Parasitic flatworm sensitivity to praziquantel is determined by amino acid variation in the binding pocket of a TRP channel.

Praziquantel (PZQ) is an essential medicine for treating parasitic flatworm infections such as schistosomiasis, which afflicts over 250 million people. However, PZQ is not universally effective, lacking activity against the liver fluke Fasciola. The reason for this insensitivity is unclear, as the mechanism of PZQ action is unknown. Here, we show PZQ activates a transient receptor potential melastatin ion channel (TRPMPZQ) in schistosomes by engaging a hydrophobic ligand binding pocket within the voltage-sensor like domain to cause Ca2+ entry and worm paralysis. PZQ activates TRPMPZQ homologues in other PZQ-sensitive flukes, but not Fasciola. However, a single amino acid change in the Fasciola TRPMPZQ binding pocket, to mimic schistosome TRPMPZQ, confers PZQ sensitivity. After decades of clinical use, the basis of PZQ action at a druggable TRP channel is resolved.

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Highly fluorinated liquid crystals with unprecedented polarity were obtained by introducing a tetrahydropyran moiety into their mesogenic core structure. The new materials exhibit an unusually favourable combination of mesophase properties, excellent solubility and low rotational viscosity,

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The reaction of [Ir(m-Cl)(COD)] 2 with various fluorous derivatives of triphenylphosphane containing a para-, meta-, or ortho-(1H,1H-perfluoroalkoxy)-substituted fluorous phosphane P(C 6 H 4 -ORf) 3 (Rf CH 2 C 7 F 15 , CH 2 CH 2 CH 2 C 8 F 17 ) and CO (1 atm) gives the corresponding trans-[Ir(mCl)(CO){P(C 6 H 4 ORf) 3 } 2 ]. The IR n CO values of these complexes give some information on the donor/ acceptor properties of the phosphanes. These fluorous derivatives of triphenylphosphane, as well as a phosphane bearing two (1H,1H-perfluoroalkyloxy) chains at the 3,5-positions, were used in association with [Rh(m-Cl)(COD)] 2 or [Rh(COD) 2 ]PF 6 in the reduction of methyl cinnamate, 2-cyclohexen-1-one, cinnamaldehyde, and methyl a-acetamidocinnamate in a two-phase system D-100/ethanol under 1 bar hydrogen at room temperature. Some differences in catalytic activity were observed in the reduction of methyl cinnamate, the most active catalyst being the rhodium complex containing the phosphane with the p-fluorous ponytail. Recycling of the fluorous catalyst was possible, particularly using the p-substituted phosphane, where no significant loss of catalyst or activity was observed, and generally with very low leaching of rhodium or phosphane in the organic phase.

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