapodands were obtained as
yellow amorphous powders with 40–65% yields. Instead of the
tosyl leaving group (compound 6), a mesyl group (compound 7)
can be used in the reaction as was discovered in the synthesis of
3 and 5. TG/DTA analysis of 5 showed gradual decomposition
◦
between 273–600 C without a clear melting point according to
the enthalpy values. Melting point measurements of each synthesis
batch varied between 56 and 77 ◦C and therefore the reported
melting points for amorphous podands should be considered as
rough estimates only.
1 and 2 with pendant methyl and ethyl groups, respectively,
were synthesized using the above mentioned reaction conditions,
but the product was collected from the filtered reaction mixture
by extraction with CH2Cl2 unlike 3–5, which are soluble in
acetonitrile and were collected from the filtrate. In addition, 1
and 2 were recrystallized from hot acetone to provide orange
crystalline solids at 23–31% yield or alternatively treated as the
‡ For some crystallization experiments the amorphous form of 1 and 2 was
used.
§ The original crystallization was made from acetone–DCM by dissolving
part of the sample in acetone and adding DCM until the sample was fully
dissolved. Later on pure acetone and acetone–DCM 3 : 1 were used.
Scheme 1 Synthetic procedure and selected crystallographic numbering for octapodands.
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Table 1 X-ray structure parameters
1A
1B
2A
2B
2C
2D
5A
Crystallization
solvent
Crystal shape
Crystal
size/mm
Formula
nitromethane– acetone
CH2Cl2
acetone–CH2Cl2 acetone–CH2Cl2 nitromethane–
CH2Cl2
acetonitrile–CH2Cl2 nitromethane–
CH2Cl2
block
0.40 ¥ 0.20 ¥
0.20
plate
0.20 ¥ 0.12 ¥
0.08
plate
0.18 ¥ 0.14 ¥
0.02
needle
0.20 ¥ 0.08 ¥
0.02
needle
0.24 ¥ 0.10 ¥
0.04
block
0.20 ¥ 0.10 ¥ 0.10
rod
0.20 ¥ 0.10 ¥ 0.10
a
C96H96N16O24
C96H96N16O24· C100H104N16O24·
C100H104N16O24·
(CH3)2CO
1972.07
11.8347(3)
20.5903(5)
22.5132(7)
113.258(2)
95.992(2)
100.282(2)
4865.6(2)
1.346
C100H104N16O24
C100H104N16O24·
C2H3Na
1955.05
12.0137(3)
20.2750(4)
22.8339(4)
115.072(1)
96.578(1)
99.681(2)
4857.3(2)
1.337
C132H160 N16O24·
1.5H2 O
2381.78
12.6739(5)
20.5874(7)
25.8506(9)
77.841(3)
77.976(2)
74.025(2)
6257.4(4)
1.264
(CH3)2CO
1915.97
11.8003(4)
20.6248(7)
21.2868(8)
110.363(2)
97.492(2)
99.820(2)
4683.8(3)
1.359
(CH3)2CO
1972.07
11.1398(3)
22.0112(6)
22.5117(6)
113.189(2)
100.427(2)
99.965(1)
4804.5(2)
1.363
FW
1857.89
12.2700(3)
19.6334(7)
20.4221(6)
75.230(2)
72.675(2)
75.364(2)
4457.3(2)
1.384
1913.99
11.9965(3)
20.2594(5)
22.8564(5)
114.695(1)
96.9670(9)
99.770(2)
4857.9(2)
1.308
˚
a/A
˚
b/A
˚
c/A
a (◦)
b (◦)
g (◦)
3
˚
Volume/A
Dc/Mg m-3
m/mm-1
0.842
22810
0.826
23546
0.820
0.810
0.787
0.802
0.719
Meas. reflns
Indep. reflns
Rint
23754
16232
21729
14853
24568
16100
23282
16813
20941
14939
15349
0.0584
15426
0.0833
0.1092
0.0979
0.1283
0.0935
0.0743
0.0671
0.0789
0.0651
0.1675
0.1458
R1 [I > 2s(I)]
0.0748
0.0824
0.2008
wR2 [I > 2s(I)] 0.2233
0.2643
1.323
0.2192
1.253
0.1581
1.127
0.1754
1.230
0.3528
1.283
GooF on F2
1.392
1.404
a Disordered solvent molecules were removed using SQUEEZE.55
Table 2 The upright resorcinol ring tilt angles against the C7–C14–C21–
C28 plane
Structure
C1–C6 (◦)
C15–C20 (◦)
1A
1B
2A
2B
2C
2D
5A
76.2
80.2
84.4
80.6
81.2
81.2
100.1
87.1
89.1
88.3
87.1
86.7
87.0
97.6
the methine carbon plane C7–C14–C21–C28 varies between 76.2◦
and 87.1◦ in structure 1A up to 100.1◦ and 97.6◦ in structure 5A
(Table 2), which is the only structure where both resorcinol rings
are pointing slightly outwards opening the resorcinarene cavity.
