Effect of substituents on the complexation of aromatic and quinoid substrates with molecular tweezers and clips

Molecular tweezers and clips of type 1-3 substituted with OAc, OH, OCONHPh, OMe, OCH2COOR and OCH2-CONHR groups in the central spacer units have been synthesized by modification, by standard methods, either of the known diacetoxy-substituted derivatives 1b, 2b and 3b, or of the correspondingly substituted bis-dienophiles 4b and 5b. The synthesis of the dimethoxy-diacetoxy-substituted tweezer 1d could be accomplished through pressure-induced repetitive Diels-Alder reactions between the bis-dienophile 4b and the newly prepared diene 6b and subsequent DDQ oxidation. The thermodynamic parameters (K-a and DeltaG) of complex formation between the new receptors and aromatic substrates such as DCNB 21, TCNB 22, TCNQ 24 and Kosower salt 25 and the maximum complexation-induced H-1 NMR shifts (Deltadelta(max.)) were determined by H-1 NMR titration experiments. It was found that the presence of substituents OH, OAc and OCONHPh in the central spacer units of the tweezers and clips 1-3 favours complex formation, whereas that of the substituents OMe, OCH2COOR and OCH2- CONHR disfavours it. This finding can be explained in terms of the size and different conformations of these groups in the tweezer and clip molecules as calculated by force-field (MMFF) techniques rather than of their influence on the electrostatic potential surfaces (EPSs) of the adjacent aromatic rings as calculated by quantum mechanical methods. The complementary natures of the negative EPSs inside the tweezer and clip cavities and the positive EPSs of the substrates forming complexes explained the high selectivity of these receptors toward electron-deficient substrates. The finding that the self-assembly of the OCH2COOCH2CH3 side chain is only observed for the benzene-spaced tweezers 1i and 1o confirms earlier results obtained for the intermolecular complexation of these receptors. Accordingly, the benzene-spaced tweezers of type I selectively bind aliphatic substrates, whereas the naphthalene-spaced tweezers of type 2 and clips of type 3 preferentially complex aromatic substrates. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.