5 research outputs found
Synthesis of Polyisobutylene Bottlebrush Polymers via Ring-Opening Metathesis Polymerization
Polyisobutylene
(PIB)-based bottlebrush polymers were synthesized
via ring-opening metathesis polymerization (ROMP) of norbornene- and
oxanorbornene-terminated PIB macromonomers (MM) initiated by Grubbs
third-generation catalyst ((H<sub>2</sub>IMes<sub>2</sub>)(pyr)<sub>2</sub>(Cl)<sub>2</sub>RuCHPh) (G3). While both MMs reached
greater than 97% conversion as measured by <sup>1</sup>H NMR, the
rate of propagation of PIB norbornene was measured to be 2.9 times
greater than that of PIB oxanorbornene MMs of similar molecular weight
(MW). The slower rate of propagation of the oxanorbornene MM was attributed
to interaction between the electron-rich oxygen bridge and the metal
center of G3, which slowed but did not inhibit polymerization. Both
types of MMs demonstrated controlled/“living” polymerization
behavior, and brush polymers with MWs up to ∼700 kg/mol with
narrow dispersity (<i>Đ</i> ≤ 1.04) were achieved
RAFT Polymerization of “Splitters” and “Cryptos”: Exploiting Azole‑<i>N</i>‑carboxamides As Blocked Isocyanates for Ambient Temperature Postpolymerization Modification
A postpolymerization
modification strategy based on ambient temperature
nucleophilic chemical deblocking of polymer scaffolds bearing <i>N</i>-heterocycle-blocked isocyanate moieties is reported. Room
temperature RAFT polymerization of three azole-<i>N</i>-carboxamide
methacrylates, including 3,5-dimethylpyrazole, imidazole, and 1,2,4-triazole
derivatives, afforded reactive polymer scaffolds with well-defined
molecular weights and narrow dispersities (<i><i>Đ</i></i> < 1.2). Model analogues possessing the same <i>N</i>-heterocycle blocking agents with varied leaving group
abilities were synthesized to determine optimal deblocking conditions.
The reactivity of the azole-<i>N</i>-carboxamide moieties
toward nucleophiles can be tuned simply by varying the structure of
the azole blocking agents (reactivity order: pyrazole < imidazole
< triazole). DBU-catalyzed reactions of thiols with imidazole-
and 1,2,4-triazole-blocked isocyanate scaffolds were shown to occur
rapidly and quantitatively under ambient conditions. Differences in
reactivity of 1,2,4-triazole- and 3,5-dimethylpyrazole-blocked isocyanate
copolymers with various nucleophiles at room temperature facilitated
sequential and postpolymerization modification. This strategy advances
the utility of blocked isocyanates and promotes the chemistry as a
powerful postmodification tool to access multifunctional polymeric
materials
Guanidine-Containing Methacrylamide (Co)polymers via <i>a</i>RAFT: Toward a Cell-Penetrating Peptide Mimic
We report the synthesis and controlled radical homopolymerization
and block copolymerization of 3-guanidinopropyl methacrylamide (GPMA)
utilizing aqueous reversible addition–fragmentation chain transfer
(<i>a</i>RAFT) polymerization. The resulting homopolymer
and block copolymer with <i>N</i>-(2-hydroxypropyl) methacrylamide
(HPMA) were prepared to mimic the behavior of cell-penetrating peptides
(CPPs) and poly(arginine) (>6 units), which have been shown to
cross cell membranes. The homopolymerization mediated by 4-cyano-4-(ethylsulfanylthiocarbonylsulfanyl)pentanoic
acid (CEP) in aqueous buffer exhibited pseudo-first-order kinetics
and linear growth of molecular weight with conversion. Retention of
the “living” thiocarbonylthio ω-end group was
demonstrated through successful chain extension of the GPMA macroCTA
yielding GPMA<sub>37</sub>-<i>b</i>-GPMA<sub>61</sub> (<i>M</i><sub>w</sub>/<i>M</i><sub>n</sub> = 1.05). Block
copolymers of GPMA with the nonimmunogenic, biocompatible HPMA were
synthesized yielding HPMA<sub>271</sub>-<i>b</i>-GPMA<sub>13</sub> (<i>M</i><sub>w</sub>/<i>M</i><sub>n</sub> = 1.15). Notably, intracellular uptake was confirmed by fluorescence
microscopy, confocal laser scanning microscopy, and flow cytometry
experiments after incubation for 2.5 h with KB cells at 4 °C
and at 37 °C utilizing FITC-labeled, GPMA-containing copolymers.
The observed facility of cellular uptake and the structural control
afforded by <i>a</i>RAFT polymerization suggest significant
potential for these synthetic (co)polymers as drug delivery vehicles
in targeted therapies
Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid β Aggregation
GM1 ganglioside is
known to promote amyloid-β (Aβ)
peptide aggregation in Alzheimer’s disease. The roles of the
individual saccharides and their distribution in this process are
not understood. Acrylamide-based glycomonomers with either β-d-glucose or β-d-galactose pendant groups were
synthesized to mimic the stereochemistry of saccharides present in
GM1 and characterized via <sup>1</sup>H NMR and electrospray ionization
mass spectrometry. Glycopolymers of different molecular weights were
synthesized by aqueous reversible addition–fragmentation chain
transfer (aRAFT) polymerization and characterized by NMR and GPC.
The polymers were used as models to investigate the effects of molecular
weight and saccharide unit type on Aβ aggregation via thioflavin-T
fluorescence and PAGE. High molecular weight (∼350 DP) glucose-containing
glycopolymers had a profound effect on Aβ aggregation, promoting
formation of soluble oligomers of Aβ and limiting fibril production,
while the other glycopolymers and negative control had little effect
on the Aβ propagation process
Antimicrobial Peptide Mimicking Primary Amine and Guanidine Containing Methacrylamide Copolymers Prepared by Raft Polymerization
Naturally occurring antimicrobial
peptides (AMPs) display the ability
to eliminate a wide variety of bacteria, without toxicity to the host
eukaryotic cells. Synthetic polymers containing moieties mimicking
lysine and arginine components found in AMPs have been reported to
show effectiveness against specific bacteria, with the mechanism of
activity purported to depend on the nature of the amino acid mimic.
In an attempt to incorporate the antimicrobial activity of both amino
acids into a single water-soluble copolymer, a series of copolymers
containing lysine mimicking aminopropyl methacrylamide (APMA) and
arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared
via aqueous RAFT polymerization. Copolymers were prepared with varying
ratios of the comonomers, with degree of polymerization of 35–40
and narrow molecular weight distribution to simulate naturally occurring
AMPs. Antimicrobial activity was determined against Gram-negative
and Gram-positive bacteria under conditions with varying salt concentration.
Toxicity to mammalian cells was assessed by hemolysis of red blood
cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed
for APMA homopolymer and copolymers with low concentrations of GPMA
against all bacteria tested, with low toxicity toward mammalian cells