LAUSR

Acidity changes of p-aminobenzoic acid (pABA) after π-stacking with substituted benzenes (SB) have been investigated using quantum mechanical calculations at the M06-2X/6-311++G(d,p) level of theory. In addition to benzene derivatives that are usually used as a model for aromatic amino acids (AA), two amino acids, tryptophan (TRP) and histidine (HIS), with different cyclic structures were also considered in this work. All substituents enhance the stacking interactions, in which enhancement is higher for electron-withdrawing substituents (EWSs). The stacking interaction (in presence of all substituents) enhances the acidity (3.42 for Br). Natural energy decomposition analysis (NEDA) shows that the polarization interactions (POL) have the largest contribution in the binding energies (ΔE) of neutral and anionic complexes, while the electrostatic effects (ES) are in better correlation with ΔE. The ΔE values are linearly dependent on the sum of electron densities (Σρ BCP ) calculated at the bond critical points (BCPs) between the rings and the Σρ RCP values calculated at the ring critical points (RCPs) in the neutral and anionic SB||pABA complexes. An excellent correlation was found between the ΔE values and a combination of electrostatic (σ meta ), resonance/induction (σ para ), and dispersion/polarizability (molar refractivity, MR) substituent constant terms. There are good relationships between pK a and the global minimum and maximum of electrostatic potential around the O (∑V min-O ) and H (V max-H ) atoms, and the results of natural population analysis (NPA). Therefore, the electrostatic and charge transfer effects play a major role in acidity.