The Rise of Radicals in Bioinorganic Chemistry

AbstractPrior to 1950, the consensus was that biological transformations occurred in two‐electron steps, thereby avoiding the generation of free radicals. Dramatic advances in spectroscopy, biochemistry, and molecular biology have led to the realization that protein‐based radicals participate in a vast array of vital biological mechanisms. Redox processes involving high‐potential intermediates formed in reactions with O2 are particularly susceptible to radical formation. Clusters of tyrosine (Tyr) and tryptophan (Trp) residues have been found in many O2‐reactive enzymes, raising the possibility that they play an antioxidant protective role. In blue copper proteins with plastocyanin‐like domains, Tyr/Trp clusters are uncommon in the low‐potential single‐domain electron‐transfer proteins and in the two‐domain copper nitrite reductases. The two‐domain muticopper oxidases, however, exhibit clusters of Tyr and Trp residues near the trinuclear copper active site where O2 is reduced. These clusters may play a protective role to ensure that reactive oxygen species are not liberated during O2 reduction.