Asymmetric and symmetric bolaform supra-amphiphiles: Formation of imine bond influenced by aggregation

Article abstract of DOI:10.1021/la405000a

A series of bolaform supra-amphilphiles with different symmetries were fabricated through dynamic benzoic imine bond formation. The pH dependence of imine formations of these supra-amphiphiles were characterazied. We found that the extent of the imine for

Full text of DOI:10.1021/la405000a

Article
pubs.acs.org/Langmuir
Asymmetric and Symmetric Bolaform Supra-Amphiphiles: Formation
of Imine Bond Influenced by Aggregation
Guangtong Wang, Guanglu Wu, Zhiqiang Wang, and Xi Zhang*
Key Lab of Organic Optoelectronics & Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing 100084,
China
S
* Supporting Information
ABSTRACT: A series of bolaform supra-amphilphiles with
different symmetries were fabricated through dynamic benzoic
imine bond formation. The pH dependence of imine
formations of these supra-amphiphiles were characterazied.
We found that the extent of the imine formation of these
supra-amphiphies were different. The supra-amphiphiles with a
poorer symmetry always exhibited a lower imine formation at a
given pH. Therefore, the varied extent of imine bond
formation indicate the different aggregations of these supra-
amphilphiles, which are controlled by the molecular symmetry
of the supra-amphiphiles.
bolaform supra-amphiphiles exhibiting different symmetries is
shown in Scheme 1. The bolaform supra-amphiphiles prepared
INTRODUCTION
■
Bolaform amphiphiles are amphiphilic molecules that contain
two hydrophilic head groups linked through a hydrophobic
skeleton.1−7 The self-assembling behaviors of bolaform
amphiphiles are quite different from simple amphiphiles
containing only one hydrophilic headgroup and one hydro-
phobic tail. In addition to the de novo synthesis, bolaform
amphiphiles can be obtained through a supramolecular
assembly strategy. Supra-amphiphiles are amphiphiles fabri-
cated by noncovalent interactions or dynamic covalent bonds,
which can produce diverse amphiphiles with various topologies
by simply mixing the building blocks together.8−10 It has also
been demonstrated that the properties of supra-amphiphiles
can readily be modulated on account of the reversible and
dynamic nature of the noncovalent interactions. Therefore,
supra-amphiphiles can be used as building blocks for controlled
self-assembly, thereby combining molecular architectures with
functional assembly.
Scheme 1. Molecular Design of Imine Bolaform Supra-
Amphiphiles and Their Building Blocks, m = 12, 10, 8; n =
10, 8, 6
As one type of linkage for the formation of supra-
amphiphiles, dynamic covalent bonds are in many ways like
noncovalent interactions, due to their dynamic and reversible
properties.11−15 They are widely used to fabricate stimuli-
responsive polymers, gels, and self-healing materials.16−25
Among various dynamic covalent bonds, the benzoic imine
bond26,27 has been commonly used for fabricating supra-
amphiphiles because of its synthetic simplicity and pH-
responsive feature in water.28−32 It was found that the pH
responsiveness of the formed imine bonds was highly
dependent on the stability of the aggregates formed by the
resulting supra-amphiphile.28,29,32
contained two alkyl chains. If the length of the two alkyl chains
is the same, then the amphiphile is considered to be a
symmetric amphiphile (e.g., imine-10/10, both alkyl chains
contain ten CH2 groups). Conversely, if the lengths of the two
alkyl chains are different, an asymmetric amphiphile is formed
(e.g., imine-12/8). This supramolecular strategy therefore
avoids a complex procedure for the synthesis of asymmetric
Herein, we discribe a series of bolaform supra-amphiphiles
fabricated with different symmetries through the use of
dynamic imine bond formation. The molecular design of the
Received: December 30, 2013
Revised: January 22, 2014
© XXXX American Chemical Society
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structures. The relationship between pH and imine bond
formation in these supra-amphiphiles is investigated. We find
that the equilibrium of imine bond formation, which is
influenced by the aggregation of the supra-amphiphiles, is
related to their molecular symmetry. In other words, the supra-
amphiphiles with varied symmetries should have different
aggregation behaviors.
EXPERIMENTAL SECTION
■
General Methods. All of the supra-amphiphiles were prepared by
simply mixing the two building blocks, which contained an aldehyde
group and an amine group, respectively, in a 1:1 molar ratio in alkaline
phosphate-buffered saline (PBS) solution (Scheme 1).
