Thiols, toxic

Cysteamine (HSCH2CH2NH2) has been found to add to Michael acceptors, such as thujone, in dimethylsulfoxide (DMSO). By contrast, no reaction occurred in nonpolar solvents. NMR spectroscopy was employed to identify good Michael acceptors and sort them into reversible and irreversible thiol sinks with a view of developing a cellular assay for thiol-trapping agents. In another paper, calculated transition-state energies of the reaction of Michael acceptors with MeSH have been used as model system to asses thiol toxicity in aqueous media. ... 

Trimethylsilyl cyanide. This reagent readily silylates alcohols, phenols, and carboxylic acids, and more slowly, thiols and amines. Amides and related compounds do not react with this reagent. The reagent has the advantage that a volatile gas (HCN is highly toxic) is the only byproduct. 

Dissolved in 20% NaOH, extracted with a small amount of C6H6, then steam distd, until clear. The soln was then cooled and acidified slightly with 15% H2SO4. The thiol was distd out, dried with CaS04 or CaCl2, and fractionally distd under N2 [Mathias and Filho J Phys Chem 62 1427 1958]. Also purified by pptn as lead mercaptide from alcoholic soln, with regeneration by adding dilute HCl to the residue after steam distn. All operations should be carried out in a fume cupboard due to the TOXICITY and obnoxious odour of the thiol. 

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

Clinical trials showed therapeutic efficacy in a broad spectrum of tumors these include SCLC, testicular tumors, sarcomas, breast cancer, renal cell cancer, pancreatic tumors and lymphomas. Ifosfamide is less myelosuppressive than cyclophosphamide but is more toxic to the bladder. Therefore it is recommended that ifosfamide is coadministered with the thiol compound mesna to avoid hemorrhagic cystitis and to reduce the risk of developing bladder cancer. Other side effects include neurotoxicity and myelosuppression. 

Unlike heliantholysin and congeners, the toxicity of metridiolysin is not prevented by sphingomyelin, but is inhibited by cholesterol in low concentration, as well as by certain related sterols (23). In addition, metridiolysin is activated by thiols such as dithiothreitol, and is reversibly inactivated by compounds having an affinity for SH-groups, such as p-hydroxy-mercuribenzoate. A third notable feature is that the action of metridiolysin on membranes involves, or is associated with, the formation of 33 nm rings demonstrable by electron microscopy of negatively stained preparations. 

Mercuric chloride, other mercury-containing antibacterials and silver will inhibit enzymes in the membrane, and for that matter in the cytoplasm, which contain thiol, -SH, groups. A similar achon is shown by 2-bromo-2-nitropropan-l,3-diol (bronopol) and iso-thiazolones. Under appropriate condihons the toxic action on cell thiol groups may be reversed by addition of an extrinsic thiol compound, for example cysteine or thioglycollic aeid (see also Chapters 12 and 23). 

Moore, M., Thor, H., Moore, G., Nelson, S., Moldeus, P. and Orrenius, S. (1985). The toxicity of acetaminophen and N-acetyl-/>-benzoquinone imine in isolated hcpatocytes is associated with thiol depletion and increased cytsolic Ca. J. Biol. Chem. 260, 13035-13040. 

Jewell, S.A., DiMonte, D., Richelmi, P., Bellomo, G. and Orrenius, S. (1986). tert-Butylhydroperoxide-induced toxicity in isolated hepatocytes contribution of thiol oxidation and lipid peroxidation. J. Biochem. Toxicol. 1, 13-22. 

Mesna -thiol uroprotectant (binds and inactivates toxic metabolite acrolein) -nausea and vomiting -rash -headache -fatigue and lethargy ... 

Copper is part of several essential enzymes including tyrosinase (melanin production), dopamine beta-hydroxylase (catecholamine production), copper-zinc superoxide dismutase (free radical detoxification), and cytochrome oxidase and ceruloplasmin (iron conversion) (Aaseth and Norseth 1986). All terrestrial animals contain copper as a constituent of cytochrome c oxidase, monophenol oxidase, plasma monoamine oxidase, and copper protein complexes (Schroeder et al. 1966). Excess copper causes a variety of toxic effects, including altered permeability of cellular membranes. The primary target for free cupric ions in the cellular membranes are thiol groups that reduce cupric (Cu+2) to cuprous (Cu+1) upon simultaneous oxidation to disulfides in the membrane. Cuprous ions are reoxidized to Cu+2 in the presence of molecular oxygen molecular oxygen is thereby converted to the toxic superoxide radical O2, which induces lipoperoxidation (Aaseth and Norseth 1986). 

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