Title

Aqueous Reversible Addition-Fragmentation Chain Transfer Polymerization of Functional Monomers and Their Incorporation Into Stimuli-Responsive, Amphiphilic Block Copolymers

Date of Award

2007

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Polymers and High Performance Materials

First Advisor

Charles L. McCormick

Advisor Department

Polymers and High Performance Materials

Abstract

Reversible addition-fragmentation chain transfer (RAFT) is arguably the most versatile living radical polymerization technique in terms of the reaction conditions and monomer selection. Since the introduction of RAFT in 1998. McCormick and coworkers have employed the RAFT process to synthesize a wide range of water soluble (co)polymers with predetermined molecular weights, low polydispersities, and advanced architectures. However the controlled polymerization of important monomers, such as unprotected, chiral, amino acid based monomers, directly in water has yet to be reported. The incorporation of these monomers into stimuli-responsive block copolymers will create novel polymer systems that can be reversibly "locked" under facile conditions and have potential applications in sequestration and targeted delivery. Additionally, the controlled synthesis of (co)polymers based on chiral, amino acids directly in water can now be achieved and their chiroptical behavior investigated. The overall goal of this research is to utilize the RAFT process for the polymerization of chiral, amino acid based monomers directly in water, to investigate the self-assembly behavior of stimuli-responsive block copolymers containing an amino acid based block, and to investigate the chiroptical properties of enantiomeric (co)polymers based on the chiral, amino acid based monomers. This work may be divided into four sections. The first section concerns the first successful RAFT polymerization of an unprotected amino acid based monomer directly in water and its incorporation into thermally responsive block copolymers. N -acryloyl L-alanine (ALAL) ( 48 ) was synthesized and its polymerization behavior in the presence of the dithioester CTP (64 ) and the trithiocarbonate EMP (67 ) was investigated. Block copolymers containing a hydrophilic block of DMA ( 58 ), a cross-linkable block of ALAL ( 48 ), and a thermally-responsive block of NIPAM ( 59 ) were subsequently synthesized, and the aqueous self-assembly behavior was investigated. The second section expands on the aqueous RAFT polymerization of an unprotected amino acid based monomer and its incorporation into dual responsive block copolymers. N -acryloyl L-valine (AVAL) ( 50 ) was synthesized, and its polymerization behavior mediated by EMP (67 ) at both 30°C and 70°C was investigated. Block copolymers containing a hydrophilic block of DMA ( 58 ) and a statistical block of the thermally-responsive monomer NIPAM (59 ) and the pH responsive monomer AVAL (50 ) were synthesized, and their aqueous self-assembly behavior was investigated. In the third section, the chiroptical properties of amino acid based (co)polymers were investigated. Chiral homo- and block copolymers based on the enantiomeric monomers ALAL (48 ) and N -acryloyl D-alanine (AVAL) (49 ) were prepared directly in water via RAFT polymerization. Enantiomeric homopolymers, block copolymers, and a statistical copolymer were synthesized, and the chiroptical activity of these biomimetic polymers and their analogous model compounds was investigated. The fourth section details work done in collaboration with Dr. Yuting Li and concerns the utilization of RAFT for the preparation of shell cross-linked micelles for potential applications in sequestration and targeted delivery. Thermally responsive micelles based on poly (ethylene oxide)-block-[( N,N -dimethylacrylamide)-stat -(N -acryloxy succinimide)]-block -(N-isopropyl acrylamide) triblock copolymer are synthesized and subsequently shell crosslinked with ethylenediamine or cystamine. When cystamine is used, fully reversible SCL micelles are formed.