New branched macrocyclic ligand and its side-arm, two urea-based receptors for anions: synthesis, binding studies and crystal structure

Abstract

The synthesis and characterization of the two new hosting molecules for anions 4(N),10(N)-bis-[2-(4-nitrophenylureido)acetamido]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (L1) and 1-((diethylcarbamoyl)methyl)-3-(4-nitrophenyl)urea (L2) are reported. L1 is a branched tetraazamacrocycle bearing two p-nitrophenylureido groups as side-arms, whereas L2 has the same linear chain and binding moiety of L1 side-arm. The best synthetic routes for use in obtaining L1 were explored, affording the synthesis of the new intermediate 4, a versatile building block for further functionalized branched macrocyclic hosts. The binding properties of both ligands towards the halides series and acetate anions (G) were investigated by NMR and UV-Vis spectroscopy in a dimethyl sulfoxide–0.5% water solution. Both ligands interact with F⁻, Cl⁻ and AcO⁻ while Br⁻ and I⁻ did not. The NMR experiments proved that the binding occurs via H-bond to the ureido fragments. Fluoride anion is basic enough to deprotonate the ureido group of both ligands, thus preventing the determination of the addition constants to both ligands; this was instead possible for Cl⁻ and AcO⁻. L1 forms G–L species of 1 : 1 ([GL1]) and 2 : 1 ([G₂L1]) stoichiometry while L2 forms only the 1 : 1 [GL2] species. The higher value of the formation constant of the [AcOL1]⁻vs. the [AcOL2]⁻ species (log K = 5.5 vs. 2.8 for the reaction AcO⁻ + L = AcOL⁻) suggested that both side-arms of L1 cooperate in binding acetate; this does not occur with Cl⁻. The results confirmed that this tetraaza-macrocyclic base acts as a preorganizing scaffold for side-arms when they are linked to it via an amide function. The crystal structure of L2·H₂O is also reported.