Normal internal coordinates, force fields, and vibrational study of species derived from antiviral adamantadine

Complete vibrational assignments have been performed for free base, cationic, and hydrochloride species derived from antiviral adamantadine by a combination of hybrid B3LYP with the 6-31G* and 6-311++G** basis sets and the scaled quantum force field methodology. Normal internal coordinates and scaling factors were used to obtain the harmonic force fields and scaled force constants of three species in gas phase and in aqueous solution. Bond lengths and angles of cationic and hydrochloride species show very good concordances with experimental amantadinium azide. The cationic species reveals a higher solvation energy value compared with antiviral agents; however, brincidofovir, the antiviral used for Ebola disease, presents a higher reactivity in contrast to adamantadine. A positive value of Mulliken charge on N1 of hydrochloride species in solution could justify the ionic character of the H29 center dot center dot center dot Cl30 bond as it is possible to observe by bond order and atoms in molecules calculations. The hydrochloride species is the most reactive in both media, while the cationic species is the least reactive. High electrophilicity and nucleophilicity indices of cationic species in both media justify its higher hydration. Good concordances were observed between experimental and predicted(1)H and(13)C NMR and electronic spectra. In solution, the three species are present as demonstrated by the experimental ultraviolet-visible spectrum of hydrochloride amantadine.

Automated summary

Vibrational assignments for various species derived from antiviral adamantadine were successfully completed using a combination of computational methods. The hydrochloride species showed the highest reactivity in both gas phase and aqueous solution, while the cationic species exhibited the lowest reactivity. Good concordance was observed between experimental and predicted results.