Vibrational Spectroscopy 73 (2014) 45–55 Contents lists available at ScienceDirect Vibrational Spectroscopy jou r n al hom ep age: www.elsevier.com/locate/vibspec Raman and SERS study on ibuprofen metal complexes with biomedical interest Sergio Bonora a , Annamaria Pisi b , Stefano Ottani c , Daniele Cesini d , Assimo Maris e , Michele Di Foggia a,b,∗ a Dept. Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, via Belmeloro 8/2, 40126 Bologna, Italy b Dept. Agricultural Sciences - DipSA, University of Bologna, Viale Fanin 44, 40127 Bologna, Italy c CNR-ISOF, via Gobetti 101, 40129 Bologna, Italy d INFN-CNAF, viale Berti Pichat 6/2, 40127 Bologna, Italy e Dept. Chemistry “Giacomo Ciamician”, University of Bologna, via Selmi 2, 40126 Bologna, Italy a r t i c l e i n f o Article history: Received 13 January 2014 Received in revised form 28 April 2014 Accepted 29 April 2014 Available online 6 May 2014 Keywords: Ibuprofen Raman spectroscopy SERS Metal-complex DFT/CPCM calculation a b s t r a c t Ibuprofen is one of the most widely used non-steroidal anti-inflammatory drugs (NSAIDs), in which the carboxylate group is available for metal–ligand interactions. The most stable geometries for ibuprofen (in both its protonated and deprotonated forms) were identified by optimizations obtained by the unres- tricted Density Functional Theory (DFT). Theoretical study of ibuprofen interacting with Ag colloid in solution, led to two (for the protonated form) and three (for the deprotonated form) different optimized geometries, corresponding to different interaction sites of the Ag 2 cluster. Frequency calculations were performed in the limit of the harmonic approximation, using the aug-cc-pVDZ basis set. Interpretation of the theoretical Raman spectra was performed by the Potential Energy Distribution (PED) analysis of the fundamental vibrations modes. Raman study on the solid Ibuprofen-metal complexes confirmed that Co 2+ gives monodentate complexes, while Zn 2+ adopts a bidentate coordination. SERS spectra of metal complexes, suggested that at ppm concentration, the formation of stable 2:1 metal complexes is excluded, while is more probable the formation of 1:1 adduct with bidentate binding on the carboxylic group. The metal reaches its total coordination shell by complexation of water molecules. © 2014 Elsevier B.V. All rights reserved. 1. Introduction An important class of non-steroidal anti-inflammatory drugs (NSAIDs) is represented by carboxylic acids derivatives as Ibuprofen (IbuH, -methyl-4-(2-methylpropyl) benzenacetic acid; Fig. 1), which is widely used in the treatment of inflammatory and painful diseases of rheumatic and non-rheumatic origin [1–3]. Some stud- ies have suggested that regular ibuprofen intake might also be an effective chemopreventive agent against breast cancer [4] and could decrease non-small cell lung cancer growth in vitro [5]. The presence of the carboxylate group can lead to the setting up of metal–ligand interactions. The synthesis and study of metal com- plexes with an active drug as ligand is a research area of increasing interest for inorganic, pharmaceutical and medicinal chemistry, in ∗ Corresponding author at: Dept. Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, via Belmeloro 8/2, 40126 Bologna, Italy. Tel.: +39 0512094280. E-mail addresses: michele.difoggia2@unibo.it, micheled@chem.unibo.it (M. Di Foggia). new drug development. The goal is to prepare new compounds with better or different pharmacological profile than the free ligand or free metal. Zinc, a relatively abundant element in biological organisms, plays an essential role in a large number of enzymatic reactions. It exhibits anti-bacterial and antiviral activities, and it has been used as therapeutic agent in the prevention, for example, of pain crisis in sickle-cell disease and in treatment of various sicknesses [6–9]. Cobalt is a trace element present in the vitamin B 12 , one of the rare examples of a naturally occurring organometallic complex pos- sessing a metal-carbon bond (Co forms a complex with a glyoxime ligand). In the vitamin B 12 , a Co 3+ ion is stabilized by a chelating tetradentate macrocycle in which four nitrogen atoms are located in equatorial positions in an octahedral geometry. More recently, complexes of Co 3+ with organic ligands have been found to possess both antiviral and antibacterial activities [10]. IbuH as well as, in a greater extent, the anion Ibu (arising from deprotonation of IbuH) are strong chelating agent, acting as a monodentate or a bidentate ligand through carboxylate oxygens. The preparation of complexes of Ibu with some different metal http://dx.doi.org/10.1016/j.vibspec.2014.04.009 0924-2031/© 2014 Elsevier B.V. All rights reserved.