Structure 5A differs from the other structures quite remarkably,
since 5 is the only podand that has long 1-decenyl groups at the
lower rim capable of packing next to each other due to van der
Waals interactions. The packing of short alkyl chain podands 1
and 2 is directed by intermolecular hydrogen bonding of nitro and
amine groups as well as p–p interactions between aromatic rings.
In general, the eight nitroaniline side arms at phenolic oxygens
can be divided into two groups depending on whether they are
bound to upright or horizontal resorcinol rings (Fig. 1): ‘top’
(O4, O6, O18 and O20, named after the oxygen atom they are
attached to) which extend on top of the resorcinarene cavity and
‘alongside’ (O11, O13, O25 and O27) which point to the sides
of the cavity. Most structures have their ‘alongside’ side arms
in a vertical position but there is a little more variation in the
‘top’ side arm positions (see Table 3 for O–C–C–N distortion
angles). In addition, podands form an upper rim interface where
the resorcinarene cavities of two molecules approach each other,
and tail-to-tail interface, where alkyl chains of the podands face
each other.
Fig. 1 Different orientations of the ‘top’ and ‘alongside’ side arms. The
horizontal conformation of ‘top’ side arms is either ‘in’ or ‘out’ of the
resorcinarene cavity.
Structure 1A has three ‘top’ side arms in horizontal orientation
(O4, O6 and O18), where side arms O4 and O6 form an intermolec-
ular p-stack at the upper rim interface (Fig. 2). The remaining
side arm O20 forms additional p-stacking with the resorcinol ring
(C1–C6) not observed in other structures. Two of the ‘alongside’
side arms, O25 and O27 have twisted vertical conformations with
distortion angles 73.6◦ and -67.4◦, respectively, and they form
intermolecular edge-to-face p-interactions between two parallel
molecules. In addition, the side arm O25 approaches the resorcinol
ring (C8–C13) forming another edge-to-face p-interaction at the
tail-to-tail interface. Side arm O13 is horizontally oriented forming
a p-stack with side arm O18 of the neighboring parallel molecule.
Side arm O11, however, is between a horizontal and a vertical
conformation forming an edge-to-face p-interaction with C22–
C27 resorcinol ring of another molecule at the tail-to-tail interface,
which explains the twisted conformation of the side arm O11.
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Table 3 O–C–C–N distortion angles of the side arms
Structure
O4 ◊ ◊ ◊ N1
O6 ◊ ◊ ◊ N3
O11 ◊ ◊ ◊ N5
O13 ◊ ◊ ◊ N7
O18 ◊ ◊ ◊ N9
O20 ◊ ◊ ◊ N11
O25 ◊ ◊ ◊ N13
O27 ◊ ◊ ◊ N15
1A
1B
2A
2B
2C
2D
5A
55.3(4)
-52.1(4)
56.8(4)
-165.0(4)
68.9(6)
-66.2(3)
-66.3(3)
70.9(10)
84.1(4)
-42.0(8)
135.1(8)a
-174.5(4)
152.1(6)a
-170.4(3)
-171.0(3)
176.9(8)
74.5(4)
63.7(5)
171.7(4)
61.0(7)
-63.4(4)
-62.8(4)
76.3(9)
171.3(3)
-177.0(3)
-72.7(5)
178.9(4)
-176.2(3)
-176.9(2)
-74.3(10)
73.6(3)
-67.4(3)
-51.6(9)a
75.8(7)
173.2(4)
-179.2(3)
178.6(2)
-170.3(9)
-64.4(5)
-63.1(5)
-62.8(6)
61.5(4)
60.4(4)
-66.1(10)
178.8(3)
-175.7(4)
-176.0(5)
168.3(3)
168.3(3)
164.0(11)
150.0(5)a
173.2(5)
-156.9(6)
156.2(4)
160.1(3)
-168.3(15)a
a For disordered side arms the distortion angle for the part with higher site occupancy is reported.
Fig. 2 Structure 1A (side view) and packing illustrating p–p-interactions between side arms ‘O4’ and ‘O6’, ‘O11’ and C22–27, ‘O20’ and C1–C6, ‘O25’
and ‘O27’ as well as ‘O25’ and C8–13. p-stacking between side arms ‘O13’ and ‘O18’ is not shown.
