Cholanamide components for organic alloys; Expanding the scope of nanoporous steroidal ureas

Article abstract of DOI:10.1039/c4cc01256a

Amide-linked side-chains can substitute for esters in crystalline nanoporous steroidal ureas (NSPUs). This efficient conjugation method increases the versatility of NPSUs, and should aid the inclusion of complex functional units in the crystal channels. The Royal Society of Chemistry 2014.

Full text of DOI:10.1039/c4cc01256a

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Cholanamide components for organic alloys;
expanding the scope of nanoporous steroidal
ureas†
Leana Travaglini,ab Lydia N. Bridglanda and Anthony P. Davis*a
Cite this: Chem. Commun., 2014,
50, 4803
Received 17th February 2014,
Accepted 24th March 2014
DOI: 10.1039/c4cc01256a
www.rsc.org/chemcomm
Amide-linked side-chains can substitute for esters in crystalline NPSUs, with particular relevance to the inclusion of complex
nanoporous steroidal ureas (NSPUs). This efficient conjugation functional units in the crystal pores.
method increases the versatility of NPSUs, and should aid the
inclusion of complex functional units in the crystal channels.
An overview of the NPSU crystal family is given in Fig. 1. The
molecules which form the crystals are represented by the general
formula 1 (Fig. 1a) and are accessible in as little as 5 steps from
The rational design of porous solids is a major goal of crystal cholic acid 2.9 The crystal structure of prototype 1a8a is shown in
engineering.1 Crystalline systems which contain pores ranging Fig. 1b, viewed down the c axis. The packing involves the formation
from B0.5 to 2.0 nm are of particular interest, as this can allow of helices with hexagonal symmetry (space group = P61) surrounding
penetration by a range of molecular guests. Such absorptive solvent-filled channels. The terminal units (NHPh and OMe in this
properties can lead to applications including gas storage,2 case) lie at the surface of these channels, largely constituting the
catalysis3 or molecular separations.4 There is thus much interest walls. The channels are unusually wide (B1.6 nm average diameter
in the preparation of nanoporous crystals, especially where for 1a), so there is room for these groups to expand without
properties can be tailored for different purposes. Success has disturbing the P61 crystal packing. Accordingly, groups R1 and R2
been achieved using various approaches, including metal– can be varied to give a range of isostructural crystals with different
organic frameworks, preformed molecular cavities (‘‘intrinsically channel diameters and surface characteristics.8b,e Moreover,
porous’’ molecules5) and covalent organic frameworks.1e,2a, f,6 because their structures are so similar, different variants can
However, the creation of pores through the crystallisation of co-crystallise in continuously variable ratios to form ‘‘organic
non-macrocyclic organic molecules (‘‘extrinsic porosity’’) alloys’’ (Fig. 1c).8c,d This facilitates tuning, and also allows very
remains a particular challenge. There are especially few examples large units to be placed in the channels (through conjugation
where pore size and material properties can be tuned,7 and even with the steroid then ‘‘doping’’ in a matrix of simpler ‘‘host’’
in those cases the possible variations within the packing motif are NPSU molecules). Studies on 1a have confirmed that it possesses
relatively narrow.
permanent porosity (as indicated by evacuation and gas adsorp-
We have recently described a family of extrinsically porous tion), and that it can take up a range of organic molecules
crystals, the ‘‘nanoporous steroidal ureas’’ (NPSUs), which including the C30 hydrocarbon squalene.8e
provides exceptional scope for variation.8 The crystals are formed
Although new NPSUs may be created by changing both R1
from esters of substituted cholanoic acids, and the variations are and R2, the latter has practical advantages. The methyl ester 1a
possible (in part) because the ester group can be changed is especially easy to synthesise,9 and modifying the methoxy
without affecting the packing (see below). Herein we report that group requires just hydrolysis and re-esterification. However
the corresponding cholanamides may also be incorporated in while this process is often straightforward, esterification can be
NPSU crystals. This discovery expands the range of potential problematic especially if the alcohol is complex, hindered and/or
hydrophilic. Amide formation is a highly reliable method of
a School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS1 1TS, UK.
E-mail: Anthony.Davis@bristol.ac.uk; Fax: +44-(0)117 9298611;
Tel: +44-(0)117 9546334
