Formation of a cationic gold(I) complex and disulfide by oxidation of the antiarthritic gold drug auranofin. 2003

Ahmed A Mohamed, and Jinhua Chen, and Alice E Bruce, and Mitchell R M Bruce, and Jeanette A Krause Bauer, and David T Hill
Department of Chemistry, The University of Maine, Aubert Hall, Orono, Maine 04469-5706, USA.

The mechanism of action of auranofin, an antiarthritic gold(I) drug, is unknown, but several studies suggest that oxidation may be important for its biochemical effect. Bulk electrolysis studies on auranofin [(Et(3)P)Au(TATG); TATG = 2,3,4,6-tetraacetyl-1-thio-d-glucopyranosato] at +1.2 and +1.6 V versus Ag/AgCl in 0.1 M Bu(4)NBF(4)/CH(2)Cl(2) results in n values of 0.5 and >2 electrons, respectively. Oxidation of auranofin with the mild oxidant, Cp(2)Fe(+), results in formation of disulfide and a digold(I) cation with a bridging thiolate ligand, [(Et(3)PAu)(2)(mu-TATG)](+) (1). The X-ray structure of the PMe(3) analogue, [(Me(3)PAu)(2)(mu-TATG)](NO(3)) (2), is reported. Compound 2 forms a tetranuclear cluster containing an almost perfect square of four gold atoms with Au.Au distances averaging 3.14 A. The complex crystallizes in the tetragonal space group P4(2)2(1)2 with cell constants a = 26.1758(6) A, b = 26.1758(6) A, c = 9.7781(3) A, alpha = beta = gamma = 90 degrees, V = 6699.7(3) A(3), Z = 4, R1 = 0.0644, and wR2 = 0.1152. A mechanism for oxidation of auranofin and possible biological implications are discussed.

UI MeSH Term Description Entries
D008968 Molecular Conformation The characteristic three-dimensional shape of a molecule. Molecular Configuration,3D Molecular Structure,Configuration, Molecular,Molecular Structure, Three Dimensional,Three Dimensional Molecular Structure,3D Molecular Structures,Configurations, Molecular,Conformation, Molecular,Conformations, Molecular,Molecular Configurations,Molecular Conformations,Molecular Structure, 3D,Molecular Structures, 3D,Structure, 3D Molecular,Structures, 3D Molecular
D009942 Organometallic Compounds A class of compounds of the type R-M, where a C atom is joined directly to any other element except H, C, N, O, F, Cl, Br, I, or At. (Grant & Hackh's Chemical Dictionary, 5th ed) Metallo-Organic Compound,Metallo-Organic Compounds,Metalloorganic Compound,Organometallic Compound,Metalloorganic Compounds,Compound, Metallo-Organic,Compound, Metalloorganic,Compound, Organometallic,Compounds, Metallo-Organic,Compounds, Metalloorganic,Compounds, Organometallic,Metallo Organic Compound,Metallo Organic Compounds
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D004572 Electrolysis Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. Electrolyses
D001310 Auranofin An oral chrysotherapeutic agent for the treatment of rheumatoid arthritis. Its exact mechanism of action is unknown, but it is believed to act via immunological mechanisms and alteration of lysosomal enzyme activity. Its efficacy is slightly less than that of injected gold salts, but it is better tolerated, and side effects which occur are potentially less serious. Crisinor,Ridaura,Ridauran,SK&F D 39162,SK&F-39162,SK&F 39162,SK&F39162
D013440 Sulfides Chemical groups containing the covalent sulfur bonds -S-. The sulfur atom can be bound to inorganic or organic moieties. Sulfide,Thioether,Thioethers,Sulfur Ethers,Ethers, Sulfur
D016877 Oxidants Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION). Oxidant,Oxidizing Agent,Oxidizing Agents,Agent, Oxidizing,Agents, Oxidizing
D018360 Crystallography, X-Ray The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) X-Ray Crystallography,Crystallography, X Ray,Crystallography, Xray,X Ray Crystallography,Xray Crystallography,Crystallographies, X Ray,X Ray Crystallographies
D018501 Antirheumatic Agents Drugs that are used to treat RHEUMATOID ARTHRITIS. Anti-Rheumatic Agent,Anti-Rheumatic Drug,Antirheumatic Agent,Antirheumatic Disease-Modifying Second-Line Drug,Antirheumatic Drug,DMARD,Disease-Modifying Antirheumatic Drug,Disease-Modifying Antirheumatic Drugs,Anti-Rheumatic Agents,Anti-Rheumatic Agents, Non-Steroidal,Anti-Rheumatic Drugs,Antirheumatic Disease-Modifying Second-Line Drugs,Antirheumatic Drugs,Antirheumatic Drugs, Disease-Modifying,Disease-Modifying, Antirheumatic Second-Line Drugs,Agent, Anti-Rheumatic,Agent, Antirheumatic,Anti Rheumatic Agent,Anti Rheumatic Agents,Anti Rheumatic Agents, Non Steroidal,Anti Rheumatic Drug,Anti Rheumatic Drugs,Antirheumatic Disease Modifying Second Line Drug,Antirheumatic Disease Modifying Second Line Drugs,Antirheumatic Drug, Disease-Modifying,Antirheumatic Drugs, Disease Modifying,Disease Modifying Antirheumatic Drug,Disease Modifying Antirheumatic Drugs,Disease Modifying, Antirheumatic Second Line Drugs,Drug, Anti-Rheumatic,Drug, Antirheumatic,Drug, Disease-Modifying Antirheumatic,Non-Steroidal Anti-Rheumatic Agents

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