1. 1 國立中正大學 化學暨生物化學研究所 碩士論文口試 莊曉涵 (Hsiao-Han Chuang) 指導教授：胡維平 (Wei-Ping Hu) 中華民國 101 年 7 月 23 日

2. 2 Content Ch 1. Excited-state double proton transfer reaction of 7- hydroxyquinoline-8-carboxylic acid Ch 2. Theoretical study on the ground- and excited-state proton transfer reactions of 2-(2’-hydroxylphenyl)thiazole (HPT)

3. 3 Content Ch 3. Theoretical study on the prebiotic synthesis of α- amino acids Ch 4. Multiple proton transfer of 3,6-bis(3- hydroxypyridin-2-yl)pyrazine-2,5-diol (PPPOH4)

4. 4 Theoretical Study on the Prebiotic Synthesis of Glycine

5. 5 Biosynthesis of Glycine (Intermediate of glycolysis) 3-Phosphoglycerate Three types of enzyme Serine Precursor of Glycine Formation of Glycine Garrett, R.H.; Grishman, C.M.; Biochemistry; 4 rd Ed.; Thomsom Learning: Singapore, 2005;pp837

6. 6 Prebiotic synthesis of Amino Acid ﹡ ﹡ Ann. Chem. Pharm. 1850, 75, 27. Strecker reaction R1 = R2 = H Amino Acid = Glycine

7. 7 Complete Strecker Reaction in Neutralized Surrounding

8. 8 Computational methods Geometry optimization ： MP2/6-31+G(d,p) Single point calculation ： CCSD(T)/aug-cc-pVTZ//MP2/6-31+G(d,p) Program ： Gaussian 09, Molpro Solvent effects –SCRF model ： PCM, SMD –Catalyst in microsolvation cluster ： H 2 O, NH 3 Gas phase (OPT) SCRF model (SP) Microsolvation cluster (OPT) SCRF model (SP)

9. 9 Mechanism of Step (1) TS 1 Int 1 TS 2 CH 2 O+NH 3 CH 2 NH+H 2 O

10. 10 Mechanism of Step (1) in Microsolvation Cluster Catalyst ： two water molecules Catalyst ： two ammonia molecules

11. 11 Potential Energy Surface of Step (1) in Microsolvation Cluster One catalyzed molecule Two catalyzed molecules Black ： Uncatalyzed Green ： NH 3 Blue ： H 2 O

12. 12 Proton Relay Mechanism Uncatalyzed reaction Reaction with two water molecules as catalyst 0 kcal/mol 29.9 kcal/mol  13.0 kcal/mol 4.6 kcal/mol  8.5 kcal/mol

13. 13 Potential Energy Surface of Step (1) with two water molecules in SCRF Model Black ： Gas phase Purple ： PCM Red ： SMD

14. 14 Mechanism of Step (2) Int 2 TS_D1 Int_D TS_D2 CH 2 NH 2 CN TS_In1 Int_In TS_In2 Direct pathway Indirect pathway TS_In1* TS_D2* J. Phys. Chem. C, 2008, 112, 2972.

15. 15 Mechanism of Step (2) in Microsolvation Cluster; Catalyst = Two H 2 O

16. 16 Mechanism of Step (2) in Microsolvation Cluster; Catalyst = Two NH 3

17. 17 Potential Energy Surface of Step (2) in Microsolvation Cluster ； Direct Pathway Black ： Uncatalyzed Green ： NH 3 Blue ： H 2 O One catalyzed molecule Two catalyzed molecules

18. 18 Potential Energy Surface of Step (2) in Microsolvation Cluster ； Indirect Pathway Black ： Uncatalyzed Green ： NH 3 Blue ： H 2 O One catalyzed molecule Two catalyzed molecules

19. 19 Potential Energy Surface of Step (2) with two ammonia molecules in SCRF Model Black ： Gas phase Purple ： PCM Red ： SMD Indirect Pathway Direct Pathway

20. 20 Dash-line ： direct pathway Solid-line ： indirect pathway Without parentheses ； MP2/6-31+G(d,p) With parentheses ： CCSD(T)/aptz//MP2/6-31+G(d,p) unit ： kcal/mol

21. 21 Conclusions 1.We investigated the prebiotic synthesis of glycine from CH 2 O, NH 3 and HCN, and simulated the solvent effect by microsolvation cluster and SCRF model (PCM and SMD). 2.Microsolvation cluster played an important role in proton relay mechanism. 3.In most cases, SCRF model predicted lower energy barriers. 4.In step one, we used two water molecules as the most effective catalyst. The result showed that it left an energy barrier about 45 kcal/mol in uncatalyzed reaction and 17 kcal/mol in two water molecules catalyzed reaction. In SMD model the energy barrier was 11 kcal/mol in two water molecules catalyzed reaction. 5.In step two, we used two ammonia molecules as the most effective catalyst. The result showed that it left an energy barrier about 43 kcal/mol in uncatalyzed reaction and 23 kcal/mol in two ammonia molecules catalyzed reaction. In SMD model the energy barrier was 12 kcal/mol in two ammonia molecules catalyzed reaction. 6.In the overall Strecker reaction, the reaction energy was exoergic about 56 kcal/mol.

22. 22 Thank you for your attention

23. 23 Supplement 1.Solvent effects 1.Microsolvation cluster 2.SCRF model 3.Hybrid model 2.Proton relay mechanism in step (2) 1.Proton relay mechanism 2.HCN tautomerization 3.HCN Tautomerization in step (2) 4.HCN Tautomerization with water molecules 3.Biosynthesis of Protein 1.Structure of DNA 2.Biosynthesis of Protein

24. 24 Solvent effects δ﹣δ﹣ δ+ Levien, I. N. Quantum Chemistry; 6th Ed.; Prentice-Hall International, Inc.: New York, 2009; pp553.

25. 25 Microsolvation cluster

26. 26 Self-consistent reaction-field model Reaction field Cavity Important physical components Electrostatic interaction Cavitation Changes in dispersion Changes in bulk slovent structure Poisson equation Cramer, C.J. Essentials of computational chemistry: theories and models; 1st Ed.; John Wiley& Sons Ltd, England, 2002, pp347.

27. 27 Hybrid model Microsolvation cluster SCRF model

28. 28 Proton Relay Mechanism Uncatalyzed reaction Reaction with two water molecules as catalyst TS_In1: 34.3 kcal/mol TS_In1: 29.3 kcal/mol TS_In1*: 35.8 kcal/mol TS_In1 *: 37.7 kcal/mol

29. 29 HCN Tautomerization 0 Method ： CCSD(T)/aptz//B3LYP/6-31+G(d,p) energy unit ： kcal/mol, bond length unit ： angstrom Relative energy 47 15

30. 30 HCN Tautomerization in Step (2) Relative energy 34.3 28.6 35.8 29.3 37.7 Method ： MP2/6-31+G(d,p) energy unit ： kcal/mol, bond length unit ： angstrom

31. 31 HCN Tautomerization with Water Molecules Relative energy 45.3 28.7 24.0 22.1 51.7 Relative energy Method ： MP2/6-31+G(d,p) energy unit ： kcal/mol, bond length unit ： angstrom

32. 32 Structure of DNA rRNA

33. 33 Biosynthesis of Protein DNA mRNA amino acid polypeptide protein tRNA ribosome Translation Transcription cell nucleus Garrett, R.H.; Grishman, C.M.; Biochemistry; 4rd Ed.; Thomsom Learning: Singapore, 2005;pp837 Wikipedia