John Chiefari

Living free radical polymerization with reversible addition - fragmentation chain transfer (the life of RAFT)

Free radical polymerization with reversible addition-fragmentation chain transfer (RAFT polymerization) is discussed with a view to answering the following questions: (a) How living is RAFT polymerization? (b) What controls the activity of thiocarbonylthio compounds in RAFT polymeriza- tion? (c) How do rates of polymerization differ from those of conventional radical polymerization? (d) Can RAFT agents be used in emulsion polymerization? Retardation, observed when high concentra- tions of certain RAFT agents are used and in the early stages of emulsion polymerization, and how to overcome it by appropriate choice of reaction conditions, are considered in detail. Examples of the use of thiocarbonylthio RAFT agents in emulsion and miniemulsion polymerization are provided. # 2000 Society of Chemical Industry

Tailored polymer architectures by reversible addition-frasmentation chain transfer

Living radical polymerization methods that allow the preparation of polymers with predetermined molecular weight, narrow molecular weight distribution and tailored architecture (e.g. block, graft, stars) are offering a vast range of new and advanced materials. With applications ranging from surfactants, dispersants, coatings and adhesives, to microelectronics, membranes, drug delivery, and biomaterials they have the potential of revolutionizing a large part of the polymer industry.

Initiating free radical polymerization

The kinetics and mechanism of the initiation and reinitiation of free radical polymerization is reviewed. The importance of understanding the kinetics, specificity and efficiency of initiation and chain transfer when predicting polymerization kinetics and polymer composition is highlighted. These factors are particularly important when making low molecular weight polymers and in living or controlled polymerization processes. Examples of RAFT polymerization and catalytic chain transfer are provided.

Quasi-block copolymer libraries on demand via sequential RAFT polymerization in an automated parallel synthesizer

A convenient synthetic method for the systematic preparation of quasi-diblock copolymer libraries utilizing a sequential RAFT polymerization strategy is described. This method utilizes a parallel synthesizer and allows the unattended and fully automated synthesis of this type of library in a short period of time. The materials obtained in this investigation have shown properties very similar to those expected in “pure” diblock copolymers as determined by differential scanning calorimetry. The described method can be a useful and less expensive alternative for the rapid preparation and screening of block copolymer libraries.

Synthesis of RAFT Block Copolymers in a Multi-Stage Continuous Flow Process Inside a Tubular Reactor

This work describes a multi-stage continuous flow polymerisation process for the synthesis of block copolymers using the RAFT polymerization method. The process retains all the benefits and versatility of the RAFT method and has been adapted for a series of monomer combinations, including acrylates, acrylamides, and vinyl monomers. It resulted in polymers with molecular weights between 13500 and 34100 g mol–1, and dispersities typically between 1.21 and 1.58. Different architectures were prepared (including combinations of hydrophilic and hydrophobic blocks) which are soluble in a range of different solvents including aqueous and organic media.

Automated parallel freeze-evacuate-thaw degassing method for oxygen-sensitive reactions: RAFT polymerization.

An automated and parallel freeze-evacuate-thaw degassing method in a commercially available synthesizer is disclosed and tested for its applicability to reversible addition-fragmentation chain transfer (RAFT) polymerization. The effectiveness of this method to eliminate oxygen in polymerization reactions is demonstrated by directly comparing it against experiments performed using conventional laboratory techniques. Apart from the demonstrated accuracy, the proposed method has also shown significant precision when performing RAFT polymerizations. The reported experimental technique can be easily adapted to other chemical systems where the removal of oxygen is mandatory. This new high-throughput method has the potential to significantly increase the productivity and/or research outcomes in laboratories where oxygen-sensitive reactions are carried out.

