Formation and Possible Reactions of Organometallic Intermediates with Active Copper(I) Catalysts in ATRP

The Cu^I complex obtained in situ from Cu^I and tris­((4-methoxy-3,5-dimethylpyridin-2-yl)­methyl)­amine (TPMA*) is currently the most reducing and the most active catalyst for atom transfer radical polymerizations (ATRP). The complex has a high affinity for alkyl halides (ATRP pathway) but also has sufficient affinity toward organic radicals to potentially participate in organometallic-mediated radical polymerization (OMRP). Thus, the radical polymerization of <i>n</i>-butyl acrylate initiated by AIBN (azobisisobutyronitrile) was significantly retarded, and the molecular weights decreased in the presence of the Cu^I/TPMA* complex. These results suggest the presence of a Cu-mediated termination processes, even after the amount of radicals generated from AIBN exceeded the initial amount of Cu^I/TPMA*. Nevertheless, in the presence of alkyl bromides, which act as ATRP initiators for acrylates, control was gained through metal-mediated halogen atom transfer, i.e., ATRP, not OMRP

Contribution of Photochemistry to Activator Regeneration in ATRP

With the recent interest in photochemically mediated atom transfer radical polymerization (ATRP), an interesting question arises: how significant are the photochemical processes in ATRP reactions that are supposed to be chemically controlled, such as initiators for continuous activator regeneration (ICAR) ATRP? A comparison of the rates of polymerization under ICAR ATRP conditions under ambient lighting and in the dark indicates negligible difference in the polymerization rate, under the conditions [MA]:[EBiB]:[TPMA*2]:[CuBr₂]:[AIBN] = 300:1:0.12:0.03:0.2 in anisole 50% (v/v) at 60 °C, where TPMA*2 is 1-(4-methoxy-3,5-dimethylpyridin-2-yl)-<i>N</i>-((4-methoxy-3,5-dimethylpyridin-2-yl)­methyl)-<i>N</i>-(pyridin-2-ylmethyl)­methanamine. This indicates that under typical ICAR conditions activator regeneration is almost exclusively due to the chemical decomposition of AIBN, not ambient lighting. To further investigate the effect of light on the activator regeneration, experiments were performed combining ICAR and photochemical processes in a 392 nm photoreactor of intensity 0.9 mW/cm². In this process, termed PhICAR (photochemical plus ICAR) ATRP, the overall rate of activator regeneration is the sum of the rates of activator regeneration by chemical (ICAR) decomposition of AIBN and the photochemical activator regeneration. At low AIBN concentrations (0.035 equiv with respect to ATRP initiator), the contribution of the photochemical processes in the 392 nm photoreactor is approximately 50%. At higher AIBN concentrations (0.2 equiv with respect to ATRP initiator), the contribution of photochemical processes to the overall polymerization drops to 15% due to the higher rate of chemically controlled processes

How are Radicals (Re)Generated in Photochemical ATRP?

The polymerization mechanism of photochemically mediated Cu-based atom-transfer radical polymerization (ATRP) was investigated using both experimental and kinetic modeling techniques. There are several distinct pathways that can lead to photochemical (re)­generation of Cu^I activator species or formation of radicals. These (re)­generation pathways include direct photochemical reduction of the Cu^II complexes by excess free amine moieties and unimolecular reduction of the Cu^II complex, similar to activators regenerated by electron-transfer (ARGET) ATRP processes. Another pathway is photochemical radical generation either directly from the alkyl halide, ligand, or via interaction of ligand with either monomer or with alkyl halides. These photochemical radical generation processes are similar to initiators for continuous activator regeneration (ICAR) ATRP processes. A series of model experiments, ATRP reactions, and kinetic simulations were performed to evaluate the contribution of these reactions to the photochemical ATRP process. The results of these studies indicate that the dominant radical (re)­generation reaction is the photochemical reduction of Cu^II complexes by free amines moieties (from amine containing ligands). The unimolecular reduction of the Cu^II deactivator complex is not significant, however, there is some contribution from ICAR ATRP reactions involving the interaction of alkyl halides and ligand, ligand with monomer, and the photochemical cleavage of the alkyl halide. Therefore, the mechanism of photochemically mediated ATRP is consistent with a photochemical ARGET ATRP reaction dominating the radical (re)­generation

