SOLVENT EFFECTS IN MOLECULAR RECOGNITION

Synthetic cyclophane hosts form stable and highly structured inclusion complexes with organic molecules in aqueous solutions. The solution geometries of these complexes are determined in a conformational analysis using Monte Carlo methods. Solvation-desolvation processes are a central factor in determining the stability of apolar inclusion complexes. The tight binding of small aromatic solutes in water is entropically unfavorable and is predominantly enthalpy-driven. A large part of the favorable enthalpy term for strong complexation in water results from its specific contributions. Electron donor-acceptor interactions stabilize complexes between electron-rich cyclophane hosts and electron-deficient aromatic substrates; however, they may be masked by specific solvation effects. Computer liquid phase simulations are undertaken to evaluate at a microscopic level the origin of such solvation effects. The progress in the modeling studies is described. Apolar complexation also occurs in organic solvents. Solvents like 2,2,2-trifluoroethanol and ethylene glycol come close to water in their ability to promote apolar complexation. Binding strength decreases from water to polar protic to dipolar aprotic and to apolar solvents. Complexation strength in solvents of all polarity including water and in binary aqueous solvent mixtures is predictable according to a linear free energy relationship between the complexation free energy and the empirical solvent polarity parameter E(T)(30).