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.
Wang
C-R
CR
Department of Physics, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada.
Hu
A
A
Lu
Q-B
QB
D001973:Bromodeoxyuridine / Q000737:chemistry* / Q000494:pharmacology*; D016923:Cell Death; D002627:Chemistry, Physical / Q000379:methods*; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004583:Electrons; D008956:Models, Chemical; D011838:Radiation-Sensitizing Agents / Q000737:chemistry* / Q000494:pharmacology*; D013053:Spectrophotometry; D013936:Thymidine / Q000737:chemistry; D013997:Time Factors; D014466:Ultraviolet Rays
D011838:Radiation-Sensitizing Agents; D004247:DNA; D001973:Bromodeoxyuridine; D013936:Thymidine