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

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. 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. 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. Theoretical Study on the Prebiotic Synthesis of Glycine

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

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

7. Complete Strecker Reaction in Neutralized Surrounding

8. Gas phase (OPT) SCRF model (SP) Microsolvation cluster (OPT) SCRF model (SP) 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：H2O, NH3

9. Mechanism of Step (1) Int 1 TS 1 CH2O+NH3 TS 2 CH2NH+H2O

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

11. Potential Energy Surface of Step (1) in Microsolvation Cluster One catalyzed molecule Two catalyzed molecules Black：Uncatalyzed Green：NH3 Blue：H2O

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

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

14. Mechanism of Step (2) Direct pathway Int_D Int 2 TS_D1 Indirect pathway TS_In1 TS_In1* TS_D2* TS_D2 CH2NH2CN TS_In2 Int_In J. Phys. Chem. C, 2008,112, 2972.

15. Mechanism of Step (2) in Microsolvation Cluster; Catalyst = Two H2O

16. Mechanism of Step (2) in Microsolvation Cluster; Catalyst = Two NH3

17. Potential Energy Surface of Step (2) in Microsolvation Cluster；Direct Pathway One catalyzed molecule Two catalyzed molecules Black：Uncatalyzed Green：NH3 Blue：H2O

18. Potential Energy Surface of Step (2) in Microsolvation Cluster ；Indirect Pathway One catalyzed molecule Two catalyzed molecules Black：Uncatalyzed Green：NH3 Blue：H2O

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

20. unit：kcal/mol 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)

21. Conclusions • We investigated the prebiotic synthesis of glycine from CH2O, NH3 and HCN, and simulated the solvent effect by microsolvation cluster and SCRF model (PCM and SMD). • Microsolvation cluster played an important role in proton relay mechanism. • In most cases, SCRF model predicted lower energy barriers. • 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. • In step two, we used two ammoniamolecules 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. • In the overall Strecker reaction, the reaction energy was exoergic about 56 kcal/mol.

22. Thank you for your attention

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

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

25. Microsolvation cluster

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

27. Hybrid model Microsolvation cluster SCRF model

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

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

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

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

32. Structure of DNA rRNA

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