Spiraling steroids: Organic crystals with asymmetric nanometer-scale channels

Article abstract of DOI:10.1002/anie.200502330

(Figure Presented) Crystals with broad robust channels are rare, especially if self-assembled without the aid of metal ions. Three such crystals were prepared based on a common steroid motif. The channels formed are chiral, directional, aligned, and wide

Full text of DOI:10.1002/anie.200502330

Communications
(MOF)[1c–g] materials. However, purely organic structures
with such dimensions are rare, especially if macrocyclic
molecules are excluded.[2] We now report a new class of
nanoporous organic crystals with chiral, unidirectional chan-
nels, tunable to diameters in excess of 14 Š.
This discovery arose from our program on steroid-based
anion receptors.[3] The “cholapod” 1 belongs to a series of
compounds derived from cholic acid 2, in which hydrogen-
bond donor units are deployed on the bile acid scaffold. The
urea groups at C7 and C12 are constrained by the axial
À
orientation of the C N bond, such that the NH groups point
towards each other. The amide moiety at C3 can also point
inwards, thus cooperating in hydrogen-bond donation to
anionic guests. Molecules from this family are powerful anion
receptors,[4] and also act as anion carriers across bilayer
membranes.[5]
Cholapod 1 was prepared from 2 via intermediate 3[6] (see
the Supporting Information; Boc = tert-butoxycarbonyl).
Crystal Engineering
DOI: 10.1002/anie.200502330
Spiraling Steroids: Organic Crystals with
Asymmetric Nanometer-Scale Channels**
Adam L. Sisson, Vicente del Amo Sanchez,
Germinal Magro, Alex M. E. Griffin, Shilen Shah,
Jonathan P. H. Charmant, and Anthony P. Davis*
Crystallization from methyl acetate, which contained small
amounts of water, gave needles up to 5 mm long and
approximately 0.2 mm wide. The crystal structure was
solved in the P61 space group.[7] The individual molecules
were found to bind one molecule of water (see Figure 1a).
The trifluoroacetamide unit rotates such that the carbonyl
group points inwards acting as an hydrogen-bond acceptor,
whereas the urea groups act as hydrogen-bond donors to the
oxygen atom from the water molecule. The hydrated steroids
form columns parallel to the crystallographic c axis, rein-
forced by hydrogen-bonding interactions between the free
Crystalline microporous (or nanoporous) solids are widely
sought and studied.[1] Such materials provide challenges for
crystal engineering and find applications in catalysis, separa-
tion techniques, gas storage, sensors, lasers, and so forth.
Robust structures with large voids are especially interesting,
as they are able to accommodate the widest range of guests.
Channels that measure ꢀ 1 nm in diameter are fairly common
in inorganic[1a–c] and, especially, metal–organic-framework
À
O H group of a water molecule contained in one complex
and a carbonyl oxygen atom of a urea group in the next
(Figure 1b). The columns then pack in a hexagonal array to
give channels centered on the c axis, defined by a right-
handed spiral of steroids (Figure 1c).[8] The internal surfaces
possess an average diameter of 16.4 Š, with a minimum value
of 14.3 Š (Figure 1d).[7] The surfaces are formed mainly from
hydrophobic CH and CF units, but also feature the carbonyl
oxygen atoms from the ester groups. Around 30% of the
crystal volume is accessible to guests. The channels are filled
with delocalized electron density, consistent with disordered
solvent molecules. Face indexing of a single crystal showed
[*] A. L. Sisson, V. del Amo Sanchez, Dr. G. Magro, A. M. E. Griffin,
S. Shah, Dr. J. P. H. Charmant, Prof. A. P. Davis
School of Chemistry
University of Bristol, Cantock’s Close
Bristol BS81TS (UK)
Fax: (+44)117-929-8611
E-mail: anthony.davis@bristol.ac.uk
[**] Financial support was provided by the EPSRC (GR/R04584/01) and
BBSRC (BBS/B/11044). Mass spectra were provided by the EPSRC
National MS Service Center at the University of Swansea.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Chemie
above. Inclusion complexes
of bile acid derivatives are
well known and well stud-
ied,[12] but the formation of
such
large,
physically
robust pores is unprece-
dented. The crystals are
chiral and also lack any
regular axis of symmetry,
so the pores are aligned in
one direction. Finally, the
interactions which govern
the packing do not seem to
involve the terminal CF3
and methyl ester groups,
both of which point into
the channels. This suggests
a
generalizable motif 4,
with potential for tuning.
These interactions suggest
the generalized motif of 4,
which can be potentially
used to tune channel width
and properties by variation
of the R1 and R2 groups.
Considering this last
Figure 1. Representations of the crystal structure of 1: a) A single molecule of 1 with the bound water
molecule (red sphere; hydrogen atoms bound to carbon have been removed for clarity). b) Columns of 1·H2O
