Direct observation of the transition state of ultrafast electron transfer reaction of a radiosensitizing drug bromodeoxyuridine

Replacement of thymidine in DNA by bromodeoxyuridine (BrdU) has long been known to enhance DNA damage and cell death induced by ionizing/UV radiation, but the mechanism of action of BrdU at the molecular level is poor understood. Using time-resolved femtosecond laser spectroscopy, we obtain the real-time observation of the transition state of the ultrafast electron transfer (ET) reaction of BrdU with the precursor to the hydrated electron, which is a general product in ionizing/UV radiation. The results show that the ET reaction is completed within 0.2 picosecond (ps) after the electronic excitation, leading to the formation of a transition state BrdU*- with a lifetime of approximately 1.5 ps that then dissociates into Br- and a high reactive radical dU*. The present results can greatly enhance our understanding not only of the mechanism of BrdU as a radio-/photosensitizer but of the role of prehydrated electrons in electron-initiated processes in biological and environmental systems.