Vibrational Study of Antiparasitic Nifurtimox Agent Combining Harmonic Force Fields with DFT Calculations

A theoretical study has been performed on the anti-chagasic nifurtimox agent (NFX), by using the hybrid B3LYP/6-311++G** calculations in the gas phase, DMSO and aqueous solution to characterize the structures and vibrational spectra. The most stable conformer predicted by calculations is in agreement with the experimental reported by X-ray diffraction with a higher solvation energy in aqueous solution (-134.81 kJ/mol) than in DMSO solution (-90.71 kJ/mol). A higher dipole moment and contraction of volume is predicted in aqueous solution probably due to the presence of strongly acceptors SO2 and NO2 groups of H bonds associated to the higher permittivity of water. Nucleophilic sites on the SO2 and NO2 groups are revealed by the mapped MEP surfaces with a higher energy value in water. The higher stability of NFX in solution is supported by NBO calculations while the frontier orbitals show that NFX is most reactive in both solutions than in the gas phase. Here, complete vibrational assignments of FT-IR and FT-Raman spectra in the three media have been performed by using the normal internal coordinates, the scaled mechanical force field (SQMFF) methodology and the Molvib program. The predicted NMR and Uv-vis spectra show good concordances with the corresponding experimental ones.