Journal of the American Chemical Society
Article
to the cationic center that would be expected to modulate both
cytotoxicity with little to no statistical decline of cell viability
over this concentration range; for the lower molecular weight
sample (DP ≈ 20), cell viability remained consistently high up
to 1 mg/mL polymer, only dropping off for structures analyzed
at 5 mg/mL. Overall, the results indicate the potential use of
PS-substituted polymer zwitterions in biological applications
and will motivate further studies as gels, delivery vehicles,
coatings, and the like.
17,18,21
solvent−zwitterion and interzwitterion interactions.
As
such, these polymer zwitterions offer opportunities in
interfacial science as surfactants, which we examined by
preparing oil-in-water (o/w) emulsions using water and a
variety of organic solvents, including 1,2,4-trichlorobenzene
(
TCB) and chloroform. When emulsions were prepared from
polymer 9a, the polymer was introduced from the aqueous
phase, whereas 9b and 9c allowed initial dissolution in
chloroform. Vortexing mixtures of any of these polymers (∼10
mg/mL) with equal volumes of water and organic solvent
afforded o/w emulsions that proved stable for days to months
The PS-substituted monomers also proved amenable to
inclusion in PS−PC and PS−PS block copolymer structures, as
Figure 3. (Left and middle) Optical microscopy image and
photographs of TCB-in-water droplets stabilized by polymer 9a
(
vial 1) and block copolymer 10c (vial 2) (opaque droplets with
dense oil settle to the bottom of the vials). (Right) Schematic
illustration of droplets stabilized by PS-substituted polymers at the
fluid−fluid interface.
water-in-oil (w/o) emulsions prepared from polymer 9c at the
same surfactant concentration but increasing the o:w ratio to
Figure 4. (A) Synthesis of block copolymers 10a−c (R = n-butyl for
2
:1, minimal temporal stability of the droplets (minutes) was
3
1
1
0a, n-octyl for 10b, and phenyl for 10c). (B) Stacked P NMR
observed. Pendant-drop tensiometry of TCB in an aqueous
solution of tri-n-butyl PS polymer (9a) was conducted with a
polymer concentration of 0.5 mg/mL to evaluate the fluid−
fluid interfacial energies of the o/w system. Notably, the initial
presence of polymer 9a in the aqueous solution reduced the
spectra of a block copolymer of 10c (PC:PS ≈ 3:2) in deuterated
methanol (red), water (green), and chloroform (blue), with schematic
depiction of polymer structure within these solvents.
copolymers were synthesized with target PC:PS ratios of 3:1,
3:2, and 1:1 to afford 10a−c. This was achieved by first
synthesizing a polyMPC macro-CTA by RAFT with a target
4
Polymers 9a and 9c formed visually uniform films of ∼100
1
nm thickness when spin coated on Si or glass substrates from
ethyl lactate solutions (15 mg/mL, 2000 rpm), as measured by
variable angle spectroscopic ellipsometry (VASE) (SI).
Contact angle (CA) measurements were performed using
water droplets on polymer 9a- and 9c-coated glass and Si
substrates, with the n-butyl R groups imparting significantly
lower CAs for 9a (15−20°) than seen for the aromatic 9c
DP of 60 (measured by H NMR as DP = 63) and then
extending this block, also by RAFT, by heating a methanol
solution of the macro-CTA (1 equiv) with 7a−c in the
presence of 0.33 equiv of ACVA for 18 h. After purification by
dialysis, first in methanol and then in water, the block
copolymer products were obtained as light-yellow solids. These
block copolymers also exhibited surfactant properties, with
long-term stabilization of oil-in water droplets, facilitated by
their amphiphilic character and the distinctly different
hydrophilicity/phobicity of the PC- and PS-based blocks.
The water solubility and surface activity of block copolymer
10c is especially interesting, since polyMPC by itself does not
act as a surfactant and the phenyl-substituted PS-homopolymer
(
40−45°). The PS−polymers also showed good thermal
stability, as seen in polymer 9c, which by thermogravimetric
analysis (TGA) displayed a degradation onset in nitrogen of
3
53 °C, which approaches that of polystyrene and confirms
that PS-substituted polymers will be useful across a broad
temperature range.
3
1
Considering that polymer zwitterions are of growing interest
9c is not soluble in water. The P NMR spectra in Figure 4B
suggest that the preferential solubility of the blocks of polymer
10c in chloroform, water, and/or methanol facilitates the
formation of switchable solution structures.
1
,8,9
in biological applications,
a preliminary investigation of the
cytotoxicity of the water-soluble, PS-substituted polymer 9a
was performed in cell culture using the human cell lines
HEK293 and MDA-MB-231. The cells were exposed to
dissolved polymer in growth medium (DMEM with 10% FBS
and 1% penicillin/streptomycin) at 0.05−5 mg/mL polymer
example, testing of polymer 9a at higher degrees of
polymerization (DP ≈ 40 and 60) revealed a low level of
1
The H NMR spectrum of 10c in methanol (red), a good
solvent for both blocks, shows clean P signals for both blocks.
In contrast, only one sharp signal is seen in deuterated water
(green), corresponding to the PC block, while the
phosphonium of the PS block is barely visible, suggesting
that the hydrophilic PC block facilitates solubility and shields
the PS block from water. The inverse was seen in the spectrum
6
530
J. Am. Chem. Soc. 2021, 143, 6528−6532