本論文分為兩大主題：一、由氨基丙二腈生成甘胺酸之反應機制。甘胺酸是蛋白質結構中最小的胺基酸，實驗家透過化學演化(chemical evolution)反應，可以利用簡單的無機物分子，合成出包含甘胺酸在內的各種有機分子。此處，我們將研究從氨基丙二腈反應產生甘胺酸的各種反應機制，並且針對部分反應過程中，分子軌域的作用情況予以討論。本研究共分為兩個部分。
第一部分　利用ab initio計算方法，我們針對化學演化中，由氨基丙二腈(amino-malononitrile)到氨基乙腈(amino-acetonitrile)之各種可能的反應路徑加以考慮，並且根據反應物所擁有的各種活化位置，探討其分支反應及其反應機制。反應路徑上所有的駐留點(stationary point)均分別利用HF/6-311G(d,p)和MP2/6-311G(d,p)幾何優選，並利用counterpoise計算方法校正BSSE，以求得位能曲面上的相對能量。此處將主要的結論歸納如下：(i) 比較各種反應機制中所需要的活化能大小，可以確認化學演化之可能性。(ii) 起始物所選擇的反應方向可以利用前線軌域理論(frontier orbitals theory)加以分析，由於H2O HOMO的對稱特性，H2O傾向於和起始物的nitrile group進行反應。(iii) 反應起始物的nitrile group與H2O作用的活化能為49.00 kcal/mol，遠低於後續反應機制中所需之活化能，因此為本研究過程之速率決定步驟。當起始物之nitrile group與H2O作用後，所放出的能量即足以完成後續反應。(iv) Boys-Bernardi counterpoise計算顯示，所有在MP2層次下之BSSE能量修正值均高於HF計算結果。
第二部分　針對最簡單的胺基酸分子，glycine，在自然界中可能的生成過程，本研究利用ab initio分子軌域理論計算方法，討論由amino acetonitrile至glycine的多種反應機構及其分支反應。研究結果顯示，最可能的二種反應途徑，在MP2/6-311G**下，其速率決定步驟所需之活化能分別為46.11與52.38 kcal/mol。考慮water-assisted reaction時，僅需一個水分子的加入，即可使能障大幅降低至10.65與21.74 kcal/mol，顯示水分子的加入具有重要的作用。藉由NBO分析其中間產物與過渡狀態，發現反應過程中，分子內作用力將明顯影響反應物之幾何結構、穩定性與反應活化能。進行分子間反應時，前線軌域理論可以提供合理的解釋，從而判斷分支反應中最可能的反應路徑。

二、1,3-丁二烯與1,4-二氮-1,3-丁二烯進行共軛雙烯[四加二]環加成反應(Diels-Alder)時，位能曲面與分子軌域作用之關係。
利用B3LYP/6-311G**研究1,3-丁二烯與1,4-二氮-1,3-丁二烯的各種旋轉異構物，於Diels-Alder反應時可能產生的各種反應途徑與過渡狀態。由於1,3-丁二烯與1,4-二氮-1,3-丁二烯均可扮演diene或dienophile，因此將產生兩種反應途經相互競爭。研究結果顯示，1,3-丁二烯通常傾向於扮演diene的角色，此時HOMO-LUMO secondary interaction以及立體結構互斥作用將影響到反應的活化能。由於二分子相互靠近時，反應能障主要受到特定π軌域之間的互斥作用所影響，其餘各分子軌域之間的安定作用和排斥作用則將大致相抵。因此，當軌域的能量過於接近時，將導致互斥作用增加而能障提升。然而，若反應物MO間的能量間隙過大，幾何結構在反應過程需要大幅度扭轉變形以增加軌域間的重疊度，將導致活化能上升。

There are two major themes in this thesis. I. The Formation of Glycine from Amino-Malononitrile. The scientific study of the origins of life was born in the 1920’s when Oparin and Haldane put forth the idea that the origin of life could be understood in terms of plausible chemical and physical process occurring on the primitive Earth. Glycine is the smallest amino acid molecule in the protein structure. It could be synthesized by the simple inorganic compound in the chemical evolution. We investigated the mechanism from amino malononitrile to glycine and the molecular orbital interaction in some reaction. There are two sections regarding to the subject studied and rendered below.

