Daniel Guyot

STRUCTURE-PROPERTY RELATIONSHIPS OF TRIMETAZIDINE DERIVATIVES AND MODEL COMPOUNDS AS POTENTIAL ANTIOXIDANTS

Twenty-five compounds (trimetazidine derivatives and other compounds, mostly having a free phenolic group) were examined for their radical scavenging and antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl) as a measure of radical scavenging capacity was assessed by two parameters, namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z, a kinetic parameter proposed here and derived from initial second-order rate constants and antioxidant/DPPH ratios. Antioxidant activities were determined by the inhibition of lipid peroxidation and albumin oxidation. The most active compounds were derivatives having a trolox or hydroquinone moiety. Physicochemical and structural properties were determined by molecular modeling as lipophilicity (virtual log P calculations) and H-Surf (solvent-accessible surface of hydroxyl hydrogen) and by quantum mechanical calculations (deltaH(ox) = oxidation enthalpy; deltaH(abs) = enthalpy of hydrogen abstraction). QSAR models were derived to identify molecular mechanisms responsible for the reactivity toward the DPPH radical and for the inhibition of lipid peroxidation. A useful prediction of antioxidant capacity could be achieved from calculated molecular properties and the kinetic parameter developed here.

Cycloaddition of germylenes to 3,5-di-t-butyl orthoquinone

Abstract The germylenes X 2 Ge, RGeX and R 2 Ge (X = halogen, OR; R = alkyl or aryl) react at room temperature with 3,5-di-t-butyl orthoquinone by regioselective cycloaddition. The corresponding substituted 2-germa-1,3-dioxolans are formed similarly in good yields, but their stabilities depend on the substituents on the metal. Some of them have also been synthesized by nucleophilic substitution from the corresponding chlorogermanes and 3,5-di-t-butyl catechol. 2-Halo(6,8-di-t-butyl)-4,5-benzo-2-germa-1,3-dioxolans undergo redistribution reactions, while the corresponding dialkyl or diaryl derivatives are very stable.

Polygermanes precurseurs d'especes du germanium a coordinance non usuelle

Several thermal or photochemical α-elimination reactions of functional polygermanes lead to germylenes, R2Ge. Photolysis of polygermanes, cyclopolygermanes and polygermylmercury compounds and also hydrogen abstraction from various organohydropolygermanes using t-BuO., lead to the formation of polymetallated chains containing one or two germanium-centered radicals. These polygermyl radicals give germylenes, R2Ge, germanium centered radicals , α-digermyl diradicals (or digermenes) [ or ] and β- or γ-polygermyl diradicals via a homolytic monoelectronic α-elimination process. In some cases the formation of α-digermyl diradicals or digermenes can also be seen as occurring through dimerization of germylenes but with lower yields. All these intermediates have been characterized by several trapping reactions with dimethyl disulfide, 2,3-dimethylbutadiene or biacetyl.

Reactions de dechlorhydratation d'organochlorohydrogermanes et -polygermanes

Abstract 1,8-Diazabicyclo[5.4.0]undec-7-ene appears to be an efficient dehydrochlorination agent for the organochlorohydrogermanes PhCl 2 GeH, R 2 ClGeH (R = Et, Ph). In diluted solutions the intramolecular α-elimination process leads to germylene through germanate formation while in concentrated solutions intermolecular reactions are predominant and give organochlorohydropolygermanes in good yields. The latter reaction is an interesting and selective way to obtain digermanes with bulky substituents (R = mesityl). Both intra- and inter-molecular dehydrochlorination mechanisms are discussed.

Addition 1, 4 de divers organo- et organohaloge´no-hydrogermanes sur la di-t-butyl-3, 5 orthoquinone

Abstract The thermal 1, 4 addition of triorganohydrogermanes R 3 GeH (R = Et, Ph) with 3, 5-di-t-butylorthoquinone leads to their corresponding mono- O -germylated catechols in good yields. Similarly, the organohalohydrogermanes give the 2, 2-diorgano- (or 2, 2-organohalo)(6, 8-di-t-butyl)-4, 5-benzo-2-germa-1, 3-dioxolanes after dehydrochlorination of transient mono- O -chlorogermylated catechols. Since these reactions are only slightly dependent on solvent and radical initiators, the mechanism probably involves monoelectronic transfer with the formation of a radical anion pair in the first step. The ESR measurements show the transient formation of a paramagnetic o -semiquinonic species which supports the proposed mechanism.