Copper(II) complexes with anti-inflammatory drugs as ligands. Solution behaviour and electrochemistry of mono- and bi-nuclear complexes

Abstract

The copper complexes of 1-methyl-5-(p-toluoyl)-1H-pyrrole-2-acetic acid (tolmetin, HL¹), α-methyl-4-(2-methylpropyl)benzeneacetic acid (ibuprofen, HL²) and 6-methoxy-α-methylnaphthalene-2-acetic acid (naproxen, HL³) common anti-inflammatory drugs, were prepared and characterized. The available evidence supports a dimeric structure for the dimethyl sulfoxide adducts, [Cu₂L₄(dmso)₂], and monomeric for the pyridine (py) analogues, [CuL(py)₂(H₂O)]. The solution behaviour of the dimers in dimethylformamide (dmf) shows that the complexes are converted into monomeric compounds by addition of more than 25% of pyridine. The cyclic voltammograms of the dimers of dmf suggest that the complexes retain the dimeric structure in solution. The EPR spectra of the monomers as CH₂Cl₂–dmf (4 : 1) glasses confirm the monomeric structure, having a d_x²–y² ground state. Paramagnetic ¹H NMR studies have shown that the H₂O molecule of the monomeric form remains co-ordinated to Cu^II in CD₃Cl, (CD₃)₂CO or CD₃CN. The crystal structure of [CuL³₂(py)₂(H₂O)] has been determined: space group P2₁, a= 16.112(3), b= 5.8692(9), c= 18.130(3)Å, β= 75.818(7)°. In this complex the copper atom is five-co-ordinate. The atoms N(1) and N(2) of the two pyridine molecules and one carboxylate oxygen atom from each of the two ligands form the basal plane of a square pyramid with a water molecule at its apex.