Extraction of Thermodynamic Parameters of Protein Unfolding Using Parallelized Differential Scanning Fluorimetry

Thermodynamic properties of protein unfolding have been extensively studied; however, the methods used have typically required significant preparation time and high protein concentrations. Here we present a facile, simple, and parallelized differential scanning fluorimetry (DSF) method that enables thermodynamic parameters of protein unfolding to be extracted. This method assumes a two-state, reversible protein unfolding mechanism and provides the capacity to quickly analyze the biophysical mechanisms of changes in protein stability and to more thoroughly characterize the effect of mutations, additives, inhibitors, or pH. We show the utility of the DSF method by analyzing the thermal denaturation of lysozyme, carbonic anhydrase, chymotrypsin, horseradish peroxidase, and cellulase enzymes. Compared with similar biophysical analyses by circular dichroism, DSF allows for determination of thermodynamic parameters of unfolding while providing greater than 24-fold reduction in experimental time. This study opens the door to rapid characterization of protein stability on low concentration protein samples

Visible Light and Sunlight Photoinduced ATRP with ppm of Cu Catalyst

Photochemically induced ATRP was performed with visible light and sunlight in the presence of parts per million (ppm) copper catalysts. Illumination of the reaction mixture yielded polymerization in case of 392 and 450 nm light but not for 631 nm light. Sunlight was also a viable source for the photoinduced ATRP. Control experiments suggest photoreduction of the Cu^II complex (ligand to metal charge transfer in the excited state), yielding a Cu^I complex, and a bromine radical that can initiate polymerization. No photoactivation of Cu^I complex was detected. This implies that the mechanism of ATRP in the presence of light is a hybrid of ICAR and ARGET ATRP. The method was also used to synthesize block copolymers and polymerizations in water

Substituted Tris(2-pyridylmethyl)amine Ligands for Highly Active ATRP Catalysts

The synthesis and application of a very active catalyst for copper-catalyzed atom transfer radical polymerizations (ATRP) with tris­([(4-methoxy-2,5-dimethyl)-2-pyridyl] methyl)­amine (TPMA*) ligand is reported. Catalysts with TPMA* ligands are approximately 3 orders of magnitude more active than those with tris­(2-pyridylmethyl)­amine (TPMA). Catalyst activity was evaluated by cyclic voltammetry, stopped-flow, and ATRP kinetics. Catalysts with TPMA* ligands perform better than those with TPMA ligands, especially at low catalyst concentrations

Reversible-Deactivation Radical Polymerization in the Presence of Metallic Copper. A Critical Assessment of the SARA ATRP and SET-LRP Mechanisms

Reversible-deactivation radical polymerization (RDRP) in the presence of Cu⁰ is a versatile technique that can be used to create well-controlled polymers with complex architectures. Despite the facile nature of the technique, there has been a vigorous debate in the literature as to the mechanism of the reaction. One proposed mechanism, named supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP), has Cu^I as the major activator of alkyl halides, Cu⁰ acting as a supplemental activator, an inner-sphere electron transfer occurring during the activation step, and relatively slow comproportionation and disproportionation. In SARA ATRP slow activation of alkyl halides by Cu⁰ and comproportionation of Cu^II with Cu⁰ compensates for the small number of radicals lost to termination reactions. Alternatively, a mechanism named single electron transfer living radical polymerization (SET-LRP) assumes that the Cu^I species do not activate alkyl halides, but undergo instantaneous disproportionation, and that the relatively rapid polymerization is due to a fast reaction between alkyl halides and “nascent” Cu⁰ through an outer-sphere electron transfer. In this article a critical assessment of the experimental data are presented on the polymerization of methyl acrylate in DMSO with Me₆TREN as the ligand in the presence of Cu⁰, in order to discriminate between these two mechanisms. The experimental data agree with the SARA ATRP mechanism, since the activation of alkyl halides by Cu^I species is significantly faster than Cu⁰, the activation step involves inner-sphere electron transfer rather than an outer-sphere electron transfer, and in DMSO comproportionation is slow but occurs faster than disproportionation, and activation by Cu^I species is much faster than disproportionation. The rate of deactivation by Cu^II is essentially the same as the rate of activation by Cu^I, and the system is under ATRP equilibrium. The role of Cu⁰ in this system is to slowly and continuously supply Cu^I activating species and radicals, by supplemental activation and comproportionation, to compensate for Cu^I lost due to the unavoidable radical termination reactions. With the mechanistic understanding gained by analyzing the experimental data in the literature, the reaction conditions in SARA ATRP can be tailored toward efficient synthesis of a new generation of complex architectures and functional materials

