Hemoglobin and Red Blood Cells Catalyze Atom Transfer\nRadical Polymerization

Abstract

Hemoglobin (Hb) is a promiscuous\nprotein that not only transports\noxygen, but also catalyzes several biotransformations. A novel in\nvitro catalytic activity of Hb is described. Bovine Hb and human erythrocytes\nwere found to display ATRPase activity, i.e., they catalyzed the polymerization\nof vinyl monomers under conditions typical for atom transfer radical\npolymerization (ATRP). N-isopropylacrylamide (NIPAAm), poly­(ethylene\nglycol) methyl ether acrylate (PEGA), and poly­(ethylene glycol) methyl\nether methacrylate (PEGMA) were polymerized using organobromine initiators\nand the reducing agent ascorbic acid in acidic aqueous solution. In\norder to avoid chain transfer from polymer radicals to Hb’s\ncysteine residues, the accessible cysteines were blocked by a reaction\nwith a maleimide. The formation of polymers with bromine chain ends,\nrelatively low polydispersity indices (PDI), first order kinetics\nand an increase in the molecular weight of poly­(PEGA) and poly­(PEGMA)\nupon conversion indicate that control of the polymerization by Hb\noccurred via reversible atom transfer between the protein and the\ngrowing polymer chain. For poly­(PEGA) and poly­(PEGMA), the reactions\nproceeded with a good to moderate degree of control. Sodium dodecyl\nsulfate (SDS) gel electrophoresis, circular dichroism spectroscopy,\nand time-resolved ultraviolet–visible (UV–vis) spectroscopy\nrevealed that the protein was stable during polymerization, and only\nunderwent minor conformational changes. As Hb and erythrocytes are\nreadily available, environmentally friendly, and nontoxic, their ATRPase\nactivity is a useful tool for synthetic polymer chemistry. Moreover,\nthis novel activity enhances the understanding of Hb’s redox\nchemistry in the presence of organobromine compounds.