Dimercaptosuccinic acid

Dimercaptosuccinic acid

Names
IUPAC name meso-2,3-dimercaptosuccinic acid
Other names succimer, APRD01236 (Drugbank), Chemet
Identifiers
CAS Number	304-55-2 Y
ChEMBL	ChEMBL1201073 N
ChemSpider	2006502 N
EC Number	259-952-2
Jmol 3D model	Interactive image
PubChem	2724354
UNII	DX1U2629QE Y
InChI InChI=1S/C4H6O4S2/c5-3(6)1(9)2(10)4(7)8/h1-2,9-10H,(H,5,6)(H,7,8)/t1-,2+ N Key: ACTRVOBWPAIOHC-XIXRPRMCSA-N N InChI=1/C4H6O4S2/c5-3(6)1(9)2(10)4(7)8/h1-2,9-10H,(H,5,6)(H,7,8)/t1-,2+ Key: ACTRVOBWPAIOHC-XIXRPRMCBX
SMILES O=C(O)[C@@H](S)[C@@H](S)C(=O)O
Properties
Chemical formula	C4H6O4S2
Molar mass	182.22 g/mol
Melting point	125 °C (257 °F; 398 K)
Related compounds
Related	Tartaric acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YN ?)
Infobox references

Dimercaptosuccinic acid (DMSA), is the organosulfur compound with the formula HO₂CCH(SH)CH(SH)CO₂H. This colorless solid contains two carboxylic acid and two thiol groups, the latter being responsible for its mildly unpleasant odour. It occurs in two diastereomers, meso and the chiral dl forms. The meso isomer is used as a chelating agent. The acid is most often used as a treatment for heavy metal toxicity, and is a water-soluble and non-toxic substance.

It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Medical uses

Dimercaptosuccinic acid (CHEMET) is indicated for the treatment of lead poisoning in children with blood level measured above 45 µg/dL. The use of DMSA is not approved for prevention of lead poisoning in anticipation of exposure in known lead contaminated environments. Its elimination half-life is 2.5-3.5 h. DMSA can cross the blood–brain barrier of mice, but not that of humans, limiting its use to extracting heavy metals from parts of the body other than the central nervous system.

Another application for DMSA is for provocation of tissue heavy metals in anticipation of a urine test. This is sometimes called a "challenge" or "provoked" heavy metals test. DMSA is used to help mobilize heavy metals stored in body tissues (and therefore not typically present in the circulation) and increase the excretion of heavy metals in the urine. In a study by Howard Frumkin et al., this sort of test was shown to not reliably provide an indication of past chronic mercury exposure, something it was often used for. A 2004 study by GP Archbold, et al. called the results of a DMSA challenge test "misleading" for the purposes of diagnosing mercury toxicity. Moreover, DMSA share the limitation of extracellular distribution, which makes it unable to cross the cell membrane and chelate heavy metals from intracellular sites.

The relative activities of a series of novel monoalkyl esters of meso-2,3-dimercaptosuccinic acid (MiADMSA) have been examined as agents for the mobilization of cadmium, lead and arsenic owing to the ability of these monoesters to cross cell membranes. The monoesters were found to be more effective than the parent compound DMSA. The complexes (monoesters of DMSA) seem to penetrate cells (not possible in the case of DMSA), which helps in targeting intracellular sites in the body and aids in the removal of toxic metal ions in the cytosol and organelles inside the cell.

Stereochemistry

The 2,3-dimercaptosuccinic acid molecule has two stereocentres (two asymmetric carbons), and can exist as three different stereoisomers. The 2S,3S and 2R,3R isomers are a pair of enantiomers, whereas the 2R,3S isomer is a meso compound and thus optically inactive.

(2R,3R)-2,3-dimercaptosuccinic acid	(2R,3S)-2,3-dimercaptosuccinic acid (meso-2,3-dimercaptosuccinic acid)	(2S,3S)-2,3-dimercaptosuccinic acid

Preparation and reactivity

DMSA may be prepared by reacting acetylenedicarboxylic acid with sodium thiosulfate or thioacetic acid followed by hydrolysis. The dimethyl ester is also known.

Meso 2,3-dimercaptosuccinic acid binds to "soft" heavy metals such as Hg²⁺ and Pb²⁺, mobilizing these ions for excretion. It binds to metal cations through the thiol groups, which ionize upon complexation.

History

DMSA was first synthesized by V. Nirenburg in the Urals Polytechnic Institute, commissioned by one of the electrical enterprises of Sverdlovsk, which consumed many tons of mercury and was looking for a medicine to prevent poisoning of personnel. In 1957, it was found by Chinese scientists that DMSA can effectively treat antimony poisoning due to overdose of tartar emetic. Pronounced protective effect in animal poisoning with arsenic and mercury was first shown by I. Okonishnikova in 1962. In 1984 the now-defunct Bock Pharmaceutical Company requested the FDA grant approval for Orphan drug status under the trade name Chemet and the FDA approved of this in 1991 providing exclusivity until 1998 which was conveyed to the successor Sanofi in 1996.

See also

• Chelation therapy
• 2,3-Dimercapto-1-propanesulfonic acid
• EDTA
• Heavy metal poisoning
• Mercury poisoning
• Succinic acid
• Tartaric acid
• DMSA scan