Density Functional Studies on Isomerization of Prostaglandin H 2 to Prostacyclin Catalyzed by Cytochrome P450

At the double : DFT studies on the biosynthesis of prostacyclin (PGI 2 , see scheme) from prostaglandin H 2 (PGH 2 ) show two reaction mechanisms through two different oxidation states, an Fe IV –porphyrin intermediate and an Fe III –porphyrin π‐cation radical, followed by a proton‐coupled electron‐transfer process. magnified image 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 π‐cation radical intermediate.