Phototunable Cell Killing by Photochromic Diarylethene of Thiazoyl and Thienyl Derivatives

We report a unique phototunable cell killing technique
using diarylethene
molecules as photo-isomerizing-molecular switches. These molecules
were delivered to DNA in the cell nucleus due to closed-form generated
by UV light, and then blue light triggered cell killing. A UV light
irradiation switches the open form, having no DNA intercalation activity,
to the closed form to induce intercalation in DNA. This isomer, thus
prepared ready for the action, exerts photocytotoxicity upon the subsequent
blue light irradiation. Molecular biological analysis clarifies that
photocytotoxicity is due to DNA double-strand breaks. Since cell death
is observed only when irradiated with light where both the open- and
closed-ring isomers have absorption, the possible mechanism of cell
death is assumed to be due to the repeated photocyclization and photocycloreversion
reactions of the diarylethene molecules, which induce irreparable
damage to DNA. This unique photo-controllable action in a cell system
can provide the basis of a novel scheme of phototherapy.