The alcohol-abuse deterrent disulfiram (DSF) is shown to have a highly selective toxicity against melanoma in culture, inducing a largely apoptotic response, with much lower toxicity against several other cell lines. Melanoma cell lines derived from different stages (radial, vertical, and metastatic phase) were all sensitive to DSF treatment in vitro; melanocytes were only slightly affected. A required role of extracellular Cu is demonstrated for DSF toxicity. Low concentrations of DSF alone decreased the number of viable cells, and the addition of CuCl2 significantly enhanced the DSF-induced cell death to less than 10% of control. Significantly, the intracellular Cu concentration of melanoma cells increased rapidly upon DSF treatment. Both the intracellular Cu uptake and the toxicity induced by DSF were blocked by co-incubation with bathocuproine disulfonic acid (BCPD, 100 μM), a non-membrane-permeable Cu chelator. Chemical studies demonstrated a complicated, extracellular redox reaction between Cu(II) and DSF, which forms the complex Cu(deDTC)2 in high yield, accompanied by oxidative decomposition of small amounts of disulfiram. The Cu complex has somewhat higher activity against melanoma and is suggested to be the active agent in DSF-induced toxicity. The redox conversion of DSF was unique to Cu(II) and not engendered by the other common biological metal ions Fe(II or III), Mn(III), and Zn(II). The implications of this work are significant both in the possible treatment of melanoma as well as in limiting the known side-effects of DSF, which we propose may be diminished by cotreatment to decrease adventitious Cu.

A new arsenic-based pincer (AsOCOAs) dehydrogenation catalyst has been synthesized, IrHCl{2,6-C 6 H 3 -(O-AsBu t 2 )} (3). Treatment with an equivalent of base (NaO-tert-butoxide) under an atmosphere of hydrogen gas affords the dihydride catalyst IrH 2 {2,6-C 6 H 3 -(O-AsBu t2 )} ( 4). The activity of 3 was explored under transfer dehydrogenation conditions with cyclooctane and tert-butyl ethylene, giving a maximum turnover number of 960 at 175 °C in 24 h. Acceptorless dehydrogenations were also explored with pyrrolidine-based molecules, ethylperhydrocarbazole ( 5), methylperhydroindole ( 6), and butylpyrrolidine (7), in which all results indicate 3 is roughly half as active as the analogous phosphine-based pincer catalyst 2. Akin to the phosphine pincer catalysts the activity was seen to steadily improve with increasing temperature, peaking at 175 °C, upon which thermal decomposition sets in.

The use of aryl chlorides as oxidants for the selective oxidation of a variety of secondary alcohols in anaerobic conditions with (NHC)-Pd and -Ni systems (NHC = N-heterocyclic carbene) at very mild temperatures is presented.

A one-pot reaction of maltol with Lawesson's reagent generates dithiomaltol, a thiopyran-4-thione, via an unusual heterocyclic atom exchange (HCAE) reaction; only pyrones with proton or aliphatic substituents undergo the HCAE substitution.

S-oxygenation of dithiocarbamate (DTC) complexes has been implicated in their function as industrial anti-oxidants, as well as in their use as pesticides and most recently in their cumulative toxicity, but little is known of the species generated. Several S-oxygenated derivatives of N,N-disubstituted DTCs have been synthesized, characterized by a variety of methods, and their structure and reactivity examined. Low-temperature reaction of bis(N,N-diethyldithiocarbamato)zinc(II), Zn(deDTC)2 1, with oxygenating reagents (hydrogen peroxide, m-chloroperbenzoic acid, urea hydrogen peroxide) yields mono-oxygenated DTC complexes (N,N-peroxydiethyldithiocarbamato)(N,N-diethyldithiocarbamato)zin(II), Zn(O-deDTC)(deDTC), 2 and bis(N,N-peroxydiethyldithiocarbamato)zinc(II), Zn(O-deDTC)2, 3. The tetraoxygenated derivative bis(N,N-diethylthiocarbamoylsulfinato)zinc(II), Zn(O(2)-deDTC)2, 4, was cleanly obtained by initial reaction of the DTC salts with stoichiometric oxidant prior to complexation with Zn(II). X-ray crystallographic analysis of 2, 3, and 4 show that the peroxydithiocarbamate ligands are S,O-bound. Similar derivatives were obtained from the homoleptic dimethyl and pyrollidine DTC Zn complexes. These oxygenated species display unique 1H and 13C NMR variable-temperature spectra, as the symmetry of DTC ligand is broken upon oxygenation; total line shape analysis (TLSA) was used to compare the energetic parameters for rotation about the C-N bond in several derivatives. Compounds 2, 3, and 4 were deoxygenated by alkyl phosphine, regenerating the parent dithiocarbamate 1. The peroxydithiocarbamate complexes were susceptible to base-catalyzed hydrolytic decomposition, giving ligand-based products indicative of S-oxidation and S-extrusion.