Density Functional Theory Study of the Attack of Ebselen on a Zinc-Finger Model

Density functional theory and solvent-assisted proton exchange are used to model the attack of ebselen 1 on a zinc-finger model, an important step in the regulation of zinc signaling by reducible selenium compounds. These calculations show that the formation of a selenosulfide bond from an Se···S intermediate complex between 1 and a Cys2His2 zinc-finger model can occur through a moderate activation barrier that is consistent with experimental observations of the relative rates of Zn(2+) release from zinc-finger transcription factors and metallothionein.