Syntheses of macrocyclic enzyme models. Part 4. Preparation and characterization of cationic octopus azaparacyclophanes

Abstract

Azaparacyclophanes bearing alkyl chains as branches of the skeleton were prepared in order to investigate their ability as macrocyclic enzyme models to incorporate various hydrophobic substrates. A water-soluble azaparacyclophane, NN′N″N‴-tetrakis-(10-trimethylammoniodecyl)-3,10,21,28-tetraoxo-2,11,20,29-tetra-aza[3.3.3.3]paracyclophane tetrabromide (7), incorporates not only non-charged, hydrophobic spin-labelled and fluorescence probes but also anionic and bulky neutral dyes. The substrate specificity exhibited by (7) is primarily due to electrostatic and hydrophobic interaction with the guest molecules. The catalytic behaviour of the azaparacyclophanes NN′N″N‴-tetrakis-{10-[dimethyl(imidazolylmethyl)ammonio]decyl}-3,10,21,28-tetraoxo-2,11,20,29-tetra-aza[3.3.3.3]paracyclophane tetrachloride (9) and NN′(N″)-bis-{10-[dimethyl(imidazolylmethyl)-ammonio]decyl}-N″(N′)N‴-bis-{10-[dimethyl(hydrogen)ammonio]decyl}-3,10,21,28-tetraoxo-2,11,20,29-tetra-aza[3.3.3.3]paracyclophane tetrachloride (10) was investigated in aqueous media containing a small amount of organic co-solvents. The azaparacyclophane (10) may provide an efficient hydrophobic field by co-operation of the macrocyclic skeleton with the four alkyl chains forming an octopus-like structure, particularly at pHs above the pK_a of the tertiary amino-group (9.2), and may selectively catalyse the hydrolysis of p-nitrophenyl carboxylates, having long alkyl chains. The pH-dependency of the binding ability of (10) toward substrates was examined by means of a fluorescence technique as well as by kinetic methods.