Drug-Induced Dynamics of Bile Colloids.

Bile colloids containing taurocholate and lecithin are essential for the solubilization of hydrophobic molecules including poorly water-soluble drugs such as Perphenazine. We detail the impact of Perphenazine concentrations on taurocholate/lecithin colloids using analytical ultracentrifugation, dynamic light scattering, small-angle neutron scattering, nuclear magnetic resonance spectroscopy, coarse-grained molecular dynamics simulations, and isothermal titration calorimetry. Perphenazine impacted colloidal molecular arrangement, structure, and binding thermodynamics in a concentration-dependent manner. At low concentration, Perphenazine was integrated into stable and large taurocholate/lecithin colloids and close to lecithin. Integration of Perphenazine into these colloids was exothermic. At higher Perphenazine concentration, the taurocholate/lecithin colloids had an approximately 5-fold reduction in apparent hydrodynamic size, heat release was less exothermic upon drug integration into the colloids, and Perphenazine interacted with both lecithin and taurocholate. In addition, Perphenazine induced a morphological transition from vesicles to wormlike micelles as indicated by neutron scattering. Despite these surprising colloidal dynamics, these natural colloids successfully ensured stable relative amounts of free Perphenazine throughout the entire drug concentration range tested here. Future studies are required to further detail these findings both on a molecular structural basis and in terms of in vivo relevance.

Group 4 catalysts for ethene polymerization containing tetradentate salicylaldiminato ligands.

The structural properties of three new classes of titanium and zirconium complex bearing tetradentate salicylaldiminato proligands are elucidated using X-ray diffraction and NMR spectroscopy. On activation with MAO co-catalyst, their behaviour in ethene polymerization depends strongly on the nature of the structure and the substitution pattern. One titanium complex based on a 2-aminobenzylamine (C3-chain) backbone has a trans arrangement of the co-ligand sites and, unsurprisingly, does not polymerize ethene. The 1,8-diaminonaphthalene (C3-chain) backbone gives a rather ring-strained cis complex, but was also unproductive. A range of cis complexes of zirconium with the 2,2'-diaminobibenzyl (C6-chain) backbone give low to moderate productivities of multimodal poly(ethene), while in contrast the structurally analogous titanium compounds provide highly active, single site catalysts. Thermal degradation of these catalysts is slowed significantly by a substitution pattern on the phenolate unit which sterically protects the imine donor unit; a phenomenon which has been previously observed in much lower activity catalysts based on 2,2'-diaminobiphenyl (C4-chain) but which does not improve the stability of the very highly active unbridged systems.

Dramatic effect of heteroatom backbone substituents on the ethylene polymerization behavior of bis(imino)pyridine iron catalysts.

Bis(imino)pyridine iron complexes bearing ether and thioether backbone substituents have been synthesized and evaluated for the polymerization of ethylene. The methoxy derivative is inactive whereas bulky phenoxides or thioether derivatives afford activities as high as the most active systems reported to date.