Vibrational study of riluzole hydrochloride, a drug used for the treatment of amyotrophic lateral sclerosis (ALS) by using DFT calculations and the SQM methodology

FLORENCIA LADETTO; MAXIMILIANO IRAMAIN; ELIDA ROMANO; SILVIA A. BRANDÁN

Viena

Conferencia; 8th International Conference on Advanced Vibrational Spectroscopy (ICAVS8); 2015

Technische Universität Wien

Benzothiazole derivatives present a wide range of biological activities1 and, in particular, riluzole is the first drug used for the treatment of patients with ALS2 and whose chemical name is the 2-amino-5-(trifluoromethoxy) benzothiazole derivative. The mechanisms by which riluzole exerts neuroprotective effects and their biological properties were evaluated and reported by different authors3 but the vibrational studies and the complete assignments of their vibrational spectra, so far, were not published. In this context, the aims of this work are: (i) to perform the complete assignment of the bands observed in the infrared spectrum by combining the available experimental infrared spectrum of riluzole hydrochloride with density functional theory (DFT) calculations, the internal symmetry coordinates and a generalized valence force field (GVFF)4 and (ii) to predict their Raman spectra at the same level of theory.The comparisons between the experimental infrared spectra with the corresponding theoretical show a reasonable agreement. In addition, the force constants of riluzole hydrochloride were also reported at the same level of theory.The initial structure of riluzole hydrochloride was modeled with the GaussView program5 and then optimized by the Gaussian program6 at the B3LYP/6-31G* theory level. Figure 1 show the optimized structure of riluzole hydrochloride with the labeling of the atoms. The harmonic force field for riluzole hydrochloride was evaluated at the B3LYP/6-31G* level using the SQMFF procedure4 with the Molvib program.7 This program was also employed to transform the resulting force fields to ?natural? internal coordinates. The natural internal coordinates for riluzole hydrochloride were defined as those reported for compounds with similar groups.8-10 Thus, the complete assignment was then performed, taking into account the resulting SQM and the potential energy distribution components (PED)  10%.The optimized riluzole hydrochloride structure has C1 symmetry and 60 normal vibration modes while riluzole has 54 vibration normal modes, which are all active in both vibrational spectra. Then, the predicted infrared spectra of riluzole8 and, of riluzole hydrochloride were compared at the same level of theory.The calculated harmonic vibrational frequencies for riluzole hydrochloride are consistent with the observed infrared spectra.The predicted Raman Spectrum and the SQM force fields for riluzole hydrochloride in in gas phase were reported.The comparison between the infrared spectra experimental and theoretical of riluzole and riluzole hydrochloride show changes in the positions and intensities of some bands, as expected due to the presence of the H and Cl atoms in riluzole hydrochloride.