Calculations Of PK_a For The Amino Acids And The Racemization Rate Constants For ?-Amino Acids Using The Density Functional Theory

In this thesis the calculation methods of both the pK_a values for amino acids and the racemization rate constant(k_rac)values for?-amino acids are researched using the Density Functional Theory?DFT?.The main contents are as follows:1.The p K_a values for amino acids were calculated by the relative Gibbs free energy change method.The results indicate that:?1?The accuracy pK_a values for 65 amino acids can be obtained when 2-amino-2,2-difluoroacetic acid and Isoleucine are selected as two reference acids.The calculated results show that the maximum deviation and the standard deviation between the calculated and experimental values are-1.18 p K_a and 0.54 p K_a for the amino group,1.20 pK_a and 0.39pK_a for the carboxyl group,respectively.?2?The p K_a values of?-H for 20?-amino acids were calculated and obtained the accuracy results when Leucine and 2-amino-2-?3-nitro ph-enyl?acetic acid are selected as two reference acids.The maximum deviation and the standard deviation between the calculated and exper imental values are-0.38 pK_a,and 0.17 pK_a,respectively.?3?The influence of the base sets and solvent models on the calculated accuracy and the consuming time were investigated,which is found that the accuracy results can be obtained when the 6-311+G?d,p?basis set and CPCM solvent model are employed to calculate pK_a values for 65 amino acids.Nevertheless,for the p K_acalculation of?-H for 20?-amino acids the matching between 6-311G?d,p?basis set and PCM solvent model is a right choice to obtain accuracy results.2.The relationship between pK_a and the atomic charge descriptors was presented,and was used to calculate the pK_a for amino acids.?1?For 65 amino acids,the pK_a values of both the amino group and the carboxyl group were calculated using the NPA charge and the calculation results are satisfactory.Unfortunately,for the pK_a calculation of?-H for 20?-amino acids were not applicable by this method.It maybe?-H for?-amino acids don't have the property of the classical acids.?2?The influence of the base sets and solvent models on the calculated accuracy and the consuming time were investigated.For the pK_a of 65 amino acids,the 6-311+G?d,p?basis set and SMD solvent model were employed,which obtained a higher accuracy result by this method.The results show that the maximum deviation and the standard deviation between calculated and experimental values are-1.50 pK_a and0.61 p K_a for the amino group,1.21 pK_a and 0.40 p K_a for the carboxyl group,respectively.3.The work in this partis original,i.e.,we have presented a novel procedure,by which the dynamic property?the racemization rate constants for?-amino acids?can be predicted by the thermodynamic property?Gibbs free energy change calculated from DFT?.By means of this method the calculation of k_racac for 20?-amino acids were performed under the DFT/B3LYP/6-311+G?d,p?,and the results are consistent with the expected.The maximum deviation and the standard deviation between the calculated and experimental values are 0.60 log(k_rac)and 0.27 log(k_rac)in gas phase,-0.38 log(k_rac)and 0.17 log(k_rac)in aqueous phase,respect ively,when Leucine and 2-amino-2-?3-nitrophenyl?acetic acid were selected as two reference acids.Therefore,the relative Gibbs free energy change method and the atomic charge descriptor method are simple,fast,effective and high-precision theoretical methods,by which some amino acid parameters such as pK_a,k_rac can be accurately calculated using DFT.