在許多生物及化學的現象和過程中，DNA鹼基對的質子轉移反應扮演著很重要的角色，例如基因的突變、輻射導致DNA的傷害，以及電荷在DNA中傳輸的動力學，對於單一鹼基對的化學變化已經有許多文獻報告，但是有關鹼基對在DNA環境中的影響之研究比較少，因此本報告中我們針對序列效應如何影響(G:C)• 沿著氫鍵N1(G)…N3(C)之質子轉移反應，採用密度泛函理論與ONIOM 分子分層
計算法求得反應之活化能與反應能，以及G:C 鹼基對穩定度(如絕熱電子親和力與
絕熱游離能)在不同的鹼基對三聚物。(G:C)· ± 沿著氫鍵N1(G)-H×××N3(C)之質子轉移
反應在序列效應下，G:C 之還原作用與氧化作用所獲得或失去的電子與電荷皆定域
在(X:Y)(G:C)· ± (X:Y)中間 G:C。理論計算結果顯示在氣相條件下，因為
(X:Y)(G:C)· ± (X:Y)之額外電子與電洞以及電荷皆定域在中間G:C，鹼基對三聚物
之鄰近鹼基對對中間G:C 鹼基對影響可以用靜電作用力模型解釋􀇶而且在水溶液
條件下，序列性應之相依性變得不明顯是因為水分子對此鹼基對三聚物之鄰近鹼
基對具有遮蔽作用。序列效應對DNA 的電子轉移以及LEE 造成DNA 傷害的影響
也會被水合效應削弱。還有對G:C 鹼基對之中間另一氫鍵N２(G)-HO2(C)之質子
轉移反應是否因堆疊作用與水合作用而促使反應進行。

The formation of base pair radical anions and cations is closely related to many fascinating research fields in biology and chemistry such as genetic mutation, radiation-induced DNA damage and dynamics of charge transfer in DNA. However, the relevant knowledge so far mainly comes from studies on isolated base pair radical anions and cations, and their behavior in the DNA environment is less understood. In this study, we focus on how the nucleobase sequence affects the properties of the guanine–cytosine (G:C) base pair radical anion and cation. The energetic barrier and reaction energy for the proton transfer along the N1(G)–H•••N3(C) hydrogen bond and the stability of (G:C)• (i.e., electron affinity and ionization potential of G:C) embedded in different sequences of base-pair trimer were evaluated using density functional theory and two-layer ONIOM method. The computational results demonstrated that the presence of neighboring base pairs has an important influence on the behavior of (G:C)• in the gas phase. The excess electron and positive hole were found to be localized on the embedded G:C and the charge leakage to neighboring base pairs was very minor in all of the investigated sequences. Accordingly, the sequence behavior of the proton transfer reaction and the stability of (G:C)• is chiefly governed by electrostatic interactions with adjacent base pairs. However, the effect of base stacking, due to its electrostatic nature, is severely screened upon hydration, and thus, the sequence dependence of the properties of (G:C)• in aqueous environment becomes relatively weak and less than that observed in the gas phase. The effect of geometry relaxation associated with neighboring base pairs as well as the possibility of proton transfer along the N2(G)–H•••O2(C) channel have also been investigated. The implications of the present findings to the electron transport and radiation damage of DNA are discussed.

目 錄
論文審定書………………………………………………………………………….. i
中文摘要…………………………………………………………………………......ii
英文摘要……………………………………………………………………….…... iii
目錄………………………………………………………………………………….iv
圖次………………………………………………………………………………….vi
表次………………………………………………………………………………...viii
英文縮寫對照表……………………………………………………………………..x
第 一 章 前言……………………………………………………………………… 1
第 二 章 鹼基序列效應對(G:C)•−之質子轉移反應與穩定度的影響………….....9
2.1 分子模型與計算方.. ………………………………………………......….9
2.2 結果與討…………………………………………………………………..11
2.2.1 額外電子的分佈…………………………………………...……….....11
2.2.2 質子轉移反應對序列的相依性…………………………………...….12
2.2.3 絕熱電子親和力對序列的相依性…………………………..………..19
2.2.4 鄰近鹼基對的幾何鬆弛效應…………………………………………21
2.2.5 沿著N2(G)-HO2(C)氫鍵的質子轉移…………………………...…23
2.2.6 與DNA 的電子傳輸與輻射傷害的關連……………………….…....25
2-3 結論……………………………………………………………………….25
第 三 章 鹼基序列效應對(G:C)·+之之質子轉移反應與穩定度的影響…………27
3.1 分子模型與計算方法…………………………………………………….27
3.2 結果與討論………………………………………………………………..29
3.2.1 環境效應對(G:C)·+之質子轉移反應的影響………………………..29
3.2.2 (X:Y)(G:C)·+(X:Y)正電洞的分佈……………………………………34
3.2.3 質子轉移反應對序列的相依性……………………………………..35
3.2.4 絕熱游離能對序列效應之相依性…………………………..……....41
v
3.2.5 沿著N2(G)-H×××O2(C)氫鍵的質子轉移……………………....……42
3.2.6 泛函數M06-2X 與B3LYP 之比較………………………….……..45
3.3 結論……………………………………………………………….….…...48
第 四 章 總結論…………………………………………………….………….….50
第 五 章 參考文獻……………………………………………………………..….52−

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