Investigation of Ultrafast Configurational Photoisomerization of Bilirubin Using Femtosecond Stimulated Raman Spectroscopy.

Phototherapy is an efficient and safe way to reduce high levels of free 4,15-bilirubin (ZZ-BR) in the serum of newborns. The success of BR phototherapy lies in photoinduced configurational and structural isomerization processes that form excretable isomers. However, the physical picture of photoinduced photoisomerization of ZZ-BR is still unclear. Here, we strategically implement tunable femtosecond stimulated Raman spectroscopy and several time-resolved electronic spectroscopies, assisted by quantum chemical calculations, to dissect the detailed primary configurational isomerization dynamics of free ZZ-BR in organic solvents. The results of this study demonstrate that upon photoexcitation, ultrafast configurational isomerization proceeds by a volume-conserving "hula twist", followed by intramolecular hydrogen-bond distortion and large-scale rotation of the two dipyrrinone halves of the ZZ-BR isomer in a few picoseconds. After that, most of the population recovers back to ZZ-BR, and a very small amount is converted into stable BR isomers via structural isomerization.