Syntheses of macrocyclic enzyme models. Part 3. Preparation and properties of water-soluble azaparacyclophanes

Abstract

Azaparacyclophanes involving quaternary nitrogens in the cyclic skeleton and bearing long alkyl chains as branches of the skeleton were prepared to investigate their ability as macrocyclic enzyme models to incorporate various hydrophobic substrates. Water-soluble azaparacyclophanes, NNN′N′N″N″N‴N‴-octamethyl-2,11,20,29-tetra-aza [3.3.3.3] paracyclophane tetraiodide (8), NNN′N′N″N″N‴N‴Nâ�—Nâ�—Nâ�—′Nâ�—′-dodecamethyl-2,11,20,29,38,47-hexa-aza [3.3.3.3.3.3] paracyclophane hexaiodide (9), and NN′N″N‴-tetrakis-(10-carboxydecyl)-2,11,20,29-tetra-aza[3.3.3.3]paracyclophane-3,10,21,28-tetraone (13), incorporate a hydrophobic spin-labelled probe, 2,2,6,6-tetramethyl-1-oxyl-4-piperidyl cyclohexlyacetate (14). The aggregation behaviour of (13) was observed in a mixed aqueous–organic solvent, the critical micelle concentration (CMC) being 3.15 × 10^–4M. The azacyclophane (13) may provide an efficient hydrophobic field by the co-operation of the macrocyclic skeleton and the four alkyl chains due to its octopus-like structure and incorporate substrates of an appropriate molecular size with positive or neutral charge as confirmed by electronic spectroscopy using organic dyes. The hydrophobic binding ability of (13) was also acknowledged by the kinetic method using p-nitrophenyl 3,5-dimethylcyclohexylacetate as a substrate.