A Neutral, Carbene-Stabilized Gold(III) Triazide

The first neutral gold­(III) triazido compounds stabilized by N-heterocyclic carbenes were prepared and structurally characterized. Various 1,3-dipolar cycloaddition reactions were examined with these compounds. Isothiocyanates and ^<i>t</i>BuNC gave the expected cycloaddition products; however, these were accompanied by reduction to gold­(I). Examination of the photophysical properties of the triazido compounds in solution revealed that photoreduction to gold­(I) species occurs readily

Gold(I) Carbene Complexes Causing Thioredoxin <b>1</b> and Thioredoxin <b>2</b> Oxidation as Potential Anticancer Agents

Gold­(I) complexes with 1,3-substituted imidazole-2-ylidene and benzimidazole-2-ylidene ligands of the type NHC-Au-L (NHC = <i>N</i>-heterocyclic carbene L = Cl or 2-mercapto-pyrimidine) have been synthesized and structurally characterized. The compounds were evaluated for their antiproliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), as well in the nontumorigenic human embryonic kidney cell line (HEK-293T), showing in some cases important cytotoxic effects. Some of the complexes were comparatively tested as thioredoxin reductase (TrxR) and glutathione reductase (GR) inhibitors, directly against the purified proteins or in cell extracts. The compounds showed potent and selective TrxR inhibition properties in particular in cancer cell lines. Remarkably, the most effective TrxR inhibitors induced extensive oxidation of thioredoxins (Trxs), which was more relevant in the cancerous cells than in HEK-293T cells. Additional biochemical assays on glutathione systems and reactive oxygen species formation evidenced important differences with respect to the classical cytotoxic Au­(I)-phosphine compound auranofin

<i>trans</i>-Thionate Derivatives of Pt(II) and Pd(II) with Water-Soluble Phosphane PTA and DAPTA Ligands: Antiproliferative Activity against Human Ovarian Cancer Cell Lines

A series of PTA and DAPTA platinum­(II) and palladium­(II) thionate complexes of the type <i>trans</i>-[M­(SN)₂P₂] were prepared from the reaction of <i>cis</i>-[MCl₂P₂] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]­nonane)] with the <i>in situ</i> generated sodium salts of the heterocyclic thiones <i>S</i>-<i>m</i>-methylpyrimidine-2-thione, <i>S</i>-4,6-dimethylpyrimidine-2-thione, <i>S</i>-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, <i>S</i>-1,3,4,-thiadiazole-2-thione, <i>S</i>-4,5-<i>H</i>-thiazolan-2-thione, and <i>S</i>-pyrimidine-4­(1<i>H</i>)-one-2-thione. The X-ray structures of six of the compounds confirm the <i>trans</i> disposition and, only in the case of [Pd₂Cl₂(<i>S</i>-pyrimidine-4­(1<i>H</i>)-one-2-thionate)₂(PTA)₂], a dinuclear structure with a Pd–Pd distance of 3.0265(14)­Å was observed. <i>In vitro</i> cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC₅₀) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines

<i>trans</i>-Thionate Derivatives of Pt(II) and Pd(II) with Water-Soluble Phosphane PTA and DAPTA Ligands: Antiproliferative Activity against Human Ovarian Cancer Cell Lines

A series of PTA and DAPTA platinum­(II) and palladium­(II) thionate complexes of the type <i>trans</i>-[M­(SN)₂P₂] were prepared from the reaction of <i>cis</i>-[MCl₂P₂] [M = Pt, Pd; P = PTA (1,3,5-triaza-7-phosphaadamantane), DAPTA (3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]­nonane)] with the <i>in situ</i> generated sodium salts of the heterocyclic thiones <i>S</i>-<i>m</i>-methylpyrimidine-2-thione, <i>S</i>-4,6-dimethylpyrimidine-2-thione, <i>S</i>-4,6-dihydroxypyrimidine-2-thione, benzothiazole-2-thione, benzoxazole-2-thione, <i>S</i>-1,3,4,-thiadiazole-2-thione, <i>S</i>-4,5-<i>H</i>-thiazolan-2-thione, and <i>S</i>-pyrimidine-4­(1<i>H</i>)-one-2-thione. The X-ray structures of six of the compounds confirm the <i>trans</i> disposition and, only in the case of [Pd₂Cl₂(<i>S</i>-pyrimidine-4­(1<i>H</i>)-one-2-thionate)₂(PTA)₂], a dinuclear structure with a Pd–Pd distance of 3.0265(14)­Å was observed. <i>In vitro</i> cytotoxicities against human ovarian cancer cell lines A2780 and A2780cisR were evaluated for ten complexes showing a high inhibition of cellular growth with a comparable inhibitory potency (IC₅₀) against A2780 cells to that of cisplatin. Notably, the compounds also show significant (up to 7-fold higher) activity in cisplatin-resistant A2780cisR cell lines

Geminal Diazides Derived from 1,3-Dicarbonyls: A Protocol for Synthesis

Geminal diazides constitute a rare class of compounds where only a limited number of methods are available for their synthesis. We present the reaction of 1,3-dicarbonyl compounds (as exemplified by malonates, 3-oxoesters, and 1,3-diketones) with molecular iodine and sodium azide in aqueous DMSO providing a general access to geminal diazides. A broad range of geminal diazides with various structural motifs including sterically demanding substituents and ordinary functional groups were synthesized, and it was shown that the diazidation of 1,3-dicarbonyls can be selectively achieved even in the presence of other 1,3-dicarbonyls with substituents at 2-position. Additionally, several diazides were studied regarding their thermal stability