Stereoisomeric selectivity of 2,3-dimercaptosuccinic acid in chelation therapy for heavy metal poisoning.

Persistent Link:
http://hdl.handle.net/10150/187045
Title:
Stereoisomeric selectivity of 2,3-dimercaptosuccinic acid in chelation therapy for heavy metal poisoning.
Author:
Fang, Xiaojun.
Issue Date:
1995
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Racemic-2,3-dimercaptosuccinic acid (rac-DMSA)¹ was synthesized and its structure in the solid state was studied by single crystal X-ray analysis. The three-dimensional structure of rac-DMSA solid is stabilized by van der Waals forces, whereas the meso-DMSA solid is stabilized by hydrogen bonding. This accounts for the drastic difference in the solubilities of DMSA stereoisomers. The behavior of DMSA stereoisomers in aqueous solution were studied by potentiometric titration, IR and ¹H NMR. Rac-DMSA irreversibly converts to the meso form at an elevated temperature under acidic conditions. Two mechanisms were proposed to explain the conversion. At high pH rac-DMSA tends to form ion-paired complexes with alkaline counter ions via two carboxylate groups. At physiological pH DMSA stereoisomers form two intramolecular six-membered rings. The formation constants and the structures of lead and zinc chelates of DMSA stereoisomers formed in aqueous solution were determined by potentiometric titration, IR and ¹H NMR. Lead and zinc complex with rac-DMSA to a greater extent than with meso-DMSA. DMSA stereoisomers tend to form dimeric chelates with Zn²⁺, but monomeric chelates with Pb²⁺. In the zinc chelates of rac-DMSA two bulky carboxylate groups of the ligand have a staggered anti-relation, whereas in the zinc chelates of meso-DMSA two carboxylate groups assumes a staggered gauche-relation. This accounts for that the formation constants of zinc chelates of rac-DMSA are invariably larger than those of the corresponding chelates of meso-DMSA. The binding sites in PbL of DMSA stereoisomers are two thiolate groups and one carboxylate group of the ligands. In the lead chelates of the stereoisomers of DMSA, rac-DMSA exists in a staggered anti-conformation, but meso-DMSA favors a staggered gauche-conformation with respect to the bulky carboxylate groups. This accounts for that the formation constants of the lead chelates of rac-DMSA are invariably larger than those of the corresponding chelates of meso-DMSA. On the basis of our studies ZnL₂ chelate of rac-DMSA has been proposed to be a more effective lead chelator than meso-DMSA for therapeutical use.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Chemistry; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Fernando, Quintus

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleStereoisomeric selectivity of 2,3-dimercaptosuccinic acid in chelation therapy for heavy metal poisoning.en_US
dc.creatorFang, Xiaojun.en_US
dc.contributor.authorFang, Xiaojun.en_US
dc.date.issued1995en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractRacemic-2,3-dimercaptosuccinic acid (rac-DMSA)¹ was synthesized and its structure in the solid state was studied by single crystal X-ray analysis. The three-dimensional structure of rac-DMSA solid is stabilized by van der Waals forces, whereas the meso-DMSA solid is stabilized by hydrogen bonding. This accounts for the drastic difference in the solubilities of DMSA stereoisomers. The behavior of DMSA stereoisomers in aqueous solution were studied by potentiometric titration, IR and ¹H NMR. Rac-DMSA irreversibly converts to the meso form at an elevated temperature under acidic conditions. Two mechanisms were proposed to explain the conversion. At high pH rac-DMSA tends to form ion-paired complexes with alkaline counter ions via two carboxylate groups. At physiological pH DMSA stereoisomers form two intramolecular six-membered rings. The formation constants and the structures of lead and zinc chelates of DMSA stereoisomers formed in aqueous solution were determined by potentiometric titration, IR and ¹H NMR. Lead and zinc complex with rac-DMSA to a greater extent than with meso-DMSA. DMSA stereoisomers tend to form dimeric chelates with Zn²⁺, but monomeric chelates with Pb²⁺. In the zinc chelates of rac-DMSA two bulky carboxylate groups of the ligand have a staggered anti-relation, whereas in the zinc chelates of meso-DMSA two carboxylate groups assumes a staggered gauche-relation. This accounts for that the formation constants of zinc chelates of rac-DMSA are invariably larger than those of the corresponding chelates of meso-DMSA. The binding sites in PbL of DMSA stereoisomers are two thiolate groups and one carboxylate group of the ligands. In the lead chelates of the stereoisomers of DMSA, rac-DMSA exists in a staggered anti-conformation, but meso-DMSA favors a staggered gauche-conformation with respect to the bulky carboxylate groups. This accounts for that the formation constants of the lead chelates of rac-DMSA are invariably larger than those of the corresponding chelates of meso-DMSA. On the basis of our studies ZnL₂ chelate of rac-DMSA has been proposed to be a more effective lead chelator than meso-DMSA for therapeutical use.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineChemistryen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairFernando, Quintusen_US
dc.contributor.committeememberPemberton, Jeanne E.en_US
dc.contributor.committeememberBurke, Michael F.en_US
dc.contributor.committeememberMiller, Walter B.en_US
dc.contributor.committeememberBates, Robert B.en_US
dc.identifier.proquest9531070en_US
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