conjugation, and many groups of interest (e.g. peptides) are
available as amines. Thus incorporation of cholanamides 3
would enhance the potential of NPSUs as functional materials.
We therefore decided to establish whether the NPSU motif could
be extended to cholanamides, at least for simple test cases.
The ability of amides 3 to participate in NPSU structures
could be compromised by steric hindrance in the case of tertiary
b Department of Chemistry, ‘‘Sapienza’’ University of Rome, Ple. Aldo Moro 5,
00185, Rome, Italy
† Electronic supplementary information (ESI) available: Details of synthetic
procedures, description of crystallisation and crystal analyses. See DOI:
10.1039/c4cc01256a
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white amorphous solids. Attempted crystallisations from other
solvents (e.g. methanol, ethanol) produced similar results.
While amides 3a–d might not crystallise as pure compounds,
this did not preclude their incorporation in NPSUs. Given that
NPSUs can form alloys,8c it seemed likely that crystals of an ester
such as 1a might accept the amides as substitutes or dopants.
Accordingly, we prepared mixtures of 3a–d with ester 1a in the
ratios 1a: 3 = 1 : 1, 2 : 1, and 5 : 1, dissolved in acetone, and
subjected them to the standard NPSU crystallisation method
(see above). All the 1 : 1 mixtures failed to give crystals, yielding
only amorphous solids. The same was true of the 2 : 1 mixtures
incorporating secondary amides 3a and 3b. However, the mixtures
1a :3c,d = 2 : 1, and all 5 : 1 mixtures, gave needle-like crystals
similar in appearance to those given by 1a (see Table 1). The
1
collected crystals were all analyzed by H NMR spectroscopy to
give the bulk compositions shown in Table 1, while the presence
of both the components within individual crystals was confirmed
by ESI-MS on single crystals. Attempts were made to detect
the amide components in the 1aÁ3b–d mixtures using single
crystal X-ray diffraction (SCXRD).10 However, while the data
yielded evidence of the second components, it was not possible
to model the amide substituents. The crystallography did provide
confirmation that the crystals were indeed NPSUs, with the P61
packing and cell parameters listed in Table 1.
Although we cannot be certain that the distribution of 1a
and 3 is random within the crystals, these results point clearly
to co-crystallisation and, most probably, the formation of solid
solutions (organic alloys). In particular, the ESI-MS spectra on
single crystals show that 1a and 3 occur together, while the
Fig. 1 The NPSU crystal family. (a) General structure of NPSU monomers.
(b) NPSU 1a in the crystal, viewed down the c axis. Terminal groups R1
(NHPh) and OR2 (OMe) are coloured gold and magenta respectively. To
show the positioning of the individual molecules, two are highlighted
(green and blue) with terminal groups in space filling mode. (c) Schematic
depictions of channels in crystals, showing the helical arrangements of R1
and R2. Left: a solid solution with two types of R2. Right: placing a bulky R2
in the channel through low-level doping.
Table 1 Solid solutions formed by steroidal ureas 3 and 1a
amides, or by the potential for new NHÁ Á ÁX hydrogen bonds in
the case of secondary amides. We chose to study examples of
both types, the secondary amides 3a,b and the tertiary amides
3c,d. Amides 3a–d were prepared from tris-urea 1a by ester
hydrolysis followed by coupling to methylamine, benzylamine,
N-methylbenzylamine and dimethylamine using 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDCI) as condensing agent.
Attempts were made to crystallise 3a–d using our standard
method for NPSUs, i.e. dissolving in acetone or methyl acetate,
adding water, and allowing the organic solvent to evaporate.
Ratio in Crystallographic unit cell detailsb
Initial crystals
Components ratio
(bulk)a
a,b [Å]
c [Å]
V [Å]3
c
c
c
1a, 3a
1a, 3b
1a, 3c
1a, 3c
1a, 3d
1a, 3d
5 : 1
5 : 1
2 : 1
5 : 1
2 : 1
5 : 1
83 : 17
76 : 24
83 : 17
91 : 9
70 : 30
83 : 17
29.0457(8) 11.4742(3) 8383.3(4)
29.0994(4) 11.4992(3) 8432.7(3)
29.0759(4) 11.4900(3) 8441.4(3)
29.0240(7) 11.4753(3) 8371.6(4)
29.1007(3) 11.4979(2) 8432.5(2)
a
b
Determined by 1H NMR integration. Standard deviations are given
c
Unfortunately these trials were unsuccessful, yielding only in parentheses. Not determined.
4804 | Chem. Commun., 2014, 50, 4803--4805
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We thank the ‘‘Sapienza’’ University of Rome for financial
support to L. T. L. B. is a member of the Bristol Centre for
Functional Nanomaterials, an EPSRC-funded Doctoral Training
Centre.
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