Syntheses of macrocyclic enzyme models. Part 6. Preparation and guest-binding behaviour of octopus cyclophanes

Abstract

The following octopus cyclophanes constructed with a rigid macrocyclic skeleton and eight flexible hydrocarbon chains were prepared: N,N′,N″,N‴-tetrakis(2-{N-[1-(N,N-ditetradecylcarbamoyl)-5-ammoniopentyl]carbamoyl}ethyl)-3,10,21,28-tetraoxo-2,11,20,29-tetra-aza[3.3.3.3]paracyclophane tetrachloride [APC(C₂Lys2C₁₄)₄] and N,N′,N″,N‴-tetrakis[2-(N-{1-(N,N-ditetradecylcarbamoyl)-1[5-(trimethylammonio)pentanecarboxamido]pentan-5-yl}carbamoyl)ethyl]-3,10,21,28-tetraoxo-2,11,20,29-tetra-aza[3.3.3.3]paracyclophane tetrabromide {APC[C₂Lys(C₅N⁺)2C₁₄]₄}. These host molecules provide cavities that are deep and hydrophobic enough to incorporate hydrophobic guests of various bulkiness through an induced-fit mechanism originating from the flexible character of the alkyl branches. Both hydrophobic and electrostatic interactions come into effect in the host–guest complexation process, so that the molecuuar recognition is exercised by the present hosts towards guest molecules. As regards the inclusion equilibrium between APC[C₂Lys(C₅N⁺)2C₁₄]₄ and pyrene, formation of both 1 : 2 and 1 : 1 (host: guest) complexes was remarkably favoured. The hydrophobic cage provided by the octopus cyclophane is highly apolar and acts to repress the molecular motion of guests; this was confirmed by fluorescence and fluorescence polarization spectroscopy, respectively. Both 2-azidobiphenyl and pyrene were simultaneously incorporated into the cyclophane cage as evidenced by kinetic analysis, and the pyrene-sensitized photolysis of the former species was enhanced under such conditions. The results imply that the octopus cyclophanes can be utilized as effective apoenzyme models for simulation of enzymatic functions.