Abstract
The gasโphase geometries of neutral, protonated, and deprotonated forms of some biologically important molecules, alanine (Ala), glycine (Gly), phenylalanine (Phe), and tyrosine (Tyr), were optimized using density functional theory at B3LYP/6โ311++G(d) and the ab initio HF/6โ311++G(d) level of theories. The neutral and different stable ionic states of Ala, Gly, Phe, and Tyr have also been solvated in aqueous medium using polarizable continuum model for the determination of solvation free energies in the aqueous solution. The gasโphase acidity constants of above four molecules have been also calculated at both levels of theories and found that the values calculated at HF/6โ311++G(d) method are in good agreement with experimental results. A thermodynamic cycle was used to determine the solvation free energies for the proton dissociation process in aqueous solution and the corresponding p__K__~a~ values of these molecules. The p__K__~a~ values calculated at B3LYP/6โ311++G(d) method are well supported by the experimental data with a mean absolute deviation 0.12 p__K__~a~ units. Additionally, the chemical hardness and the ionization potential (IP) for these molecules have been also explored at both the level of theories. The Tyr has less value of chemical hardness and IP at both levels of theories compared with other three molecules, Ala, Gly, and Phe. The calculated values of chemical hardness and IP are decreasing gradually with the substitution of the various functional groups in the side chain of the amino acids. ยฉ 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011