Atom Transfer Radical Polymerization under Biologically Relevant Conditions

This thesis describes recent progress in atom transfer radical polymerization (ATRP) under biologically relevant conditions. In plain words, the major topics can be summarized as ATRP “with Bio”, “on Bio”, “for Bio”, and “from Bio”.

The introductory chapter (Chapter I) reviews the recent development of oxygen tolerant controlled radical polymerization and the corresponding applications. The major categories include chemical approach, photo-mediated approach as well as biological approach.

Chapters II to V cover the topic of enzyme-assisted oxygen tolerant ATRP and some derivative projects. In Chapter II, the discovery of in situ deoxygenation by glucose oxidase (GOx) in ATRP reactions is discussed. With incorporating GOx and its major substrate glucose, also with sodium pyruvate – a scavenger of byproduct H2O2, ATRP can be carried out under open-to-air conditions and maintain excellent control over the polymer molecular weight (MW) and dispersity (Ɖ). In Chapter III, a follow-up project was elaborated by replacing sodium pyruvate and a second enzyme, horseradish peroxidase, to further utilize the byproduct H2O2 as radical source in order to initiate ATRP process. With such setup, the polymerization would not happen until oxygen was added, essentially became an “oxygen-fueled” polymerization. In Chapter IV, the transformation of the enzyme-assisted oxygen scavenging system from aqueous media to dispersed media is discussed. This allowed the synthesis of hydrophobic polymers under oxygen tolerant conditions and potentially applicable for an industrial production. Chapter V discussed a derivative project on synthesizing protein-polymer conjugates using photoinduced ATRP, with and without enzyme assisted deoxygenation. As a more benign light source, blue light was successfully applied to carry out photoATRP as the most harmless choice for proteins and other biomolecules.

Chapter VI to VIII cover the topic of surface modification of implant materials (i.e. titanium, polyether ether ketone (PEEK)) by surface-grafting polymers. In Chapter VI, the modification of titanium surface towards enhanced osseointegration is discussed. Titanium plates were first etched with “piranha” solution and followed by anchoring ATRP initiator using 12-(2-bromoisobutyramido)dodecanoic acid (BiBADA); then a ketone-containing copolymer was grafted from the titanium surface via surface-initiated ATRP with post-polymerization conjugation of P15 peptide – a stimulator for bone cells to grow faster. As a result, titanium plates with such surface treatment exhibited higher affinity for cells to proliferate and mineralized than native titanium plates. Chapter VII talks about the fabrication of PEEK microparticles (PMP) with further stabilization by coating polymers. The PMP was made by micro-precipitation: by adding dissolved PEEK pellets into poly(vinyl alcohol) solution. Furthermore, ATRP initiator was immobilized on the surface of PMP to enable polymers to be grafted from PMP. With coated polymer, the PMP maintained stable particle size and increased solubility in solvents, which reduced the difficult handling and manufacturing. Another published work on tacticity control in ATRP using Lewis acid is discussed in Chapter VIII. Tacticity of vinyl polymers is an important characteristic that affects the thermomechanical and surface properties. It is not easy to obtain tacticity control in ATRP due to the sp2 hybridized chain-end radicals. However, in the presence of Lewis acid like yttrium triflate (Y(OTf)3), up to 80% of total meso content (m%) can be achieved in the polyacrylamides.

The last topic discussed in this thesis is related to bio-mimicking ATRP catalysts, as described in Chapter IX and X. In Chapter IX, two novel iron-porphyrin based catalysts that mimic the structure of enzyme’s active center were discussed. Based on previous study by Dr. Antonina Simakova, naturally occurring iron-porphyrin or hemin-based catalysts catalyzed ATRP after several modifications. Herein, the iron-porphyrin catalysts were modified with amino acid mimicking moieties: an imidazole to mimic histidine and a thioether for methionine. With such adjustments, the new catalysts demonstrated improved catalytic activity in ATRP and permitted lower loading of catalyst. This discovery created the possibility for replacing the traditional copper-based catalyst by non-toxic, natural-occurring catalysts. In addition, owing to the high stability of iron-porphyrin structure, it was applied as a unique catalyst for direct polymerization of acidic monomers such as methacrylic acid via ATRP, as elaborated in Chapter X. Unlike most copper-based catalytic complexes, iron-porphyrin is very stable under acidic pH without ligand protonation and decomposition. Thus such catalysts were used for ATRP of methacrylic acid under low pH conditions, with good control over the MW and dispersity of poly(methacrylic acid).

Three ongoing projects focusing on immobilization of enzymes onto solid support (Appendix I), surface modification of macroscopic PEEK plates(Appendix II) and conjugation of hydrophobic polymers from proteins (Appendix III) are included in appendices.