Solvent and hydrogen confinement in molecular capsules-Hirshfeld surface and molecular simulation analysis.

Abstract

Hirshfeld surface analysis of the 'ordered' inner phase of the molecular capsule complex, [(chloroform)(6)@C-n-butylpyrogallol[4]arene)(6)], provides insight into the intermolecular contacts and orientation of the solvent molecules. Molecular simulations show that adding two or three hydrogen molecules to the six solvent molecules is energetically favoured, and this correlates with NMR studies.

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9882Chem. Commun., 2011, 47, 9882–9884 This journal is c The Royal Society of Chemistry 2011
Citethis: Chem. Commun.,2011,47,9882–9884
Solvent and hydrogen confinement in molecular capsules—Hirshfeld
surface and molecular simulation analysisw
Adam D. Martin,aRamiz A. Boulos,aK. Swaminathan Iyer,aAlexandre N. Sobolev,a
Charles S. Bond,aJerry L. Atwood,cScott J. Dalgarno*band Colin L. Raston*a
Received 24th May 2011, Accepted 18th July 2011
DOI: 10.1039/c1cc13038b
Hirshfeld surface analysis of the ‘ordered’ inner phase of the
molecularcapsule complex,
pyrogallol[4]arene)6], provides insight into the intermolecular
contacts and orientation of the solvent molecules. Molecular
simulations show that adding two or three hydrogen molecules to
the six solvent molecules is energetically favoured, and this
correlates with NMR studies.
[(chloroform)6@C-n-butyl-
The programmed assembly of small molecular components
into larger assemblies is an ongoing challenge in supra-
molecular chemistry.1The introduction of complementary
hydrogen bonding groups into molecular scaffolds has played
a key role in the development of some systems, an early
example of which is the assembly of the ‘tennis ball’, reported
by Rebek and co-workers.2Exploitation of these concepts
with larger molecular building blocks has led to the formation
of different structural motifs of varying size.3,4
Calix[4]arenes are cyclic, bowl shaped macrocycles that are
widely utilised in supramolecular chemistry. Their synthetic
chemistry is well explored and the general molecular frame-
work can be readily modified to afford building blocks with
desired chemical functionality.5These molecular building
blocks have been used in the formation of many non-covalent
assemblies including dimeric,6hexameric and dodecameric
capsules, and nano-tubules.7–9
We have been interested in gaining control over the assembly
of hexameric molecular capsules for some time, as they possess
large internal volumes (>1200 A˚3) which can be exploited in
the encapsulation of multiple small guest species. The first
such assembly to be structurally characterised was produced
through crystallisation of C-methylresorcin[4]arene (CMRC)
from nitrobenzene,10with the presence of water molecules
critical for the formation of a capsule based on 6 CMRCs
and 8 water molecules, which exhibit cooperative hydrogen
bonding and a shape conforming to the Archimedean snub
cube. The related C-alkylpyrogallol[4]arenes (general notation
PgCn, where n corresponds to the alkyl chain length) have been
shown to form hexameric capsules from various solvents, and
in the presence of guest species.11Increasing the number of
upper rim hydroxyl groups relative to CMRC precludes the
need for water molecules embedded in the walls of
the capsules, affording a more stable capsule motif due to
the increased number of hydrogen bonds between the
components. These capsules are relatively stable at ambient
pressure after uptake of molecular hydrogen along with
chloroform solvent molecules. The confinement of hydrogen
involves selective disassembly using the shear forces in
dynamic thin films, under an atmosphere of hydrogen gas at
close to ambient pressure.12
Crystallisation of PgCns in anti-parallel bi-layer arrays
typically results in good quality crystallographic data due to
the high degree of order within the resulting structures.13
When PgCns are crystallised as hexameric capsules, the resulting
crystals are often weakly diffracting and are of limited quality,
due to the high level of disorder present in the encapsulated
space. In this regard, solvent molecules have, on rare occasions,
been shown to play an influential role in ordering the interior
of pyrogallol[4]arene molecular capsules.14However, this
information can only be obtained when high quality crystallo-
graphic data is acquired, thereby allowing the observation
of specific intermolecular contacts on the capsule interior
(or inner phase).
