Encapsulation enhanced dimerization of a series of 4-aryl-N- methylpyridinium derivatives in water: New building blocks for self-assembly in aqueous media

Article abstract of DOI:10.1002/asia.201400006

The construction of supramolecular systems in aqueous media is still a great challenge owing to the limited sources of building blocks. In this study, a series of 4-aryl-N-methylpyridinium derivatives have been synthesized. They formed very stable host-gu

Full text of DOI:10.1002/asia.201400006

COMMUNICATION
DOI: 10.1002/asia.201400006
Encapsulation Enhanced Dimerization of a Series of 4-Aryl-N-
Methylpyridinium Derivatives in Water: New Building Blocks for Self-
Assembly in Aqueous Media
Ying Zhang,[a] Tian-You Zhou,[a] Kang-Da Zhang,[a] Jin-Ling Dai,[a]
Yuan-Yuan Zhu,[b] and Xin Zhao*[a]
Abstract: The construction of supramolecular systems in
aqueous media is still a great challenge owing to the limited
sources of building blocks. In this study, a series of 4-aryl-N-
methylpyridinium derivatives have been synthesized. They
formed very stable host–guest (1:2) complexes with CB[8] in
water (binding constants up to 1014 mÀ2) with the two guest
molecules arranged in a head-to-tail manner and the com-
plexes showed high thermostability, which was revealed by
1H NMR and UV/Vis spectroscopic studies, ITC, and crys-
tallographic analysis.
tions.[10] However, building blocks that can be used to con-
struct supramolecular architectures in the aqueous phase are
still limited. In addition, supramolecular systems usually
show low thermostability because noncovalent interactions
(except metal–ligand interactions) are weak. This low stabil-
ity dramatically limits their application. In this regard, build-
ing blocks that are stable at elevated temperatures should
be very useful for the construction of thermostable supra-
molecular architectures.
Aromatic stacking, which is also known as p–p stacking,
is one of the most widely used types of noncovalent interac-
tions in self-assembly. Although in highly polar solvents it
has advantages over hydrogen-bonding, which is dramatical-
ly weakened owing to the competition of solvent molecules,
aromatic stacking usually suffers from weak interactions and
the lack of direction. In 2001, Kim et al. found that the
bonding strength between electron-deficient viologens and
electron-rich species such as 1,4-dihydroxybenzene could be
considerably enhanced by being encapsulated in the cavity
of cucurbit[8]uril (CB[8]) to form a 1:1:1 ternary complex.[11]
Since then this type of host-stabilized donor–acceptor inter-
action has been widely employed to construct sophisticated
supramolecular systems in aqueous media.[12] Very recently,
Zhang and co-workers reported that this strategy could also
be applied to enhance p–p interactions.[13] Despite the prog-
ress that has been achieved, controlling the arrangement of
guests in the cavity of CB[8] in an accurate way remains
challenging in these systems. In this study, we constructed
a series of 4-aryl-N-methylpyridinium derivatives T1–T6 to
develop an efficient strategy to control the bonding direc-
tion of guest molecules in host CB[8] (Scheme 1).[14,15] We
anticipated that a head-to-tail arrangement of the molecules
must be adopted when they are stacked because a head-to-
head arrangement might result in strong electrostatic repul-
sion between the pyridinium units. We found that these mol-
ecules dimerized in the cavity of CB[8] to form extremely
stable host–guest complexes in aqueous solution, in which
the guest molecules aligned in a head-to-tail manner. Fur-
thermore, unusually high thermostability was also observed
for these complexes.
Molecular self-assembly is a powerful tool in constructing
well-defined aggregates that are the basis for fabricating
functional materials.[1] To apply this approach, supramolec-
ular building blocks (also known as supramolecular tectons)
must first be rationally designed and then synthesized.
Driven by noncovalent interactions, those building blocks
can spontaneously aggregate to form well-ordered supra-
molecular systems under certain conditions.[2] In this con-
text, a supramolecular tecton is the most fundamental unit,
which determines the final structure of a self-assembled ar-
chitecture. For this reason, developing new building blocks
is regarded as one of the most important themes in supra-
molecular chemistry. In the past few decades, a myriad of
supramolecular tectons have been synthesized with different
noncovalent interactions such as hydrogen-bonding,[3] coor-
dination,[4] static interactions,[5] aromatic stacking,[6] donor–
acceptor,[7] cation···p,[8] anion···p,[9] and C H···p interac-
À
[a] Y. Zhang, T.-Y. Zhou, Dr. K.-D. Zhang, J.-L. Dai, Prof. X. Zhao
Laboratory of Materials Science
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences
345 Lingling Road, Shanghai 200032 (China)
Fax : (+86)21-64166128
E-mail: xzhao@mail.sioc.ac.cn
[b] Prof. Y.-Y. Zhu
Anhui Key Laboratory of Advanced Functional Materials and Devi-
ces
School of Chemical Engineering
Hefei University of Technology
Anhui, 230009 (China)
A
1H NMR spectroscopy dilution experiment was first
carried out for compound T1 in D2O. All the protons of T1
showed very small downfield shifts (<0.03 ppm) when the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201400006.