Synthesis of Building Blocks. The synthetic routes of the
building blocks are shown in Figure 1. The other details are included
in the Supporting Information.
1
Figure 2. The H NMR spectra of supra-amphiphile, imine-10/10, in
different pH. All the spectra were obtained at 298 K. The
concentrations of all the samples were 3.0 mmol/L with D2O as a
solvent.
Figure 1. Synthesis of the building blocks (m = 8, 10, 12; n = 6, 8, 10).
Imine Formation Dependence on pH. The relationship
between the extent of imine formation and pH of each supra-
amphiphile can be characterized by 1H NMR. A series of 3.0 mmol/L
solutions of the supra-amphiphile were prepared at different pH values
(buffered by phosphate-buffered saline), ranging from 7.5−12.7.
Deuterium oxide was then added after freeze-drying. 1H NMR spectra
were obtained, and the pH tests were performed as well. All pH values
were measured by using a Mettler Toledo Delta 320 pH meter, and 1H
NMR spectra were obtained by using a JEOL JNM-ECX400
spectrometer.
Imine formation dependence on solution pH during supra-
amphiphile formation is shown in Figure 3. As can be seen in
Figure 3a, the imine formation curves of imine-10/10 and
imine-12/8 are quite different. Across the entire pH range
Critical Micelle Concentration Measurement. The critical
micelle concentrations (CMCs) of these supra-amphiphiles were
measured with the aid of Nile Red (NR) probe. The formation of the
aggregates was detected by the fluorescence of NR as hydrophobic NR
molecules could be incorporated into aggregates formed by the supra-
amphiphiles.32 A series of solutions of each supra-amphiphile with
different concentrations were prepared (pH = 12.0). NR was dissolved
in THF (2.5 mM) and added into the solutions under sonication. The
solutions were allowed to stand at least 4 h until the excessive NR
precipitated. The fluorescence spectra of the solutions were recorded
by using a HITACHI F-7000 fluorescence spectrophotometer.
RESULTS AND DISCUSSION
■
Imine Formation Dependence on pH. The extent of
imine formation of each supra-amphiphile at different pH can
1
be characterized by H NMR. As shown in Figure 2, the
aldehyde and imine protons appear at 10.2 and 8.3,
respectively. When the pH is increased, the intensity of the
aldehyde signal decreases or even disappears, while the signal of
the imine group intensifies significantly. The ratio Iimine/(Iimine
+
I
aldehyde), in which Ialdehyde is the integral value of the aldehyde
proton and Iimine is the integral value of the imine proton, is an
estimate of the percentage of imine formation. The peak at
around 8.1 is ascribed to the proton on the aromatic ring. This
peak increases as the pH goes up, indicating that more imine
bond is formed as well.
Figure 3. Imine formation dependence on pH of the supra-
1
amphiphiles obtained by H NMR in D2O at 298 K.
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investigated, much less imine-12/8 was formed compared to
imine-10/10. At pH = 12.0, 100% aldehyde conversion was
observed for imine-10/10; however, about 68% conversion was
observed for Imine-12/8. There are 20 CH2 groups in the
hydrophobic components of both imine-10/10 and imine-12/8,
but their symmetries are clearly different. It is found that the
symmetric supra-amphiphiles always exhibit a higher imine
formation at a given pH. The same phenomenon was observed
when comparing the formation of imine-8/8 and imine-10/6
(Figure 3b). On account of symmetry, the degree of imine
formation of imine-10/10 is slightly greater than imine-12/10
when pH is larger than 11 (Figure 3a), although its
hydrophobic component is relatively smaller. Similarly, the
imine formation of imine-8/8 is slightly higher than that of
imine-10/8 (Figure 3b). Imine-12/10 is the only asymmetric
supra-amphiphile which has a higher imine formation of than
that of the symmetric imine-8/8 because the length of the
hydrophobic component of imine-12/10 is much larger than
imine-8/8 (22CH2 groups vs 16CH2 groups). Therefore, only
when the difference of the hydrophobic chains is large enough,
the length of the hydrophobic chain can dominate the imine
formation.
Hydrophobicity of the Aggregates. We wondered if the
different percentage of imine formation should be related to the
aggregation of the supra-amphiphiles. To answer this question,
the CMCs of these supra-amphiphiles were measured with the
aid of the NR probe. The log C-wavelength curves are shown in
Figure 4, and CMC values obtained from the curves are
summarized in Table 1. It is found that the CMCs of the
asymmetric supra-amphiphiles (e.g., imine-12/8 and imine-10/
6) are quite close to the CMCs of their aldehyde building
blocks (aldehyde-12, aldehyde-10).
