The influence of coordination geometry on the lanthanide(III) (S)-P-NB-DOTA-tetraamide derivatives.

摘要

The rate of exchange of the coordinated water molecule in LnDOTA- and its tetraamide derivatives are known to be highly dependent upon the coordination geometry of the complex. Traditionally the development of new MRI contrast media has focused around the development of faster water exchange systems. By selection of the coordination geometry in tetraacetate DOTA derivatives, the rapid water exchange rates can be achieved, ideal for the design of conventional contrast agents. However, the discovery that PARACEST agents may also be used to generate image contrast has sparked renewed interest in more slowly exchanging systems. In this work, two approaches were taken with the intention to lock the conformation of the coordination polyhedra in lanthanide complexes: substitution of the acetate group (alpha-substitution) and introduction of a chiral amide substituent (delta-substitution). The solution structure and dynamics of a number of lanthanide(III) complexes were studied by 1H NMR, 17O NMR, CEST experiments, and spectra fittings. The results demonstrate that the tetraamide derivatives have differing conformational geometries depending upon the chirality of the pendent arms and the location of the chiral center. The influence of this effect on water exchange as well as the CEST efficiency of the complexes was studied and discussed. The TSAP isomers exhibit water exchange rates that are too fast for CEST observation while the SAP isomers have different CEST behavior depending on the arm chirality.