Spontaneous nanoaggregate formation of amphiphilic poly(amide acid)s in water

Article abstract of DOI:10.1246/cl.2010.1106

Alicyclic poly(amide acid) triethylammonium salts having alkyl ester side chains spontaneously self-assembled to form nanoaggregates in water. The nanoaggregates of poly(amide acid)s encapsulated a hydrophobic guest molecule, Nile red, within their apolar

Full text of DOI:10.1246/cl.2010.1106

doi:10.1246/cl.2010.1106
1106
Published on the web September 11, 2010
Spontaneous Nanoaggregate Formation of Amphiphilic Poly(amide acid)s in Water
Takashi Hamada, Toshio Takayama, and Kazuaki Kudo*
Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8305
(Received July 14, 2010; CL-100633; E-mail: kkudo@iis.u-tokyo.ac.jp)
Alicyclic poly(amide acid) triethylammonium salts having
alkyl ester side chains spontaneously self-assembled to form
nanoaggregates in water. The nanoaggregates of poly(amide
acid)s encapsulated a hydrophobic guest molecule, Nile red,
within their apolar microenvironment. The size of the aggregates
and the critical aggregation concentration (CAC) were consid-
erably affected by both side chain length and Mw, of the
polymers.
COOH
O
O
x
O
HNOC
HOOC
H2N Ar NH2
+
O
DMF, rt
CONH Ar
O
y
n
O
(x,y)=(1,0) or (0,1)
DAn
R = C3H7
C3PAA
Ar:
R = C9H19
R = C16H33
C9PAA
C16PAA
R
O
O
Figure 1. Synthesis of amphiphilic PAAs.
There has been a growing interest in amphiphilic polymers
because of their potential to generate assemblies such as
micelles, vesicles, and fibers.1,2 The ability to tailor such nano-
to microscale morphologies is very important because of
desirable application in areas ranging from material science to
biology such as drug delivery.3
Most of the amphiphilic polymers reported to date can be
classified into AB diblock, ABA triblock, and random copoly-
mers.4-6 Recently, several groups have demonstrated a new type
of aggregate-forming polymers, amphiphilic vinyl homopoly-
mers that have side chain with both hydrophilic and hydro-
phobic moieties on each repeating unit.7,8 Because of the limited
number of research on amphiphilic homopolymers, their
structure-property relationships are still not well understood
compared to that of amphiphilic block copolymers. Further
studies, especially those on non-vinyl amphipathic homopol-
ymers, are desirable.
determined by gel permeation chromatography (GPC) after the
conversion of the carboxylic acid moieties to the corresponding
methyl esters by treatment with diazomethane in order to avoid
aggregation during the analysis.
Although the PAAs were not soluble in water, they could
¹1
be solubilized up to 2.0 g L through the derivatization to the
corresponding triethylammonium salts according to Horie’s
report.9 The solutions were optically transparent and colorless.
Then, we checked the presence of hydrophobic microenviron-
ment in the PAA solutions by using a Nile red (NR) as a polarity-
sensitive fluorescent probe.13,14 Although NR displayed a weak
emission in water, a marked increase in the fluorescence intensity
was observed in the presence of PAAs (Figure S1).17 Interestingly,
addition of poly(amide acid) prepared from DAn and m-phenyl-
enediamine did not bring about the increase in the fluorescence
intensity of NR. This means that the alkyl ester side chain is
essential for providing effective hydrophobic environment.
We then estimated critical aggregation concentration (CAC)
of the PAAs. The plot of the fluorescence intensity of NR as a
function of the concentration of PAAs showed an inflection
point, and this point was assigned to CAC (Figure S2).17
Smaller CAC values were observed for PAAs with longer alkyl
side chains (Table 1). Such a tendency has been recognized for
wide variety of low-Mw surfactants, and can be easily explained
by considering the difference in the HLB values of the repeating
unit of PAAs.15 The CAC values also varied depending on the
Mw of C9PAAs: the increase in the Mw of PAA brought about
the decrease in the CAC value. This can be attributed to
intermolecular hydrophobic interaction, which is larger for
Poly(amide acid) (PAA),
a synthetic intermediate of
polyimide, has two hydrophilic carboxylic acid residues per
repeating unit and the rest of the unit is essentially hydrophobic.
This means that PAAs can be regarded as a candidate for
aggregate-forming amphiphilic homopolymers. Horie et al. have
shown that formation of the carboxylate salt of PAA with amines
could significantly increase the hydrophilicity resulting in the
solubilization of PAAs in water.9 However, in their work, the
aggregate-forming behavior of PAA salts was not referred to. We