parallel to the channel axis shown from two perspectives (the steroid molecules are shown in green and blue
and the hydrogen-bonding interactions in red). c) The packing of columns to give channels, viewed along the
channel axis (steroid molecules in one column are highlighted in green and blue). d) Interior surface of a
channel, calculated by using a 1.4-ꢀ probe; the surface is color coded according to the underlying atoms (red:
oxygen, blue: nitrogen, green: fluorine).
point, we examined other
steroids of type 4 from our
anion-receptor
program.
Compounds 5[13] and 6[7]
that, as expected, the channel axis coincided with the long axis
of the needles.
The contents of the channels were investigated by
1H NMRspectroscopic analysis. Crystals of 1 were removed
from the solvent, air-dried,[9] and dissolved in deuterated
acetone (99.96 atom% D) under anhydrous conditions.[7]
Integration of the NMRspectrum implied a composition of
1·0.75MeOAc·3.5H2O.[10] Even allowing for the single H2O
molecule bound to each molecule of 1, this result implies that
water is concentrated in the channels and explains our
observation that small amounts of water aid crystallization.
The solvent was lost and the crystals became opaque on
vacuum drying;[11] however, X-ray powder diffraction showed
that the channel structure was maintained.[7] Solvent
exchange was also demonstrated. Samples removed from
MeOAc were washed with diethyl ether or toluene, air-
dried,[9] and analyzed by 1H NMRspectroscopy. In both cases,
the MeOAc had disappeared and the replacement solvent was
present (approximately 0.5 equiv). Vacuum-dried samples
suspended in toluene also absorbed the solvent. When these
toluene-solvated crystals were washed briefly (approximately
30 s) with CH2Cl2, the toluene was retained. Thus, solvent
exchange is slow, which is consistent with absorption into the
nanoporous framework.
crystallized as needles and were subjected to X-ray crystallo-
graphic studies. Both 5 and 6 formed nanoporous structures in
which the disposition of the steroid nuclei was almost
identical to that in 1. However, the variation of the R1
The structure of 1 is notable in several respects. First, the
channels are among the largest observed for purely organic
systems. Second, they are persistent and accessible, as shown
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Communications
group induced significant changes. In the case of 5, the bulky
NHPh group protrudes into the channel and, more impor-
tantly, displaces the OMe unit from the channel wall. The
ester group rotates to create a more irregular, narrower pore
with an average diameter of 15.7 Š (minimum diameter=
11.6 Š; Figure 2).[7] In the case of 6, the OtBu group seems to
Figure 2. a) Orientation of the methyl ester groups in 1 and 5.
b) Interior surface of 5. In contrast to 1 (see Figure 1d) the OMe
groups are directed inwards, thus creating protrusions in the channel
wall.
create an intermediate situation, in which the ester groups are
randomly distributed between the two orientations. If an
alternating arrangement is assumed, the average and mini-
mum diameters are 16.4 and 12.3 Š, respectively.[7] The
crystal structures of 1, 5, and 6 are compared in Figure 3,
which highlights the position of the terminal R1 groups at the
channel surfaces.
To conclude, we have found a new steroid-based motif
which generates robust, asymmetric, and nanoporous struc-
tures of unusual dimensions. The channels are codirected[14]
and large enough to accommodate a wide variety of organic
molecules, including, for example, dyes or substrates for
catalysis. We will investigate such possibilities in future
investigations, with a view to the development of novel
functional organic materials.
Figure 3. Structures of 1, 5, and 6 viewed down the channel axis, with
terminal R1 groups (see 4) represented in the space-filling mode.
a) Trifluoroacetamide 1 (R1 =CF3), b) trisurea 5 (R1 =NHPh), c) carba-
mate 6 (R1 =OtBu).
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Received: July 4, 2005
Published online: October 7, 2005
Keywords: chirality · crystal engineering · inclusion compounds ·
.
microporous materials · steroids
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Angewandte
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[10] This formula implies that approximately half of the volume in
the NMRsample that was accessible to the guest species was
occupied by solvent molecules; the remainder was presumably
replaced by air during the drying process.
[11] The crystals were evacuated by using an oil pump for 24 hours.
[12] For a leading reference, see: M. Miyata, K. Sada, N. Yoswatha-
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[14] This term is used to imply that the channels are both directional
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c axis) and aligned (pointing in the same direction).
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