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

Abstract 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.