Gadobenic acid

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Gadobenic acid
Structure of Gadobenic acid.png
Clinical data
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • dihydrogen [(±)-4-carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oato(5−)]gadolinate(2−).
CAS Number
  • 113662-23-0 X mark.svgN
PubChem CID
DrugBank
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UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C22H28GdN3O11
Molar mass 667.73 g·mol−1
3D model (JSmol)
  • [H+].[H+].[Gd+3].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)C(C([O-])=O)COCc1ccccc1
  • InChI=1S/C22H31N3O11.Gd/c26-18(27)10-23(6-7-24(11-19(28)29)12-20(30)31)8-9-25(13-21(32)33)17(22(34)35)15-36-14-16-4-2-1-3-5-16;/h1-5,17H,6-15H2,(H,26,27)(H,28,29)(H,30,31)(H,32,33)(H,34,35);/q;+3/p-3 X mark.svgN
  • Key:MXZROTBGJUUXID-UHFFFAOYSA-K X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Gadobenic acid (INN, trade name MultiHance) is a complex of gadolinium with the ligand BOPTA. In the form of the methylglucamine salt meglumine gadobenate (INNm) or gadobenate dimeglumine (USAN), it is used as a gadolinium-based MRI contrast medium. [1]

BOPTA is a derivative of DTPA in which one terminal carboxyl group, –C(O)OH is replaced by -C–O–CH2C6H5. Thus gadobenic acid is closely related to gadopentetic acid. BOPTA itself was first synthesized in 1995. [2] In the "gadobenate" ion gadolinium ion is 9-coordinate with BOPTA acting as an 8-coordinating ligand. The ninth position is occupied by a water molecule, which exchanges rapidly with water molecules in the immediate vicinity of the strongly paramagnetic complex, providing a mechanism for MRI contrast enhancement. 139La NMR studies on the diamagnetic La-BOPTA2− complex suggest that the Gd complex maintains in solution the same kind of coordination as found, by X-ray crystallography, in the solid state for Gd-BOPTA disodium salt. [2]

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Related Research Articles

Coordination complex Molecule or ion containing ligands datively bonded to a central metallic atom

A coordination complex consists of a central atom or ion, which is usually metallic and is called the coordination centre, and a surrounding array of bound molecules or ions, that are in turn known as ligands or complexing agents. Many metal-containing compounds, especially those of transition metals, are coordination complexes.

Gadolinium Chemical element, symbol Gd and atomic number 64

Gadolinium is a chemical element with the symbol Gd and atomic number 64. Gadolinium is a silvery-white metal when oxidation is removed. It is only slightly malleable and is a ductile rare-earth element. Gadolinium reacts with atmospheric oxygen or moisture slowly to form a black coating. Gadolinium below its Curie point of 20 °C (68 °F) is ferromagnetic, with an attraction to a magnetic field higher than that of nickel. Above this temperature it is the most paramagnetic element. It is found in nature only in an oxidized form. When separated, it usually has impurities of the other rare-earths because of their similar chemical properties.

Hydroxide Chemical compound

Hydroxide is a diatomic anion with chemical formula OH. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. It functions as a base, a ligand, a nucleophile, and a catalyst. The hydroxide ion forms salts, some of which dissociate in aqueous solution, liberating solvated hydroxide ions. Sodium hydroxide is a multi-million-ton per annum commodity chemical. A hydroxide attached to a strongly electropositive center may itself ionize, liberating a hydrogen cation (H+), making the parent compound an acid.

Inorganic chemistry deals with synthesis and behavior of inorganic and organometallic compounds. This field covers chemical compounds that are not carbon-based, which are the subjects of organic chemistry. The distinction between the two disciplines is far from absolute, as there is much overlap in the subdiscipline of organometallic chemistry. It has applications in every aspect of the chemical industry, including catalysis, materials science, pigments, surfactants, coatings, medications, fuels, and agriculture.

The lanthanide or lanthanoid series of chemical elements comprises the 15 metallic chemical elements with atomic numbers 57–71, from lanthanum through lutetium. These elements, along with the chemically similar elements scandium and yttrium, are often collectively known as the rare-earth elements.

Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate ligand and a single central atom. These ligands are called chelants, chelators, chelating agents, or sequestering agents. They are usually organic compounds, but this is not a necessity, as in the case of zinc and its use as a maintenance therapy to prevent the absorption of copper in people with Wilson's disease.

Gadolinium(III) chloride Chemical compound

Gadolinium(III) chloride, also known as gadolinium trichloride, is GdCl3. It is a colorless, hygroscopic, water-soluble solid. The hexahydrate GdCl3∙6H2O is commonly encountered and is sometimes also called gadolinium trichloride. Gd3+ species are of special interest because the ion has the maximum number of unpaired spins possible, at least for known elements. With seven valence electrons and seven available f-orbitals, all seven electrons are unpaired and symmetrically arranged around the metal. The high magnetism and high symmetry combine to make Gd3+ a useful component in NMR spectroscopy and MRI.

In organic chemistry, the tropylium ion or cycloheptatrienyl cation is an aromatic species with a formula of [C7H7]+. Its name derives from the molecule tropine from which cycloheptatriene (tropylidene) was first synthesized in 1881. Salts of the tropylium cation can be stable, even with nucleophiles of moderate strength e.g., tropylium tetrafluoroborate and tropylium bromide (see below). Its bromide and chloride salts can be made from cycloheptatriene and bromine or phosphorus pentachloride, respectively.

