<p>STUDIA UNIVERSITATIS BABES-BOLYAI, PHYSICA, SPECIAL ISSUE, 2003</p><p>SPECTROSCOPIC INVESTIGATION OF Cu(II) MOLECULAR COMPLEXES OF ATENOLOL and METOPROLOL TARTRATE </p><p>Felicia Pop-Gozman1, I. Bratu2, O. Cozar3 and M. Bojita4</p><p>1University of Oradea, Faculty of Pharmacy, 1 Armatei Romane st., Oradea, Romania 2National R&D Institute of Isotopic and Molecular Technologies, P.O. Box 700, R-3400 Cluj-Napoca 5, Romania 3'Babes-Bolyai' University, 1 Kogalniceanu st., Cluj- Napoca, Romania 4'Iuliu Hatieganu' University of Medicine anf Pharmacy, 4 Clinicilor st., Cluj-Napoca, Romania</p><p>Abstract FT-IR spectroscopic data of atenolol and its copper complex suggest that NH2 and carboxyl groups are involved in the coordination of the metal ion. Powder EPR spectra of these complexes show a square-planar symmetry</p><p> around the metal ion with a CuN2O2 chromophore in xOy plane. A small tetragonal-octahedral distortion is present in the case of CuATE compound.</p><p>Introduction</p><p>Atenolol (C14H22N2O3) and metoprolol tatrate (C15H25NO3)2.C4H6O6 molecules are the most frequently used drugs in the treatment of cardiovascular diseases. In the last few years some molecular copper complexes of different drugs (cardiovasculares, antiinflammatories) are used because their activity is enhanced. For a better understanding of their activity, structural investigation [1-10] by different spectroscopic methods (FT IR and EPR spectroscopy) was done. </p><p>Experimental Molecular complexes of atenolol (ATE) and metoprolol tatrate (MET) with Cu(II) were obtained on going from the starting salts (sodium benzoate and copper sulphate) by co-precipitation procedure. After drying, the powder complexes were analysed by classical KBr pellet technique with an EQUINOX 55 Bruker FT IR spectrometer in the 400 - 4000 cm-1 spectral domain. The EPR spectra of the samples in the powder form were registered in the X band using an ADANI-USA spectrometer. FELICIA POP-GOZMAN, I. BRATU, O. COZAR AND M. BOJITA</p><p>Results and Discussion A comparative study of the FTIR spectra of ligands (ATE and MET) and the corresponding complex, see Figs. 1 and 2, established the molecular groups involved in the complexation. Analysing the FTIR spectrum of ATE one can see </p><p>1.0 ATE</p><p>ATE-Cu(II) 0.8 0</p><p>-100</p><p> e -200 c 0.6 n -300 a b</p><p> r -400 o s</p><p>-500 </p><p> b 0.4 A -600</p><p>-700 0.2 -800</p><p>-900 0.0 4000 3500 3000 2500 2000 1500 1000 500 Wavenumber / cm-1</p><p>Figs. 1: FT IR spectra of ATE and its copper complex</p><p>-1 that the frequency of the band at 3351 cm and assigned to NH2 group is shifted to 3441 cm-1 in the spectrum of copper complex; it is possible that some hydrogen bonds are broken during the complexation process. The band at 1631 cm -1 in the</p><p>MET</p><p>1.0</p><p>0.8 e</p><p> c 0.6 n a b r o s</p><p> b 0.4 A</p><p>0.2</p><p>0.0 4000 3500 3000 2500 2000 1500 1000 500 Wavenumber / cm-1 Fig. 2: FT IR spectra2 of MET. INVESTIGATION OF Cu(II) MOLECULAR COMPLEXES, ATENOLOL and METOPROLOL TARTRATE</p><p>FTIR spectrum of ATE, assigned to carbonyl group is shifted to 1602 cm-1 in the spectrum of the complex. It is quite evident that the complexation is produced through this molecular group. Powder EPR spectra of Cu (II) atenolol (ATE) and Cu (II) metoprolol tarate (MET) complexes obtained at room temperature exhibit the absorption signals typical of randomly oriented single state (S=1/2) species having axial symmetry (Fig. 3). The 2 2 ground state for paramagnetic electron is dx -y orbital. By comparing the shape of these EPR spectra with those obtained for others copper complexes with nitrogen and oxygen ligands we have concluded that the local symmetry around metal ions is of square-planar type with a CuN2O2 chromofore in the xOy plane [1].</p><p>The characteristic EPR parameters for CuATE compound are the following g//</p><p>=2.268, g =2.078, A// =165 G and g// =2.268, g =2.095, A// =145 G for CuMET.</p><p>The g// values suggest the presence of a small tetragonal-octahedral distortion in the case of CuATE compound [10].</p><p>A// g =2.095</p><p> g//=2.268</p><p>CuMET</p><p>2300 2500 2700 2900 3100 3300 3500 3700 3900 Field / G</p><p>Fig. 3. Powder EPR spectrum of CuMET at room temperature.</p><p>3 FELICIA POP-GOZMAN, I. BRATU, O. COZAR AND M. BOJITA</p><p>Conclusions The FT-IR data obtained for ATE and MET drugs and their copper compounds suggest that NH2 and carboxyl groups are involved in the complexation (coordination) of the metal ions. Powder EPR spectra of these complexes show a square-planar symmetry around the metal ions with a CuN2O2 chromophore in xOy plane. A small tetragonal- octahedral distortion is present in the case of CuATE compound.</p><p>References [1] O.Cozar, L.David, V.Chis, C.Cosma, V.Znamirovschi, G.Damian , Appl.Magn.Reson., 8(1995), 235. [2] E.Forizs, L.David, O.Cozar, C.Craciun, M.Venter, M.Kilyen , J.Molec.Structure, 408/409(1997), 195-199. [3] O.Cozar, L.David, V.Chis, E.Forisz, C.Cosma, G.Damian , Fressenius Journal of Analytical Chemistry, 355(1996), 701. [4] E.Forizs, L.David, O.Cozar, C.Craciun, M.Venter, M.Kilyen , J.Molec.Structure, 408/409(1997), 195-199. [5] A. Torregiani, P. Taddei, M.R. Tosi, V. Tugnolo ,.J. Molec. Struct.,565-566 (2001), 347-352. [6] G. Facchin, M.H. Torre, E. Kremer, O.E. Piro, E.J. Baran , Z. Naturforsch. 53b (1998), 871-874. [7] G. Facchin, M.H. Torre, E. Kremer , Z. Anorg. Allg. Chem., 624 (1998), 2025- 2028. [8] E.Forizs, L.David, O.Cozar, V.Chis, G.Damian , J.of Molecular Structure 482(1) (1999),143-147 [9] E.Forizs, L.David, O.Cozar, V.Chis, R.Tetean, M.Todica , Appl.Mag.Resonance 16(1999), 499-506. [10] O. Cozar, I. Bratu, L. David, C. Craciun, A. Hernanz, R. Navarro, M. de la Fuente, C. Balan , Appl.Mag.Resonance, 21(2001), 71-78.</p><p>4</p>