herein report the first example for the observation of self-
assembled nanoaggregates of amphiphilic PAA in water, along
with a brief structure-property relationship study.
We thought that the aggregating behavior of amphiphilic
PAA salt could be systematically evaluated through changing the
molecular structure of PAA. Therefore, alkyl esters of 3,5-
diaminobenzoic acid were chosen as diamines because a series
of related compounds having different lipophilicity is readily
accessible. We used spiroalicyclic DAn, which was previously
developed in our group, as a sole dianhydride.10
Table 1. Synthesis and aggregating properties of PAAs in
10 mM triethylamine (TEA)
Yield
/%
CAC
/mg mL
DH
/nm
Entry
Mw Mw/Mn
¹1
1
2
3
4
5
6
C3PAA
C9PAA
C16PAA
C9PAA
C9PAA
C9PAA
97
82
91
70
78
87
7600
7600
10700
3300
5800
14000
1.50
1.26
1.46
1.47
1.48
1.93
0.25
0.05
0.01
0.1
0.05
0.025
531
151
11
6
135
172
We employed propyl, nonyl, and hexadecyl esters of 3,5-
diaminobenzoic acid as diamine monomers.11 The PAAs were
synthesized through the reaction of each diamine with DAn by
a conventional method (Figure 1). It was revealed that the
polyaddition occurred in nonselective manner according to
1H NMR spectral analysis of PAAs.12 Mw of the PAAs was
Chem. Lett. 2010, 39, 1106-1107
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1107
C16PAA
C9PAA
C3PAA
Figure 3. SEM image of the molecular assemblies from
C9PAA with Mw = 14000.
0.001
0.01
0.1
1
10
Diameter/ µm
Figure 2. Size distribution for C3PAA, C9PAA, and C16PAA
at concentration of 2 mg mL in 10 mM TEA solutions.
water. The size and the CAC of the amphiphilic PAAs were
affected by both side chain length and Mw of the polymers. A
study of the structure of the molecular aggregates along with
more detailed alkyl chain length dependence is now under
investigation.
¹1
higher Mw PAAs; hence, such PAAs are believed to begin
aggregation at lower concentrations.
Dynamic light scattering (DLS) measurement of the PAA
solutions at a concentration above CAC was performed. All the
PAA solutions gave essentially a unimodal peak in the histogram
of hydrodynamic diameter (DH) as shown in Figure 2. This is the
first example of the observation of spontaneous molecular
aggregate formation by amphiphilic polycondensate in water.
Mean values of DH considerably varied depending on the chemi-
cal structure and Mw of PAAs (Table 1). Most of the aggregates
were much larger than common polymer micelles, and some of
them were even larger than those of the vesicles of amphiphilic
vinyl homopolymers reported by the Thayumanavan group.7
The size of the aggregate inversely correlated with the
length of alkyl chain of the ester in the diamine moieties.
Although there has been a report on a similar relationship for the
aggregate of poly[N-(2-sulfoethyl)maleamic acid-co-alkyl vinyl
ether] in water, the side chain length effect on the particle size is
much more distinct in our case.16
The sizes of C9PAA aggregates were positively corre-
lated with their Mw (Table 1, Entries 2, 4, 5, and 6), and a
PAA(Mw = 3300) showed exceptionally small aggregate size
compared to those with larger Mws. Although the structure of the
molecular aggregates is not clear at present, it is obvious that
cumulative intermolecular interaction, especially hydrophobic
interaction, is required for the formation of particles with a
diameter of >100 nm, which is considerably larger than the size
of a single polymer chain. C9PAA with Mw = 3300 is calculated
to have only five to six side chain nonyl esters per macro-
molecule, and is believed to have less efficient intermolecular
interaction compared to higher-molecular-weight analogs. In
addition, this polymer might afford the curvature required for
small particle. These might lead to the formation of particles
<10 nm in diameter.
The authors thank Prof. Tadashi Sugawara at The University
of Tokyo for the use of DLS instrumentation. This work was
financially supported by a Grant-in-Aid for Scientific Research
(No. 17550113) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
References and Notes
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The formation of nanosized C9PAA particles in water was
supported by scanning electron microscopic analysis of a dried
solution (Figure 3). Particles with a diameter of 140 to 210 nm
were observed and the size was in good agreement with those of
the values obtained by DLS.
In conclusion, we have developed novel amphiphilic
homopoly(amide acid)s showing spontaneous self-assembly in
Chem. Lett. 2010, 39, 1106-1107
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/