Altogether, the p–p interactions of 1A lead to a network like
packing instead of rows of parallel molecules found in all other
structures.
O20 (Fig. 3). The upper rim interface of 2A is held together by
intermolecular hydrogen bonding between side arms O6 and side
arms O18 and O27 (N3–O103 and N15–O109) instead of pairing
through side arms O20 (Fig. 4).
Acetone solvate 1B crystallized from acetone providing beau-
tiful block shaped crystals of relatively good quality. 1B has an
isomorphous unit cell and closely related structure to acetone
solvate 2B, structure 2C and acetonitrile solvate 2D. All of them
can be characterized by rows of molecules joined together by p-
stacks of four ‘alongside’ side arms (Fig. 3). Rows of podands pack
next to each other forming an edge-to-face p-interaction between
side arms O18 and O4. At the upper rim interface, rows are
shifted with respect to each other, and connect through intertwined
side arms O20 penetrating into the neighboring resorcinarene
cavity (edge-to-face interaction with side arm O18), as well as
O4 ◊ ◊ ◊ O4 p-stacking with another podand. At the tail-to-tail
interface intermolecular hydrogen bonds between side arms O11
(nitro and amine groups) of nearby molecules connect two layers.
In structure 2B, an acetone molecule is hydrogen bonded into
N–H (N15) group whereas in 1B the acetone molecule is simply
positioned between the side arms O4 and O6 on top of the cavity.
In 2A, which is a conformational polymorph of 2B, an acetone
molecule is hydrogen bonded into N5, and rows of podands pack
next to each other forming a more pronounced step like pattern
with intermolecular p-interactions between side arms O4 and
Structure 5A with pendant 1-decenyl groups at the lower rim
has a very symmetrical arrangement of the side arms with similar
p-stacking of four ‘alongside’ side arms as structures 1B and 2B–
D. In addition, the ‘top’ side arms are folded horizontally on top
of the cavity, where each podand finds a pair in the facing row
of podands through p–p-interactions of side arms O4 with O18,
and O6 with O20. The facing rows of podands pack next to each
other forming almost continuous layers of aromatic and aliphatic
components through the crystal (Fig. 5) and since the aromatic
part contains hydrophilic nitroaniline groups, compound 5 could
present amphiphilic properties.
An indication of the versatile possibilities for these molecules to
pack in the solid state is yet another structure of 1 obtained from
the same crystallization experiment as structure 1A containing a
disordered solvent molecule. The data completeness was too low
to provide decent temperature factors, but nevertheless, a different
unit cell¶ and packing motif were confirmed, where all side arms
◦
˚
˚
˚
¶ a = 14.6212(7) A, b = 16.7373(7) A, c = 19.5562(10) A, a = 75.57(3) , b =
◦
◦
3
˚
89.870(2) , g = 87.986(3) , V = 4631.9(4) A
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4
◦C and crystals were filtered and dried briefly under vacuum.
The X-ray diffraction patterns were compared with the calculated
patterns of structures 2A and 2B showing that fast crystallization
produced more structure 2A and slow crystallization more struc-
ture 2B (Fig. 6).ꢀ In addition, when acetone was removed rapidly
under vacuum, only amorphous product was obtained indicating
that crystallization process does not occur instantaneously.
When samples were placed under vacuum for more extended
period, their diffraction pattern changed due to the loss of
acetone and resulting changes in the lattice. After drying, unit cell
parameters for a plate and a needle were collected and the plate
matched still with the unit cell of 2A but the parameters for a needle
did not match either 2A or 2B, which indicates that structure 2A
might be more durable against collapse of the lattice when acetone
is removed since its upper rim interface is hydrogen bonded. Based
on these observations it seems that structure 2A forms faster than
2B when the system has more thermal energy (higher T), but both
2A and 2B are stable at room temperature and 4 ◦C, as well as
-100 ◦C where single crystal data were collected. However, visual
observation of the microcrystalline samples showed that they all
contained both plates and needles, and the amount of plates and
needles did not correspond to the ratio of 2A and 2B in the powder
diffraction pattern.
Amphiphilic properties
The structural mobility and amphiphilic properties of the resor-
cinarene octapodands in solution were examined using NMR
1
spectroscopy and Langmuir monolayer studies. Broad H NMR
resonances of 5 in CDCl3 indicate that conformational changes
occur approximately at the NMR timescale. Cooling to sub-zero
temperatures slowed the movement below the NMR timescale
where individual conformers could be observed as separate
resonances appearing in the spectrum. Heating the sample to
60 ◦C, on the other hand, accelerated the movement which
was observed as sharpening of individual resonances as well as
improved resolution.
