Switching between DNA binding modes with a photo- and redox-active DNA-targeting ligand

Abstract

A disulfide-functionalized bis-benzo[b]quinolizinium is presented that is transformed quantitatively into its cyclomers in a fast intramolecular [4 + 4] photocycloaddition. Both the bis-quinolizinium and the photocyclomers react with glutathione (GSH) or dithiothreitol (DTT) to give 9-(sulfanylmethyl)benzo[b]quinolizinium as the only product. As all components of this reaction sequence have different DNA-binding properties, it enables the external control and switching of DNA association. Hence, the bis-benzo[b]quinolizinium binds strongly to DNA and is deactivated upon photocycloaddition to the non-binding cyclomers. In turn, the subsequent cleavage of the cyclomers with DTT regains a DNA-intercalating benzoquinolizinium ligand. Notably, this sequence of controlled deactivation and recovery of DNA-binding properties can be performed directly in the presence of DNA.