Improved synthesis of linear poly(ethylenimine) via low-temperature polymerization of 2-isopropyl-2-oxazoline in chlorobenzene

TY - JOUR

T1 - Improved synthesis of linear poly(ethylenimine) via low-temperature polymerization of 2-isopropyl-2-oxazoline in chlorobenzene

AU - Monnery, Bryn D.

AU - Shaunak, Sunil

AU - Thanou, Maya

AU - Steinke, Joachim H G

PY - 2015/5/26

Y1 - 2015/5/26

N2 - Linear poly(ethylenimine) is a cationic polymer that is actively being progressed into clinical trials for gene therapy. The existing synthetic methodology produces a relatively broad distribution of molecular weights. We describe an improved method of polymerizing 2-alkyl-2-oxazolines as a route to linear poly(ethylenimine). By using an apolar noninterfering solvent (chlorobenzene) at low temperature (∼42 °C), the polymerization of 2-isopropyl-2-oxazoline proceeds much more rapidly than is observed in acetonitrile, and with far fewer side reactions. 1H NMR observations showed close ion pairing at the propagating center (vice free ions in acetonitrile) to form a propagating complex of greater reactivity than free oxazolinium ions. Our results indicate that uniform or near uniform ("monodisperse") polymers can be synthesized with nominal deviation from the theoretically achievable Poisson distributions.

AB - Linear poly(ethylenimine) is a cationic polymer that is actively being progressed into clinical trials for gene therapy. The existing synthetic methodology produces a relatively broad distribution of molecular weights. We describe an improved method of polymerizing 2-alkyl-2-oxazolines as a route to linear poly(ethylenimine). By using an apolar noninterfering solvent (chlorobenzene) at low temperature (∼42 °C), the polymerization of 2-isopropyl-2-oxazoline proceeds much more rapidly than is observed in acetonitrile, and with far fewer side reactions. 1H NMR observations showed close ion pairing at the propagating center (vice free ions in acetonitrile) to form a propagating complex of greater reactivity than free oxazolinium ions. Our results indicate that uniform or near uniform ("monodisperse") polymers can be synthesized with nominal deviation from the theoretically achievable Poisson distributions.

KW - RING-OPENING POLYMERIZATION

KW - MOLECULAR-WEIGHT

KW - GENE DELIVERY

KW - 2-ETHYL-2-OXAZOLINE

KW - 2-METHYL-2-OXAZOLINE

KW - POLYETHYLENIMINE

KW - TRANSFECTION

KW - POLYMERS

KW - POLY(2-ISOPROPYL-2-OXAZOLINES)

KW - POLY(2-ALKYL-2-OXAZOLINE)S

UR - http://www.scopus.com/inward/record.url?scp=84930225804&partnerID=8YFLogxK

U2 - 10.1021/acs.macromol.5b00437

DO - 10.1021/acs.macromol.5b00437

M3 - Article

SN - 0024-9297

VL - 48

SP - 3197

EP - 3206

JO - MACROMOLECULES

JF - MACROMOLECULES

IS - 10

ER -