Ion-pair induced self-assembly of molecular barrels with encapsulated tetraalkylammonium cations based on a bis-trisurea stave

Article abstract of DOI:10.1039/c2cc17699h

A bis-trisurea ligand assembles with the tetraalkylammonium halides to form the flat 'stave' structures or 'barrels' that encapsulate multiple R ₄N⁺ guests, depending on the size of the halide anion (Cl^- or Br^-)

Full text of DOI:10.1039/c2cc17699h

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COMMUNICATION
Ion-pair induced self-assembly of molecular barrels with encapsulated
tetraalkylammonium cations based on a bis–trisurea stavew
Shaoguang Li,ab Meiying Wei,ab Xiaojuan Huang,a Xiao-Juan Yanga and Biao Wu*c
Received 8th December 2011, Accepted 27th January 2012
DOI: 10.1039/c2cc17699h
A bis–trisurea ligand assembles with the tetraalkylammonium
halides to form the flat ‘stave’ structures or ‘barrels’ that
encapsulate multiple R4N+ guests, depending on the size of
the halide anion (Clꢀ or Brꢀ) and the R4N+ cation.
There is much interest in the design and synthesis of well-defined
concave space to encapsulate guest species (anions, cations or
neutral molecules) due to the great potential of such systems in
biological, analytical and catalytic applications.1 The artificial
organic columnar structures are among the most studied mole-
cular capsules, and many covalent cylindrical molecules have
been employed in this respect.2 These preorganized hosts
can readily form stable complexes with the guests since less
conformational change is required upon binding. However,
the synthesis and separation of such host molecules is much
challenging. In contrast, acyclic hosts have a proper degree of
flexibility and can undergo conformational changes on binding
with guests, and their synthesis is often relatively straightforward.3
Moreover, the flexibility of hosts is very important in
biological systems, in which recognition of a substrate may
result in a conformational change that is of major significance
for the function to be realized. For instance, the b-sheets can
roll up to form the cylindrical b-barrels, which are ubiquitous
structural motifs in various binding proteins, pores, and
enzymes.4 To access artificial b-barrels for molecular recognition,
translocation or transformation purposes, many functional
groups such as lipocalins, peptitergents, cholate derivatives,
p-octiphenyl rods and bipyridines or catechol ligands have
been utilized.5 To date, most synthetic supramolecular
‘barrel-stave’ ion channels and tubes have been identified in
solution based on indirect evidence, while the precise information
on the structure of the barrel is rare.
Fig. 1 (a) Structure of the bis–trisurea ligand L; (b) the B3LYP/
6-31G optimized ligand conformation together with its surface electrostatic
potential map.
tetraalkylammonium halides [(R4N+)Xꢀ] (R4N = TEA: tetra-
ethylammonium; TPA: tetrapropyl-ammonium; TBA: tetra-
butylammonium; X = Clꢀ or Brꢀ) with a new oligo-urea
receptor, the ethylene bridged bis–trisurea L (Fig. 1). Ligand L
can serve as a ‘stave’ to form ‘barrels’ that encapsulate the
R4N+ ions, depending on the sizes of the quaternary ammonium
cations and the anions.
The ligand L was synthesized by the reaction of p-nitro-
phenylisocyanate with 1,10-(ethane-1,2-diyl)bis(3-(2-(3-(2-amino-
phenyl)ureido)phenyl)urea) (see ESIw for details). The
conformation of L was optimized and its surface electrostatic
potential is given in Fig. 1b.7 The ethylene spacer shows an
anti arrangement with an N–CH2–CH2–N torsion angle of
1801, and the six aryl rings are nearly coplanar. Therefore, the
ligand can be viewed as a flat molecular ‘stave’. Most of
the positive charges (hydrogen bonding donors) are located
on the urea NH groups which point to the two internal cavities
of the ‘S’-shaped ligand stave, while the negative charges are
settled at carbonyl and nitro groups around the edges of the
stave. These electrostatic characters allow the ligand to
coordinate with both anions and cations or to interact with
each other. Notably, the ligand alone cannot be dissolved in
low-polarity solvents, but clear yellow solutions can result
upon addition of one equivalent of R4NX. Six compounds
were obtained from L and [(R4N+)Xꢀ]: (TEA)4LCl4ꢁH2O (1),
(TPA)3LCl3 (2), (TBA)2LCl2ꢁCHCl3 (3), (TEA)4LBr4 (4),
(TPA)3LBr3 (5) and (TBA)4LBr4 (6).
We have been working on anion coordination and developed
a series of oligo-urea receptors, which showed high affinity to
anions.6 In this work, we report on the ion-pair binding of
a State Key Laboratory for Oxo Synthesis & Selective Oxidation,
Lanzhou Institute of Chemical Physics, CAS, Lanzhou 730000, China
b Graduate University of Chinese Academy of Sciences,
Beijing 100049, China
c College of Chemistry and Materials Science, Northwest University,
Xi’an 710069, China. E-mail: wubiao@nwu.edu.cn
w Electronic supplementary information (ESI) available: Synthesis,
X-ray crystallographic details (CIF file), NMR results, and DFT
computations. CCDC 849100–849105. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c2cc17699h
Treatment of L with (TEA)Cl afforded the complex
(TEA)4LCl4ꢁH2O (1). The N–CH2–CH2–N torsion angle
retains 1801, but the four o-phenyl groups linking the urea
groups are no longer coplanar as in the optimized free ligand
c
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Chem. Commun., 2012, 48, 3097–3099 3097