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Xin Zhao et al.
could be attributed to the hypochromic effect that results
from the p–p stacking and J-type arrangement of the two
molecules of T1 in the cavity of CB[8].[17] Furthermore, it
was found that the fluorescence emission of T1 was consid-
erably enhanced and displayed a bathochromic shift after
being encapsulated, which is in agreement with the J-type
arrangement of T1 in the cavity of CB[8] (Figure S2, see the
Supporting Information).[18]
The binding behavior between CB[8] and T2–T6 was then
1
investigated by using H NMR titration, UV/Vis, and fluo-
rescence spectroscopy experiments under the same condi-
tions used for T1. T2–T6 showed similar changes in both
chemical shift and absorption to that of T1 upon the addi-
tion of CB[8] (Figure S3–S7, see the Supporting Informa-
tion), and this suggested a similar binding model to that of
T1. The binding stoichiometries were confirmed by Jobꢁs
plots to be 2:1 for T3–T6 and CB[8] (Figure S8–S11, Sup-
porting Information), respec-
Scheme 1. Chemical structures of T1–T6 and CB[8].
concentration was reduced from 12.8 mm to 0.3 mm (Fig-
ure S1, see the Supporting Information), thus suggesting
that the aggregation of T1, if any, is very weak. We thus ex-
amined its aggregation in the presence of CB[8] by H NMR
titration. As shown in Figure 1, following the addition of
1
tively. Under similar conditions,
free T2 and T2–CB[8] showed
very weak UV/Vis absorbance.
Although a satisfactory Jobꢁs
plot could not be generated for
the T2–CB[8] complex owing to
its weak UV/Vis absorption,
the binding stoichiometry be-
tween T2 and CB[8] could still
be confirmed to be 2:1 by
1H NMR titration experiments.
Similar to T1, the fluorescence
emissions of T3, T4, and T5
Figure 1. 1H NMR spectra (500 MHz) of (a) T1 (1.0 mm), (b) T1–CB[8] (0.15 equiv), (c) T1–CB[8] (0.2 equiv),
(d) T1–CB[8] (0.4 equiv), (e) T1–CB[8] (0.5 equiv), and (f) T1–CB[8] (0.6 equiv) in D2O at 258C.
were enhanced after being en-
capsulated in CB[8] (Fig-
ure S12–S14, see the Supporting
CB[8], a new set of signals appeared, accompanied by a de-
crease in the intensities of the peaks that correspond to free
T1. The new set of signals could be attributed to a complex
formed from T1 and CB[8] under a very slow exchange be-
tween complexed T1 and free T1 on the NMR time scale.
Compared with that of free T1, all of the protons of T1
showed a pronounced upfield shift after complexing with
CB[8] with the exception of the NMe group. The titration
experiment also revealed that the signals of free T1 were
significantly diminished after 0.5 equivalents of CB[8] was
added and further addition of CB[8] (0.6 equiv)[16] did not
result in any change in the signals, thereby indicating a 2:1
binding stoichiometry for T1 and CB[8]. The 2:1 binding
stoichiometry was further corroborated by a Jobꢁs plot,
which displayed the maximum change in UV/Vis absorbance
of T1 at 66.7% of free T1 in a mixture of T1 and CB[8]
(Figure 2). A UV/Vis study revealed that the maximum ab-
sorbance of T1 decreased by
Information). In contrast, the T2–CB[8] and T6–CB[8] com-
plexes were not fluorescent under similar conditions.
Reducing the concentration of an aqueous solution of
complex T1–CB[8] from 0.39 mm to 0.02 mm did not result
in any shift of the signals in the 1H NMR spectra (Fig-
ure S15, see the Supporting Information), thereby revealing
that the complex was highly stable in aqueous media. The
binding constants between CB[8] and T1–T6 were estimated
by isothermal titration calorimetry (ITC) experiments (see
Figures S16–S21 in the Supporting Information for the ITC
data and thermodynamic binding data). The ITC results also
indicated a stoichiometry of 2:1 for T1ACHTNUTRGNEUNG(-T6)–CB[8]. The
data were fitted by using a sequential binding model to give
the binding constants and the results are provided in
Table 1. The values indicate that these complexes are highly
stable, with T5–CB[8] exhibiting the largest binding constant
(1.3ꢂ1014 mÀ2), while T6–CB[8] showed the lowest value
approximately 34% and the
Table 1. Binding constants for the complexes formed between T1–T6 and CB[8].
corresponding peak was red-
shifted by 8 nm upon the addi-
tion of 0.5 equivalents of CB[8]
(Figure 2). Such phenomena
Complex
T1–CB[8]
T2–CB[8]
T3–CB[8]
T4–CB[8]
T5–CB[8]
T6–CB[8]
Binding constant
3.4
3.5
4.4
3.0
1.3
2.0
[MÀ2
]
(Æ0.9)ꢂ1012 (Æ0.8)ꢂ1012 (Æ0.6)ꢂ1013 (Æ1.3)ꢂ1013 (Æ0.4)ꢂ1014 (Æ0.5)ꢂ1012
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Xin Zhao et al.
