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Theoretical Study of Solvent and Substituent Effects on Kinetic and Mechanism of Organic Reactions and Theoretical Study of Enzyme Reactions

Irani, Mehdi | 2010

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 40817 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Gholami, Mohammad Reza
  7. Abstract:
  8. Computational chemistry is used to study solvent and substituent effects on kinetics and mechanism of some organic reactions. It also is used to study enzyme reactions and enzyme structures. Organic reactions were studied by ab initio quantum mechanics and Monte Carlo simulations. The enzyme studies were done by QM/MM and MD methods in Lund University. The studied organic reactions are 1) Reactions of hydroxylamine and aminoxide anion with methyl iodide. 2) Rearrangement of allyl p-tolyl ether. 3) Reactions of 1,4-Benzoquinone with Cyclopentadiene and Cyclohexadiene derivatives and reaction of cyclopentadiene and vinyl acetate. In the enzyme studies the catalytic reaction of Glyoxalase enzyme and effect of oxidation of some residues on Lipase B structure and active site were studied. The rate of the reaction of methyl iodide with amine oxide anion is strongly affected by water solvent. The Monte Carlo method simulates this phenomenon very well. Ab initio calculation showed that the methyl iodide reactions proceed via a SN2 mechanism. Also, the ab initio calculations showed that the TS structure of these reactions is depended to the activation energy. In another word the structure of the TS moves to the products by increasing activation energy. Ab initio calculations showed that rearrangement of allyl-p-tolyl ether has a Clisen mechanism and the mechanism is concerted asynchronies. The PCM solvent model couldn’t show the order of rate enhancement of this reaction in various solvents. Then it was concluded that the rate enhancement of this reaction in protic solvents is related to the special properties of solvents which is not implemented in the PCM solvent model. By optimizing a water molecule in reaction media the expected rate enhancement of the reaction was seen and it was concluded that rate enhancement of this reaction in water solvent is due to hydrogen bonding effect of the solvent. The ab initio calculations showed that the reason of the rate enhancement of Diels-Alder reactions in protic solvents by closing of electron donor groups to frontier carbon atoms and adding electron donor groups on diene is moving of negative charge to the hydrogen bond acceptor atoms in TS. The calculations showed that the hydrophobic effect of protic solvents affects the rate of these reactions, but this effect is not as important as hydrogen bonding effect. The Monte Carlo simulation showed that for reaction of vinyl acetate with cyclopenta diene in mixture of methanol and water vapors the reactants and transition state are solvated by water molecules. QM/MM calculations on glyoxolase I enzyme showed that the S enantiomer of substrate has a faster reaction than the R substrate and S enantiomer results D-Lactate product. The calculations showed a different mechanism for the R enantiomer but in the proposed mechanism, this enantiomer also gives the D-lactate product. MD simulations on Lipase B enzyme shows that oxidation of the special amino acids in the lipase don’t have big effect on the enzyme structure. While, the oxidation of Cys-Cys birdies strongly changes the local structure of the enzyme. The calculation showed that the oxidations rarely change the active site of the enzyme.

  9. Keywords:
  10. Solvent Effect ; Monte Carlo Method ; Molecular Dynamics ; Ab Initio Calculation ; Quantum Mechanics and Molecular Mechanics Calculation ; Enzyme Reaction

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