ABSTRACT:Investigations into the kinetics and mechanism of dithiobenzoate-mediated Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerizations, which exhibit nonideal kinetic behavior, such as induction periods and rate retardation, are comprehensively reviewed. The appreciable uncertainty in the rate coefficients associated with the RAFT equilibrium is discussed and methods for obtaining RAFT-specific rate coefficients are detailed. In addition, mechanistic studies are presented, which target the elucidation of the fundamental cause of rate retarding effects.

The “click” trick: Many reactions are classified as click reactions even though some are limited to certain applications. Thus, there is danger that the term “click” will become meaningless over time and simply a synonym for “successful”. To prevent this, the original click criteria are evaluated in this Essay specifically for the synthetic polymer field and a set of criteria are specified that distinguishes click from other efficient reactions.

A previously published simulation and data fitting procedure for the reversible addition fragmentation chain transfer (RAFT) process using the PREDICI simulation program has been extended to cumyl phenyldithioacetate mediated styrene and methyl methacrylate (MMA) bulk homopolymerizations. The experimentally obtained molecular weight distributions (MWDs) for the styrene system are narrow and unimodal and shift linearly with monomer conversion to higher molecular weights. The MMA system displays a hybrid of conventional chain transfer and living behavior, leading to bimodal MWDs. The styrene system has been subjected to a combined experimental and modeling study at 60 °C, yielding a rate coefficient for the addition reaction of free macroradicals to polymeric RAFT agent, k β, of approximately 5.6 × 105 L mol-1 s-1 and a decomposition rate coefficient for macroradical RAFT species, k - β, of about 2.7 × 10-1 s-1. The transfer rate coefficient to cumyl phenyldithioacetate is found to be close to 2.2 × 105 L mol-1 s-1. The MMA system has been studied over the temperature range 25−60 °C. The hybrid behavior observed in the MMA polymerizations has been exploited (at low monomer conversions) to perform a Mayo analysis allowing the determination of the temperature dependence of the transfer to cumyl phenyldithioacetate reaction. The activation energy of this process is close to 26 kJ mol-1. In contrast to the styrene system, the PREDICI simulation procedure cannot be successfully applied to cumyl phenyldithioacetate mediated MMA polymerizations for the deduction of k β and k - β. This inability is due to the hybrid nature of the cumyl phenyldithioacetate−MMA system, leading to a significantly reduced sensitivity toward k β and k - β.

A full kinetic scheme for the free‐radical reversible addition–fragmentation chain transfer (RAFT) process is presented and implemented into the program package PREDICI®. With the cumyl dithiobenzoate‐mediated bulk polymerization of styrene at 60 °C as an example, the rate coefficients associated with the addition–fragmentation equilibrium are deduced by the careful modeling of the time‐dependent evolution of experimental molecular weight distributions. The rate coefficient for the addition reaction of a free macroradical to a polymeric RAFT species (kβ) is approximately 5 · 105 L mol−1 s−1, whereas the fragmentation rate coefficient of the formed macroradical RAFT species is close to 3 · 10−2 s−1. These values give an equilibrium constant of K = kβ/k−β = 1.6 · 107 L mol−1. Conclusive evidence is given that the equilibrium lies well on the side of the macroradical RAFT species. The high value of kβ is comparable in size to the propagation rate coefficients reported for acrylates. The transfer rate coefficient to cumyl dithiobenzoate is close to 3.5 · 105 L mol−1 s−1. A careful sensitivity analysis was performed, which indicated that the reported rate coefficients are accurate to a factor of 2. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1353–1365, 2001

