Molecular recognition of phenethylamine, tyramine and dopamine with new anionic cyclophanes in aqueous media

Abstract

Water-soluble cyclophanes functionalized by amide groups and pendant carboxymethyl groups have been synthesized, in a single step, by a condensation reaction between ethylenediaminetetraacetic (EDTA) dianhydride and bis(4-aminophenyl) ether or bis(4-aminophenyl)methane: cyclophanes obtained are 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza-17,40-dioxa[10.1.10.1]paracyclophane (1) and 2,9,25,32-tetraoxo-4,7,27,30-tetrakis(carboxymethyl)-1,4,7,10,24,27,30,33-octaaza[10.1.10.1]paracyclophane (2). Their complexation with 2-phenylethylamine (phenethylamine), 2-(4-hydroxyphenyl)ethylamine (tyramine) and 2-(3,4-dihydroxyphenyl)ethylamine (dopamine), which have biologically important activities, has been studied by 1H NMR spectroscopy in aqueous media. The formation constants of 1∶1 host–guest complexes, K = [HG]/[H][G], have been determined as: log K = 0.8 for 1–phenethylamine; 1.2 for 1–tyramine; 1.2 for 1–dopamine; 1.6 for 2–phenethylamine; 2.0 for 2–tyramine. Dopamine and 2 form a complex with low water-solubility. The chemical shifts of aromatic protons of the host and guest molecules suggest the formation of inclusion complexes in solutions. The formation of the host–guest complexes is assisted by a hydrogen bond and/or an electrostatic interaction between the pendant –CH2CO2– group of the host and the –CH2CH2NH3+ arm of the guest molecule. The two types of molecular recognition sites of the new cyclophanes result in the selective complex formation with the aromatic amines.