Synthesis and Photophysical Properties of a Deazaflavin‐Bridged Porphyrinatoiron(III) That Mimics the Interaction of a Deazaflavin Inhibitor with the Heme‐Thiolate Cofactor of Cytochrome P450 3A4

Cytochrome P450 3A4 metabolizes a majority of administered therapeutic agents in the human liver. We recently reported the synthesis of a new inhibitor, 1 , whose binding to and displacement from the active site of CYP 3A4 can be conveniently followed by the associated changes in fluorescence intensity. Here we report the synthesis of a bichromophoric compound, 6 , in which deazaflavin was strapped over the distal side of a porphyrinatoiron(III) complex to mimic the envisaged enzyme–inhibitor interaction within the active site. Femtosecond pump–probe and fluorescence spectroscopies were used to study the photophysical processes of 6 . Rapid intramolecular energy transfer and enhanced intersystem‐crossing processes induced by the high‐spin Fe^III central ion are responsible for the complete suppression of deazaflavin fluorescence in 6 . Fluorescence quenching is less efficient in the iron‐free analogue of 6 , i.e., in 21 .