CYCLOPHANE ARENE INCLUSION COMPLEXATION IN PROTIC SOLVENTS - SOLVENT EFFECTS VERSUS ELECTRON-DONOR ACCEPTOR INTERACTIONS

This paper describes a comprehensive H-1 NMR analysis of the inclusion complexation of neutral 2,6-disubstituted naphthalene and para-disubstituted benzene derivatives by cyclophanes. The major attractive host-guest interactions in these complexes are pi-pi-stacking and edge-to-face aromatic-aromatic interactions. Individual studies investigate relative binding strength as a function of (i) the electronic properties of the guests, (ii) the nature of the solvent, and (iii) the nature of the cyclophane hosts. For these investigations, two new tetraoxa [n.1.n.1] cyclophanes with eight methoxy groups ortho to the aryl ether linkages were synthesized. A comparison between different cyclophanes shows that functional groups attached to the aromatic rings increase binding strength if they deepen the cavity without perturbing the apolar character of the binding site. Electron donor-acceptor (EDA) interactions control the relative stability of cyclophane-arene inclusion complexes in CD3OD and (CD3)2SO. Generally, electron-deficient guests form the most stable complexes with the electron-rich cyclophanes. Deviations from the EDA model in these solvents are best explained by unfavorable complexation-induced changes in the solvation of the guest functional groups. In water, such solvation effects may dominate, thus masking contributions of EDA interactions to the relative complexation strength. Electronic host-guest complementarity determines the relative association strength in water only if guest functionalities retain their favorable solvation in the complexes formed. In binary aqueous solvent mixtures, overall complexation strength increases with the amount of water added and follows a linear free energy relationship with the empirical solvent polarity parameter E(T)(30).