Density functional calculations at LSD. NLSDl6-3lG*. DZVP2 levels were performed on asoles. arines and their protona~edfonns. Geometries and dipole moments were well described by both global bases.
Energies obtained at NLSD(BP)IDzVP2 level are reasonably comparable with high level ab initio and experimental data. For atomic charges, LSD16-31Gf level gave acceptable results.
Studies on protonation of heterocyclic compounds are of great interest from not only chemical but also pharmacological points of view. The reactivity of a heterocyclic base caused by protonation may vary in characteristic way. Thus, the site of protonation is closely related to expression of biological activity and often involved directly in receptor-ligand interactions in biological systems. We have been highly motivated in these fields as being continuously interested in the mechanistic and medicinal chemistry of nitrogen heterocycles.
Recently, semiempirical,2-5 and ab iniri&8 studies on azoles and azines have been carried out in order to get quantitative and predictive tools for studying their proton affinity,9 by which more insight into their basicities can be available. Of semiempirical procedures, the AM1 method failed to treat correctly the electrostatic proximity effects,5 operating in the relative basicities and acidities of 1,2-azoles and -diazines.lo Although empirical corrections were proposed to eliminate this defect,4 further examinations seem to be necessary for proving general validity. INDO was found to be a qualitatively better approach in spite of relatively large deviations.
The experimental proton affinities could he reproduced in the correct order by high-level ab inifio calculations, nevertheless, M$ller-Plesset correlation treatment had to also be included to get approximate numerical values after taking the zero-point vibrational energy change with other energy terms into consideration.7 However, ab initio calculations at high level are seriously limited by the enormous computational efforts required for polysubstituted molecules, the ordinary building blocks found in the synthetic chemistry. In this context, an alternative method, which is computationally more effective but not at the expense of accuracy, is really needed.