Structural and vibrational characterization of di-hydrated hydrochloride tacrine combining DFT with SQMFF approach

This research is a continuation of previously reported article on anhydrous freebase, cationic and hydrochloride tacrine. Here, structures and properties of di-hydrated species of cholinesterase inhibitor tacrine have been studied in gas phase and aqueous solution by using B3LYP/6-311G* and wB97XD/6-311G* levels of theory. Both methods show strong changes in the positions of two water molecules and similar solvation energies (−192.52 kJ/mol with the B3LYP method and −191.95 kJ/mol with the other one). The B3LYP method predicts low gap values for the anhydrous (2.4572 eV) and di-hydrated (3.2708 eV) species of tacrine in gas phase than the wB97XD/6-311G* method (7.2300 eV). Hence, higher reactivities are expected for the di-hydrated species in both media. Atoms in molecules (AIM) calculations support the lower stability of di-hydrated species in solution in agreement with its higher reactivity in this medium. Complete assignments of 104 vibration modes expected for di-hydrated hydrochloride by using the scaled mechanical force field (SQMFF) methodology have been reported. Both methods predict different assignments and scaled force constants presenting higher values those calculated with the wB97XD/6-311G* method. The predicted IR, Raman and 1H NMR spectra with both methods show good correlations with the corresponding experimental ones, however, better concordances between the 13C NMR and UV spectra are observed with the wB97XD/6-311G* method.