Trihydroxyazepanes的結構與13C化學 位移之理論計算研究

Theoretical Studies of Structures and 13C NMR Chemical Shifts for Trihydroxyazepanes

葉寶玲(Pao-Ling Yeh)

指導教授 ： 王伯昌

淡江大學/理學院/化學學系博士班/博士(2011年)

https://doi.org/10.6846/TKU.2011.00740

摘要

本論文係研究三種trihydroxyazepanes異構物之穩定構形，由於七圓環醣水解酵素抑制劑結構的易變性，所以可以藉由理論計算去預測可能的結構。幾何結構最佳化是使用Gaussian 03軟體中的DFT/B3LYP/6-311++G(d,p)，得到每種異構物各有28個構形，其中能量較低為相對穩定的構形，再以Gibbs自由能算出28個構形之Boltzmann分佈。接著針對三種異構物相對穩定的構形，進行13C NMR化學位移計算，並與已報導之數值做比對。我們採用GIAO/HF、GIAO/DFT/OPBE及GIAO/DFT/B3LYP搭配四種不同的基底函數，包括6-311++G(d,p)、6-311+G(2d,p)、cc-pVDZ及cc-pVTZ做單點計算。相對穩定的構形，其13C NMR化學位移之平均絕對誤差(Mean Absolute Error，MAE)也相對較小。因為實驗的化學位移是許多構形的平均貢獻，我們考慮Boltzmann分佈將數個構形混合去進行13C NMR化學位移計算，構形混合的MAE比單一構形的MAE小，而且實驗的化學位移和理論計算的化學位移趨勢符合。其中使用HF(Hartree-Fock，HF)方法搭配cc-pVTZ基底函數，使用OPBE方法搭配6-311+G(2d,p)基底函數及使用B3LYP方法搭配cc-pVDZ基底函數，計算所得之化學位移最接近實驗值。針對其他相關結構易變的七圓環醣水解酵素抑制劑，此結果可以作為參考的依據。

關鍵字

七圓環醣水解酵素抑制劑 ； 幾何結構最佳化 ； 化學位移 ； 平均絕對誤差

並列摘要

Owing to the conformational flexibility for trihydroxyazepanes, the theoretical prediction should be helpful for generating appropriate conformations. DFT/B3LYP/6-311++G(d,p) calculations of three isomers for trihydroxyazepanes are presented to obtain 28 conformations for each isomer. The Boltzmann distribution was considered to calculate the population of each conformation. The GIAO/DFT/OPBE, GIAO/DFT/B3LYP and GIAO/HF single point calculations with four different basis sets, including 6-311++G(d,p), 6-311+G(2d,p), cc-pVDZ and cc-pVTZ of the relative stable conformations of trihydroxyazepanes were conducted to generate their 13C NMR chemical shifts. The calculated chemical shifts are compared with the experimental ones. The MAEs (Mean Absolute Error, MAE) of the 13C NMR chemical shifts for the relative stable conformations are smaller. Moreover, the experimental 13C NMR chemical shifts gave only the average contribution of all conformations. The observed average chemical shifts displays improvement over that of each individual conformation. Good choices to evaluate the theoretical chemical shifts for these conformations are HF/cc-pVTZ, OPBE/6-311+G(2d,p) and B3LYP/cc-pVDZ. The calculated 13C NMR chemical shifts are in good agreement with the experimental NMR data of trihydroxyazepanes.

並列關鍵字

conformational analysis ； NMR calculation ； trihydroxyazepane

參考文獻

[9] Walsh, C. Tetrahedron 1982, 38, 871.

[10] Rando, R. R.; Science 1974, 185, 320.

[12] Painter, G. F.; Eldridge, P. J.; Falshaw, A. Bioorg. Med. Chem. 2004, 12, 225.

[17] Magyarfalvi, G.; Pulay, P. J. Chem. Phys. 2003, 119, 1350.

[18] Wilson, P. J.; Amos, R. D.; Handy, N. C. Chem. Phys. Lett. 1999, 312, 475.