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Journal of the American Chemical Society
are more conformationally restricted with respect to each other,
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compared to the monomers. The observations here raise several
interesting questions. From a fundamental perspective, it is inter-
esting to ask whether the mixture of two morphologies after four
days is an indicator of self-selection among oligomeric amphiphiles,
driven by their preferred morphologies. Addressing these ques-
tions, along with exploring the potential utility of these assemblies
in meaningful applications, will be part of our future efforts in this
area. From an applications perspective, degradable amphiphiles
have drawn significant attention due to their potential use in bio-
logical applications such as delivery and diagnostics. The fact, that
both polymer and monomer were found to be non-cytotoxic to
cells (see SI), suggests the potential for utilizing these assemblies in
such applications.
Figure 4. TEM images of (a) M1 indicating vesicles; (b) P1 on day 4
sample revealing both micelles and vesicles; (c) R6G release from aged
differences between micellar and vesicular aggregates. While both
these assemblies would be able to sequester hydrophobic guests,
because of the hydrophobicity of the micellar interior and the ve-
sicular membranes, only the latter would be able to sequester hy-
drophilic guests. Indeed, we were unsuccessful in our attempts to
incorporate hydrophilic rhodamine 6G (R6G) within the polymer
assembly P1. Interestingly however, R6G was comfortably incorpo-
rated within the vesicular assembly formed by M1, which was ascer-
tained by comparing the absorbance-matched solutions of R6G in
water (see SI). The observed fluorescence self-quenching, due to
local concentration effects imposed by encapsulation, suggests that
the hydrophilic dye has been incorporated within the lumen of the
vesicular assemblies. If P1 indeed depolymerizes to smaller oligo-
mers, which have the propensity to form vesicular assemblies, the
ability to sequester hydrophilic molecules must evolve with time.
Indeed, we found that the hydrophilic dye can be encapsulated in
P1 on day 8. Note that our hypothesis here is that the urethane
bond hydrolyzes, but the β -thioester bonds are intact during the
aging process. If this was correct, then lowering the pH of the
solution containing the assembly based on monomer M1 or the
aged P1 should cause disassembly, because the amphiphilic charac-
ter of the constituent molecules would disappear due to the pH-
induced hydrolysis of the β -thioester. The observed decrease in
self-quenching of R6G with time at pH 5.3 in both these solutions
(Figure 4c and SI) supports this hypothesis.
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ASSOCIATED CONTENT
Supporting Information
Materials and methods, experimental details/results and characteri-
zation data (NMR, GPC, TEM). This material is available free of
AUTHOR INFORMATION
Corresponding Author
E-mail: thai@chem.umass.edu (S.T.).
Present Addresses
*University of Massachusetts, Amherst. 710 N. Pleasant Street,
Amherst, MA 01003.
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
We are grateful to partial support from the NSF (CHE-1307118)
and the NIH (GM-065255). We thank Dr. Rinat Abzalimov and
Bo Zhao for their help with mass spectra.
In summary, by designing an amphiphilic homopolymer that can
degrade both at the side chain and the main chain, we have shown
that the morphology of the assembly and its host-guest characteris-
tics can be predictably evolved. The amphiphilic polymer itself
forms a micelle-like assembly in aqueous phase, where it is capable
of acting as a nanocontainer for hydrophobic guest molecules.
Subjecting this assembly to a pH change causes it lose this contain-
er property, because of the degradation of the side chain function-
alities. On the other hand, aging this assembly in aqueous solution
results in slow depolymerization through degradation of the main
chain, where the morphology of the assembly changes from micelle-
like structures to vesicular ones. This morphological change ac-
companies an evolution in host-guest characteristics, where the
assembly changes from a nanocontainer for hydrophobic guest
molecules to one that can be a concurrent container for both hy-
drophobic and hydrophilic guest molecules. Lowering the solution
pH causes the assembly to lose its ability to encapsulate both types
of guest molecules. The evolution of these assemblies in response
to depolymerization might be reminiscent of the polymerization-
induced self-assembly process,9 which has recently gained much
attention. Note however that the process is sharply distinct, be-
cause the hydrophilic-lipophilic balance in the amphiphilic polymer
does not evolve with the depolymerization process noted here.
Therefore, the morphological changes observed here are dictated by
the molecular architecture rather than by the relative volumes of
the amphiphilic constituents. The variations in the molecular
architecture between these oligomers and the monomer likely arise
from the fact that the amphiphilic building blocks in the oligomers
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