Halide functionality dependent formation of molecular receptors and their ion recognition properties

Article abstract of DOI:10.1021/ol900565e

The halide functionality on W-bridged tripodal receptors has shown a distinct behavior on their self-assembly structures and binding ability toward HgCl₂ and ClO₄- anions. The receptors containing fluoro, chloro, and iodo groups crystallized to form hemicarcerands in the solid state, whereas the receptor with a bromo group forms a molecular capsule via C-H-Br and C-H-πinteractions. The cavity of the molecular capsule is tunable and is capable of reversible encapsulating-releasing the guest molecules by pH modulation.

Full text of DOI:10.1021/ol900565e

ORGANIC
LETTERS
2009
Vol. 11, No. 9
1867-1870
Halide Functionality Dependent
Formation of Molecular Receptors and
Their Ion Recognition Properties
Ashutosh S. Singh,† Bo-Yu Chen,†,‡ Yuh-Sheng Wen,† Chiitang Tsai,‡ and
Shih-Sheng Sun*,†
Institute of Chemistry, Academia Sinica, 115 Nankang, Taipei, Taiwan,
Republic of China, and Department of Chemistry, Chinese Culture UniVersity,
Taipei, 11114, Taiwan, Republic of China
sssun@chem.sinica.edu.tw
Received January 14, 2009
ABSTRACT
The halide functionality on N-bridged tripodal receptors has shown a distinct behavior on their self-assembly structures and binding ability
toward HgCl2 and ClO4- anions. The receptors containing fluoro, chloro, and iodo groups crystallized to form hemicarcerands in the solid
state, whereas the receptor with a bromo group forms a molecular capsule via C-H···Br and C-H···π interactions. The cavity of the molecular
capsule is tunable and is capable of reversible encapsulating-releasing the guest molecules by pH modulation.
Self-assembly is the fundamental feature of natural and
biological processes with noncovalent interactions acting as
tools to accomplish these tasks. Inspired by this biological
phenomenon, self-assembly has become a key step for
miniaturization of functional devices and the development
of future nanotechnology.1,2 The properties of a self-
assembled “superstructure” depend upon the information
encoded in individual components such as charge, magnetic
dipole, polarizability, size, shape, and surface properties, etc.
These characteristics determine the interactions among the
components to accomplish such self-assembly processes and
final products.
Podands, cavitands, hemicarcerands, and capsules are
interesting members of the receptor family,3 where the
confined interior space (or cavity) formed either by self-
assembly of the monomeric unit through noncovalent
interactions or by the metal-ligand coordination bond has
(2) (a) Conn, M. M.; Rebek, J., Jr. Chem. ReV. 1997, 97, 1647–1668.
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† Academia Sinica.
‡ Chinese Culture University.
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2407. (b) Blau, W. J.; Fleming, A. J. Science 2004, 304, 1457–1458. (c)
Schenning, A. P. H.; Meijer, E. W. Chem Commun. 2005, 3245–3258. (d)
Sofos, M.; Goldberger, J.; Stone, D. A.; Allen, J. E.; Ma, Q.; Herman, D. J.;
Tsai, W.-W.; Lauhon, L. J.; Stupp, S. I. Nat. Mater. 2009, 8, 68–75
.
10.1021/ol900565e CCC: $40.75
Published on Web 04/03/2009
 2009 American Chemical Society