Section 1
Ab initio theoretical calculation was carried out to study the hydrolysis of amino malononitrile. The proposed scheme was considered as one of the possible reaction paths that the simplest amino acid, glycine, may be synthesized by the nature. Several other probable schemes based on the potential reaction sites of amino malononitrile were also examined. The optimized structures of the species on the reaction potential energy surfaces in addition to the activation energies were calculated at both HF and MP2 levels. The basis set superposition error (BSSE) for the correction of calculated energy was also performed. It came out that one of the proposed reactions had the lower potential energy profile in the sequential processes to form the amino acetonitrile. Most of the calculated barriers in this scheme were below 60 kcal/mol. The first added H2O in the hydrolysis of amino malononitrile was calculated to be at lower barrier (49.00 kcal/mol) on attacking one of the nitrile group of amino malononitrile and successively forming an amide, rather than attacking on the amino group of amino malononitrile (82.24 kcal/mol). Further frontier orbital analysis also proved the same fact. The second H2O molecule was added to hydrolyze the forming amide and produced carboxylic acid, which then underwent decarboxylation to form amino acetonitrile. Direct decarboxylation needs around 61 kcal/mol to cross the barrier, the highest one in all the processes derived in Scheme 1. Of course, it may be assisted by the third molecule such as H2O to lower the barrier (around 20 kcal/mol). From the calculated low barriers the proposed processes in Scheme 1 may be considered as one of the acceptable mechanisms in prebiotic chemical evolution on the primitive earth.

Section 2
Ab initio theoretical calculations were carried out to study the hydrolysis of amino acetonitrile (NH2CH2CN) and amino-cyano-acetic acid (NH2(CN)CHCOOH). Each of the proposed schemes was considered to be one of the possible reaction paths by which the simplest amino acid, glycine, may be synthesized by nature. The optimized structures of the species on the potential energy surfaces were calculated at both the HF and MP2 levels. We found that the direct hydrolysis of the nitrile group of amino acetonitrile required a higher energy barrier (52.38 kcal/mol) compared to the barrier for the hydrolysis of amino-cyano-acetic acid (46.11 kcal/ mol). Our calculated potential energy profiles revealed that this glycine evolution would not occur as easily in an anhydrous atmosphere as in moist surroundings. (The difference in the barriers may be more than 30 kcal/mol.) Molecular orbital interaction between H2O and the amino acetonitrile was also studied, and we found that the crucial part of this hydrolysis process was the transfer of the hydrogen atom of H2O to the N atom of the nitrile group rather than the formation of the C-O bond between the O atom of H2O and the C atom of the nitrile group. The schematic processes with calculated lower energy barriers in the proposed schemes might be considered to be possible mechanisms in the prebiotic chemical evolution on the primitive earth.

II. MO Interaction Correlating to the Potential Energy Surface in the Diels-Alder Reaction of 1,3-Butadiene and 1,4-Diaza-1,3-Butadiene

B3LYP/6-311G** levels have been used to assess the relative energies of 24 different transition structures of 1,3-butadiene and 1,4-diazabuta-1,3-diene. Two competitive pathways leading to cycloaddition will be rationalized. In our study, most reactions prefer 1,3-butadiene acting the role of diene. The relative activation energy can be affected by the HOMO-LUMO secondary orbital interaction and steric repulsion of the transition state. Because the stabilization of most intermolecular MOs will counteract the destabilization caused by the structure distortion, the barriers will be mainly affected by the destabilization of some π-MOs of reactants. For this reason, a well overlap MOs of reactants would lead to a slightly higher barrier if these MOs were too close to each other and causing repulsion. However, if the gap between the MOs were so large that needs to distort the structure to increase the overlap of MO, this distortion would raise the barrier.

