New poly(phenyleneethynylene)s with cationic, facially amphiphilic structures

Article abstract of DOI:10.1021/ja026607s

Polymers based on meta substituted phenylene ethylene are prepared with patterned polar and nonpolar groups to favor an extended conformation. These polymers were characterized at the air-water interface by Langmuir techniques and found to form stable mon

Full text of DOI:10.1021/ja026607s

Published on Web 06/11/2002
New Poly(phenyleneethynylene)s with Cationic, Facially Amphiphilic
Structures
Lachelle Arnt and Gregory N. Tew*
Department of Polymer Science and Engineering, UniVersity of Massachusetts, Amherst, 120 GoVernors DriVe,
Amherst, Massachusetts 01003
Received April 19, 2002
Hydrophilic and hydrophobic patterning has been suggested as
an important property in guiding secondary and tertiary folds of
proteins.1 Amphiphilic protein secondary structures are common
and include â-sheets which fold with alternating polar (P) and
nonpolar (NP) amino acids and R-helices that have a seven amino-
acid repeat with a sequence of NP-P-P-NP-NP-P-NP.2 This results
in amphiphilic 2-D planes and cylinders, respectively. In addition,
the overwhelming majority of P side chains found in these systems
are charged residues so that the structures are polyelectrolytes. As
a result, these objects are markedly different from most traditional
amphiphilic polymers based on block or random copolymers. We
have recently reported on a class of facially amphiphilic polymers
based on arylamides which mimic the physical and biological
properties of natural surface active antimicrobial host defense
peptides.3 These polymers were designed to be amphiphilic along
the backbone as opposed to block or random copolymers. Using
poly(phenyleneethynylene) (PPE) as a molecular scaffold, we now
have designed cationic, amphiphilic polymers containing primary
amines and NP alkyl groups. These polymers are m-PPEs patterned
with P cationic and NP groups to favor an extended all trans
conformation. As a result, they should have some rigid rod-type
character.
Figure 1. Synthesis of cationic, amphiphilic PPE polymers via Sonogashira
conditions.
Table 1. Polymer Number, Alkyl Side Chain, Molecular Weight,
and Polydispersity Are Reported for a Series of PPE Materials
polymer number
alkyl group
M (Da)
n
PDI
1
2
3
C5H11
(S)-2-methylbutyl
C12H25
1.78 × 104
1.15 × 104
1.01 × 104
2.2
1.3
1.4
The study of nonionic amphiphilic PPEs has attracted much
attention recently. Swager and co-workers examined a series of
para substituted PPEs at the air-water interface in which the
orientation of the aromatic ring to the water surface depended on
both the substitution pattern of the P and NP groups and the pressure
of the compressed film.4 As a result, the effect on absorption and
emission spectra due to interchain association was investigated in
detail. Moore and co-workers patterned meta substituted derivatives
to favor a helical conformation in a nonsolvent and showed a
transition between random coil and helical conformations as the
nonsolvent composition was increased.5 A few other polymers have
been reported with architectures that make them facially amphiphilic
including polythiophenes and polyphenylenes.6,7
The synthesis of a cationic, amphiphilic monomer for PPE
materials began with Mitsunobu conditions for alkylation of starting
material, 3,5-diiodo-4-hydroxy-benzonitrile, followed by nitrile
reduction with borane-THF to yield the benzylamine which was
protected as the tert-butyl carbamate (Boc). This produced diiodo
monomers as stable, crystalline solids. Subsequent polymerization
of these monomers is outlined in Figure 1 and gave the desired
Boc protected polymer after precipitation.8 Molecular weight
determination was performed on protected polymers which are
freely soluble in common organic solvents and is reported in Table
1. Deprotection of the Boc group was accomplished with 4 M HCl/
Figure 2. Pressure-area isotherm for 1 indicates monolayer formation.
Extrapolation to zero pressure gives a repeat unit of 41 Å2.
dioxane. 1H and13C NMR confirm quantitative removal of the Boc
groups with no subsequent side reaction.
The ability of these materials to adopt amphiphilic conformations
was investigated at the air-water interface using Langmuir
techniques. Dilute solutions of 1 were spread onto the water surface
and compressed to give an isotherm as shown in Figure 2. The
polymer sample produces stable monolayer films with an area per
repeat unit of ∼41 Å2 which is in good agreement with molecular
models that predict 44 Å2 per repeat unit. This area was calculated
using an extended molecular length of 11.0 Å and a π-π stacking
distance of 4.0 Å. In addition, molecular dynamics calculations of
* To whom correspondence should be addressed. E-mail: tew@mail.pse.umass.edu.
9
7664
J. AM. CHEM. SOC. 2002, 124, 7664-7665
10.1021/ja026607s CCC: $22.00 © 2002 American Chemical Society

