Relaxometric and solution NMR structural studies on ditopic lanthanide(iii) complexes of a phosphinate analogue of DOTA with a fast rate of water exchange

Abstract

A novel “ditopic” ligand containing two monophosphinate triacetate DOTA-like units linked by a thiourea bridge has been synthesized and its complexes with Ln³⁺ ions (Ln = Y, Eu, Gd, Dy) investigated by NMR spectroscopy and relaxometry. The presence of one water molecule in the first coordination sphere has been determined by the measurement of the dysprosium(III)-induced ¹⁷O NMR shifts. The ¹H and ³¹P NMR spectra of the Eu^III derivative indicate a higher abundance of the fast-exchanging twisted square antiprismatic (m) isomer than the isomeric square antiprismatic (M; m/M = 3 : 2) complex. The analysis of the ⁸⁹Y and ¹³C T₁ NMR relaxation times in the Gd^III/Y^III mixed complex have provided useful structural information. Values of ca. 6.3 and 8.2 Å for the Gd⋯Y and Gd⋯C distances, respectively, have been estimated which indicate a rather compact solution structure. This result finds support in the value of the relaxivity whose increase (at 20 MHz and 298 K) on passing from the monomeric (5.7 s⁻¹ mM⁻¹) to the ditopic complex (8.2 s⁻¹ mM⁻¹) can be attributed to the doubling of the inner-sphere term following the doubling of the molecular size. The structural and dynamic relaxivity-controlling parameters were assessed by a simultaneous fitting of the variable temperature ¹⁷O NMR and ¹H NMRD relaxometric data. The mean water residence lifetime (²⁹⁸τ_M) has been found to be 53 ns, one of the shortest values reported for ditopic complexes. The reorientational correlation time is two times longer (²⁹⁸τ_R = 183 ps) than the corresponding value of the parent monomeric Gd^III complex, thus supporting the view of a limited degree of internal rotation. The possible influence of magnetic Gd–Gd coupling has been excluded by a comparison of the ¹H NMRD profiles of the homodinuclear Gd^III/Gd^III and the heterodinuclear Gd^III/Y^III complexes.