1. (a) Carruthers, W. Cycloaddition Reactions in Organic Synthesis; Pergamon: Oxford, 1990 and references therein. (b) Desimoni, G.; Tacconi, G.; Barco, A.; Polloni, G. P. National Product Synthesis through Pericyclic Reactions; ACS Monograph 180; American Chemical Society: Washington, D.C., 1983 and references therein. (c) Fringuelli, F.; Tatichi, A. Dienes in the Diels-Alder Reactions; Wiley: New York, 1990. (d) Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994, 741. (e) Pindur, U.; Lutz, G.; Otto, C. Chem. Rev. 1993, 93, 741. (f) Cativiela, C.; Garcia, J. I.; Mayoral, J. A.; Salvatella, L. Chem. Soc. Rev. 1996, 209. (g) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 497. (h) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1984, 23, 876. (i) Kagan, H. B.; Riant, O. Chem. Rev. 1992, 92, 1007. (j) Li, C.-J. Chem. Rev. 1993, 93, 2023. (k) Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie: Glassgow, 1998. (l) Li, C.-J.; Chan, T.-H. Organic Synthesis in Aqueous Media; John Wiley: New York, 1977. (m) Laschat, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 289. (n) Stipanovic, R. D. Environ. Sci. Res. 1992, 44, 319. (o) Ressig, H.-U. In Organic Synthesis Highlights; VCH: Weinheim, 1991; p 71.
2. Domingo, L. R.; Aurell, M. J.; Perez, P.; Contreras, R. J. Phys. Chem. A. 2002, 106, 6871.
3. Rowley, D.; Steiner, H. Discuss. Faraday Soc. 1951, 10, 198.
4. (a) Uchiyama, M.; Tomioka, T.; Amano, A. J. Phys. Chem. 1964, 68, 1878. (b) Tsang W. J. Chem. Phys. 1965, 42, 1805. (c) Lewis, D. K.; Bergmann, J.; Manjoney, R.; Paddock, R. J. Phys. Chem. 1984, 88, 4112.
5. Sauer, J. Angew. Chem., Int. Ed. Engl. 1967, 6, 16.
6. Loncharich, R. J.; Houk, K. N. Annu. Rew. Phys. Chem. 1988, 39, 213 and references therein.
7. Benardi, F.; Bottni, A.; Field, M. J.; Guest, M. F.; Hillier, I. H.; Robb, M. A.; Venturini, A. J. Am. Chem. Soc. 1988, 110, 3050.
8. Houk, K. N.; Li, Y.; Evanseck, J. D. Angew. Chem., Int. Ed. Engl. 1992, 31, 682.
9. Li, Y.; Houk, K. N. J. Am. Chem. Soc. 1993, 115, 7478.
10. Houk, K. N.; Li, Y.; Storer, J.; Raimondi, L.; Beno, B. J. Chem. Soc., Faraday Trans. 1994, 90, 1599.
11. Houk, K. N.; Gonzalez, J.; Li, Y. Acc. Chem. Res. 1995, 28, 81 and references therein.
12. Wiest, O.; Houck, K. N.; Black; Thomas, B., IV. J. Am. Chem. Soc. 1995, 117, 8594.
13. Goldstein, E.; Beno, B.; Houk, K. N. J. Am. Chem. Soc. 1996, 118, 6036.
14. (a) Beno, B. R.; Houk, K. N.; Singleton, D. A. J. Am. Chem. Soc. 1996, 118, 9984. (b) Singleton, D. A., Thomas, A. A. J. Am. Chem. Soc. 1995, 117, 9357.
15. Wiest, O.; Montiel, D. C.; Houk, K. N. J. Phys. Chem. A 1997, 101, 8378 and references therein.
16. Huang, C.-H.; Tsai, L.-C.; Hu, W.-P. J. Phys. Chem. A 2001, 105, 9945.
17. Leach, A. G.; Houk, K. N. J. Org. Chem. 2001, 66, 5192.
18. Sakai, S. J. Phys. Chem. A. 2000, 104, 922.
19. Isobe, H.; Takano, Y.; Kitagawa, Y.; Kawakami, T.; Yamanaka, S.; Yamaguchi, K.; Houk, K. N. J. Phys. Chem. A. 2003, 107, 682.
20. (a) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital Symmetry; Verlag Chemie, Academic Press: Veinheim, 1970. (b) Hoffmann, R. Acc. Chem. Res. 1971, 4, 1.
21. Sauer, J.; Sustmann, R. Angew. Chem., Int. Ed. Engl. 1980, 19, 779.
22. Houk, K. N.; Li, Y.; Evanseck, J. D. Angew. Chem., Intl. Ed. Engl. 1992, 31, 682.
23. (a) Fukui, K. Theory of Orientation and Stereoselection; Springer-Verlag: Heidelberg, 1979. (b) Fukui, K.; Fujimoto, H. Frontier Orbitals and Reaction Paths; World Scientific: London, 1997.
24. Hirao, H.; Ohwada, T. J. Phys. Chem. A. 2005, 109; 816.
25. (a) Alston, P. V.; Ottenbrite, R. M.; Shillady, D. D. J. Org. Chem. 1973, 38, 4075. (b) Alston, P. V.; Ottenbrite R. M. J. Org. Chem. 1975, 40, 1111. (c) Alston, P. V.; Ottenbrite, R. M.; Cohen, T. J. Org. Chem. 1978, 43, 1864. (d) Cohen, T.; Ruffner, R. J.; Shull, D. W.; Daniewski, W. M.; Ottenbrite, R. M.; Alston, P. V. J. Org. Chem. 1978, 43, 4052. (e) Alston, P. V.; Gordon, M. D.; Ottenbrite, R. M.; Cohen, T. J. Org. Chem. 1983, 48, 5051.
26. Alston, P. V.; Shillady, D. D. J. Org. Chem. 1974, 39, 3402.
27. Alston, P. V.; Ottenbrite, R. M.; Guner, O. F.; Shillady, D. D. Tetrahedron 1986, 42, 4403.
28. Kahn, S. D.; Pau, C. F.; Overman, L. E.; Hehre, W. J. J. Am. Chem. Soc. 1986, 108, 7381.
29. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T. A.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.7, 1998, Gaussian, Inc.: Pittsburgh, PA,.
30. Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
31. Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1987, 90, 2154.
32. Schaftenaar, G. Molden, version 4.2; CAOS/CAMM Center Nijmegen: Toernooiveld, Netherlands, 1991.