CALORIMETRIC STUDIES OF METAL-BINDING TO TETRACYCLINE - ROLE OF SOLVENT STRUCTURE IN DEFINING THE SELECTIVITY OF METAL ION-DRUG INTERACTIONS

Binding enthalpies (Delta H), entropies (Delta S) and free energies (D elta G) have been evaluated for complex formation of tetracycline with Mg2+, Mn2+, Ca2+, and Sr2+. From the temperature dependence of enthal pic and entropic components, the changes in heat capacities (Delta C-p ) accompanying complex formation have been determined. The magnitudes of these thermodynamic parameters show a strong correlation with the c harge-density of the metal ion, and reflect changes in the immediate h ydration sphere of the metal-drug complex that are likely to be involv ed in defining the extent of any interactions with nucleic acids. The similar binding constants exhibited by the physiologically relevant Mg 2+ and Ca2+ ions do not reflect the variation in entropic and enthalpi c factors that underlie complex formation for each of these metal ions .