Structures and Dynamics of Lanthanide(III) Complexes of Sugar-Based DTPA-bis(amides) in Aqueous Solution:  A Multinuclear NMR Study

Abstract

The structure and dynamics of the lanthanide(III) complexes of DTPA-BGLUCA3- (DTPA-bis(glucamide)), DTPA-BENGALAA3- (DTPA-bis(ethylenegalactamine−amide)), DTPA-BEA3- (DTPA-bis(ethanolamide)), and DTPA-BPDA3- (DTPA-bis(propanediolamide)) in water have been investigated. These complexes are of relevance as potential MRI contrast agents. 13C relaxation times of the Nd(III) complexes show octadentate binding of the organic ligand via the three amines, the three carboxylates, and the two amide oxygens. 17O NMR measurements indicate that the coordination sphere is completed by one water ligand. Eight diastereomeric pairs of isomers are observed for the DTPA-bis(sugaramides). Data sets obtained from variable-temperature and -pressure 17O NMR at 9.4 T and variable-temperature 1H nuclear magnetic relaxation dispersion (NMRD) on the Gd(III) complexes were fitted simultaneously to give insight into the parameters governing the water 1H relaxivity. The water exchange rates, k ex 298, on [Gd(DTPA-BPDA)(H2O)], [Gd(DTPA-BGLUCA)(H2O)] and [Gd(DTPA-BENGALAA)(H2O)] are 3.6 ± 0.3, 3.8 ± 0.2, and 2.2 ± 0.1 × 105 s-1, and the activation volumes are +6.7, +6.8, and +5.6 cm3 mol-1 (±0.2 cm3 mol-1), respectively, indicating a strongly dissociatively activated mechanism. The sugar moieties have no significant influence on the coordination of the Gd(III) ion and on the parameters governing the relaxivity, apart from the expected increase in the rotational correlation time. The relaxivity under the usual MRI conditions is limited by the water exchange rate and the electronic relaxation. The data obtained are used to explain the relaxivity of conjugates of polysaccharides and Gd(DTPA).

Structure and Dynamics of Lanthanide Complexes of Triethylenetetramine‐N,N,N′,N″,N′′′,N′′′‐hexaacetic Acid (H6ttha) and of Diamides H4ttha(NHR) Derived from H6ttha as Studied by NMR, NMRD, and EPR

“…So probably two dynamic processes occur between the isomers, one is relatively fast and the other is much slower, and most likely involves partial decoordination of the ligand. Previously, similar exchange processes have been observed in the [Ln{dtpa(NHR) 2 }] complexes [12] [19]. However, the number of different species of Ln 3 complexes of ttha or its derivatives that can be formed in aqueous solution has strongly increased with respect to the corresponding dtpa derivatives [12] [19].…”

“…Here M r is the molecular weight ( relative molar mass) of the complex under study. The value of the distance of closest approach of H 2 O protons to Gd 3 (a GdH ) was fixed at 3.5 , the same value as applied in previous studies on dtpa derivatives [12] [30]. Good fits were obtained by using this model (see Fig.…”

“…By subtracting the relaxivity of [Gd(ttha)] 3À from the observed r 1 of a Gd 3 complex of an acyclic polyaminopolycarboxylate, the inner-sphere contribution can be calculated, provided that the relaxivity of [Gd(ttha)] 3À is a reasonable estimation of outer-sphere and second-sphere relaxivity of the complex under investigation [10] [11]. However, the NMRD data of [Gd{dtpa(NHgluca) 2 }] (NHgluca d-glucamine d-gluco-2,3,4,5,6-pentahydroxyhexanamine) [12] could not be fitted with the Solomon ± Bloembergen ± Morgan equations [13 ± 15] by using this estimation for the outer-and second-sphere contribution to the relaxivity [12]; so the question arises whether [Gd(ttha)] 3À is a suitable model for outer-sphere relaxation in Gd III complexes of dtpa derivatives.…”

Stability, structure and dynamics of cationic lanthanide(iii) complexes of N,N′-bis(propylamide)ethylenediamine-N,N′-diacetic acid

“…(14) and (15). When a changeover exists from the "fast exchange" limit at high temperature, where T 2m is the principal term in the denominator of eqn.…”

Gd-Complexes of DTPA-bis(amides) Functionalized by Pyridine and Picolinamide: Synthesis, Thermodynamic Stability, and Relaxivity Properties

“…3,4 Yet, a great number of neutral Gd-complexes incorporating DTPA-bis(amide) ligands are known and some of them are known to exhibit poor water solubility. [5][6][7][8][9][10][11][12] It is worth noting that high relaxivity and noncytotoxicity in addition to high water solubility are the essential criteria for an efficient MRI CA.…”