TY - JOUR
T1 - A Vinyl Ether-Functional Polycarbonate as a Template for Multiple Postpolymerization Modifications
AU - Cho, Sangho
AU - Heo, Gyu Seong
AU - Khan, Sarosh
AU - Huang, Jessica
AU - Hunstad, David A.
AU - Elsabahy, Mahmoud
AU - Wooley, Karen L.
N1 - Funding Information:
We gratefully acknowledge financial support from the National Heart Lung and Blood Institute of the National Institutes of Health as a Program of Excellence in Nanotechnology (HHSN268201000046C) and from the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK082546). The Welch Foundation is gratefully acknowledged for support through the W. T. Doherty-Welch Chair in Chemistry, Grant No. A-0001.
Publisher Copyright:
Copyright © 2018 American Chemical Society.
PY - 2018/5/8
Y1 - 2018/5/8
N2 - A highly reactive vinyl ether-functionalized aliphatic polycarbonate and its block copolymer were developed as templates for multiple postpolymerization conjugation chemistries. The vinyl ether-functional six-membered cyclic carbonate monomer was synthesized by a well-established two-step procedure starting from 2,2-bis(hydroxymethyl)propionic acid. An organobase-catalyzed ring-opening polymerization of the synthesized monomer afforded polycarbonates with pendant vinyl ether functionalities (PMVEC). The vinyl ether moieties on the resulting polymers were readily conjugated with hydroxyl- or thiol-containing compounds via three different postpolymerization modification chemistries: acetalization, thio-acetalization, and thiol-ene reaction. Acetal-functionalized polycarbonates were studied in depth to exploit their acid-labile acetal functionalities. Acetalization of the amphiphilic diblock copolymer of poly(ethylene glycol) methyl ether (mPEG) and PMVEC, mPEG113-b-PMVEC13, with the model hydroxyl compound 4-methylbenzyl alcohol resulted in a maximum of 42% acetal and 58% hydroxyl side chain groups. Nonetheless, the amphiphilicity of the block polymer allowed for its self-assembly in water to afford nanostructures, as characterized via dynamic light scattering and transmission electron microscopy. The kinetics of acetal cleavage within the block polymer micelles were examined in acidic buffered solutions (pH 4 and 5). In addition, mPEG-b-PMVEC and its hydrolyzed polymer mPEG-b-PMHEC (i.e., after full cleavage of acetals) exhibited minimal cytotoxicity to RAW 264.7 mouse macrophages, indicating that this polymer system represents a biologically nonhazardous material with pH-responsive activity.
AB - A highly reactive vinyl ether-functionalized aliphatic polycarbonate and its block copolymer were developed as templates for multiple postpolymerization conjugation chemistries. The vinyl ether-functional six-membered cyclic carbonate monomer was synthesized by a well-established two-step procedure starting from 2,2-bis(hydroxymethyl)propionic acid. An organobase-catalyzed ring-opening polymerization of the synthesized monomer afforded polycarbonates with pendant vinyl ether functionalities (PMVEC). The vinyl ether moieties on the resulting polymers were readily conjugated with hydroxyl- or thiol-containing compounds via three different postpolymerization modification chemistries: acetalization, thio-acetalization, and thiol-ene reaction. Acetal-functionalized polycarbonates were studied in depth to exploit their acid-labile acetal functionalities. Acetalization of the amphiphilic diblock copolymer of poly(ethylene glycol) methyl ether (mPEG) and PMVEC, mPEG113-b-PMVEC13, with the model hydroxyl compound 4-methylbenzyl alcohol resulted in a maximum of 42% acetal and 58% hydroxyl side chain groups. Nonetheless, the amphiphilicity of the block polymer allowed for its self-assembly in water to afford nanostructures, as characterized via dynamic light scattering and transmission electron microscopy. The kinetics of acetal cleavage within the block polymer micelles were examined in acidic buffered solutions (pH 4 and 5). In addition, mPEG-b-PMVEC and its hydrolyzed polymer mPEG-b-PMHEC (i.e., after full cleavage of acetals) exhibited minimal cytotoxicity to RAW 264.7 mouse macrophages, indicating that this polymer system represents a biologically nonhazardous material with pH-responsive activity.
UR - http://www.scopus.com/inward/record.url?scp=85046642003&partnerID=8YFLogxK
U2 - 10.1021/acs.macromol.8b00047
DO - 10.1021/acs.macromol.8b00047
M3 - Article
C2 - 29915431
AN - SCOPUS:85046642003
SN - 0024-9297
VL - 51
SP - 3233
EP - 3242
JO - Macromolecules
JF - Macromolecules
IS - 9
ER -