Stability constants of Cu(II)-piroxicam complexes in solution: a DFT study

Knowledge of coordination modes of metal and pharmaceuticals are crucial for gaining understanding of the chemical mechanisms underlying their biological activity, in particular for systems where there is a synergism based on the fact that complexes can provide enhanced activity of the drug with fewer side effects. Quantum chemistry calculations represent a unique and complementary approach to experimental methods to understand the thermodynamics of reactions in terms of structural details of the participating species. Here, the coordination modes between Cu(II) and piroxicam and their stability constants were studied, by means of DFT molecular modeling, in gas phase and in solution (water and ethanol) at the RevTPSS/def-SVP and (SMD-and CPCM-RevTPSS)/def-SVP levels of theory, respectively. Octahedral bidentate geometries are found to be the more stable, likely due to the chelate effect. Thermodynamic results on the stability of the formed complexes revealed that complexation is favored in ethanol. The calculated logK(s) with the (SMD-RevTPSS)/def-SVP level of theory are in better agreement to the experimental values than (CPCM-RevTPSS)/def-SVP results.