Gadopentetic acid Complex of gadolinium by DTPA

Gadopentetic acid is one of the trade names for a gadolinium-based MRI contrast agent, usually administered as a salt of a complex of gadolinium with DTPA (diethylenetriaminepentacetate) with the chemical formula A2[Gd(DTPA)(H2O)]; when cation A is the protonated form of the amino sugar meglumine the salt goes under the name "gadopentetate dimeglumine". It was described in 1981 by Hanns-Joachim Weinmann and colleagues and introduced as the first MRI contrast agent in 1987 by the Schering AG. It is used to assist imaging of blood vessels and of inflamed or diseased tissue where the blood vessels become "leaky". It is often used when viewing intracranial lesions with abnormal vascularity or abnormalities in the blood–brain barrier. It is usually injected intravenously. Gd-DTPA is classed as an acyclic, ionic gadolinium contrast medium. Its paramagnetic property reduces the T1 relaxation time (and to some extent the T2 and T2* relaxation times) in NMR, which is the source of its clinical utility.

Pentetic acid DTPA: aminopolycarboxylic acid

Pentetic acid or diethylenetriaminepentaacetic acid (DTPA) is an aminopolycarboxylic acid consisting of a diethylenetriamine backbone with five carboxymethyl groups. The molecule can be viewed as an expanded version of EDTA and is used similarly. It is a white solid with limited solubility in water.

Coordination sphere

In coordination chemistry, the first coordination sphere refers to the array of molecules and ions directly attached to the central metal atom. The second coordination sphere consists of molecules and ions that attached in various ways to the first coordination sphere.

Gadolinium(III) oxide Chemical compound

Gadolinium(III) oxide (archaically gadolinia) is an inorganic compound with the formula Gd2O3. It is one of the most commonly available forms of the rare-earth element gadolinium, derivatives of which are potential contrast agents for magnetic resonance imaging.

Gadolinium oxysulfide (Gd2O2S), also called gadolinium sulfoxylate, GOS or Gadox, is an inorganic compound, a mixed oxide-sulfide of gadolinium. Its CAS number is 12339-07-0.

Nephrogenic systemic fibrosis is a rare syndrome that involves fibrosis of skin, joints, eyes, and internal organs. NSF is caused by exposure to gadolinium in gadolinium-based MRI contrast agents (GBCAs) in patients with impaired kidney function. Epidemiological studies suggest that the incidence of NSF is unrelated to gender or ethnicity and it is not thought to have a genetic basis. After GBCAs were identified as a cause of the disorder in 2006, and screening and prevention measures put in place, it is now considered rare.

MRI contrast agent Types of contrast agents used for magnetic resonance imaging

MRI contrast agents are contrast agents used to improve the visibility of internal body structures in magnetic resonance imaging (MRI). The most commonly used compounds for contrast enhancement are gadolinium-based. Such MRI contrast agents shorten the relaxation times of nuclei within body tissues following oral or intravenous administration.

Gadoxetic acid

Gadoxetic acid is a gadolinium-based MRI contrast agent. Its salt, gadoxetate disodium, is marketed as Primovist in Europe and Eovist in the United States by Bayer HealthCare Pharmaceuticals.

DOTA (chelator) Chemical compound

DOTA (also known as tetraxetan) is an organic compound with the formula (CH2CH2NCH2CO2H)4. The molecule consists of a central 12-membered tetraaza (i.e., containing four nitrogen atoms) ring. DOTA is used as a complexing agent, especially for lanthanide ions. Its complexes have medical applications as contrast agents and cancer treatments.

Metallacrown

Metallacrowns are a unique class of macrocyclic compounds that consist of metal ions and solely or predominantly heteroatoms in the ring. Classically, metallacrowns contain an [M–N–O] repeat unit in the macrocycle. First discovered by Vincent L. Pecoraro and Myoung Soo Lah in 1989, metallacrowns are best described as inorganic analogues of crown ethers. To date, over 600 reports of metallacrown research have been published. Metallacrowns with sizes ranging from 12-MC-4 to 60-MC-20 have been synthesized.

Equilibrium chemistry is concerned with systems in chemical equilibrium. The unifying principle is that the free energy of a system at equilibrium is the minimum possible, so that the slope of the free energy with respect to the reaction coordinate is zero. This principle, applied to mixtures at equilibrium provides a definition of an equilibrium constant. Applications include acid–base, host–guest, metal–complex, solubility, partition, chromatography and redox equilibria.

A metal ion in aqueous solution or aqua ion is a cation, dissolved in water, of chemical formula [M(H2O)n]z+. The solvation number, n, determined by a variety of experimental methods is 4 for Li+ and Be2+ and 6 for elements in periods 3 and 4 of the periodic table. Lanthanide and actinide aqua ions have a solvation number of 8 or 9. The strength of the bonds between the metal ion and water molecules in the primary solvation shell increases with the electrical charge, z, on the metal ion and decreases as its ionic radius, r, increases. Aqua ions are subject to hydrolysis. The logarithm of the first hydrolysis constant is proportional to z2/r for most aqua ions.

References

  1. Sweetman, Sean C., ed. (2009). "Contrast Media". Martindale: The Complete Drug Reference (36th ed.). London: Pharmaceutical Press. p. 1478. ISBN   978-0-85369-840-1.
  2. 1 2 Uggeri F, Aime S, Anelli PL, Botta M, Brocchetta M, de Haeen C, Ermondi G, Grandi M, Paoli P (1995). "Novel Contrast Agents for Magnetic Resonance Imaging. Synthesis and Characterization of the Ligand BOPTA and Its Ln(III) Complexes (Ln = Gd, La, Lu). X-ray Structure of Disodium (TPS-9-145337286-C-S)-[4-Carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa- 5,8,11-triazatridecan-13-oato(5-)]gadolinate(2-) in a Mixture with Its Enantiomer". Inorganic Chemistry. 34 (3): 633–643. doi:10.1021/ic00107a017. ISSN   0020-1669.