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 dx2–y2 ground state. Paramagnetic 1H NMR studies have shown that the H2O molecule of the monomeric form remains co-ordinated to CuII 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)A, 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.