Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents

Geraldes, Carlos F. G. C.; Urbano, Ana M.; Alpoím, Maria C.; Sherry, A. Dean; Kuan, K. T.; Rajagopalan, Raghavan; Maton, Frédéric; Müller, Robert N.

doi:10.1016/0730-725x(94)00117-l

Cited by 98 publications

(86 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite the derivatization of two terminal carboxylate groups of each DTPA residue, with a somewhat reduced Gd 3+ binding ability of the resulting amide moieties, the stability of the polymeric complexes should still be high enough to be used in vivo. This is supported by the observation that the reduced thermodynamic stability of small Gd 3+ chelates of DTPA-bis amides relative to Gd(DTPA) 2-is compensated by their comparable or even favorable conditional stability constants and selectivity factors for Gd 3+ relative to other biologically relevant cations such as Zn 2+ , leading to nonincreased in vivo dissociation of Gd 3+ (31,41,42).…”

Section: Discussionmentioning

confidence: 89%

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

et al. 2001

View full text Add to dashboard Cite

Two linear polyamide conjugates of Gd(DTPA) 2-were synthesized and characterized by high-resolution nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC). DTPA was copolymerized with two different diamines, 1,6-hexanediamine and trans-1,4-cyclohexanediamine, yielding the polymers DTPA-HMD and DTPA-CHD, with low polydispersity. Their molecular flexibility in solution was studied using 13 C spin-lattice relaxation time measurements, indicating that the cyclohexanediamine linking moiety of the DTPA-HMD polymer is more rigid than that of DTPA-CHD. The influence of the flexibility of the linking functionalities on the relaxivity of the Gd 3+ -DTPApolymer conjugates was studied by water nuclear magnetic relaxation dispersion (NMRD). The relaxivity of the Gd(DTPA-CHD) polymer was only slightly higher than that of the Gd(DTPA-HMD) polymer, and only two times higher than the usual values for small Gd-DTPA-like chelates. The low relaxivities obtained for both polymers, much lower than expected from the polymer apparent molecular weights, result from their substantial residual flexibility, and also from a too long, nonoptimal, value of the inner-sphere water exchange rate. These polymeric compounds are also cleared very quickly from the blood of rats, indicating that they are of limited value as blood pool contrast agents for MRA.

show abstract

Section: Discussionmentioning

confidence: 89%

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

et al. 2001

View full text Add to dashboard Cite

show abstract

“…A similar trend was observed also for H 5 dtpa, where constant log β 1 determined with NaCl as the supporting electrolyte is about one order of magnitude lower (9.45 [22] ) than that measured in TMAC (10.41, [22] Table 2). Accordingly to NMR-assigned sites of protonations [16] and well-known protonation Scheme of H 5 dtpa itself, [23] the first and second protonations take place on the nitrogen atoms of the ligand 6 35.23(8) …”

Section: Equilibrium Studiesmentioning

confidence: 99%

Study of Thermodynamic and Kinetic Stability of Transition Metal and Lanthanide Complexes of DTPA Analogues with a Phosphorus Acid Pendant Arm

et al. 2006

View full text Add to dashboard Cite

The thermodynamic and kinetic stabilities of the complexes of phosphonate and phenylphosphinate analogues of H 5 dtpa with selected transition-and lanthanide-metal ions are presented. Both phosphorus-containing ligands form thermodynamically very stable complexes, with stability constants comparable with or even higher than those reported for the parent H 5 dtpa. However, the kinetic inertness of their gadolinium(III) complexes against acid-and metal-assisted decomplexations is surprisingly much lower. The half-life times of gadolinium(III) complexes of the new ligands in the pres-

show abstract

“…[30] The procedure used to obtain the protonation fractions at each ligand site has been described in detail. [31] In summary, the shifts of the protonated species (δ H n L ), obtained by fitting the experimental pH titration curves by using the potentiometric protonation constants, were used to calculate the protonation fractions (%) at the nitrogen [f N = f (1) , f (2) , f (3) ] and oxygen [f O = f (4) , f (5) , f (6) ] atoms (labelled in Figure 1) of each ligand protonation state H n L (integer n = 1, 2, 3,... is the number of moles of acid added per mole of ligand). It was assumed that the protonation shifts at the various sites are additive, with a total shift (Δδ) given by the expression Δδ = ΣC N ·f N + ΣC NЈ ·f N + ΣC O ·f O , where C N = 0.75 ppm, C NЈ = 0.35 ppm and C O = 0.20 ppm are pHindependent shielding constants valid for linear poly(aminocarboxylate) ligands.…”

