Unveiling the reactivity of truxillic and truxinic acids (TXAs): deprotonation, anion…H–O, cation…O and cation…π interactions in TXA0…Y+ and TXA0…Z− complexes (Y = Li, Na, K; Z = F, Cl, Br)

Herein, we report a quantum chemistry investigation of the interaction between µ-truxinic acid, referred to as TXA ⁰, and Y ⁺ (Y = Li, Na, K) and Z ⁻ (Z = F, Cl, Br) ions using M06-2X, B3LYP and ω B97XD functionals in conjunction with the 6–31 + + G(d,p), aug-cc-pVDZ(-X2C) and 6–311 + + G (d, p) basis sets. Our computations suggest that Y ⁺ cations can bind to TXA ⁰ through several combinations of cation…O and cation-π interactions, while Z ⁻ anions generally establish anion…H–O contacts. Predicted binding energies at the M06-2X/6–311 + + G(d,p) level range between − 26.6 and − 70.2 kcal/mol for cationic complexes and − 20.4 and − 62.3 kcal/mol for anionic ones. As such, TXA ⁰ appears as an amphoteric molecule with a slight preference for electrophilic (cation.. O) attacks. Furthermore, the most favourable binding site for cations allows for the formation of O…cation…O interactions where the cation is trapped between O37 and O38 atoms of TXA ⁰. Anions do not behave uniformly towards TXA ⁰: while the fluoride anion F ⁻ induces the deprotonation of TXA ⁰, Br ⁻ and Cl ⁻ do not. All of these structural insights are supported by topological calculations in the context of the quantum theory of atoms in molecules (QTAIM). Finally, SAPT0 analyses suggest that TXA ⁰…Y ⁺ and TXA ⁰…Z ⁻ complexes are mainly stabilized by electrostatic and inductive effects, whose combined contributions account for more than 60 percent of the total interaction energy.