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

Department of Chemistry, University of Catania, viale A. Doria 6, Catania 95125, Italy.
Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy (Impact Factor: 1.98). 07/2011; 81(1):631-9. DOI: 10.1016/j.saa.2011.06.065
Source: PubMed

ABSTRACT 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 C=C(pyrimidine ring) stretch + C=N(pyrimidine ring) stretch, can be a useful vibrational marker to distinguish the neutral from the protonated forms.

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