Section: Nmr Ph Titrationsmentioning

confidence: 99%

“…The f i values for n = 1 show that the first protonation is very similar for the three ligands, where the more basic central nitrogen atom [N (2) ] is protonated preferentially to the terminal ones, as was also found for DTPA. [26,30,31] For n = 2, there is a preference for the protonation of the terminal nitrogen atoms over that of the central nitrogen atom in all ligands. However, the protonation of the two terminal nitrogen atoms is quite distinct in the three asymmetric ligands EPTPA and the two derivatives studied in this work.…”

Section: Nmr Ph Titrationsmentioning

confidence: 99%

“…[30] Changes in chemical shifts can quantitatively indicate the site of protonation. [30,31] The 1 H NMR pH titration curves for some of the protons of the ligands H 5 EPTPACH 2 OH and H 5 EPTPAC16 are shown in Figure 4. The corresponding resonances were assigned at different pH values on the basis of signal multiplicities, the signal crossovers, and COSY spectra in the whole pH range studied.…”

Section: Nmr Ph Titrationsmentioning

confidence: 99%

See 1 more Smart Citation

H₅EPTPACH₂OH: Synthesis, Relaxometric Characterization and ¹H NMR Spectroscopic Studies on the Solution Dynamics of Its Ln^III Complexes

et al. 2007

View full text Add to dashboard Cite

The synthesis and characterization of a new metal chelator, 4‐(S)‐hydroxymethyl‐3,6,10‐tri(carboxymethyl)‐3,6,10‐triazadodecanedioic acid (H5EPTPACH2OH), is reported. Protonation constants for the ligand H5EPTPACH2OH and for the previously reported H5EPTPAC16 have been determined by potentiometry, which reveals that both ligands display slightly higher protonation constants relative to that of the ligand DTPA5–. The stability constant for the [Gd(EPTPACH2OH)(H2O)]2– complex has also been determined by potentiometry. The obtained value (log KGdL = 16.7) is two orders of magnitude lower than that for the [Gd(EPTPA)(H2O)]2– complex, which indicates the destabilizing effect of the pendant hydroxymethyl group at the EPTPA backbone. The microscopic protonation scheme has been deduced from the pH dependence of the 1H NMR spectra of both H5EPTPACH2OH and H5EPTPAC16 ligands. The first two protonations occur exclusively at the backbone nitrogen atoms – the first protonation occurs preferentially at the more basic central nitrogen atom. The second proton distributes preferentially between the two terminal nitrogen atoms with the favoring of the trimethylene nitrogen atom over the ethylene nitrogen atom. The LnIII complexes of the ligand H5EPTPACH2OH have been prepared and their solution dynamics studied by 1H NMR spectroscopy. Two sets of resonances of very different intensities from two isomeric complexes have been observed. Relaxometric investigations (17O NMR and 1H NMRD) demonstrate that the [Gd(EPTPACH2OH)(H2O)]2– complex displays an accelerated water‐exchange rate (kex = 87.6 × 106 s–1) that is close to the theoretically derived optimal value. However, the kinetic stability of this complex in phosphate‐buffered solutions towards Zn2+ transmetallation is quite low, but higher than that of the corresponding methyl derivative.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

show abstract

Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents

Cited by 98 publications

References 42 publications

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

Study of Thermodynamic and Kinetic Stability of Transition Metal and Lanthanide Complexes of DTPA Analogues with a Phosphorus Acid Pendant Arm

H₅EPTPACH₂OH: Synthesis, Relaxometric Characterization and ¹H NMR Spectroscopic Studies on the Solution Dynamics of Its Ln^III Complexes

Contact Info

Product

Resources

About

Preparation, physico-chemical characterization, and relaxometry studies of various gadolinium(III)-DTPA-bis(amide) derivatives as potential magnetic resonance contrast agents

Cited by 98 publications

References 42 publications

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

Synthesis, Characterization, and Relaxivity of Two Linear Gd(DTPA)−Polymer Conjugates

Study of Thermodynamic and Kinetic Stability of Transition Metal and Lanthanide Complexes of DTPA Analogues with a Phosphorus Acid Pendant Arm

H5EPTPACH2OH: Synthesis, Relaxometric Characterization and 1H NMR Spectroscopic Studies on the Solution Dynamics of Its LnIII Complexes

Contact Info

Product

Resources

About

H₅EPTPACH₂OH: Synthesis, Relaxometric Characterization and ¹H NMR Spectroscopic Studies on the Solution Dynamics of Its Ln^III Complexes