Positive variation of the MRI signal via intramolecular inclusion complexation of a C-2 functionalized ß-cyclodextrin.

The synthesis of a new contrast agent based on a ß-cyclodextrin scaffold and bearing a flexible lipophilic spacer arm on its secondary face is reported. Intermolecular host-guest inclusion complexes were known to undergo an enhancement of the contrast imaging. We extend this concept to intramolecular complexation. Inter- and intramolecular interactions are compared by NMR spectroscopy, circular dichroism and magnetic resonance imaging using hydrocinnamic acid and adamantane carboxylic acid as external guests. This positive variation of the observed relaxivity is a key element of new strategies aiming at developing smart molecular MRI probes.

The first 2(IB),3(IA)-heterodifunctionalized ß-cyclodextrin derivatives as artificial enzymes.

Novel 2,3-heterodisubstituted ß-cyclodextrin derivatives were designed as artificial enzymes to degrade chemical warfare agents. One of them reduced the acetylcholinesterase inhibitory potential by soman faster than its monosubstituted analog.

Functionalized cyclodextrins bearing an alpha nucleophile--a promising way to degrade nerve agents.

Organophosphorus nerve agents are irreversible inhibitors of acetylcholinesterase. Current treatment of nerve agent poisoning has limited efficacy and more efficient medical countermeasures need to be developed. A promising approach is to design chemical scavengers more stable during storage and less immunogenic than bioscavengers. Furthermore, they could be produced at lowest production costs. Cyclodextrins are attractive cyclic oligosaccharides that can be used to develop chemical scavengers of organophosphorus nerve agents. Their abilities to form inclusion and non-inclusion complexes with organic substrates are useful to trap chemical warfare agents. Selective introduction of an α-nucleophile residue on the secondary face of ß-cyclodextrin allowed to obtain supramolecular derivatives active against organophosphorus compounds. The degradation activity of these monosubstituted cyclodextrins was determined against paraoxon and chemical warfare agents. These tests showed that the structure of the scavengers mainly influences the interaction between the organophosphorus substrate, or its reaction products, and the cyclodextrin moiety. All the tested G-type agents were efficiently degraded. According to the binding modes of cyclosarin, some oligosaccharidic scavengers led to an enantioselective degradation of this nerve agent. These promising derivatives open the way to further investigations of new structural modifications to reach more sophisticated and efficient scavengers for prophylactic and curative medical applications.

Sulfanyl- and selanyldifluoromethylphosphonates as a source of phosphonodifluoromethyl radicals and their addition onto alkenes.

[figure: see text] Two different strategies are shown to produce sulfanyl and selanyldifluoromethylphosphonates. Thus, treatment of sulfanyldichloromethylphosphonates by 3HF.NEt3 in the presence of zinc bromide produces the corresponding sulfanyldifluoromethylphosphonates. In addition, lithiation of difluoromethylphosphonates followed by quenching with phenylsulfanyl chloride, phenylselanyl chloride, or diphenyl diselenide yields the corresponding sulfanyl- and selanyldifluorophosphonates. Generation of phosphonodifluoromethyl radicals from such precursors in the presence of alkenes produces the expected adducts.