Spectroscopic properties of neuroleptics: IR and Raman spectra of Risperidone (Risperdal) and of its mono- and di-protonated forms

Structures and IR and Raman spectra of Risperidone in its neutral, mono- and di-protonated forms were calculated in gas phase by DFT-B3LYP/6-31G* level. Mono-protonation occurs at the nitrogen atom of the piperidine ring, while nitrogen atom of the pyrimidine ring is the preferred site for the second protonation. The lowest-energy structure of the mono-protonated Risperidone is characterized by formation of a strong seven-membered O(pyrimidine ring)⋯+H–N(piperidine ring) intramolecular hydrogen-bonded cycle. In the high-energy spectral region (3500–2500 cm−1), the bands of the N–H+ stretches and the changes in wavenumbers and IR intensities of the C–H stretches near to the piperidine nitrogen atom (Bohlmann effect) are potentially useful to discriminate conformations and protonation states. Di-protonated structures can be identified by the presence of an isolated absorption peak located in the low-energy IR region (660–690 cm−1), attributed to the out-of-plane N–H+(pyrimidine ring) bending deformation. The most intense Raman band of neutral Risperidone placed at ca. 1500 cm−1, assigned to CC(pyrimidine ring) stretch + CN(pyrimidine ring) stretch, can be a useful vibrational marker to distinguish the neutral from the protonated forms.

Graphical abstractMolecular structures of neutral, mono- and di-protonated Risperidones.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights• We simulate IR and Raman spectra of neutral, mono- and di-protonated Risperidones. • We used DFT-B3LYP/6-31G* level of calculation. • We identify vibrational markers useful to distinguish different protonation states.