SOLVENT EFFECTS IN MOLECULAR RECOGNITION

Synthetic cyclophane receptors form stable and highly structured inclu sion complexes with aromatic solutes in the liquid phase. The major ho st-guest interactions in these complexes are pi-pi-stacking and edge-t o-face aromatic-aromatic interactions. Electron donor-acceptor (EDA) i nteractions control the relative stability of cyclophane-arene inclusi on complexes in organic solvents. Generally, electron-deficient benzen e and naphthalene derivatives form the most stable complexes with elec tron-rich cyclophanes. In water, however, unfavorable complexation-ind uced changes in the solvation of guest functional groups may entirely mask contributions of EDA interactions to the relative complexation st rength. Similarly, complexation-induced changes in the solvation of ho st substituents may also strongly affect the measurable complexation s trength. The inclusion complexation of benzene derivatives in water is strongly exothermic, accompanied by an unfavorable entropic term. A l arge part of the favorable enthalpy change results from solvent-specif ic 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 proti c, 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-cycloph ane inclusion complex is enthalpically driven. The exothermicity gener ally increases from apolar solvents, to dipolar aprotic solvents, to p rotic solvents. Strong dual isoequilibrium relationships correlate the thermodynamic parameters DELTA-G-degrees, DELTA-H-degrees, and T-DELT A-S-degrees for pyrene complexation in the different environments. Dif ferential solvent interactions are responsible for these unprecedented compensation effects.