Estimation Of The Hydroxyl And Carboxyl Molecular PK_a Values By Using ABEEMσπ Method

In a living body,proton dissociation or acceptance is a fundamental process,which plays an important role.pKa is a physical quantity that is used to discribe ability of dissociation or acceptance of a proton in an aqueous solution.Atomic charge is also an important physical quantity which used by chemists to discuss the properties of molecules.In this paper,a series of molecules and their ions are selected which contain hydroxyl group,thiol group or carboxyl group.The relationship between charge and pKa is discussed,and the linear equations are obtained between the atomic charge of different series molecules and the known experimental pKa values.The pKa values of these compounds are estimated by using this equation,and the estimated results are in good correspondence with the experimental values or the pKa values calculated by other researchers.The contents are as follows:1.The relationship between atomic charges which are calculated by ab initio method and pKa values.Gaussian09 package and B3LYP/6-311++G(d,p)method are used to optimize molecular structures and ionic structures which contain hydroxyl,thiol and carboxyl groups and to obtain their stable structures.Mulliken charges and NBO charges of molecules and ions which contain hydroxyl group or thiol group are calculated by HF/STO-3G,HF/6-31G,HF/3-21G methods,respectively.In the gas and liquid phase,whether it is the molecular state or ionic state,the charges of some atoms in the molecules calculated by the HF/STO-3G have a good linear relationship with the pKa values.2.The relationship between ABEEMσπ charges and pKa values.ABEEMσπ parameters have been calibrated through a regression and least-square optimization procedure to reproduce HF/STO-3G charge distribution via a Mulliken population analysis for hydroxyl and carboxyl and ions with carboxyl.ABEEMσο charges are calculated by these new parameters and previous parameters.We explore that the ABEEMσπ charges and the experimental pKa values have a certain linear relationship.Then their linear equation is used to estimate the pKa values of these molecules by the charges which are calculated by the ABEEMaσπ method and linear equations.3.The estimated pKa values of compounds with hydroxyl group or carboxyl group were in agreement with the experimental values and other research groups.The study includes 12 small molecules with hydroxyl group,one Tyr dipeptides,six Ser dipeptides,protonated and neutral Trp-cage proteins(including 304 atoms).The pKa values of the above mentioned research systems are estimated by the method described above.The estimated results are very close to the experimental values of pKa,especially for the pKa values of amino acid residues of the Trp-cage protein.The predicted result is Tyr3>Ser13>Ser14,which is in agreement with the result which Toru and his coworkers use the solvation free energy method to calculate the pKa.We also explore to estimate pKa values of residues of protein lysozyme(1960 atoms),and the estimated pKa values related to the position of hydrogen atoms,which can provide the certain basis for the more reasonable protein structure.The charges of the atoms in a compound are calculated fast and accurately by ABEEMσπ theory,and it can estimate values through the relationship between charge and pKa.