Dynamic self-assembly of molecular capsules via solvent polarity controlled reversible binding of nitrate anions with C3 symmetric tripodal receptors

Article abstract of DOI:10.1039/c1cc12757h

A series of N-bridgehead tripodal receptors bearing amide functionality is reported which displays reversible binding of nitrate anions via solvent polarity controlled molecular capsule formation through a dynamic self-assembly process. The Royal Society of Chemistry 2011.

Full text of DOI:10.1039/c1cc12757h

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Dynamic self-assembly of molecular capsules via solvent polarity
controlled reversible binding of nitrate anions with C3 symmetric
tripodal receptorsw
Ashutosh S. Singh and Shih-Sheng Sun*
Received 11th May 2011, Accepted 13th June 2011
DOI: 10.1039/c1cc12757h
A series of N-bridgehead tripodal receptors bearing amide
functionality is reported which displays reversible binding of
nitrate anions via solvent polarity controlled molecular capsule
formation through a dynamic self-assembly process.
Reversible binding in a controlled manner to external stimuli
is the sole essence of dynamic self-assembly processes1 and
non-covalent interactions are the primary tools to accomplish
this phenomenon.2 Various multi-component molecular
Fig. 1 Design principle for a hydrogen-bonded self-assembly of a
assemblies constructed from well-designed complementary
building blocks have been reported in the literature.3 The
interconversion between two or more discrete and structurally
well defined assemblies can be achieved by external stimuli
such as solvents,3a–e concentration3a,f–i and temperature.3h–j In
organic supramolecular systems, the hydrogen bonding and
p–p interactions typically dominate in the self-assembly processes
and the polarity of the surrounding medium has a great impact
on the final self-assembly of supramolecular structures, typically
the most thermodynamically stable one. Nevertheless, the
design of molecular capsules for selective recognition and
encapsulation of specific guest(s) through hydrogen bonding
interactions by appropriately matched hydrogen-bond donor–
acceptor pairs is still a complicated and difficult task.
dimeric capsule.
self-assembled molecular capsule, which reversibly binds weakly
coordinating nitrate anions through dynamic self-assembly/
disassembly via conversion between a nitrate-encapsulated
complex and its self-assembled dimer by simply modulating
the polarity of surrounding medium, from a polar DMSO to a
less polar chloroform.
To explore the effect of the functional group on the guest
binding, receptors 1–3 with interior amide functionality have
been synthesized and the trigonal planar nitrate anion has
been employed as the guest molecule.5 Nitrate complexes 2a
and 3a were isolated as the precipitate by addition of nitric
acid in aqueous methanol to a suspension of corresponding
receptors 2 and 3, respectively, in chloroform and their
identities were confirmed by high-resolution electrospray
ionization mass spectrometry (HRESIMS) and NMR spectra.
In a previous report, we have shown the halide functionality
dependent capsule formation in both solid and solution
states.4 The incorporation of suitable functional groups in
the structural framework of the tripodal receptors would
provide additional intermolecular interactions for assembling
two individual receptors to form a molecular capsule by
pre-organized non-covalent interactions. The design principle
is illustrated in Fig. 1. We envision that it is possible to
assemble two convergent tripodal receptors into a capsule
via a subtle balance of hydrogen bond donor (D)–hydrogen
bond acceptor (A) interactions on each tripodal arm. Herein,
we report the solvent polarity dependent reversible binding
of conformationally flexible, acyclic receptors to form a
Institute of Chemistry, Academia Sinica, 115 Nankang, Taipei,
Taiwan, Republic of China. E-mail: sssun@chem.sinica.edu.tw;
Fax: +011-886-2-27831237; Tel: +011-886-2-27898596
w Electronic supplementary information (ESI) available: Experimental
characterization data, titration spectra and crystallographic details.
CCDC 777052. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c1cc12757h
Fig. 2 A schematic representation of receptors employed for studies,
the solvent dependent formation of a nitrate-encapsulated complex,
and reversible binding of the nitrate anion through interconversion
between a nitrate-encapsulated complex and a self-assembled capsule.
