Electron transfer reaction mechanism of cisplatin with DNA at the molecular level.
The cytotoxicity of cisplatin as a very effective chemotherapeutic anticancer drug is known to arise from its capacity to damage DNA. However, the mechanism of action of cisplatin at the molecular level, in particular, the reaction dynamics of cisplatin with DNA, remains elusive, and the reason why cisplatin binds to the guanine bases rather than to S-donor ligands available in cells remains a mystery. Using time-resolved femtosecond laser spectroscopy, for the first time, we reveal the high reactivity of cisplatin with electrons and its preferential electron-transfer reaction with the DNA guanine base. The results not only provide a molecular mechanistic understanding of cisplatin in cancer therapy but may have far-reaching significance for understanding the role of polar molecules such as NH3 and NH2 in biological reactions.
Lu
Q-B
QB
Department of Physics, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, N2L 3G1, Canada. qblu@uwaterloo.ca
Kalantari
S
S
Wang
C-R
CR
D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004579:Electron Transport; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet; D013057:Spectrum Analysis / Q000379:methods; D013997:Time Factors
D000970:Antineoplastic Agents; D004247:DNA; D002945:Cisplatin