臺灣博碩士論文加值系統

酗酒者飲過量的酒精和脂質過氧化皆會導致環外DNA加合物的存在。這些DNA加合物參與致癌的啟動。本篇使用DFT和DFT-D方法來對cyclic 1,N2-propanoguanine 此種環外加成產物進行研究，分別計算各種可能的穩定錯配結構:cyclic 1,N2-propanoguanine與腺嘌呤、胸腺嘧啶、胞嘧啶和鳥嘌呤。結構最佳化之後分別使用M06/6-311++G**, ωB97XD/6-311++G** 和 MP2/6-311++G** 計算單點能量。反應焓使用M06/6-31+G* 和ωB97XD/6-31+G*方法計算。並比較cyclic 1,N2-propanoguanine adduct 與DNA鹼基的能量，來得知最穩定的結構。在液態的計算方面使用CPCM模型，可以考慮到溶液極化現象。M06方法在氣態所得的鍵能順序是: CPr-Gua-G(2)(-23.2kcal/mol) > CPr-Gua-C(1) (-16.1kcal/mol) > CPr-Gua-A(2)(-10.6kcal/mol) > CPr-Gua-T(2)(-9.6 kcal/mol)，以鳥嘌呤和胞嘧啶與cyclic 1,N2-propanoguanine所形成的錯配結構最為穩定。

關鍵字: 密度泛函理論, 加成產物, 錯配。

The alcohol abusers drinking excessive alcohol and lipid peroxidation lead to a presence of exocyclic DNA adducts. These DNA adducts suggest their involvement as initiators of carcinogenesis. The misincorporation properties of the exocyclic DNA adduct, cyclic 1,N2-propanoguanine adducts have been investigated, using DFT and DFT-D methods. Several different possible stable mispairing conformations, cyclic 1,N2-propanoguanine to A,T,C and G have been considered . The single point energy calculations have been carried out at M06/6-311++G**, ωB97XD/6-311++G** and MP2/6-311++G** on corresponding optimized geometries. The reaction enthalpy values at the M06/6-31+G* and ωB97XD/6-31+G* levels were employed for these model calculations. The energies were compared among the cyclic 1,N2-propanoguanine adduct with DNA bases to find the most stable conformer. The solvent phase calculations have also been carried out using the CPCM model, which accounts for the overall polarizability of the solvent, was also employed. The computed binding energy values lies in the order CPr-Gua-G(2)(-23.2kcal/mol) > CPr-Gua-C(1) (-16.1kcal/mol) > CPr-Gua-A(2)(-10.6kcal/mol) > CPr-Gua-T(2)(-9.6 kcal/mol) in the gas phase at M06 level, which indicate that guanine and cytosine are more favorable for mispairing with the cyclic 1,N2-propanoguanine adducts.

Keywords: DFT, adduct, misincorporation.

Abstract.................................................................iii
中文摘要....................................................................v
CHAPTER 1..................................................................1
1.1 Introduction.......................................................1
CHAPTER 2..................................................................4
2.1 Model System and Computational Details.............................4
CHAPTER 3..................................................................7
3.1 Optimized geometric parameters for cyclic 1,N2-propanoguanine adduct
and DNA bases complexes:...........................................7
3.2 Energetic parameters for cyclic 1,N2-propanoguanine-DNA
complexes.........................................................13
3.3 CPr-Gua−A, CPr-Gua−T, CPr-Gua−C, and CPr-Gua−G Complexes..........14
3.3.1 Cyclic 1,N2-propanoguanine adduct and adenine (CPr-Gua−A) complexes.................................................................14
3.3.2 Cyclic 1,N2-propanoguanine adduct and thymine (CPr-Gua−T) complexes.................................................................17
3.3.3 Cyclic 1,N2-propanoguanine adduct and cytosine (CPr-Gua−C) complexes.................................................................20
3.3.4 Cyclic 1,N2-propanoguanine adduct and guanine (CPr-Gua−G) complexes.................................................................23
CHAPTER 4.................................................................25
4.1 Summary and conclusion............................................25
References................................................................32
Supplementary Material....................................................34

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