Considerations involving paramagnetic coordination compounds as useful NMR contrast agents (original) (raw)
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Trends in NMR studies of paramagnetic Gd(III) complexes as potential contrast agents in MRI
Magnetic Resonance Imaging, 1991
The paramagnetic Gd(II1) complexes with polyaminocarboxylate ligands are intensively studied as possible Contrast Agents for Magnetic Resonance Imaging (M.R.I.). Their ability to enhance the solvent proton relaxation rate is mainly determined by the molecular reorientational time (T,&. In order to increase vR we studied the formation of non-covalent interactions between functionalized Gd(III)-complexes and micelles. The N.M.R.D. (Nuclear Magnetic Relaxation Dispersion) profiles of aqueous solutions of these paramagnetic complexes with hexadecyltrimetbylammonium bromide (CTABr) were measured and the results could be accounted for by difference in negative charge and number of hydrophobic aromatic residues among the different complexes.
Synthesis and Evaluation of a Gd (III) Complex as T 1 -Weighted MRI Contrast Agent
https://ijshr.com/IJSHR\_Vol.4\_Issue.3\_July2019/IJSHR\_Abstract.0016.html, 2019
A hexadentate ligand, H4mum consisting of two phenyl moieties with four acetate arms was designed and synthesized. A water-soluble Gd(III) complex (1) was synthesized by reacting ligand H4mum with GdCl3·xH2O in 1:1 molar equivalent. Tb (III) congener (complex 2) of complex 1 was also synthesized and used for determining the number of coordinated water molecules present in the inner-coordination sphere of the complex by luminescence lifetime measurements. It was confirmed that the complex consisted of two directly coordinated-water molecules. At 25 °C and pH ~ 7.4 in HEPES buffer, the complex offered longitudinal relaxivity r1 value of 8.34 mM–1s–1 at a magnetic field of strength 1.41 T. However, with increasing filed strength to 14.1 T, the r1 relaxivity value slightly deceased to 7.62 mM–1s–1 at the same experimental conditions. The complex stability under physiological conditions was investigated by measuring r1 relaxivity in the presence of various physiological anions. In the presence of almost 100 equivalents (~ 50.0 mM) excess of these anions the r1 value remained almost constant, justified the complex stability under physiological conditions. Finally, phantom MR imaging under clinical scanner at 1.5 T showed positive contrast efficiency of the complex. Keywords: MRI, Contrast agents, Gadolinium (III) complex, Relaxivity, Hydration state, High field.
Insights into the use of paramagnetic Gd(III) complexes in MR-molecular imaging investigations
Journal of Magnetic Resonance Imaging, 2002
Can gadolinium III [Gd(III)] complexes be considered good candidates for magnetic resonance (MR)-molecular imaging studies? In this review article, we examine the principal issues that are the basis of successful use of Gd-based protocols in molecular imaging applications. High relaxivity is the primary requisite. Therefore, the design of such paramagnetic probes has to be pursued keeping in mind the relationships between structure, dynamics, and the relevant parameters involved in paramagnetic relaxation processes. Moreover, the limited number of target molecules on cellular membranes makes it necessary to define strategies aimed at delivering many Gd-containing moieties to the sites of interest. Examples are reported for the attainment of very high relaxivities for the design of new routes for pursuing the accumulation of small sized Gd(III) complexes at the targeting sites. An efficient cellular uptake of Gd-containing probes is the key step for attaining the visualization of targeted cells by MR imaging, and selected examples are reported. In this context, the problem of the assessment of the minimum amount of Gd(III) complexes necessary for the MR imaging-visualization of cells has been addressed by reporting the authors' observations on the cell-internalization of Gd(III) complexes. A particularly efficient delivery system is represented by Gd-loaded apoferritin, which allows the MR visualization of hepatocytes when the number of Gd-complexes per cell is 4 Ϯ 1 ϫ 10 7 . Finally, the potential of responsive systems is considered by outlining the exploitation of the amplification effect brought about by the action of a specific enzymatic activity on the relaxivity of a suitably functionalized Gd(III) complex.
Innovative magnetic resonance imaging diagnostic agents based on paramagnetic Gd(III) complexes
Biopolymers, 2002
complexes are under intense scrutiny as contrast agents for magnetic resonance imaging (MRI). They act by enhancing tissutal proton relaxation rates. Much has already been done in order to get an in-depth understanding of the relationships between structure, dynamics, and contrastographic ability of these paramagnetic complexes. Their potential in the assessment of flow, perfusion, and capillary permeability has already been established. The next challenges are in the field of molecular imaging applications, which would allow the attainment of early diagnosis based on the recognition of specific reporters of the onset of the pathological state. To this end, Gd(III) complexes have to be endowed with improved targeting capabilities by conjugating suitable recognition synthons on their surfaces. Small peptides are candidates of choice for the attainment of this goal. Moreover, the intrinsic low sensitivity of the NMR techniques implies the need to deliver large amounts of contrast agents to the target in order to get its visualization in the resulting images. Highly efficient delivery systems have been identified, which bring a great promise for the development of innovative diagnostic agents based on Gd(III) complexes.
