The effect of anion-π interactions on the properties of pyrazinamide and some related compounds

Abstract

The effects of anion-π interaction on the protonation tendency and amide functional group properties of pyrazinamide (PZA) and related compounds have been investigated by the quantum mechanical methods. The pyrazine ring were replaced by pyrimidine and triazine rings in order to investigate the effect of second and third nitrogen heteroatoms and their positions on the amide functional group. The increase in the number of nitrogen heteroatoms of the ring rises the anion-π interaction energy. Thermodynamic properties calculated in the water solvent by the SCRF continuum solvation method using the IEF-PCM model, confirm the decrease in the proton affinity and basicity with solvation, while the anion-π interactions increase those in both gas phase and solvation media. The effect of anion type, via the anion-π interaction, on the basicity is approximately negligible. Well-defined relations are established between the anion-π interaction energies ΔE and the valence natural orbital energies ∑NAO of protonated site, charge transfer between two units and the minimum value of electrostatic potential Vmin around the oxygen atom. In addition, linear relationships are observed between the ΔE value and the distance between anion and the center of heterocyclic ring (ranion···π), the topological properties of electron charge density ρ and the 1H NMR absolute shielding constant (δ1 H) of proton. In agreement with the ΔE changes, the effects of second and third heteroatoms are additive on the charge transfer Δq, |∑NAO| and proton affinity.