Syntheses of macrocyclic enzyme models. Part 2. Preparation and substrate-binding properties of [10.10]paracyclophanes

Abstract

A water-soluble [10.10]paracyclophane (7) was found to form association complexes in 1 : 1 stoicheiometry with a series of p-nitrophenyl carboxylates bearing an alicyclic moiety (8)–(12). The hydrolysis of the substrate ester trapped in the paracyclophane cavity was moderately (by 6.5-fold) to significantly (by 99-fold) retarded relative to that in bulk solution. The binding constant for complex formation is relatively large (2.0 × 10³–2.8 × 10⁴ I mol^–1) and increases as the hydrophobicity of the substrate increases. The geometrical mode for interaction of the paracyclophane with the substrate is most plausibly face-to-face type. Formation of the association complex with (7) was also detected spectroscopically by using 4-cyano-1-dodecylpyridinium iodide (13) or a nitroxide radical bearing a hexadecanoyl moiety (14) as a pseudo-substrate. The CT probe (13) exhibited a new CT-transition band at 330 nm upon complex-formation with (7), which suggests that the micro-environment of the chromophore is less polar than in water but more polar than in methanol. The nitroxide radical (14) was found to lose its rotational mobility significantly upon complex-formation with (7); the rotational correlation time increases from 0.2–0.8 × 10^–10 s in ethanol or benzene to 7.7–11.6 × 10^–10 s. On the other hand, the isotropic nitrogen hyperfine splitting constant for (14) bound with the paracyclophane is practically the same as that expected in water without complexation with (7). The nature of the substrate-binding site of (7) was characterized on the basis of these spectral data.