Studies Of Several Reactions In Solution Using Multi-level Quantum Mechanics And Molecular Mechanics Method

Bimolecular nucleophilic substitution reactions have been widely studied in gas phase,but in reality,many bimolecular nucleophilic substitution reactions occur in aqueous solution.The results of bimolecular nucleophilic substitution reaction in simple gas phase environment can't be simply extended to liquid phase environment,and many bimolecular nucleophilic substitution reactions in aqueous solution have not been systematically studied.Therefore,we want to study the mechanisms of several bimolecular nucleophilic substitution reactions in aqueous solution.Compared with the reaction in gas phase,in aqueous solution,the whole reaction environment is very different from the gas phase environment because of the existence of water solvent molecules,which even directly participate in the reaction process.For example,the participation of the water molecules can induce a transition state in aqueous solution.Besides the bimolecular nucleophilic substitution reactions,the existence of water molecules affects the chemical reaction process and even changes the reaction mechanism.Thus,it is very meaningful to study the reaction system in aqueous solution.Therefore,we choose to study the process of bimolecular nucleophilic substitution reaction or related reactions in aqueous solution.However,compared with the simplicity of the gas phase,the existence of water solvent molecules in aqueous solution will bring a lot of degrees of freedom to the calculation,so it is impossible to directly use the relatively accurate quantum mechanical(QM)method for the whole system.Therefore,in order to keep the accuracy of calculation as much as possible and to ensure the efficiency of calculation,we choose to use multi-level quantum mechanics(QM)and molecular mechanics(MM)methods(ESP/MM?DFT/MM?CCSD(T)/MM)to study several bimolecular nucleophilic substitution reactions in aqueous solution.In the course of the study,we used SPC/E water molecular model to simulate the aqueous solution to obtain the structural evolution of the solute part at the atomic level during the whole reaction process,to obtain the chemical reaction path at high accuracy,“golden standard”CCSD(T)level of theory,and to compare the results with the reactions in gas phase.Bimolecular nucleophilic substitution reaction in aqueous solution:for CN^-+CH₃F?CH₃CN+F^-reaction system,we calculate the reaction energy barrier height is 19.7kcal/mol at the DFT/MM theoretical level,consistent with the experimental results of 23.0kcal/mol;the calculated reaction free energy is-43.5 kcal/mol,which is consistent with the estimated reaction free energy-39.7 kcal/mol based on gas phase data and Born solvation model;this is also the first attempt to theoretically calculate the reaction system in liquid phase environment.For[X^-+CH₃Y,X=PH₂,HS;Y=F,Cl,Br,I]series of S_N2 reactions,the eight S_N2 reaction systems are calculated and compared at the theoretical levels of DFT/MM and CCSD(T)/MM.In addition to the bimolecular nucleophilic substitution reaction in aqueous solution,the chemical reaction process changes due to the presence of water molecules:for CO₂+OH^-?HCO₃^-reaction system,we selecte SPC/E model to simulate the aqueous solution environment,reveal the reason why water molecules participate in the induced transition state.The calculated free energy reaction barrier at CCSD(T)/MM level is 11.8 kcal/mol,which is consistent with the experimental measurement value 12.1 kcal/mol.For SH+OH^-?S^-+H₂O(SH=C₇H₇NO)reaction system,the reaction barrier 26.7 kcal/mol calculated at the level of CCSD(T)/MM is in strong agreement with the experimental value 27.3 kcal/mol.Furthermore,we plot the detailed NEB energy reaction path in aqueous solution for detailed analysis of the structural evolution process.In this article,we introduce the development of computational chemistry and the background of the thesis in chapter 1;the second chapter introduces the main theoretical methods used in scientific research;the third chapter introduces a series of S_N2 reaction studies on CN^-+CH₃F?CH₃CN+F^-and X^-+CH₃Y[X=PH₂,HS;Y=F,Cl,Br,I];the fourth chapter introduces the two reactions of CO₂+OH^-?HCO₃^-and SH+OH^-?S^-+H₂O(SH=C₇H₇NO)in in aqueous solution.The fifth chapter is summary and outlook.