Synthesis of Amphiphilic Poly(<i>N</i>-vinylpyrrolidone)-<i>b</i>-poly(vinyl acetate) Molecular Bottlebrushes

Well-defined molecular bottlebrushes with poly­(<i>N</i>-vinylpyrrolidone) and poly­(<i>N</i>-vinylpyrrolidone)-<i>b</i>-poly­(vinyl acetate) (PNVP-<i>b</i>-PVOAc) side chains were prepared via a combination of atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer (RAFT). A macro chain transfer agent poly­(2-((2-ethylxanthatepropanoyl)­oxy)­ethyl methacrylate) (PXPEM) was prepared by attaching xanthate chain transfer agents onto each monomeric unit of poly­(2-hydroxyethyl methacrylate). Subsequently, a RAFT polymerization procedure was used to synthesize molecular bottlebrushes with PNVP side chains with controlled molecular weight and low polydispersity by grafting from the PXPEM backbone. The side chains were then chain extended with PVOAc, yielding a bottlebrush macromolecule with PNVP-<i>b</i>-PVOAc side chains. The comb-like shape of the chain extended bottlebrushes was confirmed by atomic force microscopy (AFM)

ATRP under Biologically Relevant Conditions: Grafting from a Protein

Atom transfer radical polymerization (ATRP) methods were developed in water-based media, to grow polymers from proteins under biologically relevant conditions. These conditions gave good control over the resulting polymers, while still preserving the protein’s native structure. Several reaction parameters, such as ligand structure, halide species, and initiation mode were optimized in water and PBS buffer to yield well-defined polymers grown from bovine serum albumin (BSA), functionalized with cleavable ATRP initiators (I). The CuCl complex with ligand 2,2′-bipyridyne (bpy) provides the best conditions for the polymerization of oligo­(ethylene oxide) methacrylate (OEOMA) in water at 30 °C under normal ATRP conditions (I/CuCl/CuCl₂/bpy = 1/1/9/22), while the CuBr/bpy complex gave better performance in PBS. Activators generated by electron transfer (AGET) ATRP gave well-controlled polymerization of OEOMA at 30 °C with the ligand tris­(2-pyridylmethyl)­amine (TPMA), (I/CuBr₂/TPMA = 1/10/11). The AGET ATRP reactions required slow feeding of a very small amount of ascorbic acid into the aqueous reaction medium or buffer. The reaction conditions developed were used to create a smart, thermoresponsive, protein–polymer hybrid

Dynamic Thiol–Michael Chemistry for Thermoresponsive Rehealable and Malleable Networks

The thiol–Michael adduct is used as a thermoresponsive dynamic cross-linker in polymeric materials. Recently, the thiol–Michael reaction between thiols and conjugated alkenes has been used as a ligation reaction for polymer synthesis and functionalization. Here, the thiol–Michael reaction is demonstrated to be thermally responsive and dynamic. Small molecule model experiments demonstrate the potential for the thiol–Michael adducts to be used in dynamic covalent chemistry. Thiol–acrylate adducts are incorporated into a cross-linker to form a soft polymeric material. These thiol–Michael cross-linked materials display healing after being cut and malleability characteristics at 90 °C. Additionally, the data suggest that there is limited creep and stress relaxation at room temperature with complete recovery of creep once the strain is removed. These thiol–Michael cross-linked polymers show dynamic properties upon thermal stimulus, with long-term stability against mechanical deformation in the absence of this stimulus, opening the way for them to be used in various applications