Cyclophanes host models

The problem of binding purely covalent substrates is expectedly difficult because of the lack of centers capable of providing a strong electrostatic attraction. For these compounds it is necessary to elaborate receptors able to bind substrates effectively via van der Waals interactions, which are much weaker than the Coulomb forces operating in the previously mentioned complexes. A set of models designed for this purpose is shown in Scheme 4.68. Cyclophanes of the general formula 226 have been synthesized as hosts for aromatic hydrocarbons. The presence of a hydrophobic cavity of... 

The first practical application for cyclophanes was found in host-guest chemistry [4]. Molecular recognition of ions and neutral molecules in functionalized cavities of cyclophanes has been demonstrated for numerous examples. Here, special interest has been attracted by complexes in water since it can directly model molecular recognition events in biological systems. The development of suitable water soluble hosts with high binding selectivity is an active field of research [5] that has recently been reviewed [6]. 

As mentioned above, a possible explanation of the always-dominating enthalpic force in the complexation with synthetic hosts may be the unusual water configuration in the corresponding cavities. Molecular modeling shows that, e.g., inside Cyclophane 2, only five water molecules can be accommodated, which on the average can only materialize two hydrogen bondr. 

Murakami, Y. Kikuchi, J. Ohno, T. Hayashida, O. Kojima, M. Syntheses of macrocyclic enzyme models. 7. Octopus cyclophanes having L-aspartate residues as novel water-soluble hosts. Aggregation behavior and induced-fit molecular recognition. J. Am. Chem. Soc. 1990.112 (21). 7672-7681. 

To get hosts capable of binding aliphatic guests, novel cyclophanes (29, 30) having naphthylphenylmethane skeletons instead of diphenylmethane skeletons were designed based on CPK model studies [12]. In their most expanded conformations, these hosts are expected to provide wider cavities of about 5.4 A in their shorter width of their open ends. 

Abstract. The inclusion behavior of the octopus cyclophane constructed with a rigid macrocyclic skeleton and eight hydrocarbon chains was studied in aqueous media by means of fluorescence and electronic absorption spectroscopy. Both hydrophobic and electrostatic interactions came into effect in the host-guest complexation process. The cyclophane acted as an effective apoenzyme model for constitution of an artificial vitamin B -dependent holoenzyme by simultaneous incorporation of pyridoxal-5 -phos-phate and a hydrophobic alkylammonium substrate into the host cavity to give the Schiff-base species, showing the substrate selectivity. 

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