Thermodynamics of the As(III)-thiol interaction: arsenite and monomethylarsenite complexes with glutathione, dihydrolipoic acid, and other thiol ligands.
Colorimetric (near-UV absorption spectroscopy) and calorimetric (isothermal titration calorimetry) methods have been used to quantify the equilibrium and thermodynamics of arsenite and monomethylarsenite (MMA) coordinating to glutathione (GSH) and the dithiols dimercaptosuccinic acid (DMSA), dihydrolipoic acid (DHLA), and dithiothreitol (DTT). We found that both arsenite and MMA form moderately stable complexes (beta = 10(6)-10(7)) with GSH; that arsenite forms a particularly stable 2:3 complex (beta approximately 10(18)) with the biological cofactor DHLA; that MMA has a somewhat higher affinity than arsenite for thiol ligands; and that entropic factors modulate the overall stability of As(III) complexes with thiols, which are favored by the exothermic formation of As(III)-thiolate bonds. The implications of these results for arsenic toxicity are discussed.
Spuches
Anne M
AM
Department of Chemistry, 6128 Burke Laboratory, Dartmouth College, Hanover, New Hampshire 03755.
Kruszyna
Harriet G
HG
Rich
Anne M
AM
Wilcox
Dean E
DE
D001149:Arsenates / Q000737:chemistry; D001151:Arsenic / Q000737:chemistry*; D020261:Arsenic Poisoning; D018053:Arsenites / Q000737:chemistry*; D002151:Calorimetry; D002412:Cations; D004229:Dithiothreitol / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry*; D008024:Ligands; D009942:Organometallic Compounds / Q000737:chemistry; D004113:Succimer / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013816:Thermodynamics; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*
D001149:Arsenates; D018053:Arsenites; D002412:Cations; D008024:Ligands; D009942:Organometallic Compounds; D013438:Sulfhydryl Compounds; D008063:Thioctic Acid; C015144:dihydrolipoic acid; D004113:Succimer; D005978:Glutathione; C015001:arsenite; D001151:Arsenic; D004229:Dithiothreitol