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Fig. 3 (a) The ‘‘face-to-face’’ dimerization of two ligands in 2 and the
binding of six Clꢀ anions; (b) two TPA+ cations are encapsulated in
the molecular barrel; (c) infinite tube connected by Clꢀ ions.
chloride ions in 1, there are only three Clꢀ ions per ligand L
in 2, which are hydrogen-bonded by six urea groups. This is
probably because that the electrostatic repulsive force in
complex 2 (two encapsulated cations) is weaker than in 1
(three cations) and could be overcome by less Clꢀ anions. Such
functional plasticity (being adaptable to different activities
without global structural changes)5a is important for the
artificial ‘barrel-stave’ supermolecules.
Fig. 2 (a, b) The molecular ‘barrel’ formed by slipped dimerization of
two ligands in complex 1 which encapsulates three TEA+ cations and
binds eight Clꢀ ions outside; (c) the barrels are further linked by
chloride–water interactions to form an infinite tube.
but form a curved surface with dihedral angles of 65.61 and
61.01 (rings I/II and III/IV; Fig. 1), respectively. Two curved
staves dimerize through a pair of weak C–Hꢁ ꢁ ꢁO hydrogen
bonds between CH and nitro groups of the terminal aromatic
rings, forming a molecular ‘barrel’ (Fig. 2a and b). The
internal space of the barrel is measured to be 9.1 ꢂ 7.9 ꢂ
20.9 A3. Surprisingly, the six urea groups within one ligand are
all oriented to the outside of the barrel. This is remarkable
since they are expected to converge to bind anions. Accord-
ingly, four Clꢀ anions are hydrogen-bonded by these urea NH
groups at the outside (Fig. 2a and Table S2, ESIw).
Switching the cation to TBA+, the (TBA)2LCl2ꢁCHCl3 (3) was
isolated. In contrast to the anti conformation of the ethylene
group in the barrels 1 and 2, the N–CH2–CH2–N torsion angle is
61.51 in 3. Thus the ligand molecule is no longer a stave but is
more like a thread, which folds around two Clꢀ anions for about
one and two-third circles, forming a helical foldamer similar to
some other oligoureas.6f One Clꢀ ion accepts six N–HꢁꢁꢁCl
bonds with three alternate urea groups while the other one is
bound by four N–HꢁꢁꢁCl bonds and two C–HꢁꢁꢁCl contacts with
the cation and solvent molecules (Fig. S1, Table S4, ESIw).
From the above results, it appears that the size of the R4N+
cation can greatly affect the self-assembly process. This size
dependence is also reflected in the bromide salt (R4N)Br.
Treatment of L with (TEA)Br gave the complex (TEA)4LBr4
(4). Although its composition is very similar to the chloride
analogue 1, the structure is significantly different. In compound
4, the whole molecule is only slightly bent, showing a dihedral
angle of 33.01, which is too flat to form a dimerized barrel.
Four Brꢀ ions are located above and below the ligand
molecule and are hydrogen-bonded by six urea groups
(Fig. 4 and Table S5, ESIw). By using (TPA)Br, a barrel
structure (TPA)3LBr3 (5) was constructed, which is essentially
isomorphous to the chloride barrel 2. Two curved ligand
Within the huge columnar space of the barrel, three TEA+
cations are tightly encapsulated in a linear fashion through
C–HTEAꢁ ꢁ ꢁOurea-carbonyl hydrogen bonding and C–Hꢁ ꢁ ꢁp inter-
actions. Two adjacent TEA+ guests are 6.8 A apart (Nꢁ ꢁ ꢁN
separation, Fig. 2c). This multiple inclusion of ionic guests
with close approach is quite unusual due to the electrostatic
repulsion. Nevertheless, such phenomena are common in
biological systems such as the potassium and ammonium ion-
channels, which accommodate multiple K+ and NH4+ guests.8
In the current case, the electrostatic repulsion of the guests
might be diminished by the negative charges (ꢀ8) of the bound
anions as well as the C–Hꢁ ꢁ ꢁO and C–Hꢁ ꢁ ꢁp interactions.
A similar complex (TPA)3LCl3 (2) was isolated by using
(TPA)Cl. The N–CH2–CH2–N torsion angle is 1801, and the
ligand also adopts a curved confirmation with dihedral angles
of 55.61 and 51.81, respectively, between rings I/II and III/IV.
Two bent ligands are linked by four pairs of weak C–Hꢁ ꢁ ꢁO
hydrogen bonds (Fig. 3, Table S3, ESIw) between C–H and
nitro groups of the terminal aryl rings to create a molecular
‘barrel’. However, in complex 2 the two ligand staves are not
slipped as in 1; they are face-to-face dimerized. The dimensions
of the barrel are 10.3 ꢂ 9.5 ꢂ 19.7 A3. Two TPA+ cations are
trapped with a separation of 8.2 A (Fig. 3c). Compared to 1,
the diameter of the barrel 2 is larger but the length is shortened
to encapsulate two bigger guests. Moreover, instead of four