Interestingly, the rate of the conformational change could
be adjusted by dissolving 5 in a more polar solvent, such as
[D6]acetone, in which sufficient resolution could be obtained at
30 ◦C (Fig. 7). In [D6]DMSO the effect was even more profound.
The behavior where polar solvent increases the mobility of polar
parts of the molecule is known for amphiphiles,57,58 and is expected
to cause the observed changes for the octapodands as well.
For 3 and 4 the polarity of the solvent had a similar effect in the
1H resonances whereas for 2 the effect was not as clear. Podand
1, which contains short methyl groups at the lower rim, showed
separate 1H resonances for upright and horizontal resorcinol rings
Fig. 3 Packing of structures 2A (top), 2B, 2C, 2D and 1B (bottom)
showing intermolecular hydrogen bonding (donor–acceptor) and omitting
hydrogen atoms; solvent molecules are shown as CPK models except for
structure 2C, in which solvent molecules were removed by SQUEEZE.
have a vertical arrangement and podands are arranged in rows as in
acetone solvate 1B but where the upper rim interface is connected
by intermolecular hydrogen bonding as in acetone solvate 2A.
◦
at 30 C indicating slower boat-to-boat interconversion than for
other podands. At -30 ◦C all nitroaniline protons except a proton
ortho to the -NH group appear as two separate patterns in the
spectrum and belong either to the upright or horizontal resorcinol
ring according to 1H, 1H COSY and NOE spectra. NMR spectra
are given in the ESI.†
Powder X-ray diffraction
To elucidate the polymorphism and relative stability of the acetone
solvates 2A (plate) and 2B (needle) powder X-ray diffraction
experiments were carried out. Compound 2 was crystallized
several times from acetone varying the crystallization speed and
temperature. Fast crystallizations were conducted at room tem-
perature by letting acetone evaporate overnight, which provided
microcrystalline products. Slow crystallization was performed at
Amphiphilicity of the podands 3–5 was confirmed by recording
isotherms for monolayers of the podands on water, whereas 2 did
ꢀ Since powder X-ray patterns were measured at ambient temperature and
single crystal data at 173 K, it should be noted that comparison between
them has some limitations.
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Fig. 4 Comparison of polymorphs 2A and 2B; intramolecular hydrogen bonds are shown with dashed lines (donor–acceptor), hydrogens are omitted
for clarity.
Fig. 5 Structure 5A top view as a CPK model (a), solvent molecules are omitted for clarity. Packing (omitting hydrogens) viewed perpendicular to the
plane of rows of podands (b), 90◦ rotation counterclockwise (c) illustrating p-interactions between pairs of podands. H2O is shown as a CPK model and
disorder is not shown for clarity.
Table 4 Isotherm parameters of the monolayers, areas are given as
2
˚
A /molecule. Alim is the extrapolation of the linear part of the isotherm
on the x axis, A0 and A1 represent apparent molecular areas for surface
tensions at 0 and 1 mN m-1 respectively
3
4
5
collapse
8.6
18.2
12.8
pressure/mN m-1
2
˚
collapse area/A
191
221
227
219
157
187
200
192
166
197
210
201
2
˚
Alim/A
2
˚
A0/A
2
˚
A1/A
m-1 with increasing chain length but monolayers of compound
5 collapsed at 12.8 mN m-1 which is probably caused by the
disruption of terminal double bond to the aliphatic layer (Fig. 8).
2
˚
Collapse areas varied between 157 and 191 A /molecule (Table 4),
which are consistent when compared with the solid state structures
2
˚
(~170–250 A ). The relatively low collapse pressures recorded for
these three octapodands can be interpreted as a consequence
of the high flexibility of their polar head group preventing the
amphiphiles from packing in a two dimensional interfacial solid
phase. For compound 4 unexpected behaviour was observed in
further studies with different alkali and earth alkali metal salts
dissolved in the subphase since the collapse area showed quite large
variation when recorded on subsequent days in water. A possible
Fig. 6 Powder X-ray diffraction patterns (A) 2A calculated structure,
(B) fast crystallization of 2 at RT (C) 2B calculated structure, (D) slow
crystallization of 2 at 4 ◦C.
