New ligand bearing preorganized binding side-arms interacting with ammonium cations: Synthesis, conformational studies and crystal structure

Abstract

The synthesis and characterization of the new tetraazamacrocycle 4-(N),10-(N)-bis[2-(3-hydroxy-2-oxo-2H-pyridin-1-yl)acetamido]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (L) is reported. L shows two 3-(hydroxy)-1-(carbonylmethylen)-2(1H)-pyridinone moieties as side-arms of a tetra-aza-macrocyclic base. The key coupling of side-arms was studied and the most significant results were obtained by activating the 3-(benzyloxy)-1-(carboxymethyl)-2(1H)-pyridinone as pentafluorophenol ester. The acid–base properties of L and its capability to interact with simple ammonium cations were investigated by potentiometric measurements in aqueous solution (298.1 ± 0.1 K, I = 0.15 mol dm⁻³). Protonated species of L can bind NH₄⁺ or primary ammonium cations such as MeNH₃⁺ discriminating them from secondary or tertiary ammonium cations such as Me₂NH₂⁺ or Me₃NH⁺ which are not bound in aqueous solution.

¹ H and ¹³C NMR spectra showed the existence in solution of two conformers on the NMR time scale due to the rotational restriction of the two N–CO groups. The activation parameters were determined by dynamic variable-temperature NMR analysis.

Molecular dynamics calculations gave results in agreement with the experimental data for both conformation and ammonium-binding studies, underlining that the transformation of the two secondary amines of the macrocyclic base to amide functions, forces the side-arms to remain fixed in position, almost face to face and thus to be preorganized to interact with other species. The crystal structure of the [HL]Cl·8H₂O species shows the high number of preorganized hydrogen bond sites capable, in this case, of interacting directly with five H₂O molecules.