been employed for various applications.4 The dynamic nature
of self-assembled molecular receptors has also been studied
in depth for its potential applications, such as molecular or
drug delivery5 and molecular catalysis.6
Mercury and its salts (such as HgCl2) are highly toxic and
environmentally hazardous pollutants because of their physi-
cal existence in all three forms (solid, soluble in water, and
gaseous state) and readiness to release into biological cycles.7
During the course of searching for effective ion recognition
receptors, we have synthesized a series of podands bearing
different halide functionality (Scheme 1). We envisioned that
Receptors 1, 2, and 4 crystallized with rhombohedral
symmetry, forming hemicarcerands through self-assembly
in the solid state. Their patterns of intermolecular interactions,
however, are different. The crystal packing diagram of
receptor 1 shows that the structures are stabilized through
weak C-H···O interactions (dC-H···O 2.52 Å). In receptor 2,
molecules are stabilized through C-H···Cl and C-H···π
interactions, respectively. Each arm of the tripodal unit is
linked with its neighboring unit by aliphatic C-H···Cl
interactions (dC-H···Cl 2.90 and 3.03 Å) in the same plane and
through aromatic C-H···Cl interactions (dC-H···Cl 2.91 Å) with
molecules in the adjacent plane.8 In receptor 4, molecules
are stabilized through aliphatic and aromatic C-H···π
interactions (Figure 1). In all three receptors (1, 2, and 4),
Scheme 1. Synthesis of Tripodal Podands
incorporating various halides to the framework of a tripodal
podand would modulate the binding angle toward Hg(II) via
the inductive effect exerted by the halides with different
degrees of electronegativity. The different sizes of the halides
are expected to impart a steric requirement during the
crystallization and result in different macroscopic packing
outcomes. Moreover, the flexible nature of the podand
structure also increases the possibility of modulating the guest
binding with external stimuli such as pH. Herein, we report
the synthesis and the effect of halide substitution at the para
postion of aromatic rings of a N-bridged tripodal podand on
the self-assembly process and its binding ability for HgCl2
and the unexpected discovery of proton-assisted binding for
-
ClO4 anions.
The studied podands were synthesized by simple SN2
substitution of their corresponding phenols on tris(2-chlo-
roethyl)amine hydrochloride, obtained by condensation of
commercially available triethanolamine with SOCl2. These
1
receptors have been fully characterized by H NMR, 13C
NMR, high-resolution mass spectrometry, and single-crystal
X-ray diffraction. The single crystals of these receptors
suitable for X-ray diffraction studies were obtained by slow
evaporation of their methanolic solution at room temperature
over a period of 1-2 days.
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1998, 394, 764–766. (b) Chapman, R. G.; Olovsson, G.; Trotter, J.; Sherman,
J. C. J. Am. Chem. Soc. 1998, 120, 6252–6260. (c) Rebek, J., Jr. Acc. Chem.
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Figure 1. Crystal structure of 1 (top), 2 (middle), and 4 (bottom),
showing pattern of intermolecular noncovalent interactions in their
crystal packings.
each tripodal unit is surrounded by six other ligands (see
the Supporting Information) occupying a chair conformation.
The shortest N···N distance in the 1D plane (along c-axis) is
(5) Ghosh, S.; Reches, M.; Gazit, E.; Verma, S. Angew. Chem., Int. Ed.
2007, 46, 2002–2004, and references therein.
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11.06, 13.32, and 12.85 Å in the crystal structures of 1, 2,
and 4, respectively.
In crystal structure 3, however, two tripodal units self-
assemble to form a molecular capsule (32) via intermolecular
C-H···π and C-H···Br interactions. Like receptors 1, 2, and
4, each tripodal unit of 3 is hexagonally surrounded by six
other ligands forming a chair conformation (Supporting
Information). Each of the two molecules of 3 in the crystal
structure is stabilized in a staggered conformation. Two units
of 3 are flipped inward toward each other in a face-to-face
fashion (dN1···N1 4.17 Å) and held together via C-H···π
interactions (dC-H···π 3.27 Å, Figure 2b) from the ortho C-H
Figure 3.
1H NMR spectrum (400 MHz) recorded after 10 h of
dissolving crystals of the molecular capsule (32, 3.18 × 10-2 M)
in CD3CN at 293 K. The orange circles represent the peaks from
the molecular capsule (32) and the brown circles represent the peaks
from the open form (free receptor 3).
Figure 2. Illustration of the crystal structure of molecular capsule
32. (a) Lateral view of molecular capsule (each half of capsule is
shown by different color) and (b) front view of molecular capsule
showing each arm of capsule is in staggered form to each other.
Figure 4. Crystal structure of mercury complex (1a) obtained after
complexation of receptor 1 with HgCl2.
of the aromatic ring, creating a cavity inside the capsule.
Three types of interactions are present in the crystal packing:
(a) C-H···π interactions, (b) C-H···Br interactions, and (c)
π···π interactions. One arm of each half of molecular capsule
is linked with that of a neighboring capsule (through π···π
stacking, dπ···π 3.72 Å) to form a 1D helical chain, and the
remaining two arms of each half are linked with a lateral
neighboring capsule to form an overall 3D network. The
molecular capsule is stable in MeCN solution as confirmed
NMR titrations (Figure 5). The titration results showed that
receptor 1 selectively associated with HgCl2 with an as-
sociation constant of 35 M-1 at 293 K. Although receptor 1
also interacted with Cd(II) and Zn(II), the Cd(II) and Zn(II)
ions exhibited tendency to bind with water present in
deuterated solvent and these complexes were not stable in
solution (see the Supporting Information).
1H NMR titration of receptor 3 with HgCl2 showed
surprising results. After addition of 0.3 equiv of HgCl2 to 3
in CD3CN, each peak shifted slightly downfield to peaks in
the aromatic region as well as in the aliphatic region (Figure
5, top) along with the appearance of small new peaks in the
downfield positions next to the major peaks. Although the
pattern of peak shifting in the aliphatic region was similar
to the titration studies of 1 with HgCl2, the peak near 3.0
ppm became broad with increasing equivalents of HgCl2.
The new peaks in the aromatic and aliphatic regions are
similar to the spectrum corresponding to the molecular
capsule form, as shown in Figure 3, that was acquired by
directly dissolving crystals of 32 (molecular capsule) in
CD3CN. This result indicates that three species (3, HgCl2
adduct of 3 and molecular capsule, 32) were in equilibria
1
by the ESI-mass spectrum (m/z 1228.86) and H NMR
1
spectrum. Figure 3 shows the H NMR spectrum recorded
after 10 h of dissolving the crystals of 32 (molecular capsule
form) in CD3CN at 293 K. It is clear to see that an
equilibrium was established between the capsule form and
the monomeric form with a dissociation constant of ca. 8.8
M at 293 K.
The binding ability of these tripodal receptors has been
explored for Hg(II) and HgCl2. Interestingly, only the podand
having a fluoro functional group (1) was found to bind with
HgCl2 to form a mercury complex (1a) (Figure 4). Other
receptors (2, 3, and 4) in the presence of HgCl2 only
crystallized to give 2, 3, and 4, respectively. The excellent
solubility of the mercury complex (1a) in MeCN (insoluble
1
1
in CHCl3, MeOH, and acetone) allowed us to perform H
during the course of H NMR titrations. This result also
Org. Lett., Vol. 11, No. 9, 2009
1869