To this end we structurally authenticated a hexameric
capsule based on six C-n-butylpyrogallol[4]arenes (PgC4)
containing six inner phase chloroform molecules with resolved
disorder. Crystallising the capsules with hydrogen also
included was not possible due to slow diffusion of the gas into
solution. A detailed analysis of the crystal structure is reported
herein, along with Hirshfeld surface analysis of the confined
solvent molecules. We also report the results of molecular
simulations of molecular capsules containing six chloroform
molecules, with then successive inclusion of hydrogen mole-
cules, in rationalising the uptake of hydrogen in a chloroform
solution of the aforementioned molecular capsule.12
aCentre for Strategic Nano-Fabrication, School of Biomedical and
Chemical Sciences, University of Western Australia, 35 Stirling
Highway, Crawley, Western Australia 6009, Australia.
E-mail: colin.raston@uwa.edu.au; Fax: +61(8) 6488 1005;
Tel: +61(8) 6488 3326
bSchool of Engineering and Physical Sciences, Heriot-Watt
University, Riccarton, Edinburgh, EH14 4AS, Scotland.
E-mail: S.J.Dalgarno@hw.ac.uk
cDepartment of Chemistry, University of Missouri at Columbia,
601 S. College Ave, Columbia, MO 65211, USA.
Fax: +1 573 882 2754; Tel: +1 573 882 8374
w CCDC 826189. For crystallographic data in CIF or other electronic
format see DOI: 10.1039/c1cc13038b
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This journal is c The Royal Society of Chemistry 2011 Chem. Commun., 2011, 47, 9882–98849883
Hirshfeld surface analysis is gaining prominence as a tool
for mapping the interactions between molecules in the solid
state,15–17and is employed here for the first time in exploring
the restricted surface of the relatively ordered confined space
inside a molecular capsule. A recent study has established its
effectiveness for mapping the surface of capsules with pores,
which confine C70molecules.18
Crystals consisting of PgC4-based hexameric capsules
suitable for single crystal X-ray diffraction studies were grown
from a chloroform/ethyl acetate mixture containing thiostrepton,
a peptide-like natural product.z They belong to the space
group P%1, and the asymmetric unit contains (i) three PgC4
molecules and three chloroform molecules equally disordered
over two positions, Fig. 1a, which define the molecular
capsules through an inversion centre, Fig. 1b, and (ii) some
disordered ethyl acetate and chloroform molecules which
occupy interstitial voids exo to the capsule. Hirshfeld surface
analysis of the chloroform molecules within the cavity of the
capsule (which are modelled as fully ordered) shows that the
three crystallographically independent chloroform molecules
in the asymmetric unit have identical fingerprint plots, Fig. 2.
Each chloroform molecule contains a short contact where
the hydrogen of the chloroform is directed towards the centre
of a phenyl ring from a PgC4 molecule, and this CH???p
interaction (14–15% of the Hirshfeld surface) is solely responsible
for the short contacts seen on the fingerprint plot. This
interaction can be viewed as a ‘‘wing at the left of the plot,
Fig. 2a. Cl???C interactions comprise 14–15% of the Hirshfeld
surface, and are responsible for the bright streak in the centre
of the plot. These contacts arise from interactions between a
chlorine atom and various carbon atoms from the methylene
bridges of the PgC4molecules.
Cl???O interactions account for 27–33% of the Hirshfeld
surface of the chloroform molecules, and are associated with
phenolic oxygen atoms. Chlorine atoms are directed towards
the centre of the hexameric capsule, and correspond to some of
the long contacts observed in the structure. The other domi-
nant interaction present for the chloroform molecules is from
Cl???H contacts. These make up 21–36% of the Hirshfeld
surface and are due to interactions with phenolic hydroxyls or
long contacts directed towards the centre of the hexameric
capsule. Cl???Cl interactions are also observed, comprising
15–23% of the Hirshfeld surface. They can be observed as a
bright streak in the very top right hand corner of the
fingerprint plot, and are from interactions between endo
chloroform molecules. Disordered water molecules present in
the structure prevent the Hirshfeld surface analysis of the
chloroform and ethyl acetate molecules exo to the cavity of
the hexameric capsules.
Materials Studio V4.1.0.0 was used for the molecular simu-
lations of capsules based on six C-methyl-pyrogallol[4]arenes,
encapsulating six chloroform molecules, with the starting
geometries obtained from the above crystal structure. The
n-butyl chains were replaced by methyl groups to reduce the
effect the flexible butyl chains will have on the volumetric
calculation from the Connolly surface of the capsule with
minimal change to the chemical environment. Consecutively
one, two, three and four hydrogen molecules were randomly
placed in the cavity containing the six chloroform molecules,
with each of the structures minimised (supplementary infor-
mation) and the subsequent energy for three sets of calcula-
tions per included hydrogen molecule examined along with
related Connolly surfaces.