Fig. 4 The flat ‘stave’ structure of complex 4. Countercations and
solvents are omitted for clarity.
c
3098 Chem. Commun., 2012, 48, 3097–3099
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because the Brꢀ is too big or the hydrogen bonds are too weak
to form a folded structure. It can be concluded that the
bis–trisurea L shows interesting ion-pair binding behavior
with [(R4N)X] salts. The synergetic effect of both the cation
and anion might be a key to the construction of the ‘barrels’.
The assembly of L with the [(R4N)X] salts in solution was
investigated by NMR spectroscopy (in DMSO-d6, CDCl3, and
THF-d8; 1H NMR and 2D-DOSY). Unfortunately, in these
experiments, there was no evidence that the cations are
encapsulated (Fig. S4–S8, ESIw), which indicates that the
‘barrels’ might only exist in the solid state with the assistance
of crystallization.
In conclusion, the self-assembly of a bis–trisurea ligand (L)
with six tetraalkylammonium salts has been investigated.
Remarkably, the ligand exhibits considerable flexibility to
form ‘barrel’ structures that encapsulate multiple R4N+ guests
while binding the anions at the outside. The size of both the
R4N+ cation and the halide anion (Clꢀ or Brꢀ) has great
influence on the final structure. This work further proves the
ability of oligo-urea ligands to direct the formation of rich
anion-based supramolecular architectures.
Fig. 5 Summary of the ion-pair induced self-assembly of complexes 1–6.
The ligand ‘stave’ underwent dramatic conformational changes when
treated with different tetraalkylammonium halides to form the ‘barrel’
(complexes 1, 2 and 5), ‘stave’ (4 and 6), and foldamer (3) structures.
staves form a barrel (10.1 ꢂ 9.8 ꢂ 19.7 A3) which encapsulates
two TPA+ guests (separated by 8.6 A). Two Brꢀ anions are
bound by four urea groups, while the third one links two
remaining urea groups from two barrels (Fig. S2 and Table S6,
ESIw). Finally, the assembly of the largest (TBA)Br with L
resulted in a stave complex (TBA)4LBr4 (6) which is similar to 4.
The ligand stave preserves roughly the flat conformation
(Fig. S3 and Table S7, ESIw).
Notes and references
1 For selected reviews on artificial capsules or tubes, see: (a) J. Rebek,
Jr., Angew. Chem., Int. Ed., 2005, 44, 2068; (b) H. M. Keizer and
R. P. Sijbesma, Chem. Soc. Rev., 2005, 34, 226; (c) J. Rebek, Jr.,
Acc. Chem. Res., 2009, 42, 1660; (d) P. Ballester, Chem. Soc. Rev.,
2010, 39, 3810.
The formation of the ion-pair complexes is summarized in
Fig. 5. The ligand exhibits considerable plasticity to adapt for
the formation of ‘stave-barrels’, which is dependent on the size
of both the R4N+ cation and the Xꢀ anion. The sizes of the
TEA+, TPA+, and TBA+ ions are approximately 5.0 ꢂ 5.0,
7.3 ꢂ 7.3, and 10.1 ꢂ 10.1 A2, respectively. For the Clꢀ ion,
the smallest TEA+ ion templated the formation of a ‘‘thin and
long’’ barrel (1) that is about 2.5 times the size of the cation.
Two ligand staves are slipped to completely encapsulate the
three guests. The bigger TPA+ ion modulated a relatively
‘‘wide and short’’ barrel (2), in which two TPA+ ions can fit
perfectly. In contrast, the biggest guest TBA+ cannot be
embedded in a barrel but forms a Clꢀ binding foldamer (3).
On the other hand, the anion also plays an important role in
the assembly process. In all cases multiple anions are bound by
the urea NH groups, and it is the difference between the Clꢀ
and Brꢀ ion in the N–Hꢁ ꢁ ꢁX hydrogen bonding that actually
influences the electronic and conformational properties of the
ligand L. In the Brꢀ binding systems, while the largest TBA+
ion again cannot fit in a barrel but resulted in a flat stave (4), it
is surprising that the smallest TEA+ ion also led to a stave (6)
rather than a barrel as in the case of the Clꢀ compound 1.
There could be two reasons for the latter case: first, the weaker
hydrogen bonds between L and Brꢀ anions could not efficiently
balance the electrostatic repulsive forces of three close TEA+
guests (as barrel 1); and second, the larger Brꢀ ions bound
over the convex surface of the stave could not lead to a proper
radian for the concave side to form a ‘‘thin’’ barrel for TEA+.
Instead, a relatively ‘‘wider’’ barrel can be realized in the
presence of TPA+, which seems to be a better guest for the
stave L. In any case, the foldamer motif was not yielded either
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7 The structure of L was optimized at the B3LYP/6-31G level using
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c
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