Michael A. Müller, Martin Gaplovsky, Jakob Wirz, Wolf-D. Woggon, "Synthesis and Photophysical Properties of a Deazaflavin-Bridged Iron(III)-Porphyrin that Mimics the Interaction of a Deazaflavin Inhibitor With the Heme-Thiolate Cofactor of Cytochrome P450 3A4", Helv. Chim. Acta 2006, 89, 2987-3001.


Abstract: 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 an iron(III)-porphyrin 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, 21.