Concerted Interaction of Cisplatin and Excess Electron toGuanine-Cytosine Base Pair: A Theoretical Study

• Main Authors: Kun-Ho Lin, 林昆禾
• Other Authors: Hsing-Yin Chen
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/58381571681433548915

碩士 === 高雄醫學大學 === 醫藥暨應用化學研究所 === 99 === Cisplatin is a famous anticancer drug that has been used for treatment in various types of tumor. It is well-established that when cisplatin interacts with DNA, it tends to bind simultaneously with both N7 atoms of two successive guanines. Previous theoretical study has pointed out the possibility of proton transfer from N1 of guanine to N3 of cytosine induced by cisplatin. In the past decade, some researches demonstrated that excess electrons can cause single- and double-strand breaks or proton transfer in DNA. Very recently, Zheng et al. irradiated cisplatin-containing DNA by LEEs and found that the yield of strand break increases compared to the condition without cisplatin; however, the underlying principle is not clear yet. We therefore invoke density functional theory (DFT) calculations to investigate the cisplatin-mGmC complex ( [PtII-mGmC]2+ ) and its three reduction states ( [PtII-mGmC]‧+, [PtII-mGmC]0 and [PtII-mGmC]‧- ). We will focus on the issues regarding 1) activation energies and reaction energies for the proton-transfer reaction, 2) the spatial distribution of excess electron, 3) adiabatic electron affinity ( AEA ) and 4) binding energies between cisplatin and mGmC. Furthermore, we also investigate the complex of cisplatin and guanosine dinucleotide and its electron adduct ( [PtII-GpG]2+ and [PtII-GpG]‧+ ). Briefly, our computational results reveal that cisplatin-DNA complex displays very different proton-transfer behaviors and structural features when it is reduced.