Thomas P. Davis

Handbook of radical polymerization

Introduction (Krzysztof Matyjaszewski and Thomas P. Davis). Contributors. 1. Theory of Radical Reactions (Johan P. A. Heuts). 2. Small Radical Chemistry (Martin Newcomb). 3. General Chemistry of Radical Polymerization (Bunichiro Yamada and Per B. Zetterlund). 4. The Kinetics of Free Radical Polymerization (Christopher Barner-Kowollik, Philipp Vana, and Thomas P. Davis). 5. Copolymerization Kinetics (Michelle L. Coote and Thomas P. Davis). 6. Heterogeneous Systems (Alex M. van Herk and Michael Monteiro). 7. Industrial Applications and Processes (Michael Cunningham and Robin Hutchinson). 8. General Concepts and History of Living Radical Polymerization (Krzysztof Matyjaszewski). 9. Kinetics of Living Radical Polymerization (Takeshi Fukuda, Atsushi Goto, and Yoshinobu Tsujii). 10. Nitroxide Mediated Living Radical Polymerization (Craig J. Hawker). 11. Fundamentals of Atom Transfer Radical Polymerization (Krzysztof Matyjaszewski and Jianhui Xia). 12. Control of Free Radical Polymerization by Chain Transfer Methods (John Chiefari and Ezio Rizzardo). 13. Control of Stereochemistry of Polymers in Radical Polymerization (Akikazu Matsumoto). 14. Macromolecular Engineering by Controlled Radical Polymerization (Yves Gnanou and Daniel Taton). 15. Experimental Procedures and Techniques for Radical Polymerization (Stefan A. F. Bon and David M. Haddleton). 16. Future Outlook and Perspectives (Krzysztof Matyjaszewski and Thomas P. Davis). Index.

Bioapplications of RAFT Polymerization

A living radical polymerization (LRP) is a free radical polymerization that aims at displaying living character, (i.e., does not terminate or transfer and is able to continue polymerization once the initial feed is exhausted by addition of more monomer). However, termination reactions are inherent to a radical process, and modern LRP techniques seek to minimize such reactions, therefore providing control over the molecular weight and the molecular weight distribution of a polymeric material. In addition, the better LRP techniques incorporate many of the desirable features of traditional free radical polymerization, such as compatibility with a wide range of monomers, tolerance of many functionalities, and facile reaction conditions. The control of molecular weight and molecular weight distribution has enabled access to complex architectures and site specific functionality that were previously impossible to achieve via traditional free radical polymerizations. These LRPs are classified in three different subgroups: (1) stable free-radical polymerization such as nitroxide mediated polymerization (NMP),1,2 (2) degenerative transfer polymerization, such as iodine transfer polymerization (ITP and RITP),3,4 single electron transfer-degenerative transfer living radical polymerization(SET-DTLRP),5,6reversibleaddition-fragmentation chain transfer (RAFT),7,8 and macromolecular design via the interchange of xanthates (MADIX)9,10 polymerization, and (3) metal mediated catalyzed polymerization, such as atom transfer radical polymerization (ATRP),11-14 single electron transfer-living radical polymerization (SET-LRP),15 and organotellurium mediated living radical polymrization16-19 Among the existing LRP techniques, RAFT and MADIX are probably the most versatile processes, as they are tolerant * E-mail: T.P.D., T.Davis@UNSW.edu.au; S.P., S.Perrier@ chem.usyd.edu.au. † Centre for Advanced Macromolecular Design (CAMD), School of Chemical Sciences & Engineering, UNSW. ‡ Centre for Advanced Macromolecular Design (CAMD), School of Biotechnology & Biomolecular Sciences, UNSW. § The University of Sydney. Chem. Rev. 2009, 109, 5402–5436 5402

Photo-responsive systems and biomaterials: photochromic polymers, light-triggered self-assembly, surface modification, fluorescence modulation and beyond

There has been considerable interest in the application of photochromism to photo-responsive systems which has led to the development of new tailored smart materials for photonics and biomedical fields. Within a polymeric matrix photochromic isomerizations can be stimulated by light to reversibly alter the physical and chemical properties of a material such as LC phase, shape, surface wettability, permeability, solubility, self-assembly, size and fluorescence. The underlying principles behind photo-responsive behavior, subsequent applications and relevant examples are discussed in this review.

Kinetic Analysis of Reversible Addition Fragmentation Chain Transfer (RAFT) Polymerizations: Conditions for Inhibition, Retardation, and Optimum Living Polymerization

Careful simulations of conversion vs. time plots and full molecular weight distributions have been performed using the PREDICI(R) program package in conjunction with the kinetic scheme suggested by the CSIRO group for the reversible addition fragmentation chain transfer (RAFT) process to probe RAFT agent mediated polymerizations. In particular, conditions leading to inhibition and rate retardation have been examined to act as a guide to optimum living polymerization behavior. It is demonstrated that an inhibition period of considerable length is induced by either slow fragmentation of the intermediate RAFT radicals appearing in the pre-equilibrium or by slow re-initiation of the leaving group radical of the initial RAFT agent. The absolute values of the rate coefficients governing the core equilibrium of the RAFT process - at a fixed value of the equilibrium constant - are confirmed to be crucial in controlling the polydispersity of the resulting molecular weight distributions. A higher interchange frequency effects narrower distributions. It is further demonstrated that the size of the rate coefficient controlling the addition reaction of propagating radicals to polyRAFT agen, k(beta), is mainly responsible for optimizing the control of the polymerization. The fragmentation rate coefficient k(-beta), of the macroRAFT intermediate radical, on the other hand, may be varied over orders of magnitude without affecting the amount of control exerted over the polymerization. On the basis of the basic RAFT mechanism, its value mainly governs the extent of rate retardation in RAFT polymerizations.

