IR, Raman, SERS and DFT study of paroxetine I.B. Cozar, L. Szabó, D. Mare, N. Leopold, L. David, V. Chis ß ⇑ Faculty of Physics, Babes ß-Bolyai University, Koga ˘lniceanu 1, 400084 Cluj-Napoca, Romania article info Article history: Available online 21 December 2010 Keywords: IR Raman SERS DFT Paroxetine abstract Structural investigations by different vibrational spectroscopic methods (FTIR, Raman and SERS), as well as density functional theory (DFT) calculations were performed on paroxetine (IUPAC name: (3S,4R)-3- [(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine. After the identification of the lowest energy conformer of the investigated molecule, the FTIR, FT-Raman and SERS spectra were assigned on the basis of DFT calculations at B3LYP/6-31G(d) level of theory. The very good correlation found between experimental and theoretical data is a clear evidence for a reliable assignment of the vibrational bands. The molecular electrostatic potential was calculated and used for the prediction of preferred adsorption sites of the paroxetine molecule on the silver nanoparticles surface. Based on SERS spectra analysis it is shown that the molecule is adsorbed on the silver surface through the benzodioxol ring, in a tilted orientation. Ó 2010 Elsevier B.V. All rights reserved. 1. Introduction Structural investigations on compounds of biomedical and pharmacological interest are increasingly reported in the last years in the scientific literature. For this goal, experimental methods like FTIR, Raman, SERS, NMR and quantum chemical calculations based on density functional theory (DFT) were successful used [1–5]. Thus, the structural characterization of paroxetine (3S,4R)-3- [(1,3-benzodioxol-5-yloxy)methyl]-4-(4-fluorophenyl)piperidine, a selective serotonin reuptake inhibitor antidepressant is welcome in this context. Paroxetine (Fig. 1) is used to treat major depression, obsessive–compulsive, panic, social anxiety, and generalized anxi- ety disorders in adult outpatients [6–8]. The structures of (3R,4S)- and (3S,4R)-4-(4-fluorophenyl)- 3-hydroxylmethyl-1-methylpiperidine compounds, which are intermediates in the synthesis of paroxetine and femoxetine pharmaceuticals, were studied previously by vibrational circular dichroism (VCD) spectroscopy [9]. X-ray structure of paroxetine hydrochloride salt has been reported [10–12] being shown that it exists in a non-hygroscopic hemihydrate form, thermodinamically the most stable, or a hygroscopic anhydrate form, the last one con- verting to form one when exposed to humid conditions or when compressed. b-Cyclodextrin inclusion complexes of paroxetine were produced as way of enhancing its chemical stability and solu- bility and have been quite recently investigated by Caira et al. [13]. The structural investigations by vibrational spectroscopic meth- ods (FTIR, Raman and SERS), as well as density functional theory (DFT) based calculations performed on paroxetine molecule are re- ported in this paper. To the best of our knowledge, assignment of the normal vibrational modes of paroxetine based on IR and Raman spectroscopies coupled with quantum chemical calculations has not been done so far. Raman scattering offers important structural information mak- ing it a powerful molecular investigation tool. When the molecules are adsorbed to rough metal surfaces the Raman cross section is enhanced several orders of magnitude and analytes in the micro- molar concentration can be investigated [14]. The potential to combine high sensitivity with the structural information content of Raman spectroscopy makes SERS spectroscopy a powerful tool in a variety of fields including biospectroscopy [15]. For a proper understanding of the IR and Raman spectra a reli- able assignment of all vibrational bands is essential. DFT calcula- tions, particularly those based on hybrid functional methods [16] have evolved to a powerful quantum chemical tool for the determi- nation of the electronic structure of molecules. In this framework, the B3LYP hybrid exchange–correlation functional is one of the most used since it proved its ability in reproducing various molec- ular properties, including vibrational spectra. The combined use of B3LYP functional and standard split valence basis set 6-31G(d) has been previously shown [16,17] to provide an excellent compromise between accuracy and computational efficiency of vibrational spectra for large and medium-size molecules. 2. Experimental 2.1. Methods The FTIR spectrum of paroxetine powder sample was recorded at room temperature on a conventional Equinox 55 (Bruker, 0022-2860/$ - see front matter Ó 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2010.12.020 ⇑ Corresponding author. Tel.: +40 264 405300; fax: +40 264 591906. E-mail address: vasile.chis@phys.ubbcluj.ro (V. Chis ß). Journal of Molecular Structure 993 (2011) 243–248 Contents lists available at ScienceDirect Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc