Metal ion interactions with drugs: Electrochemical study of complexation of various bivalent metal ions with nimesulide and ibuprofen

The present study reports the stability constants of complexes of two NSAIDs: nimesulide and ibuprofen with Co2 +, Ni2 +, Cu2 +, Zn2 +, Cd2 +, Sn2 +, Hg2 + and Pb2 + ions in water-ethanol medium 50% v/v at three different temperatures (298 K, 308 K and 318 K), keeping ionic strength constant (0.1 M KNO3). Experiments were conducted in 1000 mL jacketed glass reaction vessels under nitrogen atmosphere. Hydrogen ion concentrations were measured and the stability constants were calculated from the pH-metric titration curves. The order of the stability constants of the formed complexes decreases in the sequence Cu2 + > Co2 + > Cd2 + > Zn2 + > Ni2 + > Sn2 + > Pb2 + ≈ Hg2 + for nimesulide (D1) and Cu2 + > Co2 + > Zn2 + > Ni2 + > Cd2 + > Sn2 + > Pb2 + > Hg2 + for ibuprofen (D2). The effect of temperature was also studied and the corresponding thermodynamic functions ΔG, ΔH and ΔS were derived and discussed. The formation of metal complexes has been found to be spontaneous and entropically favorable. The method of Calvin and Bjerrum as adopted by Irving and Rossotti has been employed to determine log K1 values. This order is in good agreement with the Irving-Williams order of stability.