not form a monolayer on water due to the short ethyl chains at
the lower rim. Compounds 3 and 4 formed monomolecular layers
showing an increase in the collapse pressure from 8.6 to 18.2 mN
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Conclusions
Resorcinarene octapodands 1–5 exhibit versatile self-assembling
properties, and show high conformational mobility due to boat-
to-boat interconversion as well as the rotation around upper rim
side arm -OCH2CH2N- linkers. Structural mobility is observed
in the solid state as conformational polymorphism of 2, and as
disordered side arms and large temperature factors for nitroaniline
groups. The different packing motifs observed for compounds
1 and 2 suggests that there are more than one almost equally
favorable conformations in the solid state, probably depending
on whether p–p-interactions or H-bonds form first during the
crystallization process. The ratio of polymorphs 2A and 2B
can be controlled by changing crystallization conditions, namely
temperature and speed of solvent evaporation, which indicates
that these molecules approach the limit where further structural
flexibility leads to random precipitation instead of organized
crystal structures. The X-ray diffraction data obtained for 2A and
2B also implies that 2A with more extensive hydrogen bonding
at the upper rim might be more stable against collapsing when
acetone is removed from the lattice.
Compound 5 formed crystals from nitromethane–CH2Cl2 with
continuous aliphatic and aromatic layers, where aliphatic groups
of the molecule as well as p-interactions between side arms control
the crystallization process. The conformational mobility, which
leads to polymorphism and versatile conformations of the side
arms observed in all crystal structures was further demonstrated
in solution by 1H NMR, where long chain octapodands 3–5
showed remarkable conformational flexibility and amphiphilic
properties, which were confirmed by forming Langmuir mono-
layers. In contrast to the solid state structures, where the binding
cavity of resorcinarenes was quite often blocked by side arms,
conformational mobility of boat-to-boat interconversion and side
arm rotation could lead to successive opening and closing of the
binding cavity of the podands in solution. NMR spectra recorded
in various solvents and temperatures showed how the energetics
of these events can be tuned when the lower rim substituents are
changed from methyl to ethyl or to longer alkyl chains.
Fig. 7 1H NMR spectra of 5 in (A) [D6]DMSO, (B) [D6]acetone and
(C) CDCl3; resonances at 2.9–8.7 ppm, a: NH, b: nitroaniline ArH, c:
OCH2CH2N, d: resorcinarene core ArH, e: ArCH, f: alkyl tail CH CH2,
g: alkyl tail CH CH2.
Conformational polymorphism of resorcinarenes and other
macrocyclic compounds has remained largely unexplored even
though the importance of new polymorphs can be easily observed
in the field of host–guest chemistry. Further chemical modification
of the investigated podands could provide a variety of host
molecules in which the binding properties in the solid state could
be tuned by changing crystallization conditions. In addition,
the amphiphilicity could be utilized in preparing self-assembling
structures, such as monolayers, vesicles or micellar structures with
novel binding properties.
Experimental Methods
General
Fig. 8 Isotherms of podands 3, 4 and 5.
All chemicals and solvents were purchased from Sigma–Aldrich
and they were used as received. Acetonitrile was dried with CaCl2
and distilled over molecular sieves. NMR spectra were recorded
explanation could be found from the structural properties of the
compound, since different conformations of the polar and flexible
upper rim might lead to different packing also at the air–water
interface. However, further experiments are required to confirm
these preliminary observations.
1
with a Bruker Avance DRX (500 MHz for H and 126 MHz for
13C) spectrometer at 30 ◦C unless otherwise stated. J values are
given in Hz. ESI-MS spectra were measured with a Micromass
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LCT (ESI-TOF) instrument. Melting points were determined
with a Metler Toledo FP62 apparatus and are uncorrected.
Elemental analyses were performed on a Vario EL III apparatus.
Thermogravimetric/differential thermal analysis was measured
with a Perkin Elmer Diamond TG/DTA. Samples were placed in
a platinum sample pan and measured with a temperature program
25–900 ◦C at 10 ◦C min-1.
