| Popis: |
M4DOTA, [(2S,5S,8S,11S)-4,7,10-tris-carboxymethyl-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid (2e), and M4DOTMA, (R)-2-[(2S,5S,8S,11S)-4,7,10-tris-((R)-1-carboxyethyl)-2,5,8,11-tetramethyl-1,4,7,10-tetraazacyclododecan-1-yl]propionic acid (3e), are derivatives of ligand DOTA (1e) that form sterically crowded lanthanide chelates. M4DOTMA forms highly symmetric and totally rigid single Y(3+) and Yb(3+) species in which the ring substituents occupy corner positions in a square antiprismatic arrangement as shown by molecular mechanics calculations and by a quantitative interpretation of the relative magnitudes of the paramagnetic (1)H NMR shifts of dipolar origin. The NMR spectrum of YbM4DOTMA(-) displays two intense methyl peaks outside the 0-10 ppm range whose shift difference is strongly temperature dependent. YbM4DOTMA(-) (3d) could be a useful probe in magnetic resonance thermometric imaging. With only four methyl substituents on the tetraaza ring, M4DOTA forms three Yb(3+) species in solution. The methyl substituents prevent the inversion of configuration of the ethylenic groups but not of the acetate arms. Although the methyl groups are likely to preferably occupy ring corner positions, the dipolar equations do not allow one to distinguish with certainty between the two available corner (equatorial) orientations. Reliably applying the dipolar equations is less obvious than usually assumed. A single methyl substituent as in ligand MDOTA (5e) suffices to rigidify the tetraaza cycle but not the acetate arms. Racemic YbMDOTA(-) (5d) is present in solution as four totally asymmetric topomers with the methyl groups occupying either one of the two equatorial positions. A complete assignment of the solution structures on the basis of the dipolar equations is again uncertain. The nuclear magnetic relaxation dispersion curves of the Gd(3+) chelates of all the methylated DOTA ligands including DOTMA, (R)-2-[4,7,10-tris-((R)-carboxyethyl)- 1,4,7,10- tetraazacyclododecan-1-yl]propionic acid, are very similar, and intermolecular conformational processes appear to have no influence on the relaxivity of these small complexes for which the relaxation T(1) is mainly determined by the rotational correlation time (tau(r)). The hydration number of the Tb(3+) chelates measured by fluorescence decreases from DOTMA to M4DOTMA presumably because steric crowding leads to an increase of the metal-water distance. |
