Singlet oxygen oxidation products of biliverdin IXα dimethyl ester.

Biliverdin IXα is a naturally occurring linear tetrapyrrolic product of the enzymatic oxidative ring cleavage of heme. Evidence is mounting that biliverdin possesses antioxidant properties in mammals but its mode of action is unclear. We present the single crystal X-ray structure analysis of two regioisomeric biladien-1,19-diones-ab that are derived from biliverdin IXα dimethyl ester by addition of two vicinal trans-methoxy groups to the 4,5- or 15,16-double bonds, respectively. The compounds were likely formed by photosensitized singlet oxygen addition, followed by Lewis acid-catalyzed methanol-induced ring-opening of the intermediate epoxide, and OH-to-OMe substitution. We thus present structural evidence for a possible reaction mechanism by which biliverdin can act as an antioxidant.