Martine Perrée-Fauvet

Oxidation of phenols by molecular oxygen catalysed by transition metal complexes. Comparison between the activity of various cobalt and manganese complexes and the role of peroxy intermediates

The oxidation reactions of hindered phenols by molecular oxygen catalysed by monomeric and polymeric cobalt–Schiff base complexes, cobalt and manganese porphyrins, and (pyridine)cobaloxime are described; the rate and selectivity of these reactions are very dependent on the catalyst and on the solvent.A new product has been isolated, 1,3,5-tri-t-butyl-4-oxocyclohexa-2,5-dienylperoxy(pyridine)co-baloxime, and was fully characterised by its elemental analysis and spectroscopic methods. The reactivity of peroxy compounds derived from 2,4,6-tri-t-butylphenol which are postulated as intermediates in the oxidation of this phenol has been studied. Thermal decomposition of 1,3,5-tri-t-butyl-4-oxocyclohexa-2,5-dienyl(pyridine)cobaloxime indicates that the formation of this complex from the phenol, O2, and (pyridine)cobaloxime(II) is reversible and that it is converted into 2,6-di-t-butyl-1,4-benzoquinone only in the presence of a proton source. The corresponding hydroperoxide is probably an intermediate in this transformation as its decomposition in the presence of the cobalt(II) or manganese(III) complexes yields the same final products as the overall oxidations.

Antimalarial acridines: Synthesis, in vitro activity against P. falciparum and interaction with hematin

A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure-activity relationship showed that two positives charges as well as 6-chloro and 2-methoxy substituents on the acridine ring were required to exert a good antimalarial activity. The best compounds possessing these features inhibited the growth of the chloroquine-susceptible strain with an IC(50)0.07 microM, close to that of chloroquine itself, and that of the three chloroquine-resistant strains better than chloroquine with IC(50)0.3 microM. These acridine derivatives inhibited the formation of beta-hematin, suggesting that, like CQ, they act on the haem crystallization process. Finally, in vitro cytotoxicity was also evaluated upon human KB cells, which showed that one of them 9-(6-ammonioethylamino)-6-chloro-2-methoxyacridinium dichloride 1 displayed a promising antimalarial activity in vitro with a quite good selectivity index versus mammalian cell on the CQ-susceptible strain and promising selectivity on other strains.

Porphyrin-netropsin : a potential ligand of DNA

Abstract The synthesis of a water-soluble cationic porphyrin bearing a netropsin motif on a glycine side arm is reported. Molecular modelling revealed that this molecule should exhibit good sequence-specific binding to DNA.

A Facile Route for the Preparation of 9-Acridinecarboxamide Derivatives

Abstract The synthesis of 9-acridinecarboxamide derivatives has been improved through the choice of better reaction conditions and the devising of an original treatment step. Extended amino chains are thus easily and reliably coupled to the commercially available 9-acridinecarboxylic acid in 75% yields.