End-Functionalized Polymers and Junction-Functionalized Diblock Copolymers Via RAFT Chain Extension with Maleimido Monomers

Abstract

A new strategy is described for functionalizing the ω-terminal end of polymers synthesized by reversible addition - fragmentation chain transfer (RAFT) polymerization that provides spatially controlled bioconjugation sites. Traditional methods for preparing ω-functional polymers require the reduction of the RAFT chain-transfer agent to yield secondary or tertiary thiols of low reactivity or the synthesis of novel chain-transfer agents that contain reactive groups. As an additional strategy, N-substituted maleimido monomers have been used in a modified block polymerization to add a single maleimido unit onto the RAFT polymer with nearly quantitative efficiency. Unique reactive groups contained in the N-substituent are thereby added to the ω-terminal end of the polymer and are subsequently available for conjugation reactions. This technique has been demonstrated using N-(2-aminoethyl)maleimide trifluoroacetate to introduce a single primary amine to the ω-terminus of poly(dimethylaminoethyl methacrylate) and poly(N-isopropyl acrylamide) and to a specialized block copolymer for siRNA delivery. Evidence for retention of functional RAFT endgroups is provided by synthesis results where chainextended polyDMAEMA (Mn = 10 600 g/mol, Mw/Mn = 1.14) was used as a macro chain transfer agent for the polymerization of styrene, yielding a diblock polymer of low polydispersity (Mn) 20 300 g/mol, Mw/Mn = 1.11). It is thus also possible to construct diblock copolymers with a bioconjugation site precisely located at the junction between the two blocks. The chain-extended polymers are functionalized with an amine-reactive fluorescent dye or folic acid at conjugation efficiencies of 86 and 94%, respectively. The versatile chain-extension technique described here offers unique opportunities for the synthesis of well-defined polymeric conjugates to molecules of biological and targeting interest.

Department(s)

Materials Science and Engineering

Keywords and Phrases

copolymer; methacrylic acid butyl ester; monomer; n (2 aminoethyl)maleimide trifluoroacetate; poly(dimethylaminoethyl methacrylate); poly(n isopropyl acrylamide); polymer; propylacrylic acid; small interfering RNA; styrene; trifluoroacetic acid; unclassified drug, article; drug conjugation; drug delivery system; drug structure; drug synthesis; proton nuclear magnetic resonance; reverse transcription polymerase chain reaction, Magnetic Resonance Spectroscopy; Maleimides; Molecular Weight; Polymers

International Standard Serial Number (ISSN)

1043-1802

Document Type

Article - Journal

Document Version

Citation

File Type

text

Language(s)

English

Rights

© 2009 American Chemical Society (ACS), All rights reserved.

Publication Date

01 Jun 2009

PubMed ID

19480416

Link to Full Text

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