Investigation into thiol-(meth)acrylate Michael addition reactions using amine and phosphine catalysts

This work describes a study into thiol–ene based Michael addition reactions. Different catalysts, primary and tertiary amines and phosphines, were investigated for the reaction of a range of thiols with dimers and oligomers of some (meth)acrylates. Primary and tertiary amines are efficient catalysts for the thiol–ene reaction, although these catalysts require several hours to reach high conversion. Moreover, the phosphine catalysts, dimethylphenylphosphine (DMPP) and tris-(2-carboxyethyl)phosphine (TCEP), were investigated in detail. DMPP is an efficacious catalyst yielding complete conversion in few minutes under optimized conditions. Importantly, the concentration of DMPP should be kept at catalytic levels to avoid the formation of by-products, originating from the addition of DMPP to the vinyl group. Furthermore, TCEP is an efficient catalyst for thiol–ene reactions in aqueous media when the pH of the medium is higher than 8.0 since at acidic pH the formation of by-products is observed.

Cu(0)-Mediated Living Radical Polymerization: A Versatile Tool for Materials Synthesis

Materials Synthesis Athina Anastasaki,†,‡ Vasiliki Nikolaou,† Gabit Nurumbetov,† Paul Wilson,†,‡ Kristian Kempe,†,‡ John F. Quinn,‡ Thomas P. Davis,†,‡ Michael R. Whittaker,†,‡ and David M. Haddleton*,†,‡ †Chemistry Department, University of Warwick, Library Road, CV4 7AL, Coventry, United Kingdom ‡ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 399 Royal Parade, Parkville, Victoria 3152, Australia

Honeycomb structured porous films prepared from carbohydrate based polymers synthesized via the RAFT process

Carbohydrate based polystyrene was synthesized via RAFT polymerization. The RAFT agents were based on α-D-glucose, β-cyclodextrin and modified cellulose to obtain polystyrene with a polar head or polystyrene with a star or comb structure, respectively. The polymerizations were carried out in different solvents. The molecular weight of the linear polymer was found to develop according to the expected values, but the synthesis of the carbohydrate based polymers was influenced by other parameters. The molecular weight for the star polymer synthesis showed a pronounced deviation due to the reduced accessibility of the RAFT group at higher conversions of the polymerization. Films of these carbohydrate containing polystyrenes were cast from carbon disulfide and dichloromethane producing highly regular honeycomb structured films with pore diameters between 0.5 and 4 µm. The pore size was influenced by the polymers used as well as by the casting conditions.

RAFT polymerization and thiol chemistry: a complementary pairing for implementing modern macromolecular design.

Reversible addition fragmentation chain transfer (RAFT) polymerization is one of the most extensively studied reversible deactivation radical polymerization methods for the production of well-defined polymers. After polymerization, the RAFT agent end-group can easily be converted into a thiol, opening manifold opportunities for thiol modification reactions. This review is focused both on the introduction of functional end-groups using well-established methods, such as thiol-ene chemistry, as well as on creating bio-cleavable disulfide linkages via disulfide exchange reactions. We demonstrate that thiol modification is a highly attractive and efficient chemistry for modifying RAFT polymers.

Polymerization-induced self-assembly (PISA) - Control over the morphology of nanoparticles for drug delivery applications

In this paper, we describe the synthesis of asymmetric functional POEGMA-b-P(ST-co-VBA) copolymers in methanol, yielding in one-pot polymerization a range of nanoparticle morphologies, including spherical micelles, worm-like, rod-like micelles and vesicles. The presence of the aldehyde group was then exploited to form crosslinks or to conjugate chemotherapy compounds, such as doxorubicin, via pH-breakable bonds (Schiff base or imine) directly to the preformed nanoparticles. The influence of the nanoparticle morphologies on the MCF-7 breast cancer cell line uptake was investigated using flow cytometry and confocal microscopy. Finally, the IC50 of DOX, following nanoparticle delivery, was studied showing significant influence of the nanoparticle carrier morphology on therapeutic efficacy for breast cancer.

Efficient Usage of Thiocarbonates for Both the Production and the Biofunctionalization of Polymers

End group modification of polymers prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization was accomplished by conversion of trithiocarbonate into reactive functions able to conjugate easily with biomolecules or bioactive functionality. Polymers were prepared by RAFT, and subsequent aminolysis led to sulfhydryl-terminated polymers that reacted in situ with an excess of dithiopyridyl disulfide to yield pyridyl disulfide-terminated macromolecules or in the presence of ene to yield functional polymers. In the first route, the pyridyl disulfide end groups allowed coupling with oligonucleotide and peptide. The second approach exploited thiol-ene chemistry to couple polymers and model compounds such as carbohydrate and biotin with high yield.