Oxygen-Tolerant Photo-Induced Miniaturized Accelerated Atom Transfer Radical Polymerization (OPTIMA-ATRP) for...

Conjugates of synthetic polymers with biomolecules, forming polymer bioconjugates (PBCs), are used to improve the pharmacokinetic properties of many biological therapeutics. Growing synthetic polymers from biomolecules via reversible deactivation radical polymerization (RDRP) demonstrated enormous potential as an alternative to the "grafting to" method in synthesizing biohybrids. However, conventional "grafting from" approaches applied to biomolecules are hindered by large reaction volumes, long reaction times, rigorous deoxygenation, and complex workflows, rendering them unsuitable for synthesizing libraries of PBCs needed to collect large data sets for emerging materials discovery. Herein, Oxygen-tolerant photo-induced miniaturized accelerated atom transfer radical polymerization (OPTIMA-ATRP) in water was developed for the polymerization of hydrophilic (meth)acrylate monomers under ambient or sub-ambient (4°C) temperature and atmospheric conditions, without prior degassing, in < 10 min. Sodium pyruvate (SP) in conjunction with UV light (380-395 nm, 28.5-30 mW/cm²) promoted rapid controlled polymerization in water, on an ultra-small scale (< 50 µL) in micropipette tips or 96-well plate. By exploiting this OPTIMA-ATRP, cost-effective syntheses of several types of PBCs (e.g., DNA-, peptide-, lipid-, and protein-polymer hybrids) were carried out using a parallel, high-throughput approach. This technique enables rapid optimization of biohybrid synthesis, previously inaccessible under conventional conditions, and empowers non-specialists to use ATRP in various areas.