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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

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ContentCh 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)

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ContentCh 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)

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Theoretical Study on the Prebiotic Synthesis of Glycine

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Biosynthesis of Glycine

(Intermediate of glycolysis)

3-PhosphoglycerateThree types of enzyme

Serine

Precursor of Glycine

Formation of Glycine

Garrett, R.H.; Grishman, C.M.; Biochemistry; 4rd Ed.; Thomsom Learning: Singapore, 2005;pp837

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Prebiotic synthesis of Amino Acid

O

R1 R2

KCN

NH4Cl

NH2

NR1R2

H+ NH2

R1

R2 OH

O

aldehyde or ketone £\-aminonitrile amino acid

﹡ ﹡

 Ann. Chem. Pharm. 1850, 75, 27.

•Strecker reaction

R1 = R2 = HAmino Acid = Glycine

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Complete Strecker Reaction in Neutralized Surrounding

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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

Gas phase(OPT)

SCRF model(SP)

Microsolvation cluster(OPT)

SCRF model(SP)

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Mechanism of Step (1)

TS 1 Int 1

TS 2

CH2O+NH3

CH2NH+H2O

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Mechanism of Step (1) in Microsolvation Cluster

Catalyst ： two water molecules

Catalyst ： two ammonia molecules

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Potential Energy Surface of Step (1) in Microsolvation Cluster

One catalyzed molecule Two catalyzed molecules

Black ： UncatalyzedGreen ： NH3

Blue ： H2O

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Proton Relay Mechanism•Uncatalyzed reaction

•Reaction with two water molecules as catalyst

0 kcal/mol

0 kcal/mol

29.9 kcal/mol 13.0 kcal/mol

4.6 kcal/mol 8.5 kcal/mol

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Potential Energy Surface of Step (1) with two water molecules in SCRF Model

Black ： Gas phasePurple ： PCMRed ： SMD

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Mechanism of Step (2)

Int 2

TS_D1

Int_D

TS_D2

CH2NH2CN

TS_In1

Int_In TS_In2

Direct pathway

Indirect pathway

TS_In1*TS_D2*

J. Phys. Chem. C, 2008, 112, 2972.

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

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

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Potential Energy Surface of Step (2) in Microsolvation Cluster ； Direct Pathway

Black ： UncatalyzedGreen ： NH3

Blue ： H2O

One catalyzed molecule Two catalyzed molecules

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Potential Energy Surface of Step (2) in Microsolvation Cluster ； Indirect Pathway

Black ： UncatalyzedGreen ： NH3

Blue ： H2O

One catalyzed molecule Two catalyzed molecules

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Potential Energy Surface of Step (2) with two ammonia molecules in SCRF Model

Black ： Gas phasePurple ： PCMRed ： SMD

Indirect PathwayDirect Pathway

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Dash-line ： direct pathwaySolid-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

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Conclusions1. 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).

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.

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Thank you for your attention

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Supplement

1. Solvent effects1. Microsolvation cluster2. SCRF model3. Hybrid model

2. Proton relay mechanism in step (2)1. Proton relay mechanism2. HCN tautomerization3. HCN Tautomerization in step (2)4. HCN Tautomerization with water molecules

3. Biosynthesis of Protein 1. Structure of DNA2. Biosynthesis of Protein

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Solvent effects

δ﹣

δ+

δ+

δ+

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

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Microsolvation clusterMicrosolvation cluster

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Self-consistent reaction-field model

Reaction fieldCavity

•Important physical componentsElectrostatic interactionCavitationChanges in dispersionChanges in bulk slovent structure

•Poisson equation

)r(4

)(2

r

Cramer, C.J. Essentials of computational chemistry: theories and models; 1st Ed.; John Wiley& Sons Ltd, England, 2002, pp347.

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Hybrid model

Microsolvation clusterSCRF model

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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

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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

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HCN Tautomerization in Step (2)

Relative energy

Relative energy

34.3 28.6

35.8

29.3

29.3 37.7

Method ： MP2/6-31+G(d,p)energy unit ： kcal/mol, bond length unit ： angstrom

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HCN Tautomerization with Water Molecules

Relative energy 45.3 28.7 24.0 22.1

51.7Relative energyMethod ： MP2/6-31+G(d,p)energy unit ： kcal/mol, bond length unit ： angstrom

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Structure of DNA

rRNA

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Biosynthesis of Protein

DNA mRNA

amino acid

polypeptide protein

tRNA

ribosomeTranslationTranscription

cell nucleus

Garrett, R.H.; Grishman, C.M.; Biochemistry; 4rd Ed.; Thomsom Learning: Singapore, 2005;pp837Wikipedia