Density Functional Studies on Isomerization of Prostaglandin H2 to Prostacyclin Catalyzed by Cytochrome P450

Abstract

Reaction mechanisms for the isomerization of prostaglandin H(2) to prostacyclin catalyzed by cytochrome P450 are investigated by the unrestricted Becke's three-parameter plus Lee-Yang-Parr density functional level of theory. The results show that the homolytic O-O bond cleavage of endoperoxide in prostaglandin H(2) is the rate-limiting step and that the isomerization proceeds through proton-coupled electron transfer. We located two reaction pathways through an Fe(IV)-porphyrin intermediate and an Fe(III)-porphyrin pi-cation radical intermediate.