c
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However, the formation of the nitrate complex from receptor 1
is solvent dependent (see Fig. 2). Upon addition of nitric
acid in aqueous methanol to a suspension of receptor 1 in
chloroform, solution color immediately changed from moss
green to orange followed by precipitation. The 1H NMR
spectrum measured in DMSO-d6 (see Fig. S3, ESIw) showed
two well-separated amide N–H peaks at 10.4 and 10.0 ppm
with an integrated area of 2 : 1 ratio, which intuitively
suggested the formation of two different species. However,
only one peak was observed for aliphatic C–H protons
adjacent to the central bridged N-atom and it is downfield
shifted compared to the peak of free receptor 1. This observation
suggests that the centrally bridged N-atom of both components in
the mixture is in the protonated form. It is expected that the
meta proton relative to the methoxy group in receptor 1 is
susceptible to electrophilic nitration. Negative mode HRESIMS
of the nitrate complex of 1 in CHCl3/MeOH (1 : 1, v/v)
solution showed expected peak cluster for 1a at m/z
886.3306 ([1a-H]ꢀ, calcd. m/z 886.3299) and another peak
cluster at m/z 1021.2855 for the nitration [1b-H]ꢀ species
(calcd m/z 1021.2852).
the proton attached to the bridged N-atom (dN–Hꢁ ꢁ ꢁO, 2.171 A
and yN–Hꢁ ꢁ ꢁO, 111.61). One ortho hydrogen atom of the
C-terminal aromatic ring at each arm shows C–Hꢁ ꢁ ꢁp inter-
action with the C-terminal aromatic ring at the neighboring
arm (dC–Hꢁ ꢁ ꢁp, 3.195 A and yC–Hꢁ ꢁ ꢁp, 177.71) in a tilted edge-to-
face form.6 The N–H bonds of the amide groups in each arm
ꢀ
protrude inside towards center in plane, bound to NO3
anions inside the cavity by strong H-bonds between the
O-atoms of the nitrate anion and three amide N–Hs (dN–Hꢁ ꢁ ꢁO
,
2.215 A and yN–Hꢁ ꢁ ꢁO, 157.31). The formation of salts that can
be crystallized and examined by X-ray diffraction represents
an interesting concept for the anion recognition.
A DMSO-d6 solution of a mixture of complexes 1a and 1b
was subjected to titration with CDCl3 (see Fig. S22, ESIw).
The amide N–H peak of 1b at 10.4 ppm was initially upfield
shifted until the ratio of DMSO-d6/CDCl3 (v/v) at 1 : 1 and
followed by downfield shift with increasing concentration of
CDCl3. The other amide N–H peak of 1a at 10.0 ppm was
gradually upfield shifted with increasing concentration of
CDCl3.7 A similar pattern was observed in the aromatic region
when pure nitrate complex 1b (in DMSO-d6) was titrated with
CDCl3 (see Fig. 4). In particular, the doublet at 7.64 ppm
(h protons) showed a remarkable downfield shift with increasing
amount of CDCl3. The identity of the new species formed
upon changing the solvent polarity was probed by HRESIMS.
HRESIMS has been successfully utilized for detection of
supramolecular species in solution.8 The HRESIMS of the
new species formed in a 1 : 1 ratio of DMSO/CHCl3 (v/v)
solution displayed a peak cluster at m/z 1920.5249, which
corresponds to the [M + H]+ ion where M represents a
self-assembled homodimer 102 (calcd m/z 1920.6059 for
[M + H]+). Thus, the interior nitrate anion was released
from the receptor via the formation of the neutral self-
assembled homodimer at 1 : 1 ratio (v/v) of DMSO-d6/CDCl3.
After partial evaporation of CDCl3 from the sample used for
titration, the resulting 1H NMR spectrum was identical to that
of nitrate-encapsulated complex 1b (shown as a red color
spectrum in Fig. 4). Thus, solvent polarity dependent equilibrium
shown in Fig. 2 is fully reversible. More interestingly, leaving
the original solution of capsule 102 for one week, the peak
On the other hand, addition of nitric acid into an aceto-
nitrile solution of receptor 1 at 25 1C yielded 1b as the sole
product in a 92% yield and exhibited a single amide N–H peak
at 10.4 ppm in the 1H NMR spectrum recorded in DMSO-d6.
The isolated complex showed three peaks for the amide
N-terminal phenyl ring at 7.15, 7.35, and 7.52 ppm with an
equal integration area, as anticipated from the expected
structure of complex 1b. Negative mode HRESIMS confirmed
a single peak cluster for the [MꢀH]ꢀ ion at m/z 1021.2855
(calcd m/z 1021.2852) for the nitrate-encapsulated nitro-
substituted complex 1b. The structure of 1b was further
confirmed by COSY, HSQC, HMBC, and ROESY spectra
(see Fig. S8–S11, ESIw). The nitrate complex 1a was prepared
in a 94% yield by slow evaporation of a mixture solution
obtained after dropwise addition of nitric acid in aqueous
methanol to the suspension of receptor 1 in methanol at 25 1C.
The 1H NMR spectrum of nitrate-encapsulated complex 1a
showed a single peak at 10.0 ppm for the amide N–H protons.