The reversible addition fragmentation chain transfer (RAFT) bulk polymerization of a fast propagating monomer (methyl acrylate, MA) has been studied using 1-phenylethyl dithiobenzoate (1-PEDB) and 2-(2-cyanopropyl) dithiobenzoate (CPDB) as RAFT agents at 60 °C. Rate retardation with increasing initial RAFT agent concentrations is common to both 1-PEDB-and CPDB-mediated MA polymerizations and occurs in comparable magnitude. A pronounced inhibition period is observed in 1-PEDB-mediated MA polymerizations, whereas the corresponding CPDB-mediated polymerizations show considerably less inhibition. The cause for this inhibition may either be associated with the leaving group of the initial RAFT agent or with the slow fragmentation of the initial intermediate macroRAFT radical. The present experimental data suggest that slow fragmentation is the probable cause for inhibition. We conclude that the radical intermediate formed by addition of radicals to the initial RAFT agent is different in stability than the macroRAFT radical formed analogously from macroRAFT agent. The inhibition period is effectively reduced by the use of CPDB as the initial RAFT agent in methyl acrylate polymerizations.

Biotechnology, biomedicine, and nanotechnology applications would benefit from methods generating well-defined, monodisperse protein-polymer conjugates, avoiding time-consuming and difficult purification steps. Herein, we report the in situ synthesis of protein-polymer conjugates via reversible addition-fragmentation chain transfer polymerization (RAFT) as an efficient method to generate well-defined, homogeneous protein-polymer conjugates in one step, eliminating major postpolymerization purification steps. A water soluble RAFT agent was conjugated to a model protein, bovine serum albumin (BSA), via its free thiol group at Cys-34 residue. The conjugation of the RAFT agent to BSA was confirmed by UV-visible spectroscopy, matrix-assisted laser desorption ionization--time of flight (MALDI-TOF), and 1H NMR. BSA-macroRAFT agent was then used to control the polymerization of two different water soluble monomers, N-isopropylacrylamide (NIPAAm) and hydroxyethyl acrylate (HEA), in aqueous medium at 25 degrees C. The growth of the polymer chains from BSA-macroRAFT agent was characterized by size exclusion chromatography (SEC), 1H NMR, MALDI-TOF, and polyacrylamide gel electrophoresis (PAGE) analyses. The controlled character of the RAFT polymerizations was confirmed by the linear evolution of molecular weight with monomer conversion. The SEC analyses showed no detectable free, nonconjugated polymer formation during the in situ polymerization. The efficiency of BSA-macroRAFT agent to generate BSA-polymer conjugates was found to be ca. 1 by deconvolution of the SEC traces of the polymerization mixtures. The structural integrity and the conformation-related esterase activity of BSA were found to be unaffected by the polymerization conditions and the conjugation of the polymer chain. BSA-poly(NIPAAm) conjugates showed hybrid temperature-dependent phase separation and aggregation behavior. The lower critical solution temperature values of the conjugates were found to increase with the decrease in molecular weight of poly(NIPAAm) block conjugated to BSA.

This highlight describes recent developments in reversible addition-fragmentation transfer (RAFT) polymerization. Succinct coverage of the RAFT mechanism is supplemented by details of synthetic methodologies for making a wide range of architectures ranging from stars to combs, microgels, and blocks. In addition, RAFT reactions in different media such as emulsion and ionic liquids receive attention. Finally, a specific example of a novel material design is briefly introduced, whereas polymers prepared via RAFT are adopted for microporous/honeycomb membrane design.

Eight xanthates were synthesized to induce living free radical polymerization of vinyl acetate. Four compounds, methyl (4‐methoxyphenoxy)carbonothioylsulfanyl acetate, methyl (methoxycarbonothioyl)sulfanyl acetate, methyl (ethoxycarbonothioyl)sulfanyl acetate and methyl (isopropoxycarbonothioyl)sulfanyl acetate were identified as suitable MADIX/RAFT agents, yielding low polydispersity (PDI < 1.2) poly(vinyl acetate) of molecular weights exceeding 5 × 104 g · mol−1. All suitable MADIX/RAFT agents exhibited extended periods of inhibition (0.3 h < tinh < 10 h) and moderate rate retardation. The ability of these compounds to control vinyl acetate polymerization can be correlated with the electron density on the central carbon atom of the xanthate. Electrospray ionization mass spectrometric analysis was performed to complete the investigation on the new MADIX/RAFT agents.