Novel optically-active bis(amino acid) ligands and their complexation with gadolinium

Abstract

A condensation reaction of glyoxal with (S)-histidine and (S)-aspartic acid yielded a new optically-active bis(amino acid) ligand, N-[(S)-1-carboxy-2-(imidazol-4-yl)ethyl]-N′-[(S)-1,2-dicarboxyethyl]ethylenediamine. Two bis(amino acid) ligands with picolyl (pyridylmethyl) groups were synthesized by condensation reactions of glyoxal with the picolyl derivative of (S)-histidine and that of (S)-aspartic acid: the obtained ligands are N,N′-bis(2-pyridylmethyl)-N-[(S)-1-carboxy-2-(imidazol-4-yl)ethyl]-N′-[(S)-1,2-dicarboxyethyl]ethylenediamine and N,N′-bis(2-pyridylmethyl)-N,N′-bis[(S)-1-carboxy-2-(imidazol-4-yl)ethyl]ethylenediamine. The protonation constants of these ligands were determined by potentiometry, and the corresponding protonation sites were located on the basis of ¹H NMR spectra obtained at different pD values. The formation constants of the Gd³⁺ complexes were determined by potentiometric titrations, and the NMR relaxivities r₁ and r₂ by the measurements of the NMR relaxation times.