Conspectus Atom-transfer radical polymerization (ATRP) is a well-known technique for the controlled polymerization of vinyl monomers under mild conditions. However, as with any other radical polymerization, ATRP typically requires rigorous oxygen exclusion, making it time-consuming and challenging to use by nonexperts. In this Account, we discuss various approaches to achieving oxygen tolerance in ATRP, presenting the overall progress in the field. Copper-mediated ATRP, which we first discovered in the late 1990s, uses a CuI/L activator that reversibly reacts with the dormant C­(sp3)–X polymer chain end, forming a X–CuII/L deactivator and a propagating radical. Oxygen interferes with activation and chain propagation by quenching the radicals and oxidizing the activator. At ATRP equilibrium, the activator is present at a much higher concentration than the propagating radicals. Thus, oxidation of the activator is the dominant inhibition pathway. In conventional ATRP, this reaction is irreversible, so oxygen must be strictly excluded to achieve good results. Over the last two decades, our group has developed several ATRP techniques based on the concept of regenerating the activator. When the oxidized activator is continuously converted back to its active reduced form, then the catalytic system itself can act as an oxygen scavenger. Regeneration can be accomplished by reducing agents and photo-, electro-, and mechanochemical stimuli. This family of methods offers a degree of oxygen tolerance, but most of them can tolerate only a limited amount of oxygen and do not allow polymerization in an open vessel. More recently, we discovered that enzymes can be used in auxiliary catalytic systems that directly deoxygenate the reaction medium and protect the polymerization process. We developed a method that uses glucose oxidase (GOx), glucose, and sodium pyruvate to very effectively scavenge oxygen and enable open-vessel ATRP. By adding a second enzyme, horseradish peroxidase (HPR), we managed to extend the role of the auxiliary enzymatic system to generating carbon-based radicals and changed ATRP from an oxygen-sensitive to an oxygen-fueled reaction. While performing control experiments for the enzymatic methods, we noticed that using sodium pyruvate under UV irradiation triggers polymerization without the presence of GOx. This serendipitous discovery allowed us to develop the first oxygen-proof, small-molecule-based, photoinduced ATRP system. It has oxygen tolerance similar to that of the enzymatic methods, exhibits superior compatibility with both aqueous media and organic solvents, and avoids problems associated with purifying polymers from enzymes. The system was able to rapidly polymerize N-iso­propyl­acryl­amide, a challenging monomer, with a high degree of control. These contributions have substantially simplified the use of ATRP, making it more practical and accessible to everyone.

Photoinduced atom transfer radical polymerization (photo-ATRP) has risen to the forefront of modern polymer chemistry as a powerful tool giving access to well-defined materials with complex architecture. However, most photo-ATRP...

Hyperbranched polymethacrylates were synthesized by green‐light‐induced atom transfer radical polymerization (ATRP) under biologically relevant conditions in the open air. Sodium 2‐bromoacrylate (SBA) was prepared in situ from commercially available 2‐bromoacrylic acid and used as a water‐soluble inibramer to induce branching during the copolymerization of methacrylate monomers. As a result, well‐defined branched polymethacrylates were obtained in less than 30 min with predetermined molecular weights (36 000

Over the last decade, photoinduced ATRP techniques have been developed to harness the energy of light to generate radicals. Most of these methods require the use of UV light to initiate polymerization. However, UV light has several disadvantages: it can degrade proteins, damage DNA, cause undesirable side reactions, and has low penetration depth in reaction media. Recently, we demonstrated green-light-induced ATRP with dual catalysis, where eosin Y (EYH 2 ) was used as an organic photoredox catalyst in conjunction with a copper complex. This dual catalysis proved to be highly efficient, allowing rapid and well-controlled aqueous polymerization of oligo(ethylene oxide) methyl ether methacrylate without the need for deoxygenation. Herein, we expanded this system to synthesize polyacrylates under biologically relevant conditions using Cu II /Me 6 TREN (Me 6 TREN = tris[2-(dimethylamino)ethyl]amine) and EYH 2 at ppm levels. Water-soluble oligo(ethylene oxide) methyl ether acrylate (average M n = 480, OEOA 480 ) was polymerized in open reaction vessels under green light irradiation (520 nm). Despite continuous oxygen diffusion, high monomer conversions were achieved within 40 min, yielding polymers with narrow molecular weight distributions (1.17 ≤ D̵ ≤ 1.23) for a wide targeted DP range (50−800). In situ chain extension and block copolymerization confirmed the preserved chain end functionality. In addition, polymerization was triggered/halted by turning on/off a green light, showing temporal control. The optimized conditions also enabled controlled polymerization of various hydrophilic acrylate monomers, such as 2-hydroxyethyl acrylate, 2-(methylsulfinyl)ethyl acrylate), and zwitterionic carboxy betaine acrylate. Notably, the method allowed the synthesis of well-defined acrylate-based protein-polymer hybrids using a straightforward reaction setup without rigorous deoxygenation.

Exosomes are 30−200 nm sized extracellular vesicles that are increasingly recognized as potential drug delivery vehicles. However, exogenous exosomes are rapidly cleared from the blood upon intravenous delivery, which limits their therapeutic potential. Here, we report bioactive exosome-tethered poly-(ethylene oxide)-based hydrogels for the localized delivery of therapeutic exosomes. Using cholesterol-modified DNA tethers, the lipid membrane of exosomes was functionalized with initiators to graft polymers in the presence of additional initiators and crosslinker using photoinduced atom transfer radical polymerization (ATRP). This strategy of tethering exosomes within the hydrogel network allowed their controlled release over a period of 1 month, which was much longer than physically entrapped exosomes. Exosome release profile was tuned by varying the crosslinking density of the polymer network and the use of photocleavable tethers allowed stimuli-responsive release of exosomes. The therapeutic potential of the hydrogels was assessed by evaluating the osteogenic potential of bone morphogenetic protein 2-loaded exosomes on C2C12 and MC3T3-E1 cells. Thus, ATRP-based exosome-tethered hydrogels represent a tunable platform with improved efficacy and an extended-release profile.