Thus, it is clear that two nitrate-encapsulated complexes 1a
and 1b were simultaneously obtained upon addition of nitric
acid to receptor 1 in a mixture solution of CHCl3/MeOH.
The single crystals of 1a suitable for X-ray diffraction were
grown from DMSO-d6 at room temperature over a period of
four weeks. The crystal structure of complex 1a is shown in
Fig. 3 and confirmed the identity of the 1 : 1 nitrate complex.
In the discrete C3 symmetric crystal structure of 1a, an O-atom
of each aliphatic arm of the receptor is hydrogen-bonded to
Fig. 3 Crystal structure of the nitrate-encapsulated complex 1a (left)
and its space-filling model (right). All H-atoms have been omitted for
clarity except for methyl C–Hs and those interacting with the nitrate
anion. All bond distances are in A unit.
Fig. 4 1H NMR (400 MHz, 20 1C) titration spectra of nitrate
complex 1b (40.7 mM) in a DMSO-d6 solution with varying amount
of CDCl3.
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8564 Chem. Commun., 2011, 47, 8563–8565
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In conclusion, solvato-controlled interconversion between
the nitrate complex and self-assembled molecular capsule is
reported. The present concept can be explored in future for
recognition, transport and delivery of weakly coordinating
guest molecules in a reversible manner.
We are grateful to the National 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 099-2811-M-001-120). Mass spectrometry
analyses were performed by Mass Spectrometry facility of the
Institute of Chemistry, Academia Sinica.
Notes and references
Fig. 5 A schematic representation of solvent polarity dependent
self-assembled homodimer formation via reversible binding of the
nitrate anion by the amide functionalized tripodal receptor.
1 (a) J.-M. Lehn, Supramolecular Chemistry Concepts and Perspectives,
VCH, Weinheim, 1995; (b) J.-M. Lehn, Chem.–Eur. J., 1999, 5,
2455–2463.
2 (a) L. J. Prins, D. N. Reinhoudt and P. Timmerman, Angew. Chem.,
Int. Ed., 2001, 40, 2382–2426; (b) T. Rehm and C. Schmuck, Chem.
Commun., 2008, 801–813; (c) H. Dube, D. Ajami and J. Rebek, Jr.,
Angew. Chem., Int. Ed., 2010, 49, 3192–3195.
cluster at m/z 1920.5249 corresponding to [102 + H] disappeared
completely and a new single peak cluster at m/z 1981.5674
corresponding to the self-assembled capsule with one encapsulated
nitrate anion (102a) appeared (see Fig. S30, ESIw). A DMSO-d6
solution of receptor 10, which was isolated from nitrate complex
1b after washing with 10% K2CO3 and extraction with ethyl
acetate, was titrated with CDCl3 (see Fig. S23, ESIw) and a similar
pattern was observed in the aromatic region as that of complex 1b
(Fig. 4). This further confirms that capsule formation takes place
with release of nitric acid (Fig. 5) and without protonation of the
central N-atom. The self-association constant for the formation
of neutral homodimer 102 was evaluated by a concentration
dependent 1H NMR study in a 1 : 1 mixture of DMSO-d6/CDCl3
(Fig. S24, ESIw). The steep curve profile precluded a precise
determination of the self-association constant but yielded a lower
limit of 106 Mꢀ1 for the self-association constant.
3 (a) C. Provent, E. Rivara-Minten, S. Hewage, G. Brunner and
A. F. Williams, Chem.–Eur. J., 1999, 5, 3487–3494; (b) L. Pirondini,
A. G. Stendardo, S. Geremia, M. Campagnolo, P. Samori,
J. P. Rabe, R. Fokkens and E. Dalcanale, Angew. Chem., Int. Ed.,
2003, 42, 1384–1387; (c) K. Suzuki, M. Kawano and M. Fujita,
Angew. Chem., Int. Ed., 2007, 46, 2819–2822; (d) J. Betancourt,
M. Martin-Hidalgo, V. Gubala and J. M. Rivera, J. Am. Chem.
Soc., 2009, 131, 3186–3188; (e) S. Liu and B. C. Gibbs, Chem.
Commun., 2011, 47, 3574–3576; (f) K. Harano, S. Hiraoka and
M. Shionoya, J. Am. Chem. Soc., 2007, 129, 5300–5301;
(g) S. Hiraoka, T. Yi, M. Shiro and M. Shionoya, J. Am. Chem.
