Amphiphilic block copolymers, materials which contain regions of differing chemical properties, show great promise as potential drug delivery devices. Kinetic measurements of the controlled radical polymerizations by Reversible Addition-Fragmentation Chain Transfer polymerization (RAFT) were employed to optimize the syntheses of block copolymers with differing monomer type, chain length, and chain rigidity. A variety of methacrylate and acrylate monomers displayed similar reactivity for synthesis of homopolymers. However, block copolymers displayed decreased reactivity mainly due to increased steric hindrance and other reactivity complexities. The synthesis of a variety of different chain lengths of copolymer and their effects on micellization are currently being investigated. The inclusion of random copolymer blocks along with more hydrophobic monomers such as alkenes and styrene are being investigated in order to better control micellization. Further optimization of the synthesis of copolymers with ideal chain length, hydrophobicity, and chain rigidity will allow us to synthesize promising amphiphilic macromolecules for medicinal applications.

1. Kinetic Determination in Optimization of Chain Length, Hydrophobicity, and Chain Rigidity of Amphiphilic
Block Copolymers by RAFT Controlled Radical Polymerizations
Kevin Kawchak, Gregg Wilmes*, David Arnold
Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197
Introduction: Amphiphilic block copolymers, materials which contain regions of differing chemical properties, show great promise as potential drug delivery devices. Kinetic measurements of the controlled radical polymerizations by
Reversible Addition-Fragmentation Chain Transfer polymerization (RAFT) were employed to optimize the syntheses of block copolymers with differing monomer type, chain length, and chain rigidity. A variety of methacrylate and acrylate
monomers displayed similar reactivity for synthesis of homopolymers. However, block copolymers displayed decreased reactivity mainly due to increased steric hindrance and other reactivity complexities. The synthesis of a variety of
different chain lengths of copolymer and their effects on micellization are currently being investigated. The inclusion of random copolymer blocks along with more hydrophobic monomers such as alkenes and styrene are being
investigated in order to better control micellization. Further optimization of the synthesis of copolymers with ideal chain length, hydrophobicity, and chain rigidity will allow us to synthesize promising amphiphilic macromolecules for
medicinal applications.
RESULTS CHAIN LENGTH OPTIMIZATION OF MICELLIZATION
NONTRADITIONAL MONOMERS ADDRESS
-Percent conversion vs. Time results allowed group
CHAIN RIGIDITY AND HYDROPHOBICITY
to better calculate reagent ratios in order to achieve -Effective micellization is influenced by block copolymer chain
desired chain lengths.
length.
-Plots of homopolymer and copolymer reveal
reactivities of alternate monomers. -Chains of too short of length will fail to aggregate into the large
micelle structure. Chains too long will have a large degree of
-Homopolymer displayed most conversion of monomer steric strain and be unable to form the micelle structure.
to polymer due to less steric effects and the lack of
additional reactions experienced in copolymer. -Optimization by group is underway: larger macromolecules are -Poly(1-hexene) introduces a more hydrophobic block to the
thought to exhibit more micellization. core micelle.
-Poly(tert-butyl acrylate)-b-Poly(methyl acrylate) is
considerably faster than Poly(methyl acrylate)-b- -A more hydrophobic block increases the core’s ability to
Poly(tert-butyl acrylate) due to sterics in adding the
tert-butyl acrylate monomer.
CHAIN RIGIDITY shield medication from the cellular environment.
-Results from polymerization using RAFT radical method
were ineffective due to the highly stable alkene radical
Medicine insertion on
the end of each
intermediate.
polymer chain may
aid an infected cell.
Percent Conversion Poly(methyl acrylate) -A rigid hydrophobic block allows amphiphilic copolymer to pack
-Percent conversion of monomer to polymer is
calculated by evaluating 1H-NMR spectrum for each tightly within micelle.
time point.
-Within the 3D environment of the micelle, less rigid chains are
-Monomer peaks are integrated against polymer peaks more susceptible to tangling, which decreases the micelle effect. -A random copolymer of poly(methyl acrylate) and poly(1-hexene)
as monomer concentration decreases throughout introduces additional hydrophobicity to an acrylate based core
polymerization. -Recent results published by group indicate chain rigidity is a micelle.
@ 55min = 77% main factor in the ability to form micelles.1
-1H-NMR also was used to determine complete -Integration of methyl acrylate to alkene allows the stable alkene
conversion. Also, Poly(tert-butyl acrylate) was found to
radical to react with acrylate.
dissociate when reacted for extended periods of time.
13C-NMR data was used to evaluate lack of
HYDROPHOBIC BLOCK SELECTION -Results from polymerization using RAFT radical polymerization
conversion between Poly(1-hexene) and Poly(1- showed some evidence of alkene integration .
hexene), Poly(methyl acrylate ) copolymer because of
overlapping peaks in 1H-NMR. -Liu et al. have demonstrated high levels of comonomer
incorporation.2
-Amine based methacrylate may introduce a degree of chain rigidity
-Introduction of a more hydrophobic monomer allows for enhanced with addition of the methyl group on the backbone.
protection of the attached medicine from a hydrophilic environment.
-However, most strongly hydrophobic monomers lack reactivity for -A more rigid backbone allows micelles to aggregate in a more linear.
-Chromatograms of Poly(tert butyl acrylate) as a low temperature radical polymerizations closely packed region.1
function of retention time show the lower molecular
weight polymer eluting last.
-In GPC, as polymer chains get longer, the larger
molecule passes through the column first. The
samples taken at longer time points illustrate this, as
METHODS CONCLUSIONS AND FUTURE WORK
they reached the detector first. S S R R' S S R R' S S
R' + + R
-Kinetic experiments have provided information on reaction rates and the
-GPC results of homopolymer allowed for an Z Z Z effect on molecular weights.
approximation of DP to use in determining how much -Homopolymer and block copolymer were synthesized using a RAFT chain transfer agent, which allowed
of the second monomer to add. for a dormant state to limit chain growth and lower dispersity. -Optimization of chain length size may aid in the ability to make polymer of
predictable chain lengths.
1H-NMR -Monomer:Polymer ratios were collected to calculate percent conversion. Spin-lattice (T1) and
spin-spin (T2) were measured in amphiphilic copolymers to detect evidence of micellization.1
-Alkene and acrylate/alkene copolymer have failed to demonstrate high
degrees of polymerization.
SEC -Molecular weights and dispersity of homopolymer and block copolymer were detected
using Size Exclusion Chromatography in a THF mobile phase.
-Styrene monomer provides the opportunity for a high degree of
hydrophobicity with increased reactivity over alkenes.3
-GPC data of the diblock copolymer yielded an
overall Mw for both monomer type.
-When combined with 1H-NMR data, an estimation
for the Mn of the second block could be made.
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-Since the second monomer may also polymerize to
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monomer type did not incorporate into the diblock www.kevinskawchak.com/Kevin S Kawchak Thesis Eastern Michigan University.pdf •Eastern Michigan University Department of Chemistry for research
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