Thiols arsenical, react with

Thus, all the biological systems that we have studied to date confirm that the arsenical reacts with the thiol groups of proteins, predominantly, and most likely does damage by shutting down enzymes that have thiol groups at the active sites. 

Minimal Interactions with Assay Components. If a buffer binds to or reacts with a component of the system, it should be avoided. For example, borate buffers can complex with alcohols and carbohydrates and great care should be exercised when utilizing these compounds. Some arsenate-based buffers have oxidizing potential with respect to thiols. Buffers should also have a low binding capacity with respect to divalent cations. 

Just as arsenate itself reacts with thiols (Section II,B), arsonic acids are also reduced by them, with formation of dialkyl alkyldithioarsonites (123,124), as follows ... 

Trivalent arsenic forms strong bonds with sulfur, and thiols are therefore used for derivatizing both lewisite and CVAA, forming the same derivative (19). Lewisite reacts with mono and dithiols the reaction with dithiols occurring rapidly at ambient temperature. In a competitive environment, lewisite reacts almost exclusively with dithiols rather than monothiols (35). Three dithiols, 1,2-ethanedithiol, 1,3-propanedithiol and 2,3-dimercaptopropan-l-ol (British Anti-Lewisite, BAL) have been used for biomedical sample analysis of CVAA to form cyclic derivatives (14a, b) and (15). Unlike derivatiza-tion of TDG, CVAA can be derivatized direcdy in an aqueous solution. 2,3-Dimercaptotoluene, which has been used extensively for environmental analysis (19), does not appear to have been used. 

Some years later, stereoselective syntheses of a variety of optically active esters of arsinthious acids were reported. The esters were prepared by treating secondary chloroarsines with thiols in the presence of (—)-N,N-diethyl-a-methylbenzylamine. The n-pentyl ester 135, when allowed to react with n-propylmagnesium bromide, gave (R)-(—)-65 with low stereoselectivity and inversion at arsenic as indicated in equation 19 (Table... 

The trivalent forms of arsenic apparently exerts their toxic effects chiefly by reacting with the sulfhydryl groups of vital cellular enzymes. Pyruvate dehydrogenase seems to be a particularly vulnerable site in the metabolism, because it contains the thiol lipoic acid that is especially reactive with trivalent arsenicals. 

Chlorine, phosgene. Lewisite, and SM all react with thiol groups as well as produce oxidants. The arsenic group in Lewisite has a high affinity to the alpha and gamma thiol groups of lipoic acid found in enzymes (e.g., pyruvate oxidase). Oxidants occur as part of the normal metabolism of cells (redox homeostasis). In the diseased state (e.g., exposure to a chemical agent), there is an acute... 

Adamsite 1 is the most difficult of the organoarsenicals to analyze. It has very high thermal stability and does not hydrolyze readily in the environment. Like most arsenicals, attempts to assess Adamsite by gas chromatography (GC) lead to rapid column deterioration and Adamsite carmot be derivatized with thiol derivatives <2003JCH(1000)253>. Schoene etal. developed two derivatization reactions for Adamsite. In the first, it was reacted with bromine in AcOH to give 2,2, 4,4, 6,6 -hexabromodiphenylamine 37. The alternative derivatization involved pyrolytic ethylation with dimethylformamide diethyl acetal (DMFDEA) and pyridine to yield 10-ethyl-5,10-dihydrophenarsazinine 38. The reaction mixture, which is Adamsite, EtOH, pyridine, and DMFDEA 39, was stored for 3 days in a closed vial at 90 °C. On column injection of 1 pi from this solution, no ethyl derivative could be detected, whereas splitless injection at 290°C injector temperature afforded EtPA 38 in the expected amount (Scheme 14) <1996JCH(719)401>. 

Arsenic and antimony show a fairly strong affinity for sulphur. Halides RMCI2 (M = As, Sb) react with H S or NaSH to give oligomeric sulphides (RMS) and with thiols to yield RM(SR )2. Dithiols afford stable and relatively harmless products. This property was used to combat the notorious Lewisite. 

In connection with lipoic acid chemistry, mention should be made of arsenic compounds, some of the oldest and best-known poisons used throughout history. More recently, organic derivatives have been used as fungicides and insecticides. The more important arsenic compounds from a toxic stand point are trivalent compounds. Arsenite (0=As — O ) for instance is noted for its tendency to react rapidly with thiol groups, especially dithiols such as reduced lipoic acid. The result is that by blocking oxidative enzymes which require lipoic acid, arsenite causes the accumulation of pyruvate and other a-keto acids. 

More recently Racket 116) reported that purified GSSG reductase of yeast and liver react also with DPNH, but at a slower rate than with TPNH. The DPNH-GSSG reaction is dependent on phosphate or arsenate and is inhibited by neutral salts, while the TPNH-GSSG reductase can be coupled to homocystine reduction. It should be remembered that a disulfide-thiol type of exchange reaction, described by Eldjam et al. (6) can explain the homocystine GSH interaction. 

---