Synthesis and Physicochemical Characterization of Carbon Backbone Modified [Gd(TTDA)(H2O)]2− Derivatives

The present study was designed to exploit optimum lipophilicity and high water-exchange rate (kex) on low molecular weight Gd(III) complexs to generate high bound relaxivity (r1b), upon binding to the lipophilic site of human serum albumin (HSA). Two new carbon backbone modified TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid) derivatives, CB-TTDA and Bz-CB-TTDA, were synthesized. The complexes [Gd(CB-TTDA)(H2O)]2− and [Gd(Bz-CB-TTDA)(H2O)]2− both display high stability constant (log KGdL = 20.28 and 20.09, respectively). Furthermore, CB-TTDA (log K(Gd/Zn) = 4.22) and Bz-CB-TTDA (log K(Gd/Zn) = 4.12) exhibit superior selectivity of Gd(III) against Zn(II) than those of TTDA (log K(Gd/Zn) = 2.93), EPTPA-bz-NO2 (log K(Gd/Zn) = 3.19), and DTPA (log K(Gd/Zn) = 3.76). However, the stability constant values of [Gd(CB-TTDA)(H2O)]2− and [Gd(Bz-CB-TTDA)(H2O)]2− are lower than that of MS-325. The parameters that affect proton relaxivity have been determined in a combined variable temperature 17O NMR ...