Solvent effects on chemical processes. 4. Complex formation between naphthalene and theophylline in binary aqueous-organic solvents

The standard free energy change for complex formation is written as a sum of effects arising from solvent-solvent interactions (the general medium effect), solvent-solute interactions (the solvation effect), and solute-solute interactions (the intersolute effect). The general medium effect is given by gA(–_o), where g is a curvature correction factor to the solvent surface tension , A is the change in surface area as the two solvent cavities containing the substrate (naphthalene) and ligand (theophylline) collapse into a single cavity containing the complex, and _o is the value of surface tcnsion at which there is no net solvophobic interaction; is defined to be the value appropriate to the equilibrium mean solvation shell composition. The solvation effect is modeled by equilibrium stoichiometric formation of solvated species. All data are related to the fully aqueous system to give _MG^o, the solvent effect on the free energy change, as an explicit function of solvent composition. Solvent effects on bimolecular association are related to solvent effects on the solubilities of the substrate, ligand, and complex. Approximation methods for interpreting such systems are described and are applied to the naphthalene-theophylline complex. It is shown that complex destabilization in mixed aqueous-organic solvents (relative to the fully aqueous system) may receive contributions from both the general medium and the solvation effects, and that these contributions can be quantitatively estimated.