Figure 6. pH-modulated reversible exchange between molecular
capsule 32 (top) and its anion complex 3a (bottom). Each half is
shown by a different color, and all H-atoms (except for N···H) have
been removed for clarity.
distance between the centrally bridged N-atoms in anionic
complex (3a) is 6.98 Å. The crystal of molecular capsule
(32) was recovered by slow evaporation of a CHCl3 layer of
anionic complex (3a) after washing with H2O/Et3N solution.
In conclusion, we have demonstrated that the formation
of molecular receptors of different topology can be manipu-
lated by simply varying the halide substitution on the
N-bridged tripodal podand. We have also introduced a simple
strategy to assemble a molecular capsule with an interior
hydrophobic cavity based on arrays of C-H···π and C-H···Br
interactions. The aliphatic chain and tertiary N-atom provide
opportunities to modulate the cavity size of the capsule, and
it is also possible to make it water soluble by incorporating
suitable functionality. Further research working to explore
applications of molecular capsules of this kind is in progress.
Figure 5.
1H NMR spectra (400 MHz) of tripodal podand 3 (1.59
× 10-2 M, top) and 1 (1.27 × 10-2 M, bottom) titrated with solution
of HgCl2 in CD3CN at 293 K.
signifies that the rate of capsule formation is in competition
to the complexation of 3 with HgCl2. Perhaps this is the
reason why only crystals of the molecular capsule (32) were
obtained during the crystallization of 3 with HgCl2.
The binding ability of molecular capsule (32) toward
environmentally hazardous perchlorate anion has also been
studied in the solid state. The crystal of the anionic complex
(3a), suitable for single X-ray diffraction, was obtained by
slow evaporation of CHCl3 layer of molecular capsule (32)
after extraction with dilute perchloric acid. Single crystal
analysis showed that the centrally bridged N-atoms of 3 were
protonated and the two perchlorate anions were sandwiched
between them (Figure 6) via electrostatic interactions.9 The
Acknowledgment. We are grateful to the National Science
Council of Taiwan (Grant No. 97-2628-M-001-015-MY3)
and Academia Sinica for support of this research. A.S.S.
thanks the postdoctoral fellowship sponsored by the National
Science Council of Taiwan (Grant No. 097-2811-M-001-
074).
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Supporting Information Available: Detailed experimen-
tal procedures, spectra, and single-crystal X-ray crystal-
lographic files (CIF). This material is available free of charge
via the Internet at http://pubs.acs.org.
(7) Boening, D. W. Chemosphere 2000, 40, 1335–1351.
OL900565E
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