Synthesis and characterization of the novel monoamide derivatives of Gd-TTDA

Yun-Ming Wang*, Cha Ru Li, Yu Chin Huang, Ming Hung Ou, Gin Chung Liu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


For this study, the N′-monoamide derivatives of TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid), N′-methylamide (TTDA-MA), N′-benzylamide (TTDA-BA), and N′-2-methoxybenzylamide (TTDA-MOBA), were synthesized. Their protonation constants and stability constants (log KML's) formed with Ca 2+, Zn2+, Cu2+, and Gd3+ were determined by potentiometric titration in 0.10 M Me4NCl at 25.0 ±0.1°C. The relaxivity values of [Gd(TTDA-MA)]-, [Gd(TTDA-BA)]-, and [Gd(TTDA-MOBA)]- remained constant with respect to pH changes over the range 4.5-12.0. The 17O NMR chemical shift of H2O induced by [Dy(TTDA-MA)(H2O)] - at pH 6.80 showed 0.9 innersphere water molecules. Water proton relaxivity values for [Gd(TTDA-MA)(H2O)]-, [Gd(TTDA-BA)(H2O)]-, and [Gd(TTDA-MOBA)(H 2O)]- at 37.0 ± 0.1°C and 20 MHz are 3.89, 4.21, and 4.25, respectively. The water-exchange lifetime (τM) and rotational correlation time (τR) of [Gd(TTDA-MA)(H 2O)]-, [Gd(TTDA-BA)(H2O)]-, and [Gd(TTDA-MOBA)(H2O)]- are obtained from reduced the 17O relaxation rate and chemical shifts of H2 17O. The 2H NMR longitudinal relaxation rates of the deuterated diamagnetic lanthanum complexes for the rotational correlation time were also thoroughly investigated. The water-exchange rates (kex 298) for [Gd(TTDA-MA)(H2O)]-, [Gd(TTDA-BA)-(H2O)]-, and [Gd(TTDA-MOBA)(H 2O)]- are lower than that of [Gd(TTDA)(H 2O)]2- but significantly higher than. those of [Gd(DTPA)(H2O)]2- and [Gd(DTPA-BMA)(H2O)]. The rotational correlation times for [Gd(TTDA-BA)(H2O)]- and [Gd(TTDA-MOBA)(H2O)]- are significantly longer than those of [Gd(TTDA)(H2O)]2- and [Gd(DTPA)(H2O)] 2- complexes. The marked increase of the relaxivity of [Gd(TTDA-BA)(H2O)]- and [Gd(TTDA-MOBA)(H 2O)]- results mainly from their longer rotational correlation time. The noncovalent interaction between human serum albumin (HSA) and [Gd(TTDA-BA)(H2O)]- and [Gd(TTDA-MOBA)(H 2O)]- complexes containing a hydrophobic substituent was investigated by measuring the water proton relaxation rate of the aqueous solutions. The binding association constant (KA) values are 1.0 ± 0.2 × 103 and 1.3 ± 0.2 × 103 M-1 for [Gd(TTDA-BA)(H2O)]- and [Gd(TTDA-MOBA)(H2O)]-, which indicates a stronger interaction of [Gd(TTDA-BA)(H2O)]- and [Gd(TTDA-MOBA)(H2O)]- with HSA.

Original languageEnglish
Pages (from-to)382-392
Number of pages11
JournalInorganic Chemistry
Issue number2
StatePublished - 24 Jan 2005

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