4 research outputs found
Cationic Poly(benzyl ether)s as Self-Immolative Antimicrobial Polymers
Self-immolative polymers (SIMPs)
are macromolecules that spontaneously
undergo depolymerization into small molecules when triggered by specific
external stimuli. We report here the first examples of antimicrobial
SIMPs with potent, rapid, and broad-spectrum bactericidal activity.
Their antibacterial and hemolytic activities were examined as a function
of cationic functionality. Polymers bearing primary ammonium cationic
groups showed more potent bactericidal activity against Escherichia coli, relative to tertiary and quaternary
ammonium counterparts, whereas the quaternary ammonium polymers showed
the lowest hemolytic toxicity. These antibacterial polycations undergo
end-to-end depolymerization when triggered by an externally applied
stimulus. Specifically, poly(benzyl ether)s end-capped with a silyl
ether group and bearing pendant allyl side chains were converted to
polycations by photoinitiated thiol–ene radical addition using
cysteamine HCl. The intact polycations are stable in solution, but
they spontaneously unzip into their component monomers upon exposure
to fluoride ions, with excellent sensitivity and selectivity. Upon
triggered depolymerization, the antibacterial potency was largely
retained but the hemolytic toxicity was substantially reduced. Thus,
we reveal the first example of a self-immolative antibacterial polymer
platform that will enable antibacterial materials to spontaneously
unzip into biologically active small molecules upon the introduction
of a specifically designed stimulus
Templated Ring-Opening Metathesis (TROM) of Cyclic Olefins Tethered to Unimolecular Oligo(thiophene)s
We developed a fully abiotic approach
to template the synthesis
of discrete unimolecular polyolefins. Discrete, unimolecular oligo(thiophene)s
with alternating sequence were obtained by iterative convergent/divergent
couplings and then functionalized with pendant cyclic olefin monomers
in the side chains. Upon treatment with the Grubbs third-generation
catalyst in dilute solution (0.15 mM in DCM at 0 °C), the pendant
monomers undergo templated ring-opening metathesis (TROM). Then, the
daughter olefin is liberated from the parent thiophene by hydrolysis.
Cyclooctenes undergo TROM to afford macrocyclic products that exactly
replicate the chain length of the parent oligomer, as evidenced by
MALDI MS/MS and NMR. Norbornene derivatives also undergo TROM and
replicate unimolecular chain lengths, but in contrast, they exclusively
form the linear oligomeric products with styrenic end groups. A template
that was functionalized with one norbornene unit at the α chain
end, followed by five cyclooctene units along the template, underwent
TROM to afford the macrocyclic daughter olefin. Intertemplate metathesis
is suppressed by tuning the concentration and reaction time. Using
this strategy, we can effectively replicate the unimolecular nature
of a template, made by labor-intensive iterative synthesis, to produce
a discrete daughter oligomer by chain growth. We also demonstrate
that the templates are recyclable upon hydrolytic cleavage of daughter
oligomer, attachment of fresh daughter monomer, and repetition of
the TROM process
Spirothiopyran-Based Reversibly Saturable Photoresist
Super-resolution
lithography holds the promise of achieving three-dimensional
(3D) nanopatterning at deep subwavelength resolutions with high throughput.
3D super-resolution lithography schemes demonstrated thus far have
all been serial in nature, primarily due to the lack of a photoresist
chemistry that not only couples a saturable reversibly switchable
reaction with a writing step but also has a low saturation threshold.
Here, we demonstrate that combining the reversible photoisomerization
of spirothiopyran with the thiol-Michael conjugate addition reaction
achieves the necessary photochemical characteristics. Green light
was found to saturate inhibition of the thiol-Michael addition writing
step at very low intensity thresholds. By formulating a spirothiopyran-functionalized
polyethylene glycol copolymer, we demonstrate spatial control over
cross-linking using inhibition by green light. Kinetics measurements
combined with photokinetic simulations show that interference lithography
on a spirothiopyran maleimide-based writing system using conventional
light sources (e.g., a 2 W green laser) should deliver super-resolution
features (∼45 nm wide lines) in thick films (tens of microns)
over large areas (hundreds of microns on a side). The unique combination
of reversible photochromic switching of spirothiopyran with the thiol-Michael
addition reaction marks an important step toward realizing a highly
parallelized 3D super-resolution writing system
A Critical Evaluation of Random Copolymer Mimesis of Homogeneous Antimicrobial Peptides
Polymeric synthetic mimics of antimicrobial
peptides (SMAMPs) have
recently demonstrated similar antimicrobial activity as natural antimicrobial
peptides (AMPs) from innate immunity. This is surprising, since polymeric
SMAMPs are heterogeneous in terms of chemical structure (random sequence)
and conformation (random coil), in contrast to defined amino acid
sequence and intrinsic secondary structure. To understand this better,
we compare AMPs with a “minimal” mimic, a well-characterized
family of polydisperse cationic methacrylate-based random copolymer
SMAMPs. Specifically, we focus on a comparison between the quantifiable
membrane curvature generating capacity, charge density, and hydrophobicity
of the polymeric SMAMPs and AMPs. Synchrotron small-angle X-ray scattering
(SAXS) results indicate that typical AMPs and these methacrylate SMAMPs
generate similar amounts of membrane negative Gaussian curvature (NGC),
which is topologically necessary for a variety of membrane-destabilizing
processes. Moreover, the curvature generating ability of SMAMPs is
more tolerant of changes in the lipid composition than that of natural
AMPs with similar chemical groups, consistent with the lower specificity
of SMAMPs. We find that, although the amount of NGC generated by these
SMAMPs and AMPs are similar, the SMAMPs require significantly higher
levels of hydrophobicity and cationic charge to achieve the same level
of membrane deformation. We propose an explanation for these differences,
which has implications for new synthetic strategies aimed at improved
mimesis of AMPs