Thermodynamic stability and physicochemical characterization of ligand (4S)-4-benzyl-3,6,10-tris(carboxymethyl)-3,6,10-triazadodecanedioic acid (H 5 [(S)-4-Bz-ttda]) and its complexes formed with lanthanides, calcium(II), zinc(II), and copper(II) ions

Tsan Hwang Cheng, Tzu Ming Lee, Ming Hung Ou, Cha Ru Li, Gin Chung Liu, Yun-Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A derivative of H 5 ttda (=3,6,10-tris (carboxymethy -3,6,10-triazadodecanedioic acid = N-{2-[bis(carboxymethyl)amino]ethyl}-N- {(3-[bis(carboxymethyl)amino]propyl}glycine), H 5 [(S)-4-Bz-ttda] (=(4S)-4-benzyl-3,6,10-tris(carboxymethyl)-3,6,10-triazadodecanedioic acid = N-{(2S)-2-[bis (carboxymethyl)amino]-3-phenylpropyl}-N- {3-[bis(carboxymethyl)amino]propyl}glycine; 1) carrying a benzyl group was synthesized and characterized. The stability constants of the complexes formed with Ca 2+ , Zn 2+ , Cu 2+ and Gd 3+ were determined by potentiometric methods at 25.0±0.1° and 0.1M ionic strength in Me 4 NNO 3 . The observed water proton relaxivity value of [Gd{(S)-4-Bz-ttda}] 2- was constant with respect to pH changes over the range pH 4.5-12.0. From the 17 O-NMR chemical shift of H 2 O induced by [Dy{(S)-4-Bz-ttda}] 2- at pH 6.80, the presence of 0.9 inner-sphere water molecules was deduced. The water proton spin-lattice relaxation rate for [Gd{(S)-4-Bz-ttda}] 2- at 37.0±-0.1° and 20 MHz was 4.90±0.05mM -1 s -1 . The EPR transverse electronic relaxation rate and 17 O-NMR transverse-relaxation time for the exchange lifetime of the coordinated H 2 O molecule (τ M ), and 2 H-NMR longitudinal-relaxation rate of the deuterated diamagnetic lanthanum complex for the rotational correlation time (τ R ) were thoroughly investigated, and the results were compared with those previously reported for the other lanthanide(III) complexes, The exchange lifetime (τ M ) for [Gd{(S) Gdl(S)-4-Bz-ttda}] 2- (2.3 ± 1.3 ns) was significantly shorter than that of the [Gd(dtpa)(H 2 O)] 2- complex (dtpa = diethylenetriaminepentaacetic acid). The rotational correlation time τ R for [Gd{(S)-4-Bz-ttda}]2- (70 ± 6 ps) was slightly longer than that of the [Gd(dtpa)(H 2 O)] 2- complex. The marked increase of relaxivity of [Gd{(S)-4-Bz-ttda}] 2- mainly resulted from its longer rotational time rather than from its fast water-exchange rate. The noncovalent interaction between human serum albumin (HSA) and the [Gd{(S)-4-Bz-ttda}] 2- complex containing the hydrophobic substituent was investigated by measuring the solvent proton relaxation rate of the aqueous solutions. The association constant (K A ) was less than 100 M -1 , indicating a weaker interaction of [Gd{(S)-4-Bz-ttda}] 2- with HSA.

Original languageEnglish
Pages (from-to)1033-1050
Number of pages18
JournalHelvetica Chimica Acta
Volume85
Issue number4
DOIs
StatePublished - 13 May 2002

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