Correlation of Water Exchange Rate with Isomeric Composition in Diastereoisomeric Gadolinium Complexes of Tetra(carboxyethyl)dota and Related Macrocyclic Ligands

The solution structure and dynamics of metal-bound water exchange have been studied in a series of diastereoisomeric gadolinium complexes of tetra(carboxyethyl) derivatives of 1,4,7,10-tetraazacyclodecane. The structures of the (<i>RRRS</i>), (<i>RSRS</i>), and (<i>RRSS</i>) ligands and the Eu, Gd, and Tb complexes of the (<i>RRRR</i>) isomer have been determined by X-ray crystallography. Luminescence measurements on the Eu and Tb complexes revealed an integral hydration state (<i>q </i>= 1) in each case for the Eu isomers, whereas nonintegral values were measured for the (<i>RRRR</i>) and (<i>RRRS</i>) Tb isomers (e.g., [(<i>RRRR</i>)-Tb·<b>1</b>]<sup>-</sup>, <i>q</i> = 0.60). The ratio of the twisted and regular monocapped square antiprismatic isomers has been measured in solution by <sup>1</sup>H NMR for the Eu and Tb complexes and followed the order, (<i>RRRR</i>) > (<i>RRRS</i>) > (<i>RSRS</i>) > (<i>RRSS</i>). Water exchange rates in the gadolinium complexe have been determined by <sup>17</sup>O NMR and were fastest for the (<i>RRRR</i>) isomer [τ<sub>m</sub> = 68 ns (298 K)] and correlated very well with the proportion of the twisted square anti-prismatic isomer. The rate of water exchange in the (<i>RRRR</i>) Gd complexes is likely to be sufficiently fast so as not to limit the overall relaxivity in higher MW conjugates.