Multi-level Quantum Mechanics And Molecular Mechanics Study Of The Reaction Of NH₂Cl+OH^- And The Reaction Of 8-OHGrad In Aqueous Solution

In contrast to reactions in gas phase, the solvent of the reactions in water alters the reaction barrier height and then alters the reaction rates. Furthermore, solvent molecules may take part in the solute reaction progress and change the reaction mechanism. Therefore, the study of the reaction process in water is of great value. However, taking the solvent into consideration makes the quantum calculation of reaction process quite unpractical due to sampling over a large number of degrees of freedom. Therefore, in this thesis, a multilayered quantum mechanics and molecular mechanics approach(CCSD(T)/MM, DFT/MM and ESP/MM) was employed to study two systems in water, to obtain the reaction pathways, barrier heights and reaction rates in high accuracy CCSD(T) level. The water was modeled by an explicit SPC/E solvent module. At the mean time, analysis and comparison was made between our results and gas phase results.The SN2 reaction at nitrogen: NH2 Cl + OH- → NH2OH+Cl- in water was introduced firstly with two exchange-correlation functionals in quantum calculation region both of which will be shifted from DFT to CCSD(T) level in this thesis. It was the first time for this reaction system to be studied in water theoretically. The obtained activation barriers at DFT/MM level of theory yielded a big difference at 21.8 kcal/mol under B3 LYP and 27.4 kcal/mol under M06-2X functional respectively. When shifted from DFT to CCSD(T) level, the barrier heights became very close: 22.4 kcal/mol under CCSD(T)(B3LYP)/MM and 22.9 kcal/mol under CCSD(T)(M06-2X)/MM levels of theory. The free reaction energy obtained under CCSD(T)(M06-2X)/MM showed excellent agreement with the one estimated with gas phase related data. In all, it was necessary to apply the CCSD(T) level calculation in theoretical studies. Water solution also played a significant role in reshaping the reaction profile, and water solvent contributed 13.3 kcal/mol and 14.6 kcal/mol to barrier heights under CCSD(T)(B3LYP)/MM and CCSD(T)(M06-2X)/MM levels respectively. Also, this SN2 reaction at nitrogen reacted faster than the corresponding reaction at carbon.The second system calculated in this thesis was the water assisted hydrogen transfer reaction of the adduct of hydroxyl radical and guanine—8-OHGrad. We optimized the reactant, transition state and product geometries; calculated the minimum energy pathways; analyzed the charge distribution along the reaction revolution and calculated the water contribution to the reaction under MPWB1K/aug-cc-pVDZ level. The calculation results showed that the reaction energy of the water-assisted hydrogen transfer of 8-OHGrad radical was 15.8 kcal/mol, which was much lower than the gas phase value. The water polarization effect to solute increased the barrier height by 12.85 kcal/mol and the solvation energy lowed the barrier height by 24.7 kcal/mol. Combining the two effects, the water contribution lowed the reaction barrier height by 11.91 kcal/mol, so we can say that the water solvent accelerated the reaction rate.