Accession Number : ADA468881


Title :   Thiodiglycol, the Hydrolysis Product of Sulfur Mustard: Analysis of In Vitro Biotransformation by Mammalian Alcohol Dehydrogenases using Nuclear Magnetic Resonance


Descriptive Note : Journal article


Corporate Author : ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD


Personal Author(s) : Brimfield, A. A. ; Novak, Mark J. ; Hodgson, Ernest


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA468881


Report Date : 2006


Pagination or Media Count : 10


Abstract : Thiodiglycol (2,2'-bis-hydroxyethylsulfide, TDG), the hydrolysis product of the chemical warfare agent sulfur mustard, has been implicated in toxicity of sulfur mustard through the inhibition of protein phosphatases in mouse liver cytosol. The absence of any inhibitory activity when TDG was present in assays of pure enzymes, however, led us to investigate the possibility for metabolic activation of TDG to inhibitory compound(s) by cytosolic enzymes. We have successfully shown that mammalian alcohol dehydrogenases (ADH) rapidly oxidize TDG in vitro, but the classic spectrophotometric techniques for following this reaction provided no information on the identity of TDG intermediates and products. The use of proton NMR to monitor the oxidative reaction with structural confirmation by independent synthesis allowed us to establish the ultimate product, 2-hydroxyethylthioacetic acid, and to identify an intermediate equilibrium mixture consisting of 2-hydroxyethylthioacetaldehyde, 2-hydroxyethylthioacetaldehyde hydrate and the cyclic 1,4-oxathian-2ol. The intermediate nature of this mixture was determined spectro-photometrically when it was shown to drive the production NADH when added to ADH and NAD.


Descriptors :   *MUSTARD AGENTS , *HYDROLYSIS , REPRINTS , ALCOHOLS , DEHYDROGENASES , NUCLEAR MAGNETIC RESONANCE , IN VITRO ANALYSIS


Subject Categories : BIOCHEMISRTY
      TOXICOLOGY
      CHEMICAL, BIOLOGICAL AND RADIOLOGICAL WARFARE


Distribution Statement : APPROVED FOR PUBLIC RELEASE