Allyl glycidyl ether, polymerized from potassium alkoxide/naphthalenide initiators under both neat and solution conditions was shown to be a highly-controlled process. In both cases, molar masses (10–100 kg/mol) were determined by the reaction stoichiometry, and low polydispersity indices (1.05–1.33) could be obtained with a full understanding of the dominant side reaction, isomerization of the allyl side chain, being developed. The degree of isomerization of allyl to cis-prop-1-enyl ether groups (0 – 10 % mol.) was not correlated to the molar mass or polydispersity of the polymer but was dictated by the polymerization temperature. This allows the extent of isomerization to be reduced to essentially zero under either melt or solution conditions at polymerization temperatures of less than 40 °C.
Reactivity ratios were evaluated for anionic ring-opening copolymerizations of ethylene oxide (EO) with either allyl glycidyl ether (AGE) or ethylene glycol vinyl glycidyl ether (EGVGE) using a benzyl alkoxide initiator. The chemical shift for the benzylic protons of the initiator, as measured by 1H NMR spectroscopy, were observed to be sensitive to the sequence of the first two monomers added to the initiator during polymer growth. Using a simple kinetic model for initiation and the first propagation step, reactivity ratios for the copolymerization of AGE and EGVGE with EO could be determined by analysis of the 1H NMR spectroscopy for the resulting copolymer. For the copolymerization between EO and AGE, the reactivity ratios were determined to be rAGE = 1.31 ± 0.26 and rEO = 0.54 ± 0.03, while for EO and EGVGE, the reactivity ratios were rEGVGE = 3.50 ± 0.90 and rEO = 0.32 ± 0.10. These ratios were consistent with the compositional drift observed in the copolymerization between EO and EGVGE, with EGVGE being consumed early in the copolymerization. These experimental results, combined with density functional calculations, allowed a mechanism for oxyanionic ring-opening polymerization that begins with coordination of the Lewis-basic epoxide to the cation to be proposed. The calculated transition-state energies agree qualitatively with the observed relative rates for polymerization.
Viruses
have evolved specialized mechanisms to efficiently transport
nucleic acids and other biomolecules into specific host cells. They
achieve this by performing a coordinated series of complex functions,
resulting in delivery that is far more efficient than existing synthetic
delivery mechanisms. Inspired by these natural systems, we describe
a process for synthesizing chemically defined molecular constructs
that likewise achieve targeted delivery through a series of coordinated
functions. We employ an efficient “click chemistry”
technique to synthesize aptamer-polymer hybrids (APHs), coupling cell-targeting
aptamers to block copolymers that secure a therapeutic payload in
an inactive state. Upon recognizing the targeted cell-surface marker,
the APH enters the host cell via endocytosis, at which point the payload
is triggered to be released into the cytoplasm. After visualizing
this process with coumarin dye, we demonstrate targeted killing of
tumor cells with doxorubicin. Importantly, this process can be generalized
to yield APHs that specifically target different surface markers.
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