Soc., 2002, 124, 14510–14511; (h) T. Haino, T. Fujii, A. Watanabe
and U. Takayanagi, Proc. Natl. Acad. Sci. U. S. A., 2009, 106,
10477–10481; (i) F. Weng, J. Zhang, X. Ding, S. Dong, M. Liu,
B. Zheng, S. Li, L. Wu, Y. Yu, H. W. Gibson and F. Huang, Angew.
Chem., Int. Ed., 2010, 49, 1090–1094; (j) L. D. Shirtcliff, H. Xu and
F. Diederich, Eur. J. Org. Chem., 2010, 846–855; (k) J. Tian,
S. J. Dalgarno and J. L. Atwood, J. Am. Chem. Soc., 2011, 133,
1399–1404; (l) Y. R. Hristova, M. M. J. Smulders, J. K. Clegg,
B. Breiner and J. R. Nitschke, Chem. Sci., 2011, 2, 638–641.
4 A. S. Singh, B.-Y. Chen, Y.-S. Wen, C. Tsai and S.-S. Sun, Org.
Lett., 2009, 11, 1867–1870.
The complete solvato-controlled reversible conversion
between a nitrate-encapsulated complex and its homodimer is
summarized in Fig. 5. Upon protonation of the centrally bridged
N-atom after addition of HNO3, the convergent cone shape
conformation forms via hydrogen bonds between the proton of
the bridged N-atom and the aliphatic O-atoms as well as bꢀy
C–Hꢁ ꢁ ꢁp interactions. The in situ generated cavity entraps NO3
anions by H-bonds and electrostatic interaction. Upon lowering
the solution polarity, the intramolecular hydrogen-bonding inter-
actions between the amide N–H protons and the O-atoms of
ortho substituted nitro groups predominate over intermolecular
hydrogen bonding interactions between the amide N–H protons
and O-atoms of nitrate anions in a less polar environment. Thus,
the nitrate anion is released out of the tripodal cavity in the nitric
acid form followed by self-assembly of two discrete receptors to
form a pseudo trigonal bipyramidal dimeric capsule (102). Upon
partial evaporation of CDCl3, the capsule disassembles and the
nitrate anion is again trapped inside the tripodal cavity. The
nitrate-encapsulated self-assembled capsule (102a) is a more
thermodynamically stable product than 102, which is likely a
kinetic product. The re-protonation of the tertiary amino-sites
in capsule 102 resulted in an electropositive interior cavity that
re-encapsulated the nitrate anion into the capsule because of
the increased electrostatic interaction between the capsule and
nitrate anion.
5 Amide N–Hs are well known to form hydrogen-bonding inter-
actions with various anions in both natural and artificial systems.
(a) T. Martin, U. Obst and J. Rebek, Jr., Science, 1998, 281,
1842–1845; (b) P. D. Beer and P. A. Gale, Angew. Chem., Int. Ed.,
2001, 40, 486–516; (c) C. R. Bondy and S. J. Loeb, Coord. Chem.
Rev., 2003, 240, 77–99; (d) S. O. Kang, R. A. Begum and
K. Bowman-James, Angew. Chem., Int. Ed., 2006, 45, 7882–7894;
(e) C.-L. Chen, Y.-S. Chen, C.-Y. Chen and S.-S. Sun, Org. Lett.,
2006, 8, 5053–5056; (f) C.-L. Chen, T.-P. Lin, Y.-S. Chen and
S.-S. Sun, Eur. J. Org. Chem., 2007, 3999–4010; (g) D.-W. Yoon,
D. E. Gross, V. M. Lynch, C.-H. Lee, P. C. Bennett and
J. L. Sessler, Chem. Commun., 2009, 1109–1111.
6 R. Annunziata, M. Benaglia, F. Cozzi and A. A. Mazzanti,
Chem.–Eur. J., 2009, 15, 4373–4381.
7 The upfield shift of proton signals for nitrate complex 1a in
DMSO-d6 upon titrating with CDCl3 was attributed to the solvent
polarity difference between the pure DMSO-d6 and the mixture of
DMSO-d6/CDCl3. The controlled experiment with receptor 1 in
DMSO-d6 titrated with CDCl3 also showed similar upfield shifting
for all proton signals.
8 (a) K. C. Russell, E. Leize, A. V. Dorsselaer and J.-M. Lehn, Angew.
Chem., Int. Ed. Engl., 1995, 34, 209–213; (b) B. Olenyuk,
J. A. Whiteford, A. Fechtenkotter and P. J. Stang, Nature, 1999,
398, 796–799; (c) C.-Y. Chen, T.-P. Lin, C.-K. Chen, S.-C. Lin,
M.-C. Tseng, Y.-S. Wen and S.-S. Sun, J. Org. Chem., 2008, 73,
900–911.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 8563–8565 8565