An Atom-Economic Enzymatic Cascade Catalysis for High-Throughput RAFT Synthesis of Ultrahigh Molecular Weight Polymers.

High-throughput synthesis of well-defined, ultrahigh molecular weight (UHMW) polymers by green approaches is highly desirable but remains unexplored. We report the creation of an atom-economic enzymatic cascade catalysis, consisting of formate oxidase (FOx) and horseradish peroxidase (HRP), that enables high-throughput reversible addition-fragmentation chain transfer (RAFT) synthesis of UHMW polymers at volumes down to 50 μL. FOx transforms formic acid, a C 1 substrate, and oxygen to CO 2 and H 2 O 2 , respectively. CO 2 can escape from solution while H 2 O 2 is harnessed in situ by HRP to generate radicals from acetylacetone for RAFT polymerization, leaving no waste accumulation in solution. Oxygen-tolerant RAFT polymerization using enzymatic cascade redox cycles was successfully performed in vials and 96-well plates to produce libraries of well-defined UHMW polymers, and represents the first example of high-throughput synthesis method of such materials at extremely low volumes.