techniques using SHELX-97 software package.62 The hydrogen
atoms were calculated to their idealized positions with isotropic
temperature factors (1.2 or 1.5 times the C temperature factor)
and refined as riding atoms unless otherwise mentioned. All
¯
compounds crystallized as triclinic P1 with Z = 2. Crystal
structure analysis was done using Mercury CSD 2.3 software.63
Crystallographic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the Cambridge
Structural Data Center as supplementary publication nos. CCDC
781919–781925.† Copies of the data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
General procedure for resorcinarene octapodands
Resorcinarene, dibenzo-18-crown-6 (0.16 molar equivalents) and
dry Cs2CO3 or K2CO3 (16 molar equivalents) were suspended in
dry acetonitrile under nitrogen atmosphere and refluxed for 15
min followed by an addition of 8 molar equivalents of 654 or 7 in
acetonitrile. The yellow suspension was refluxed for 24 h, filtered
with suction and evaporated under reduced pressure. The residue
was suspended in water and extracted with dichloromethane; or-
ganic layer was dried over MgSO4 and evaporated to dryness. The
product was purified with flash chromatography (SiO2; CHCl3–
MeOH), dissolved in acetone and precipitated from water with an
addition of NaCl, or recrystallized from acetone. The product was
filtered with suction and dried under vacuum. Detailed synthetic
procedure for each podand along with spectroscopic data is
provided in the ESI.†
Langmuir monolayer studies
Langmuir isotherms were recorded using a 112D Nima Technol-
ogy (Coventry, U.K.) system. Spreading solutions were prepared
by dissolving 2–5 in chloroform at 2 mg ml-1 concentration
and diluted to 0.5 mg ml-1 by weighing the amount of solvent.
Monolayers were prepared on purified water (Millipore Milli-Q
water system, resistivity ≥18 MX·cm) by adding 20 ml of spreading
solution on the surface and recording the isotherm after 15 min
with compression rate set at 5 cm2 min-1 from 85 to 14 cm2 or
until a collapse point was observed. Each isotherm was recorded
at least three times to ensure the reliability of the results.
o-Nitro-N-(2-methanesulfonyloxyethyl)aniline 7
o-Nitro-N-(2-hydroxyethyl)-aniline59,60 (2.74 g, 15.0 mmol) was
dissolved in 5 ml of pyridine under nitrogen atmosphere and
cooled in an ice bath. Methanesulfonylchloride (1.4 ml, 18.1 mmol)
was added drop wise into the solution. After mixing one hour
in an ice bath and one hour in the room temperature, reaction
was quenched by adding 50 ml of water. The orange crystals
were filtered with suction, washed with water and dried under
vacuum. The product was recrystallized from hot chloroform–
hexane, filtered and dried under ◦vacuum to afford yellow–orange
crystals (3.0 g, 76%). mp 82–83 C; (Found: C, 41.55; H, 4.5; N,
10.8. C9H12N2O5S requires C, 41.5; H, 4.65; N, 10.8%); dH(500
Acknowledgements
This work was financially supported by Academy of Finland
(projects 117945 and 116503) and National Graduate School of
Organic Chemistry and Chemical Biology. We are grateful to Mr
Reijo Kauppinen for his help with the NMR studies.
Notes and references
1 J. Vicens and V. Bo¨hmer, Topics in Inclusion Science, Vol. 3: Calixarenes:
A Versatile Class of Macrocyclic Compounds, Kluwer Academic Pub-
lishers, Netherlands, 1991, pp.264.
2 L. Mandolini and R. Ungaro, Calixarenes in Action, Imperial College
Press, Singapore, 2000, pp.271.
3 C. D. Gutsche, Calixarenes Revisited, The Royal Society of Chemistry,
UK, 1998, pp. 233.
4 P. Timmerman, W. Verboom and D. N. Reinhoudt, Tetrahedron, 1996,
52, 2663–2704.
5 S. M. Biros and J. Rebek Jr, Chem. Soc. Rev., 2007, 36, 93–104.
6 W. Sliwa and C. Kozlowski, Calixarenes and resorcinarenes, Wiley-
VCH, Germany, 2009, pp. 316.
7 Y. Liu, H. Wang, L. Wang, Z. Li, H. Zhang and Q. Zhang, Tetrahedron,
2003, 59, 7967–7972.
3
MHz, CDCl3) 3.05 (s, 3H; CH3), 3.73 (q, J (H,H) = 5.7, 2H;
NCH2), 4.46 (t, 3J (H,H) = 5.6, 2H; OCH2), 6.73 (m, 1H; ArH),
6.89 (dd, 3J (H,H) = 8.6, 4J (H,H) = 0.9, 1H; ArH), 7.48 (m, 1H;
ArH), 8.18 (br, 1H; NH), 8.20 (dd, 3J (H,H) = 8.6, 4J (H,H) = 1.6,
1H; ArH); dC(126 MHz, CDCl3) 37.9 (CH3), 42.1 (NCH2), 66.8
(OCH2), 113.5 (ArH), 116.5 (ArH), 127.3 (ArH), 133.0 (ArNO2),
136.6 (ArH), 144.7 (ArNH); m/z (ESI-TOF) 283 (M + Na+, 100%)
261 (M + H+, 8), 187 (60), 165 (M+ - SO3CH3, 38).
