Rapid Prediction Of PK_a Values For Compounds Containing Amino Group

The extent of dissociation for ionic compounds in solution is reflected by the dissociation constant pKa.Also,atomic charge is a significant physical quantity of a molecule.In this thesis,a series of amino-containing molecules and cations have been chosen as the training sets.Furthermore,we have explored the linear relationship between group charges and experimental pKa values.We have obtained the linear equations between them.The equations have been used to estimate the pKa values of molecules containing amino group,amino acid,dipeptide and biomacromolecular protein.The predicted pKa values are in good linear relationship with the experimental values and other calculational results.The detailed contents are as follows.1.The relationship between ab initio Mulliken atomic charge and experimental pKa value.B3LYP/6-311++G(d,p)level of theory has been used to optimize the geometry structures of the amino molecules.We have investigate the relationships of the group charges with the experimental pKa values and obtained the linear equations.2.The relationship between ABEEM?? charge and pKa value.ABEEM?? tapes and parameters(valence state electronegativity ?*and hardness 2?*)are labeled and calibrated.ABEEM?? parameters have been used to calculate the atomic charges of the molecules mentioned aboue.The linear equations of qNH2 and qNc group charges,including with their corresponding experimental values are in order pKa=-26.5382qNH2+7.2558 and pKa=-32.1 670gNc+25.3496,respectively.3.The test sets are 44 small organic molecules 29 amino cations,23 dipeptides,and predicted with lysine residues of 7 proteins.Equations can be employed to predict the pKa values of the small organic moleacles,which are in good agreement with their experimental pKa values.For the amino acid dipeptides,what we can find is that pKa values can be affected by different spatial structures of the molecules and the intramolecular hydrogen bond.For lysine residues in 7LYZ,1NFN,and 1OMU proteins the amino group in the lysine residues present in the-NH3+ structure when the lysine residue located in the surface and outside of the protein the whose pKa value is in the range of 9.00-11.00.The linear equation of pKa=-32.1670qNc+25.3496 is used to calculate lysine residues.For the resides in the 2SNM and 1L54 proteins,the linear equation,pKa=-26.5382qNH2+7.2558,is used to calculate the pKa values whose values are less then 7.00,since lysine residues in proteins are folded and buried and they are neuteal.For the resides in the 2SNM and 1L54 proteins,if there are the hydrogen bond interaction,solt bridges and so on between the-NH3+ amino group in lysine resides and other atoms of the protein,the equation,pKa=-26.5382qNH2+7.2558,was carried out to estimate the pKa values of these residues,whose values are smaller than 7.00.The atomic charges of these systems mentioned above can be quickly and accurately calculated by using residues ABEEM?? model.Afterwards,the pKa value of the molecules containing the amino functional group can be quickly and exactly predicted by using the linear equations between the group charges and the pKa values.