The molecular simulations show that the integrity of the
minimized capsule [(chloroform)6@(PgC4)6] incorporating three
hydrogen molecules is maintained, Fig. 3, held together through
a network of hydrogen bonds. The pyrogallol[4]arenes adopt a
rectangular conformation, with two opposing arms (aromatic
rings) directed away from each other, whilst the other two are
aligned parallel with each other. Neighbouring pyrogallol[4]arenes
are oriented at approximately 451 along the long axis relative
to each other.
TheConnolly surface representsthe solvent-accessiblesurface of
a chosen molecule,19and for the capsule [(chloroform)6@(PgC1)6],
Fig. 1
capsules confining chloroform molecules, displayed as space filling.
Asymmetric unit (a) and unit cell (b) of PgC4-based hexameric
Fig. 2
an inner phase chloroform molecule, and (c) disurfaces of the three
chloroform molecules in the asymmetric unit.
Hirshfeld surface fingerprint plot (a), and dnormsurface (b), for
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9884Chem. Commun., 2011, 47, 9882–9884This journal is c The Royal Society of Chemistry 2011
the Connolly surface increases for the addition of up to three
hydrogen molecules, Fig. 4, and decreases upon the addition
of a fourth hydrogen molecule. The decrease in the volume
(B9 A˚) can be translated to a slight ‘breaking up’ of the
capsule which is due to a weakening of the non-bond energies
between the PgC1units suggesting that the integrity of the
capsule is reduced upon addition of a fourth hydrogen
molecule.
The stability of the capsule [(chloroform)6@(PgC1)6] is
increased for the addition of up to three hydrogen molecules
as indicated by the negative values of the difference in energy,
Fig. 4. Upon addition of a fourth molecule, the total energy
increases to approximately 1.4 kcal mol?1compared to the
hydrogen deficient capsule. The lowest energies correspond to
the addition of one and three hydrogen molecules, with energy
differences of ?1.5 kcal mol?1and ?1.8 kcal mol?1respectively.
These values average to a hydrogen loading capacity of 2
molecules per capsule which agree with the hydrogen loading
capacityof approximately 30 mol% observed experimentally.12
In conclusion we have used a combination of X-ray diffrac-
tion, Hirshfeld surface analysis and molecular simulations to
further understand the properties of the inner phase of PgCn-
based hexameric capsules. The dominance of chlorine-based
interactions rather than CH???p interactions are established,
and the addition of successive hydrogen molecules using
molecular simulations correlates well with the uptake of
hydrogen in the system established using1H NMR spectro-
scopy. The results obtained through these studies are consis-
tent with a uniform uptake of solvent and gas molecules for
each hexameric capsule, rather than a broad distribution that
averages to give the experimentally observed loading.
Support of this work by the Australian research Council is
gratefully acknowledged.
Notes and references
z Slow evaporation of a 24:24:1 CHCl3:EtOAc:EtOH solution of
PgC4/Thiostrepton (2:1) resulted in the formation of large colourless
single crystals suitable for X-ray diffraction studies. The presence of
Thiostrepton was found necessary for crysallisation of the capsule.
The crystals are in a triclinic cell and structure solution was performed
in the space group P%1.
Materials Studio (MS) V4.1.0.0 was used for the molecular
modelling. The crystal structure of [(chloroform)6@(PgC4)6] reported
above (CCDC 826189) and the butyl chains were substituted with
methyl chains. The structure was minimized in a periodic cell in vacuo
using the Forcite module using the smart minimizer with ultra-fine
quality and the atom-based summation method for the van der Waals
calculation and the Ewald summation method for the electrostatic
calculation. The Dreiding Force Field was used and a convergence
criterion of the average energyderivative was less than 2? 10?5kcal/mol.
The Connolly radius used for the calculation was 1.0 A˚with a Grid
interval of 0.75 A˚. Number of replicates for random inclusion of
hydrogen molecules = 3.
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Fig. 3
fining six chloroform and three hydrogen molecules. (a) Space filling
for the C-methylpyrogallol[4]arenes, and (b) space filling representa-
tion for the chloroform and hydrogen molecules.
Minimized structure of the molecular capsule, [(PgC1)6], con-
Fig. 4
nal crystal structure energy (left axis), and volume of the Connolly
surface (right axis) for sequential addition of one to four hydrogen
molecules within the capsule interior.
Difference in average minimised energy compared with origi-
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