8 M. M. Reinoso Garc´ıa, W. Verboom, D. N. Reinhoudt, E. Malinowska,
M. Pietrzak and D. Wojciechowska, Tetrahedron, 2004, 60, 11299–
11306.
X-Ray crystallography
9 M. A. Sarmentero and P. Ballester, Org. Biomol. Chem., 2007, 5, 3046–
Powder X-ray diffraction patterns were measured on a PANalyti-
cal X’Pert Pro system in reflection mode using monochromatized
3054.
10 U. Darbost, M. Rager, S. Petit, I. Jabin and O. Reinaud, J. Am. Chem.
Soc., 2005, 127, 8517–8525.
11 S. Busi, H. Saxell, R. Fro¨hlich and K. Rissanen, CrystEngComm, 2008,
10, 1803–1809.
12 H. Mansikkama¨ki, M. Nissinen and K. Rissanen, CrystEngComm,
2005, 7, 519–526.
13 A. J. McConnell, C. J. Serpell, A. L. Thompson, D. R. Allan and P. D.
Beer, Chem.–Eur. J., 2010, 16, 1256–1264.
14 M. H. Filby, T. D. Humphries, D. R. Turner, R. Kataky, J. Kruusma
and J. W. Steed, Chem. Commun., 2006, 156–158.
15 S. Le, Gac and I. Jabin, Chem.–Eur. J., 2008, 14, 548–557.
16 M. Me´nand and I. Jabin, Chem.–Eur. J., 2010, 16, 2159–2169.
˚
Cu-Ka radiation (l = 1.54178 A) at ambient temperature. The 2q
angle range was 3–30◦.
Single crystal X-ray data were recorded on a Nonius Kappa
CCD diffractometer with Apex II detector using graphite
˚
monochromatized Cu-Ka [l = 1.54178 A] radiation at a tempera-
ture of 173 K. The data were processed and absorption correction
was made to all structures with Denzo-SMN v0.97.638.61 The
structures were solved by direct methods (SHELXS-97) and
refined (SHELXL-97) against F2 by full-matrix least-squares
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 906–914 | 913
©

View Article Online
17 F. Perret, A. N. Lazar and A. W. Coleman, Chem. Commun., 2006,
2425–2438.
18 A. W. Coleman, F. Perret, A. Moussa, M. Dupin, Y. Guo and H. Perron,
Top. Curr. Chem., 2007, 277, 31–88.
41 P. Thue´ry, M. Nierlich, R. Calemczuk, M. Saadioui, Z. Asfari and
J. Vicens, Acta Crystallogr., Sect. B: Struct. Sci., 1999, B55, 95–
103.
42 J. L. Atwood, L. J. Barbour and A. Jerga, Chem. Commun., 2002,
19 Y. Sun, C. Yan, Y. Yao, Y. Han and M. Shen, Adv. Funct. Mater., 2008,
18, 3981–3990.
2952–2953.
43 S. H. Dale, M. R. J. Elsegood and C. Redshaw, CrystEngComm, 2003,
5, 368–373.
44 A. Nangia, Acc. Chem. Res., 2008, 41, 595–604.
45 P. K. Thallapally, G. O. Lloyd, T. B. Wirsig, M. W. Bredenkamp, J. L.
Atwood and L. J. Barbour, Chem. Commun., 2005, 5272–5274.
46 J. L. Atwood, L. J. Barbour and A. Jerga, Science, 2002, 296, 2367–
2369.
20 Y. Sun, Y. Yao, C. Yan, Y. Han and M. Shen, ACS Nano, 2010, 4,
2129–2141.
21 B. Kim, S. L. Tripp and A. Wei, J. Am. Chem. Soc., 2001, 123, 7955–
7956.
22 A. Wei, B. Kim, S. V. Pusztay, S. L. Tripp and R. Balasubramanian, J.
Inclusion Phenom. Macrocyclic Chem., 2001, 41, 83–86.
23 A. Wei, Chem. Commun., 2006, 1581–1591.
24 J. Liu and A. Wei, Chem. Commun., 2009, 4254–4256.
25 H. Kitagawa, M. Kawahata, R. Kitagawa, Y. Yamada, M. Yamanaka,
K. Yamaguchi and K. Kobayashi, Tetrahedron, 2009, 65, 7234–7239.
26 A. W. Coleman, S. Jebors, P. Shahgaldian, G. S. Ananchenko and J. A.
Ripmeester, Chem. Commun., 2008, 2291–2303.
27 A. Shivanyuk, J. Am. Chem. Soc., 2007, 129, 14196–14199.
28 K. Helttunen and P. Shahgaldian, New J. Chem., 2010,
DOI: 10.1039/C0NJ00123F.
