Spectroscopic and DFT studies of flurbiprofen as dimer and its Cu(II) and Hg(II) complexes

doi:10.1016/j.saa.2009.02.022

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Volume 73, Issue 1, July 2009, Pages 181-194

https://doi.org/10.1016/j.saa.2009.02.022 Get rights and content

Abstract

The vibrational study in the solid state of flurbiprofen and its Cu(II) and Hg(II) complexes was performed by IR and Raman spectroscopy. The changes observed between the IR and Raman spectra of the ligand and of the complexes allowed us to establish the coordination mode of the metal in both complexes. The comparative vibrational analysis of the free ligand and its complexes gave evidence that flurbiprofen binds metal (II) through the carboxylate oxygen. The fully optimized equilibrium structure of flurbiprofen and its metal complexes was obtained by density functional B3LYP method by using LanL2DZ and 6-31 G(d,p) basis sets. The harmonic vibrational frequencies, infrared intensities and Raman scattering activities of flurbiprofen were calculated by density functional B3LYP methods by using 6-31G(d,p) basis set. The scaled theoretical wavenumbers showed very good agreement with the experimental values. The electronic properties of the free molecule and its complexes were also performed at B3LYP/6-31G(d,p) level of theory. Detailed interpretations of the infrared and Raman spectra of flurbiprofen are reported. The UV–vis spectra of flurbiprofen and its metal complexes were also investigated in organic solvents.

Introduction

Flurbiprofen (FBF) {(R,S)-[2-(2-fluoro-4-biphenyl)]propionic acid} is a non-steroidal anti-inflammatory drug (NSAID) known by the trade name ANSAID and marketed by Pfizer used to treat rheumatoid arthritis, osteoarthritis, and mild to moderate pain [1]. It is a racemic mixture with presumed differential activities of the (−)-(S)- and (+)-R-isomers. The (S)-enantiomer of NSAIDs only exhibits pharmacological activity through the inhibition of the cyclooxygenase (COX) system, while an (R)-enantiomer is not only biologically inactive but also shows negative effects, such as gastrointestinal toxicity and chiral inversion [2]. The two polymorphic forms were identified by using thermoanalytical and spectral methods [3].

The crystal structure of flurbiprofen has been determined and hydrogen-bonded dimer units were found in the crystal [4]. Also, Yates et al. [5] have studied the theoretical NMR spectra of FBF using density functional theory (DFT) together with the gauge including projector augmented wave (GIPAW) method.

The investigation of vibrational spectra of some NSAIDs has been given by several researchers [6], [7], [8]. In our previous study, we have also investigated Raman and infrared spectra of Fenbufen, which is one of the NSAID's [9]. Firstly, the objective of the present work is to study theoretically the structural properties of FBF as a dimer using the density functional theory calculations and to investigate the vibrational properties using Raman and infrared spectroscopy. B3LYP/6-31G(d,p) level has been used to support our wavenumber assignments.

Many drugs possess toxicological and pharmacological properties modified using metal complexes and probably the most widely studied complexes in this respect contain the Cu(II) ion which has proved beneficial in many diseases such as tuberculosis, gastric ulcers, rheumatoid arthritis and cancers [10], [11], [12], [13]. A range of Cu complexes has been studied as anti-inflammatory agents, ranging from simple Cu salts to monomeric and dimeric Cu(II)–carboxylato complexes [14].

The toxicity of metals such as mercury on a biological system may result from blocking the essential functional group of the biomolecules. Hg(II) has also been used in medicine for many years [15]. Although a variety of complexes containing cupper(II) have been synthesized, only one study has been reported for the NSAID–Hg(II) complex [16]. In that study, Demertzi et al. [16] have reported the reactions of diclofenac with Zn(II), Cd(II) and Hg(II) in aqueous solutions. Secondly, in the present study, we report the synthesis and the characterization of a new mercury(II)–flurbiprofen complex. Although the synthesis and pharmalogical activity of Cu(II) metal complex of FBF has been studied [17], the structural determination is incomplete and conflicting. Therefore, we investigated it again experimentally by means of vibrational spectroscopy and electronic spectroscopy of the Cu(II) complex together with the Hg(II) complex of FBF. To better understand the structural and bonding characteristics of Cu(II) and Hg(II) complexes, a series of DFT calculation have been carried out.

Section snippets

Experimental

FBF in solid state was purchased from Sigma–Aldrich Chemical Company, USA and used as such without further purification to record FT-IR, FT-Raman and electronic spectra.

Structure of flurbiprofen dimmer

FBF molecule basically consists of two hexagonal rings and one propionic acid chair. In the CSD molecular structure database, two crystal structures of flurbiprofen, one in a monomer and one in a dimer form, are found (Cod name is FLUBIP) [25] (Fig. 1). The dimeric flurbiprofen contains hydrogen bonds between the two oxygen atoms of the carboxyl groups of two adjacent molecules [4]. There are several formal single bonds in the flurbiprofen, including that connecting the two aromatic rings,

Conclusions

The frequency assignments were performed for the first time from the FT-IR and the FT-Raman spectra recorded for the flurbiprofen dimer and its copper and mercury complexes. The theoretical DFT calculations of the vibrational spectra of the flurbiprofen presented in this paper were compared with the experimental vibrational spectra of the solid flurbiprofen dimer. Vibrational spectroscopic data support the formation of dimeric Cu(II) and Hg(II) complexes in which the COO⁻ group behaves as a

Acknowledgements

We would like to thank the Research Fund of Kocaeli University (2007/072) for financial support of this research. We wish to thank Baybars Koksoy for his valuable contribution.

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Spectroscopic and DFT studies of flurbiprofen as dimer and its Cu(II) and Hg(II) complexes

Abstract

Introduction

Section snippets

Experimental

Structure of flurbiprofen dimmer

Conclusions

Acknowledgements

J. Mol. Catal. B: Enzym.

Int. J. Pharm.

Chem. Phys.

J. Mol. Struct.

Vib. Spectrosc.

J. Inorg. Biochem.

Chem. Phys. Lett.

Polyhedron

J. Inorg. Chem.

Polyhedron

Inorg. Chem. Commun.

J. Inorg. Biochem.

Goodmann and Gillman's the Pharmacological Basis of Therapeutics

Acta Crystallogr. Sect. B

Phys. Chem. Chem. Phys.

The Metals of Life

J. Med. Chem.

J. Med. Chem.