A re-examination of the circular dichroism of the calicheamicin enediyne/dienone chromophoric interaction.

A series of calicheamicin derivatives have been made in an effort to delineate the origin of the strong circular dichroism (CD) of calicheamicin reported previously. The CD spectrum of calicheamicin (I) was compared with that of fragments II and III, which contain either the enediyne/dienone or a thiobenzoate chromophore alone. NaBH(4) reduction of calicheamicin produced two analogues (IV and V) that have no dienone. This allowed the assessment of possible exciton coupling between the enediyne on the warhead and the thiobenzoate on the tail. It was found that the strong negative 312/272 nm exciton split in the CD of calicheamicin is due largely to the enediyne/dienone interaction. Contributions from the thiobenzoate or its interaction with the enediyne have been ruled out. [structure: see text]