Methylselenol release as a cytotoxic tool: a study of the mechanism of the activity achieved by two series of methylselenocarbamate derivatives

Cytotoxic activity is related to the progressive release of active fragments, methylselenol and phenols. The structural variations influence the relative reactivity of the target atoms to the nucleophilic agent, as well as the overall stability and the accessibility to the hydrolysis point.

Reversible blockade of gap junctional communication by 2,3-butanedione monoxime in rat cardiac myocytes

2,3-Butanedione monoxime (BDM), a nucleophilic agent endowed with a “phosphatase-like” activity, is often used as a tool for investigating the effects of changes in phosphorylation level of protein constituents on membrane channel function. BDM produced a rapid, dosc-dependent, and reversible abolition of the cytosolic continuity existing between cells via gap junctional channels. The persistence of this effect when a nonhydrolyzable analogue of ATP [adenosine 5'-O-(3-thiotriphosphate) (ATP(gamma)S)] was introduced in the cytosol suggests that the acute suppressant effect of BDM was not due to dephosphorylation. However, the higher reversibility after BDM withdrawal in presence of ATP(gamma)S could signify that a protein-dephosphorylating activity gradually occurred during the oxime treatment. Junctional uncoupling took place even when the moderate increase in cytosolic Ca2+ concentration induced by BDM was prevented by ryanodine. These results are consistent with the model of dual mechanism of BDM action proposed for some other membrane channels, consisting of a quick channel block and a parallel slow inhibition, plausibly through dephosphorylation.

Übergangsmetall-Carben-Komplexe, CXXXIV [1]. Synthese neuer Mono- und Biscarben-Komplexe der VI. Nebengruppe; Röntgenstruktur des ersten Bis[amino(alkoxy)carben]-Komplexes / Transition Metal Carbene Complexes, CXXXIV [1]. Synthesis of New Mono- and Bis-Carbene Complexes of Group VIb Elements; Structure of the First Bis[amino(alkoxy)carbene]-Complex

The hexacarbonyl compounds of chromium, molybdenum and tungsten react with the highly nucleophilic agent Li NiPr2 and in a subsequent alkylation with (Et3O)BF4 to give the carbene complexes (CO)5M[C(N′Pr2)OEt] (1, 3, 4). In case of W(CO)6 and Mo(CO)6 the novel biscarbene complexes cis(CO)4M[C(NiPr2)OEt]2 (2, 5) are additionally obtained. Reaction conditions, properties and spectroscopic data of the new compounds are reported. The molecular structure of cis(CO)4W[C(NiPr2)OEt]2 (4) was determined by X-ray crystallography

Electrochemical investigation of radical-anion reactions of 5-nitro-2-furfuryl derivatives

In the studies on nucleophilic substitution of 5-nitro-2-furfuryl derivatives the function of nucleophilic agent was substituted by electrolysis. The electrochemical reduction of these substances and the follow-up reactions of the intermediates were studied by cyclic voltammetry, dc-polarography and ESR spectroscopy. The primary reduction step is the uptake of a single electron giving rise to the radical anion R-CH2-X- which spontaneously splits off the anion X- and forms the neutral 5-nitro-2-furfuryl radical R-CH2.. This radical may either dimerize to 1,2-bis(5-nitro-2-furyl)ethane or yield 5-nitro-2-methylfuran (VI) through abstraction of hydrogen from the solvent or from the supporting electrolyte or through the uptake of an electron and the following protonation. The mechanism found here confirms the validity of the formerly suggested radical-anion mechanism in the nucleophilic substitution of some 5-nitro-2-furfuryl derivatives.

Übergangsmetall-Komplexe mit Schwefelliganden, V. Synthese, Reaktivität und Struktur von Carbonyl-, Phosphin-und Hydrazin- Eisen(II)-Komplexen mit zwei- und vierzähnigen Schwefelliganden / Transition Metal Complexes with Sulfur Ligands, V. Synthesis, Reactivity and Structure of Carbonyl-, Phosphine-, and Hvdrazin-Iron(II). Complexes with Two-and Fourdentate Sulfur Ligands

Reaction of FeCl3 · 4 H2O with dttd2-, the dianion of 2,3,8,9-dibenzo-1.4,7,10-tetru-thiadecane, leads to the solvated [Fe(dttd)], which coordinates CO, PMe3 and N3H4 yielding [Fe(CO)2dttd], [Fe(PMe3)2dttd], [Fe(CO)PMe3(dttd)], [Fe(N2H4)2dttd] and [Fe(N2H4)CO(dttd), respectively. With H2S and [Fe(dttd)] the Fe(III) complex (PPN)2[Fe2(S)2(dttd)2] is obtained. PPh3 cannot be coordinated to [Fe(dttd)], whereas the reaction between [Fe(PPh3)(CO)3I2] and LiSC6H4SCH3yields [Fe(PPh3)CO(CH3SCeH4S)2] besides the major product [Fe(CO)2(CH3SCeH4S)2]. A PPh3 complex can be obtained also with o-benzenedithiolate, C6H4S22-: Reacting [Fe(PPh3)(CO)3I3] with Li2S2C6H4 yields the binuclear [Fe(PPh3)(CO)2C6H4S2]2. Oxidation of [Fe(N3H4)CO(dttd)] by various agents leads to [Fo(CO)dttd]2 without evidence of formation of a N2 complex intermediate. Nucleophilic attack of [Fe(CO)2(CH3SC6H4S)2] by lithium organyls as e.g. LiPh leads to the benzoylato complex [Li(THF)3][Fe(CO)(PhCO)(CH3SC6H4S)2]; the structures of the starting complex as well as of the adduct have been elucidated by X-ray structure determination. Nucleophilic attack of the corresponding [Fe(CO)2dttd] by LiPh occurs reversibly at the Fe center; by cleavage of a Fe-S bond [Fe(Ph)(CO)2dttd′]- is formed, where dttd′ is acting as a tridentate ligand. This result shows how the reactions of formally equivalent complexes like [Fe(CO)2(CH3SC6H4S)2] and [Fe(CO)2dttd] depend strongly upon the denticity of the sulfur ligands. The dependence upon the character of the nucleophilic agent is shown by the reaction of [Fe(CO)2dttd] with Li[BEt3H]; in this case again a CO ligand is attacked reversibly yielding the formyl complex [LiBEt3][Fe(HCO)CO(dttd)], the structure of which could be elucidated so far only spectroscopically as well as by elemental analysis.[Fe(Ph)(CO)gdttd′]- forms salts like e.g. (AsPh4)[Fe(Ph)(CO)2dttd]; in solution they slowly loose CO yielding e.g. binuclear (AsPh4)2[Fe(Ph)dttd]3. Attempts to isolate the anion as [Li(TMED)3]+ salt load to the loss of CO as well as of phenyl ligands yielding the paramagnetic [Fe(TMED)dttd], which is also obtained directly from [Fe(dttd)] and TMED. The phenyl complex [Fe(Ph)dttd]22- is also formed by reaction of [Fe(dttd)] with LiPh; on reaction with dimethyl-formamide it yields [Fe(DMF)dttd]2. A series of the above described compounds has been investigated by Mößbauer spectroscopy.