Stability constants and molecular modeling of Cu(II)/AcO and Cu(II)/diclofenac complexes in ethanol

Abstract

The speciation of diclofenac and copper complexes in ethanolic solutions is investigated. Current studies of coordination of Cu(II) and nonsteroidal anti-inflammatory drugs (NSAID) successfully describe structural features of Cu(II)/NSAID compounds in their solid state; however, stability of species in solution has been less explored. In order to approach the Cu(II)/Diclofenac speciation, the model system Cu(II)/Acetate was also investigated. A chemical model, which consists of a number of chemical equilibriums that involve the more stable species formed in solution, is proposed and proved to be consistent with experimental UV–Vis spectrums. Thermodynamic stability constants are reported, for the global complexation equilibriums iCu2++jL↔CuiLj2i-j, where L = Acetate or Diclofenac; for i=1, j=2 and for i=2, j=2,3,4. Molecular modeling, by applying quantum chemistry methods, based on density functional theory, is carried out to structurally characterize the neutral species present in the systems. Gibbs free energies in solution for the dimerization process 2CuL2→Cu2L4 were evaluated by means of thermodynamic cycles based on theoretical chemistry protocols. Although reduced solubility of diclofenac limits the use of water for speciation studies, results from experiments in ethanol might provide useful structural information to discuss the nature of Cu(II)/Dic complexes.