1H, 13C NMR, and electronic absorption spectroscopic studies of the interaction of cyanide with aurothiomalate

Is local biotransformation the key to understanding the pharmacological activity of salicylates and gold drugs?

“…Hydrogen cyanide and cyanogen chloride are identified products from PMN or isolated myeloperoxidase [2]. There is considerable chemical evidence that cyanide displaces thiol ligands from the gold in polymeric gold complexes [3,4]. By analogy, cyanide would be expected to displace gold from its binding site on albumin, thus generating aurocyanide as shown in Fig.…”

“…The transformation may be non-enzymatic, although being driven by the enzymatic production of highly reactive species that are normal products of activated leukocytes, such as singlet oxygen, hydrogen peroxide, hypochlorite, hydroxyl radical and nitric oxide. 3. The transformed drug products may have either:…”

13C-n.m.r. studies of the binding of 1,3-diazinane-2-selenone and 1,3-diazipine-2-selenone to gold(I) drugs

“…The exchange reactions of gold(I) drugs with thiols, CN ) and selenols have been reported [1][2][3][4][5][6][7][8]. These ligands, when added to e.g.…”

“…These ligands, when added to e.g. (Autm) n , usually eject thiomalate (Htm) as a free ligand, forming Au(SR) À 2 [3][4][5], Au(CN) À 2 [6,7] or Au(SeR) À 2 [8,9] type complexes respectively. Thiones, on the other hand, do not eject Htm as a free ligand.…”

Applications of NMR spectroscopy in understanding the gold biochemistry

“…The exchange reactions of gold(I) drugs with various biological ligands have been studied in detail using NMR spectroscopy [17,[25][26][27][28][29][30]. Proton, carbon-13 and nitrogen-15 NMR have proved to be very useful in the structural characterization of gold thiolates metabolites [17,[30][31][32]. The sensitivity of 13 C and 15 N can be enhanced by using isotopically enriched samples or by polarization transfer techniques such as INEPT or DEPT.…”