47 J. L. Atwood, L. J. Barbour and A. Jerga, Angew. Chem., Int. Ed., 2004,
43, 2948–2950.
48 S. J. Dalgarno, J. Tian, J. E. Warren, T. E. Clark, M. Makha, C. L.
Raston and J. L. Atwood, Chem. Commun., 2007, 4848–4850.
49 J. L. Atwood, L. J. Barbour, P. K. Thallapally and T. B. Wirsig, Chem.
Commun., 2005, 51–53.
50 A. V. Yakimov, M. A. Ziganshin, A. T. Gubaidullin and V. V.
Gorbatchuk, Org. Biomol. Chem., 2008, 6, 982–985.
51 K. Salorinne and M. Nissinen, Org. Lett., 2006, 8, 5473–5476.
52 K. Salorinne and M. Nissinen, Tetrahedron, 2008, 64, 1798–1807.
53 K. Salorinne, T. Tero, K. Riikonen and M. Nissinen, Org. Biomol.
Chem., 2009, 7, 4211–4217.
54 K. Salorinne, D. P. Weimann, C. A. Schalley and M. Nissinen, Eur. J.
Org. Chem., 2009, 6151–6159.
55 P. Van, der Sluis and A. L. Spek, Acta Crystallogr., Sect. A: Found.
Crystallogr., 1990, A46, 194–201.
56 J. H. Burns, J. C. Bryan, M. C. Davis and R. A. Sachleben, J. Inclusion
Phenom. Mol. Recognit. Chem., 1996, 26, 197–207.
57 K. Miyazawa and F. M. Winnik, Macromolecules, 2002, 35, 9536–9544.
58 T. Kai, X. Sun, K. M. Faucher, R. P. Apkarian and E. L. Chaikof, J.
Org. Chem., 2005, 70, 2606–2615.
29 D. Volkmer, M. Fricke, D. Vollhardt and S. Siegel, J. Chem. Soc., Dalton
Trans., 2002, 4547–4554.
30 P. Shahgaldian, M. A. Sciotti and U. Pieles, Langmuir, 2008, 24, 8522–
8526.
31 L. Nault, A. Cumbo, R. F. Pretoˆt, M. A. Sciotti and P. Shahgaldian,
Chem. Commun., 2010, 46, DOI: 10.1039/b926025k.
32 S. Ehrler, U. Pieles, A. Wirth-Heller and P. Shahgaldian, Chem.
Commun., 2007, 2605–2607.
33 H. Mansikkama¨ki, M. Nissinen and K. Rissanen, Angew. Chem., Int.
Ed., 2004, 43, 1243–1246.
˚
34 H. Mansikkama¨ki, S. Busi, M. Nissinen, A. Ahman and K. Rissanen,
Chem.–Eur. J., 2006, 12, 4289–4296.
35 M. Makha, C. W. Evans, A. N. Sobolev and C. L. Raston, Cryst. Growth
Des., 2008, 8, 2929–2932.
36 D. Sun and C. A. Reed, Chem. Commun., 2000, 2391–2392.
37 B. Ma, Y. Zhang and P. Coppens, J. Org. Chem., 2003, 68, 9467–9472.
38 G. R. Desiraju, Angew. Chem., Int. Ed., 2007, 46, 8342–8356.
39 E. Nomura, M. Takagaki, C. Nakaoka and H. Taniguchi, J. Org.
Chem., 2000, 65, 5932–5936.
59 J. M. McManus and R. M. Herbst, J. Org. Chem., 1959, 24, 1042–1043.
60 L. Westerheide, F. K. Mu¨ller, R. Than, B. Krebs, J. Dietrich and S.
Schindler, Inorg. Chem., 2001, 40, 1951–1961.
61 Z. Otwinowski and W. Minor, Methods Enzymol., 1997, 276, 307–326.
62 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008,
A64, 112–122.
63 C. F. Macrae, I. J. Bruno, J. A. Chisholm, P. R. Edgington, P. McCabe,
E. Pidcock, L. Rodriguez-Monge, R. Taylor, J. van de Streek and P. A.
Wood, J. Appl. Crystallogr., 2008, 41, 466–470.
40 T. Gruber, M. Peukert, D. Schindler, W. Seichter, E. Weber and P.
Bombicz, J. Inclusion Phenom. Macrocyclic Chem., 2008, 62, 311–324.
914 | Org. Biomol. Chem., 2011, 9, 906–914
This journal is
The Royal Society of Chemistry 2011
©