Figure 2. UV/Vis spectra of T1 (37.5 mm) without and with CB[8]
(18.8 mm) in a sodium phosphate buffer (0.1m, pH 7.0) at 258C (top), and
Jobꢁs plot indicating a 2:1 stoichiometry for T1 and CB[8] (bottom). The
total concentration used for generating the Jobꢁs plot was 10 mm.
(2.0ꢂ1012 mÀ2). The difference might be attributed to their
different hydrophobic features.
To obtain detailed information about the arrangement of
the molecules in the cavity of CB[8], single crystals of com-
plex T1–CB[8], suitable for crystallographic analysis, were
grown by slow evaporation of an aqueous solution of T1
and CB[8] (2:1) at 258C.[17] The crystal structure clearly re-
veals that two molecules of T1 are encapsulated inside one
CB[8] molecule (Figure 3). The anisole unit and the pyridi-
nium segment of the molecule are almost coplanar (the di-
hedral angel between anisole unit and pyridinium segment
is 6.48). Furthermore, the two encapsulated molecules are
antiparallel to each other and adopt a head-to-tail offset
stacking with a mean distance of 3.8 ꢃ, a typical distance
for aromatic stacking. Single crystals of complex T2–CB[8]
were also grown in a similar way and elucidated;[19] this re-
vealed that compound T2 adopted almost the same arrange-
ment in the cavity of CB[8] as that of compound T1
(Figure 3).
Figure 3. Crystal structures of complexes T1–CB[8] (top) and T2–CB[8]
(bottom) indicate the head-to-tail offset stacking of a pair of T1 or T2 in
the cavity of CB[8].
1
Variable-temperature H NMR experiments revealed that
these 2:1 complexes had high thermostability. Figure 4
1
shows the H NMR spectra of complex T1–CB[8] and free
T1 at different temperatures. It was found that both the sig-
nals that correspond to complex T1–CB[8] and free T1 shift-
ed downfield with increasing temperature; this is attributed
to the inherent effect upon raising the temperature. No sig-
nals of the free T1 were observed for the solution of T1–
Figure 4. Partial 1H NMR spectra of T1–CB[8] (2:1) and T1 in D2O at
different temperatures. The concentration of T1 was 1.0 mm.
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Xin Zhao et al.
CB[8] (2:1) even at 758C,[20] thus indicating that T1 was still
encapsulated in the cavity of CB[8] at this temperature. A
rapid exchange between the free T1 and encapsulated T1 at
elevated temperatures could be considered, but this was
ruled out by variable-temperature 1H NMR experiments
that were carried out for a mixture of T1 and CB[8] (2:0.6),
in which both the bound T1 and free T1 coexisted and dis-
played distinct peaks. With increasing temperature, the two
sets of signals that correspond to bound T1 and free T1
shifted downfield, respectively, but no merging of the two
sets of signals was observed even at 608C (Figure S22, see
the Supporting Information). This result suggests that the
complex T1–CB[8] and free T1 exist in the aqueous solution
independently at elevated temperatures (608C), thus indi-
cating the high thermostability of complex T1–CB[8]. It
should be noted that at 758C all the aromatic peaks became
very broad, thus suggesting that at this temperature, ex-
change between complex T1–CB[8] and excess T1 occurs at
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1
a rate comparable to the H NMR time scale. Other com-
plexes also showed a high thermostability, as revealed by
1
the variable-temperature H NMR experiments (Figure S23–
S27, see the Supporting Information).
In summary, a new model for encapsulation-enhanced ar-
omatic stacking has been developed. These 4-aryl-N-methyl-
pyridinium derivatives spontaneously dimerize in the cavity
of CB[8] and the resulting host–guest complexes have very
high stability in aqueous media. Their high thermostability
should be very useful in fabricating supramolecular systems
that can survive at elevated temperatures in aqueous media.
The head-to-tail arrangement of the dimers provides excel-
lent direction control when the two building blocks are
bound together. Further studies on using these novel build-
ing blocks to construct complicated supramolecular systems
such as supramolecular polymers[21] are now in progress.
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Acknowledgements
[13] Y. Liu, K. Liu, Z. Wang, X. Zhang, Chem. Eur. J. 2011, 17, 9930–
9935.
We thank the National Natural Science Foundation of China (Nos.
21172249, 91127007) for financial support. We also thank Mrs. Wen-Min
Wu, Prof. Guang-Yu Li, and State Key laboratory of Bioorganic and Nat-
ural Products Chemistry for the help with ITC, variable-temperature
1H NMR and 2D COSY spectroscopic experiments.
[14] Compounds T1, T3, T4, T5 and T6 have already been reported but
they all have not been used for this purpose. See: a) C. Altomare, P.
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[15] Two molecules with similar structures to those of T1 and T3 have
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[16] CB[8] did not dissolve in water owing to its poor solubility.
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Keywords: cucurbit[8]uril · dimerization · head-to-tail ·
host–guest systems · self-assembly
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Received: January 1, 2014
Published online: April 23, 2014
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