Monovalent Gold

Survival was reduced in adult mice infected with various viruses - including Semliki Forest vims, various strains of yellow fever vims, and West Nile vims - after intraperitoneal injection of gold sodium thiomalate. Adverse effects of therapeutic monovalent gold compounds may be linked to their ability to induce membrane proliferation. For example, the virulent strain of Semliki Forest virus in adult mice is characterized by the development of numerous membrane vesicles in brain with mature vims budding from these stmctures. In contrast, infection of the avirulent strain of Semliki Forest vims results in the formation of very few membrane vesicles and no mature vims particles in adult mouse brain. Proliferation of smooth membrane vesicles from whole mouse brain was induced in mice treated with gold sodium thiomalate. In certain vims infections, smooth membranes are a prerequisite for vims RNA synthesis and maturation. The ability of a virus to stimulate the smooth membranes may be the limiting factor in determining both the extent of viral RNA synthesis and maturation. This mechanism could 

Carcinogenicity and teratogenicity of Myo-chrisine (C4H3AuNa204S), the disodium salt of gold sodium thiomalate (C4H4AuNa04S), is reported at high doses in rats and rabbits. Renal adenomas are documented in rats at 

0 mg Au/kg BW weekly for 45 weeks followed by 6.0 mg/kg BW daily for 47 weeks this dosage is equivalent to twice that administered to humans at the low dose and 42 times at the high dose. Adenomas produced were similar to those produced in rats by chronic administration of other gold compounds, lead, and other heavy metals. There is no report of Myochrisine-associated renal adenomas in humans. 

Gold salts injected subcutaneously over a 10-day period induced an autoimmune syndrome similar to that of HgCli in brown Norway rats. The auto-immune syndrome in both cases was characterized by a marked increase in IgE production, lymphoprolifera-tion, T cell-dependent polyclonal B cell activation, hypergammaglobulinaemia, and tissue injury widi necrotizing leucocytoclastic vasculitis in the gut at day 15 post-injection. 

Gold also induced granulomata and neutrophil infiltrates in the lung at day 15 post-injection. 

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When trivalent gold is mixed with sulfite and thiosulfate, it is reduced to monovalent gold. Kato et al. studied the stoichiometry of the redox reaction and arrived at the conclusion that the predominant gold species in the system is [Au(S203)2], a monovalent gold thiosulfate complex. If the solution contains only sulfite but no thiosulfate, the gold complex takes the form of [Au(S03)2] , a monovalent gold sulfite complex ... 

Hubert Schmidbaur, Andreas Grohmann, M. Elena Olmos and Annette Schier of bis(ylide) complexes of monovalent gold (equation 53)227. 

FIGURE 12. Heterometallic cluster compounds of monovalent gold containing gold-carbon bonds... 

The steady state radiolysis of gold compounds is mainly concerned with the reduction of trivalent gold to the metal (13, 16). The reported yield, G(-Aum)eq = 2.3 0.2 (16), has been interpreted to arise from 2GH2o2 + Gh — G0h, where the G s stand for the primary radiolytic yields. From the point of view of pulse radiolytic investigation, Au1 is, however, more interesting. Since monovalent gold is unstable except when complexed (17), the choice of a suitable compound is very limited. 

However, the monovalent gold compounds bring symptomatic relief to rheumatoid arthritis in patients. A few classical examples of this class of compounds are discussed below. Examples auranfin aurothioglucose aurothioglycanide sodium aurothiomalate. 

Discuss the monovalent gold eompounds as NSAID. Give the synthesis of auranotin and aurothioglucose along with their usage. 

Anti-HIV activity of monovalent gold compounds were associated with inhibition of reverse transcriptase (RT), an enzyme that converts RNA into DNA in the host cell. Other reports indicate that Au" " inhibits the infection of cells by HIV strains without inhibiting the RT activity, with the critical target site tentatively identified as a glycoprotein of the viral envelope. Other reports show that Au(CN)2 at concentrations as low as 20 xg/L is incorporated into a T-cell line susceptible to HIV infection, and retards the proliferation of HIV in these cells. This concentration is well tolerated in patients with rheumatoid arthritis, suggesting that Au(CN)2 may have promise for existing HIV patients. 

Trivalent gold is sigiuficantly more toxic to aquatic biota than monovalent gold. Gold, as tetrachloroaurate (AuCl ), depressed... 

Monovalent gold salts impacted metabolism of seleifium, copper, and zinc. Intravenous Au" " may adversely affect the availability of seleifium for synthesis of selenoenzymes. Rats given gold sodium thiomalate iv at 25.0 or 50.0 xmol/kg BW had sigifificantly altered seleifium deposition, as measured by radioselenium-75. These effects included the almost complete cessation of Se exhalation as dimethyl sulfide and the accumulation of Se in blood plasma. Direct chemical reaction with nucleophilic selenium metabolites in the body may underlie these alterations. Auranofin inhibited selenium-glutathione peroxidase in bovine erythrocytes this enzyme... 

The presence of cyanide ions greatly alters this behavior because they form a very stable complex with monovalent gold. The electrode reaction between metallic and monovalent gold now reads ... 

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