(DOTA-bis(amide)}lanthanide complexes: NMR evidence for differences in water-molecule exchange rates for coordination isomers

Two derivatives of 1,4,7,10-tetraazacyclododecane with trans-acetate and tr ans-amide side-chain ligating groups have been prepared and their complexes with lanthanide cations examined by multinuclear NMR spectroscopy. These l anthanide complexes exist in aqueous solution as a mixture of slowly interc onverting coordination isomers with H-1 chemical shifts similar to those re ported previously for the major (M) and minor (m) forms of the tetraacetate ([Ln(dota)](-)) and tetraamide ([Ln(dtma)](3+)) complexes. As in the [Ln(d ota)](-) and [Ln(dtma)](3+) complexes, the m/M ratio proved to be a sensiti ve function of lanthanide size and temperature. An analysis of 1H hyperfine shifts in spectra of the Yb3+ complexes revealed significant differences b etween the axial (D-1) and non-axial (D-2) components of the magnetic susce ptibility tensor anisotropy in the m and M coordination isomers and the ene rgetics of ring inversion and m double left right arrowM isomerization as d etermined by two-dimensional exchange spectroscopy (EXSY). O-17 shift data for the Dy3+ complexes showed that both have one inner-sphere water molecul e. A temperature-dependent O-17 NMR study of bulk water linewidths for solu tions of the Gd3+ complexes provided direct evidence for differences in wat er exchange rates for the two coordination isomers. The bound-water lifetim es (tau (298)(M)) in the M and m isomers of the Gd3+ complexes ranged from 1.4-2.4 mus and 3-14 ns, respectively. This indicates that 1) the inner-sph ere water lifetimes for the complexes with a single positive charge reporte d here are considerably shorter for both coordination isomers than the corr esponding values for the [Gd(dtma)](3+) complex with three positive charges , and 2) the difference in water