Vibrational Study of Mono and Diprotonated Species of Potent Anti-acid Ranitidine Hydrochloride Combining DFT with SQMFF Calculations

Abstract

Structural and vibrational studies of mono (M) and diprotonated (D) species of ranitidine hydrochloride (RH) have been performed by combining B3LYP/6-31G* calculations with the scaled quantum mechanical force field (SQMFF) methodology. Four M structures in the gas phase and aqueous solution and two D E/Z and Z/E isomers in solution were considered. The M and D free base, cationic, and hydrochloride species show higher dipole moment values and expansion of volumes in solution, while higher solvation energies are predicted for both D (E/Z) and (Z/E) species. NBO and AIM studies suggest high stabilities of D (Z/E) cationic and hydrochloride species in solution. Gap values show that the M and D species are the most reactive in both media. M and two D forms were completely assigned, and their force constants were reported. The D hydrochloride (E/Z) form shows two IR bands at 2718 and 2625 cm-1 assigned to νN6-H34 and νN5-H44 stretching modes where the formation of O3-H34···N6 bond justifies the strong shifting of N6-H34 stretching mode towards lower wavenumbers. The IR bands at 2563, 2515, and 2475 cm-1 assigned to the two D species, together with the absence of an intense band at 1764 cm-1, show clearly that M species is not present in the solid phase, but the two D hydrochloride (E/Z) and (Z/E) species.