Enhancement of MHC-I Antigen Presentation via Architectural Control of pH-Responsive, Endosomolytic Polymer Nanoparticles

Protein-based vaccines offer a number of important advantages over organism-based vaccines but generally elicit poor CD8+ T cell responses. We have previously demonstrated that pH-responsive, endosomolytic polymers can enhance protein antigen delivery to major histocompatibility complex class I (MHC-I) antigen presentation pathways thereby augmenting CD8+ T cell responses following immunization. Here, we describe a new family of nanocarriers for protein antigen delivery assembled using architecturally distinct pH-responsive polymers. Reversible addition-fragmentation chain transfer (RAFT) polymerization was used to synthesize linear, hyperbranched, and core-crosslinked copolymers of 2-(N,N-diethylamino)ethyl methacrylate (DEAEMA) and butyl methacrylate (BMA) that were subsequently chain extended with a hydrophilic N,N-dimethylacrylamide (DMA) segment copolymerized with thiol-reactive pyridyl disulfide (PDS) groups. In aqueous solution, polymer chains assembled into 25 nm micellar nanoparticles and enabled efficient and reducible conjugation of a thiolated protein antigen, ovalbumin. Polymers demonstrated pH-dependent membrane-destabilizing activity in an erythrocyte lysis assay, with the hyperbranched and cross-linked polymer architectures exhibiting significantly higher hemolysis at pH ≤ 7.0 than the linear diblock. Antigen delivery with the hyperbranched and cross-linked polymer architecture enhanced in vitro MHC-I antigen presentation relative to free antigen, whereas the linear construct did not have a discernible effect. The hyperbranched system elicited a four- to fivefold increase in MHC-I presentation relative to the cross-linked architecture, demonstrating the superior capacity of the hyperbranched architecture in enhancing MHC-I presentation. This work demonstrates that the architecture of pH-responsive, endosomolytic polymers can have dramatic effects on intracellular antigen delivery, and offers a promising strategy for enhancing CD8+ T cell responses to protein-based vaccines.

Water as Solvent in Polyimide Synthesis: Thermoset and Thermoplastic Examples

A combination of increasingly stringent environmental legislation and economic competition is driving industrial processes further and further towards the three “E”s of chemical manufacture: economy, efficiency and environmental impact. In this paper, we present a novel aqueous method for the synthesis of polyimides. The products resulting from this process perform similarly, through both qualitative and quantitative comparisons, to those conventionally produced using high boiling dipolar aprotic solvent. This highly efficient one-pot method potentially provides economic advantage through low solvent cost and environmental impact benefit from the manageable aqueous waste.

Water as Solvent in Polyimide Synthesis II: Processable Aromatic Polyimides

Some representative thermal, chemical and mechanical characteristics of ‘commercial type’ polyimides are presented in this second paper in a series on using water as solvent in polyimide synthesis. The commercial types of polyimide that have been produced in this study are closely related to Kapton, Upilex R®, Upilex S®, Avimid N® and PMR-15. The chemical characterization of these materials using both nuclear magnetic resonance and Fourier Transform infrared indicate very pure and fully imidized products. The thermal and mechanical data from techniques such as thermogravimetric analysis, differential scanning calorimetry and dynamic mechanical thermal analysis reveal properties that are at least, equivalent to their commercial counterparts. Some improvement in processability is noted in pure materials, mixtures and chemically modified analogues of these well known polyimides. In addition this highly efficient one-pot method potentially provides economic advantages through low solvent cost and environmental impact benefits.

Water as Solvent in Polyimide Synthesis III: Towards the Synthesis of Polyamideimides

Four different approaches to the synthesis of polyamideimides, which employ aqueous imidization, were studied in order to assess the viability of their preparation in water. Building on previous studies of synthesizing polyimides in water both one- and two-step methods were explored. The first direct method for polyamideimide synthesis forms both the amide and imide linkages simultaneously and is limited to appropriately activated diamine monomers. The second direct method uses commercially sourced diaminobenzanilide with standard tetracarboxylic acids in an imidization step to give the polyamideimide. This method, demonstrates the viability of using amide-containing diamines in a polyimidization step to synthesize the desired polymer. The third and fourth methods are both two-step processes and use aqueous imidization to produce imide-containing monomers with either amine or carboxylic acid terminal functionality. This is followed by standard amidation to produce high-quality polyamideimides.