Contrast Media & Molecular Imaging, 2014
To study the physicochemical properties of lanthanide complexes derived from a bifunctional chelating agent based on a PMN-tetraacetic acid moiety {PMN-tetraacetic acid (1): [2,6-pyridinediylbis(methylene nitrilo)-tetraacetic acid]}, 4carboxylic acid substituted pyridine derivative (2) was synthesized. This ligand forms heptadentate (N 3 O 4 ) Ln(III) complexes (Ln = Gd, Eu, Tb), with two water molecules completing the inner coordination sphere of the metal. The parameters that govern the relaxivity of the Gd(III) complex and the luminescence of Eu(III) and Tb(III) complexes were obtained by 17 O and 1 H NMR studies and time-resolved fluorescence experiments, respectively. The gadolinium and terbium complexes show interesting properties either for MRI or FOR optical imaging; that is, for the Gd complex, a high proton relaxivity (r 1 = 6.4 s À1 mM À1 at 20 MHz) with short water residence time (τ M = 38.5 ns); for the Tb complex, a luminescence lifetime of 1.22 ms at room temperature and a luminescence quantum yield of 10%. The kinetic stability of these complexes toward blood protein, cation or bioactive oxyanion was also examined. The Gd(2)(H 2 O) 2 complex does not interact with human serum albumin, but undergoes a transmetalation reaction with Zn(II) in a phosphate buffer solution (pH 7.4), rather similar to that of Gd-DTPA-BMA(H 2 O). On the other hand, as observed for Eu and Tb complexes, these chelates do not form ternary complexes with bidentate anions such as L-lactate, citrate or carbonate. Finally, a phosphatidylserinespecific hexapeptide (TLVSSL) was grafted on Gd or Tb chelates, and the Gd-peptide conjugate was used in vitro for targeting apoptotic cells.
Gadolinium (III) complex equilibria: The implications for Gd(III) MRI contrast agents
Magnetic Resonance in Medicine, 1990
A computer model of blood plasma which has allowed the effect of Gd(II1) contrast agents to be simulated has been developed. Initial binding of Gd(II1) is to transfemn. At high concentration the metal ion binds to citrate and salicylate. At a concentrate of M , GdCI3 is predicted to effect a redistribution of the in vivo Zn(II), Ca(II), and Fe(I1) complexes present in blood plasma. There is little effect on the Cu(I1) distribution. At a concentration below lo-' M EDTA and DTPA have little effect on the free Gd( 111) metal ion concentration. Above this concentration though, the metal ion is bound aimost exclusively to the EDTA or DTPA. An attempt is made to relate the toxicity of GdC13, [Gd(EDTA)]-, and [Gd( DTPA)]'-to the thermodynamic stability of these complexes. The effect of substitution kinetics is also discussed.
Inorganic Chemistry, 2006
Hydroxypyridinone-based Gd(III) complexes have previously been shown to exhibit high relaxivity, especially at the clinically relevant high magnetic fields relevant for present and future clinical use. This is due to more than one coordinated water molecules that exchange rapidly with bulk solvent.. These complexes, however, present poor water-solubility. Heteropodal complexes which include a terephthalamide moiety maintain the high relaxivity characteristics of the HOPO family and have been functionalized with solubilizing substituents of various charges. The charge of the substituent significantly affects the stability of the Gd(III) complex, with the most stable complex presenting a neutral charge. The solubilizing substituent also moderately affects the affinity of the complex for physiological anions, with the highest affinity observed for the positively charged complex. In any case, only two anions, phosphate and oxalate, measureably bind the Gd(III) complex with weak affinities for these two anions that are comparable to other q=1 complexes and much weaker than DO3A, q=2 based complexes. Furthermore, unlike poly(amino-carboxylate) based complexes, HOPO-based Gd(III) complexes do not show any noticeable interaction with carbonates. The nature of the substituent can also favorably stabilize the coordination of a third water molecule on the Gd(III) center and lead to a nine-coordinate ground state. Such complexes that attain q = 3 incorporate a substituent β to the terminal amide of the TAM podand which are hydrogen-bond acceptors, suggesting that the third water molecule is coordinated to the metal center through a hydrogen-bond network. These substituents include alcohols, primary amines, and acids. Moreover, the coordination of a third water molecule has been achieved without destabilizing the complex.