Table 1. CMCs of the Supra-Amphiphiles and Their
Building Blocks (pH = 12.0, 298 K)
amphiphile
CMC (mmol L−1
)
amphiphile
CMC (mmol L−1
)
aldehyde-12
aldehyde-10
aldehyde-8
imine-12/10
imine-12/8
imine-10/10
imine-10/8
0.25
0.72
2.10
0.20
0.25
0.47
0.78
imine-10/6
imine-8/8
imine-8/6
amine-10
amine-8
0.80
2.00
2.10
>50
>50
>50
amine-6
observed when the environment is more hydrophobic.33 So log
C-wavelength curves in Figure 4 can also indicate the
hydrophobicity of the aggregates formed by the supra-
amphiphiles. The log C-wavelength curves of symmetric
supra-amphiphiles (imine-10/10 and imine-8/8) are substan-
tially different from their aldehyde building blocks, and the
fluorescence wavelength of their NR-loaded aggregates are also
longer, indicating less hydrophobic aggregates. However, the
log C-wavelength curves of the asymmetric supra-amphiphiles
(imine-12/8, imine-10/6, and imine-8/6) are nearly coincident
with their aldehyde building blocks. It implies that the
aggregation of every asymmetric supra-amphiphile should be
very similar with the corresponding aldehyde building block.
In other shaped supra-amphiphiles reported previously, the
imine bond formation of the supra-amphiphiles with longer
hydrophobic tails is usually higher. It has been suggested that
the amphiphiles with longer hydrophobic components are
easier to form stable aggregates in water, and the aggregation
pushes the imine bond formation equilibrium toward forming
the imine bond.28,29,32 However, for the series of supra-
amphiphiles we prepared, a longer hydrophobic component
does not always lead to a higher imine formation. The reason is
suggested that except for the aggregation of supra-amphiphiles,
the aldehyde building block also have a tendency to aggregate
itself. When the lengths of the hydrophobic tails of the two
building blocks are too different (e.g., imine-12/8), the building
block with much longer hydrophobic tail, (aldehyde-12), will
prefer to aggregate itself, leaving the other building block
(amine-8) free in solution.34−37 This tendency prevents the two
building blocks from reacting with each other and forming the
supra-amphiphile (imine-12/8). The self-aggregation between
the aldehyde building blocks becomes insignificant only when
the tail lengths of the two building blocks are the same. Thus,
they can aggregate together and convert to the corresponding
supra-amphiphiles. In addition, in CMC measurement, both
CMC values and the log C-wavelength curves of the
asymmetric bolaform supra-amphiphiles (imine-12/8 and
imine-10/6) are nearly the same with that of their aldehyde
building blocks, providing another indication that in the
solution of these asymmetric bolaform supra-amphiphiles, the
aggregates consist mostly of the aldehyde building block,
without the participation of the amine building block.
The wavelength of NR fluorescence is very sensitive to the
polarity of the environment. A more significant blue shift can be
CONCLUSIONS
■
In summary, we have prepared a series of bolaform supra-
amphiphiles with different symmetries by using dynamic imine
bond formation, studied imine bond formation at different pH
values, and found that a strong relationship existed between the
imine formation and the symmetries of the bolaform supra-
amphiphiles. The asymmetric bolaform supra-amphiphiles
always have a low imine formation at a given pH. It indicates
Figure 4. The CMC measurements of the supra-amphiphiles and their
aldehyde-containing building blocks using the NR probe at pH = 12.0,
298 K.
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ASSOCIATED CONTENT
* Supporting Information
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covalent bond of Se-N: Towards controlled self-assembly and
disassembly. Chem.Eur. J. 2013, 19, 9506−9510.
■
S
Details of synthesis and imine formation dependence on pH of
imine-8/6. This material is available free of charge via the
Internet at http://pubs.acs.org.
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stimuli-responsive with dynamic covalent bonds. Polym. Chem. 2013,
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AUTHOR INFORMATION
Corresponding Author
*E-mail: xi@mail.tsinghua.edu.cn.
Notes
■
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This work was financially supported by the National Basic
Research Program of China (Grant 2013CB834502), and the
Foundation for Innovative Research Groups of the NSFC
(Grant 211210004). We thank Fei Li, Kai Liu, and Yu Yi for
helpful discussions.
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