C O M M U N I C A T I O N S
Figure 4. Emission spectra of 1 as water is added to the solution. The
concentration of each spectrum is identical. The inset shows emission of 1
near the upper and lower limit concentrations of leakage experiments.
Figure 3. Graph showing the percentage of lysed vesicles over time as
the concentration of 1 is increased. 100% lysis was determined by the
addition of 50 µL of 0.2% Triton X-100.
extended, or all trans, backbone is favored over other conformations
because of the substitution pattern of P and NP groups. A helical
conformation in which the NP groups fold in the interior while P
side chains are exposed to the solvated exterior cannot be ruled
out at this time; however, the observed emission spectra are different
from those reported for helical PPEs.11
We report the synthesis of new PPE derivatives containing polar
cationic and nonpolar alkyl groups. These groups are patterned to
favor an extended conformation and produce facially amphiphilic
polymers. Langmuir and emission experiments are in agreement
with an extended amphiphilic structure. Vesicle leakage experiments
indicate that these polymers are membrane active. From these
preliminary observations and others in the literature,5,7 it can be
expected that polymers with facially ionic amphiphilicity will
organize into interesting supramolecular structures.
two extended oligomers were performed in Materials Studio and
gave an area of 44.7 Å2. The modeled orientation assumes the
polymer molecules are standing up with their aromatic rings
perpendicular to the water surface. In this configuration, the polar
cationic amine salts are immersed in the water layer and the
hydrophobic alkyl chains completely removed from the aqueous
surface.
Langmuir experiments indicate that this polymer is highly
amphiphilic and prefers to form monolayers at the air-water
interface. The surface activity of this cationic polymer was explored
further by monitoring the disruption of phospholipid vesicles.3
Large unilamellar vesicles (LUV) with 10 mol % excess negative
charge were prepared by reverse phase evaporation of a SOPS:
SOPC (1:9) solution.9 Leakage of calcein was monitored at 515
nm as a function of polymer concentration and is shown in Figure
3. The rate and percentage of lysed LUVs as measured by calcein
leakage increases as the concentration of 1 is increased. Initially
the rate of leakage is fast but slows down as less free polymer is
left in solution. The ability of these polymers to induce calcein
leakage from anionic LUV confirms their surface active nature.
Higher polymer concentration experiments suffered from polymer
aggregation.
Acknowledgment. Financial support for this work is gratefully
acknowledged from the National Science Foundation through
MRSEC at UMass. We thank Professor Hsu for use of the Langmuir
trough and Daniel J. Duffy.
Supporting Information Available: Experimental procedures and
compound characterization (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
On the basis of the design of 1, we also expected that the polymer
could self-assemble in aqueous solution.7 In fact, it appears from
the LUV leakage experiments that this is true. To investigate if 1
is aggregated in aqueous solution, we monitored the emission
spectra as a function of water composition starting with neat DMSO.
The emission spectra shown in Figure 4 were obtained as a function
of water composition. The concentration of the sample was kept
constant to directly observe the effect on quantum yield. It can be
seen from Figure 4 that the intensity of emission decreases with
increasing water concentration and the band is broadened and
slightly red-shifted. The insert in Figure 4 shows the emission
spectra taken at concentrations from the leakage experiments and
are very similar to the 90% water spectrum. These observations
are in agreement with intermolecular aggregation of polymer chains
in an extended conformation as the water content is increased.4,10
The slight red-shift indicates tight packing of the chromophores
does not occur in the aggregate. Spectra taken in CHCl3 or THF as
solvent give emission maxima close to that observed for DMSO
((2 nm), indicating that the observed change with water addition
is not related simply to solvent polarity. The formation of an
References
(1) Eisenberg, D.; Weiss, R. M.; Terwillinger, T. C. Proc. Natl. Acad. Sci.
U.S.A. 1984, 81, 140-144.
(2) DeGrado, W. F.; Lear, J. D. J. Am. Chem. Soc. 1985, 107, 7684-7689.
(3) Tew, G. N.; Lui, D.; Chen, B.; Doerksen, R. J.; Kaplan, J.; Carroll, P. J.;
Klein, M. L.; DeGrado, W. F. Proc. Natl. Acad. Sci U.S.A. 2002, 99,
5110-5114.
(4) Kim, J.; Swager, T. M. Nature 2001, 411, 1030-1034.
(5) Nelson, J. C.; Saven, J. G.; Moore, J. S.; Wolynes, P. G. Science 1997,
277, 1793-1795.
(6) Reitzel, N.; Greve, D. R.; Kjaer, K.; Howes, P. B.; Jayaraman, M.; Savoy,
S.; McCullough, R. D.; McDevitt, J. T.; Bjornholm, T. J. Am. Chem. Soc.
2000, 122, 5788-5800. Bo, Z.; Rabe, J. P.; Schulter, A. D. Angew. Chem.,
Int. Ed. 1999, 38, 2370-2372.
(7) Bockstaller, M.; Kohler, W.; Wegner, G.; Vlassopoulos, D.; Fytas, G.
Macromolecules 2001, 34, 6359-6366.
(8) Giesa, R. J. Macromol. Sci., ReV. Macromol. Chem. Phys. 1996, 36, 631-
670. Bunz, U. H. F. Chem. ReV. 2000, 100, 1605-1644.
(9) Wilschut, J.; Duzgunes, N.; Fraley, R.; Papahadjopoulos D. Biochemistry
1980, 19, 6011-6021.
(10) Halkyard, C. E.; Rampey, M. E.; Kloppenburg, L.; Studer-Martinez, S.
L.; Bunz, U. H. F. Macromolecules, 1998, 31, 8655-8659.
(11) Prince, R. B.; Saven, J. G.; Wolynes, P. G.; Moore, J. S. J. Am. Chem.
Soc. 1999, 121, 3114-3121.
JA026607S
9
J. AM. CHEM. SOC. VOL. 124, NO. 26, 2002 7665