Porphyrines de bismuth et de bore (vers une bi-a-radioimmunothérapie)

Le bismuth possède un isotope radioactif (213Bi) générateur de particules a qui présentent des propriétés radiophysiques compatibles avec une utilisation en radioimmunothérapie. Le bismuth ne peut former de liaisons stables avec un anticorps, il est donc nécessaire de le complexer avec un ligand bifonctionnel capable de réaliser une liaison covalente avec l anticorps. Le bore dix (10B) est connu pour générer des particules a par bombardement de neutrons. Son utilisation en thérapie (BNCT) fait l objet de nombreuses études. Pour une meilleur efficacité, nous proposons de rassembler ces deux générateurs a sur une même molécule: la bi a radioimmunothérapie. Nous avons donc développé des porphyrines à anse capable de chélater rapidement le bismuth de manière stable. De plus, des porphyrines comportant des atomes de bore ont été obtenues. La mise en commun des avancées dans chaque thématique nous a permis d obtenir une nouvelle classe de composés pour la bi a radioimmunothérapie.Bismuth has a radioactive isotope (213Bi) generating particles a which exhibit radiological and physical properties compatible with radioimmunotherapy. However, bismuth cannot form stable motifs with an antibody, thus it is necessary to complex the former within a bifunctional ligand lable to be linked to an antibody through a covalent bond. Another atom: boron ten (10B) is known to generate particles a by bombardment of neutrons. Its use in therapy (BNCT) being the subject of many studies. In order to improve the therapeutic effeciency, we propose to gather these two generators of particle a on the same molecule to carry out a bi-a-radioimmunotherapy. For this purpose, we developed a series of porphyrins with handle capable to chelate very quickly bismuth in a stable way. Moreover, porphyrins incorporating boron atoms were obtained. The pooling of the results obtained in each domain enabled us to obtain a new class of tailor-made molecules for bi a radioimmunotherapy.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

The coordination of bismuth by porphyrins

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Bismuth insertion in functionalized porphyrins: influence of the structure delivering substituted malonic acid groups

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Synthesis of a boronic ester-appended bismuth(III) porphyrin as a potential alpha-particle bi-emitter

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Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

The aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target

Stereoselective synthesis of (2S,3S,4R,5S)-3,4-dihydroxy-2,5-dihydroxymethyl pyrrolidine from l-sorbose

International audienceOne of the most frequently synthesized iminosugar derivatives is DMDP. Starting from l-sorbose, a practical method for the synthesis of derivatives of this five-membered iminocyclitol has been developed, involving straightforward steps and a convenient selective reduction of a ketoxime intermediate

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

The aim of this review is to provide an update on the current use of cyclodextrins against organophosphorus compound intoxications. Organophosphorus pesticides and nerve agents play a determinant role in the inhibition of cholinesterases. The cyclic structure of cyclodextrins and their toroidal shape are perfectly suitable to design new chemical scavengers able to trap and hydrolyze the organophosphorus compounds before they reach their biological target

Functionalization of porphyrins: towards the synthesis of bifunctional chelates for bismuth coordination

International audienceWe report the condensation of 3-chloromethyl-benzoyl chloride with two atropisomers ααββ and αβαβ of meso-5,10,15,20-tetrakis-(2-amino)phenylporphyrin (TAPP), followed by the reaction of the anion of either cyano-acetic acid ethyl ester or (4-nitro-phenyl)-acetic acid ethyl ester to prepare various pre-organized strapped porphyrins. These two reagents were selected as both allow the easy formation of the anion in the α position of the ester group while their electron-withdrawing group (EWG) can be further transformed in a reactive functional group. In the ααββ series, this reaction leads to three isomeric porphyrins differing only by the location of their ethoxycarbonyl groups, oriented either towards the center of the porphyrin or maintained outside of the cavity. In the αβαβ series, as expected, a single porphyrin is obtained in which both straps bear an ethoxycarbonyl group, precursor of a hanging carboxylic function and a cyano or a 4-nitro-phenyl group, which can be reduced to an amine function, suitable for the coupling on a biomolecule

Steric decompression of picket-strapped porphyrins for the synthesis of side-differentiated chelates.

International audienceA general method to synthesize various alphabeta alphabeta bis-strapped porphyrins, with a different functionalization on each side of the macrocycle, is described. The resulting new chelates may find applications as analogues of heme protein active sites, bifunctional chelates, or specific bis-chelating molecules with potential medical utility