Synthesis and physicochemical characterization of two gadolinium(III) TTDA-like complexes and their interaction with human serum albumin

Ming Hung Ou, Chien Hung Tu, Su Ching Tsai, Wei Thung Lee, Gin Chung Liu, Yun-Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Two novel derivatives of TTDA (3,6,10-tri(carboxymethyl)-3,6,10- triazadodecanedioic acid), TTDA-BOM and TTDA-N′-BOM, each having a benzyloxymethyl group, were synthesized. 17O NMR longitudinal and transverse relaxation rates and chemical shifts of aqueous solutions of their Gd(III) complexes were measured at variable temperature with a magnetic field strength of 9.4 T. The water exchange rate (kex298) values for [Gd(TTDA-BOM)(H2O)]2- (117 × 106 s-1) and [Gd(TTDA-N′-BOM)(H2O)]2- (131 × 106 s-1) are significantly higher than those of [Gd(DTPA)(H2O)]2- (4.1 × 106 s -1) and [Gd(BOPTA)(H2O)]2- (3.45 × 106 s-1). The rotational correlation time (τR) values for [Gd(TTDA-BOM)(H2O)]2- (119 ps) and [Gd(TTDA-N′-BOM)(H2O)]2- (125 ps) are higher than those of [Gd(DTPA)(H2O)]2- (103 ps) and [Gd(TTDA)(H2O)]2- (104 ps). The stepwise stoichiometric binding constants of [Gd(TTDA-BOM)(H2O)]2- and [Gd(TTDA-N′-BOM)(H2O)]2- bound to HSA are obtained by ultrafiltration studies. Fluorescent probe displacement studies exhibit that [Gd(TTDA-BOM)(H2O)]2- and [Gd(TTDA-N′-BOM)(H 2O)]2- can displace dansylsarcosine from HSA with inhibition constants (Ki) of 1900 and 1600 MM, respectively; however, they are not able to displace warfarin. These results indicate that [Gd(TTDA-BOM)(H2O)]2- and [Gd(TTDA-N′-BOM)(H 2O)]2- have a weak binding to site II on HSA. In addition, the mean bound relaxivity (r̄1b) and bound relaxivity (r 1b) values for the [Gd(TTDA-BOM)(H2O)] 2-/HSA and [Gd(TTDA-N′-BOM)(H2O)]2-/HSA adducts are obtained by ultrafiltration and relaxivity studies, respectively. The bound relaxivity of these adducts values are significantly higher than those of [Gd(BOPTA)(H2O)]2-/HSA and [Gd(DTPA-BOM 3)(H2O)]2-/HSA. These results also suggest that bound relaxivity is site dependent. In binding sites studies of Gd(III) chelates to HSA, a significant decrease of the relaxation rates (R 1 obs) was observed for the [Eu(TTDA-BOM)(H2O)] 2- complex which was added to the [Gd(TTDA-N′-BOM)(H 2O)]2-/ HSA solution, and this indicated that these Gd(III) complexes share the same HSA binding site. Finally, as measured by the Zn(II) transmetalation process, the kinetic stability of these Gd(III) complexes are significantly higher than that of [Gd(DTPA-BMA)(H2O)].

Original languageEnglish
Pages (from-to)244-254
Number of pages11
JournalInorganic Chemistry
Volume45
Issue number1
DOIs
StatePublished - 9 Jan 2006

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