SOLVENT EFFECTS IN MOLECULAR RECOGNITION

Synthetic cyclophane receptors form stable and highly structured inclusion complexes with aromatic solutes in the liquid phase. The major host-guest interactions in these complexes are pi-pi-stacking and edge-to-face aromatic-aromatic interactions. Electron donor-acceptor (EDA) interactions control the relative stability of cyclophane-arene inclusion complexes in organic solvents. Generally, electron-deficient benzene and naphthalene derivatives form the most stable complexes with electron-rich cyclophanes. In water, however, unfavorable complexation-induced changes in the solvation of guest functional groups may entirely mask contributions of EDA interactions to the relative complexation strength. Similarly, complexation-induced changes in the solvation of host substituents may also strongly affect the measurable complexation strength. The inclusion complexation of benzene derivatives in water is strongly exothermic, accompanied by an unfavorable entropic term. A large part of the favorable enthalpy change results from solvent-specific contributions. Negative heat capacity changes are measured for all inclusion complexes in water. Arene complexation occurs in solvents of all polarity. Binding free energy decreases from water to polar protic, to dipolar aprotic, and to apolar solvents and can be predicted in a linear free energy relationship with the empirical solvent polarity parameter E(T)(30). In all solvents, the formation of a pyrene-cyclophane inclusion complex is enthalpically driven. The exothermicity generally increases from apolar solvents, to dipolar aprotic solvents, to protic solvents. Strong dual isoequilibrium relationships correlate the thermodynamic parameters DELTA-G-degrees, DELTA-H-degrees, and T-DELTA-S-degrees for pyrene complexation in the different environments. Differential solvent interactions are responsible for these unprecedented compensation effects.