Anhydrides as acylating agents in the enzymatic resolution of an intermediate of (-)-Paroxetine

A new chemoenzymatic method for the preparation of an intermediate of (-)-Paroxetine is reported. Cyclic anhydrides are used as acylating agents in the lipase-catalyzed esterification of trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-phenyloxycarbonylpiperidine in organic solvents. The best enantioselectivities are obtained with two different lipases from Candida antarctica. These two lipases show opposite stereochemical preference in these processes, so that both enantiomers can be obtained in their optically pure forms. The (3S,4R) isomer is an intermediate for the synthesis of (-)-Paroxetine.     

Complexation behavior of a highly preorganized 7,7-diphenylnorbornane-derived macrocycle: towards the design of molecular clocks

The syntheses of two new cyclophane hosts, 4 and 6, are described. The main difference between them is the higher degree of preorganization of 4 as a consequence of the inclusion of the 7,7-diphenylnorbornane (DPN) subunit. The inner cavity of 4 adopts a belt-shaped structure, while 6 has a twisted geometry. In the solid state, the molecules of macrocycle 6 are stacked along an axis to form nanotubular structures. Compounds 4 and 6 form two of the strongest complexes between arene cyclophanes and Ag(+) reported up to date. The silver cation is located inside the cavity of the macrocycles. The stability of 4.Ag(+) is considerably higher than that of 6.Ag(+). The additional stabilization of 4.Ag(+) is attributed to higher preorganization of macrocycle 4. DNMR experiments as well as theoretical calculations carried out with 4.Ag(+) show evidence of Ag(+)-hopping between two different binding sites inside the macrocycle. This phenomenon could be the basis for the design of molecular clocks.     

Trends in exchange coupling for trimethylenemethane-type Bis(semiquinone) biradicals and correlation of magnetic exchange with mixed valency for cross-conjugated systems

A magnetostructural correlation (conformational electron spin exchange modulation) within an isostructural series of biradical complexes is presented. X-ray crystal structures, variable-temperature electron paramagnetic resonance spectroscopy, zero-field splitting parameters, and variable-temperature magnetic susceptibility measurements were used to evaluate molecular conformation and electron spin exchange coupling in this series of molecules. Our combined results indicate that the ferromagnetic portion of the exchange couplings occurs via the cross-conjugated pi-systems, while the antiferromagnetic portion occurs through space and is equivalent to incipient bond formation. Thus, molecular conformation controls the relative amounts of ferro- and antiferromagnetic contributions to exchange coupling. In fact, the exchange parameter correlates with average semiquinone ring torsion angles via a Karplus-Conroy-type relation. Because of the natural connection between electron spin exchange coupling and electronic coupling related to electron transfer, we also correlate the exchange parameters in the biradical complexes to mixed valency in the corresponding quinone-semiquinone radical anions. Our results suggest that delocalization in the cross-conjugated, mixed-valent radical anions is proportional to the ferromagnetic contribution to the exchange coupling in the biradical oxidation states.     

Instabilities of micellar systems under homogeneous and non-homogeneous flow conditions

The rheological behavior of a cetylpyridinium chloride 100 mmol l^–1/sodium salicylate 60 mmol l^–1 aqueous solution was studied in this work under homogeneous (cone and plate) and non-homogeneous flow conditions (vane-bob and capillary rheometers), respectively. Instabilities consistent with non-monotonic flow curves were observed in all cases and the solution exhibited similar behavior under the different flow conditions. Hysteresis and the sigmoidal flow curve suggested as characteristic of systems that show constitutive instabilities were observed when running cycles of increasing and decreasing stress or shear rate, respectively. This information, together with a detailed determination of steady states at shear stresses close to the onset of the instabilities, allowed one to show unequivocally that "top and bottom jumping" are the mechanisms to trigger the instabilities in this micellar system. It is shown in addition that there is not a true plateau region in between the "top and bottom jumping". Finally, the flow behavior beyond the upturn seemed to be unstable and was found accompanied by an apparent violation of the no-slip boundary condition.     

dc Josephson effect in metallic single-walled carbon nanotubes

The dc Josephson effect is investigated in a single-walled metallic carbon nanotube connected to two superconducting leads. In particular, by using the Luttinger liquid theory, we analyze the effects of the electron-electron interaction on the supercurrent. We find that in the long junction limit the strong electronic correlations of the nanotube, together with its peculiar band structure, induce oscillations in the critical current as a function of the junction length and/or the nanotube electron filling. These oscillations represent a signature of the Luttinger liquid physics of the nanotube, for they are absent if the interaction is vanishing. We show that this effect can be exploited to reverse the sign of the supercurrent, realizing a tunable π-junction.     

Dual functional polyelectrolyte multilayer coatings for implants: permanent microbicidal base with controlled release of therapeutic agents

Here we present a new bifunctional layer-by-layer (LbL) construct made by combining a permanent microbicidal polyelectrolyte multilayered (PEM) base film with a hydrolytically degradable PEM top film that offers controlled and localized delivery of therapeutics. Two degradable film architectures are presented: (1) bolus release of an antibiotic (gentamicin) to eradicate initial infection at the implant site, or (2) sustained delivery of an anti-inflammatory drug (diclofenac) to cope with inflammation at the site of implantation due to tissue injury. Each degradable film was built on top of a permanent base film that imparts the implantable device surface with microbicidal functionality that prevents the formation of biofilms. Controlled-delivery of gentamicin was demonstrated over hours and that of diclofenac over days. Both drugs retained their efficacy upon release. The permanent microbicidal base film was biocompatible with A549 epithelial cancer cells and MC3T3-E1 osteoprogenitor cells, while also preventing bacteria attachment from turbid media for the entire duration of the two weeks studied. The microbicidal base film retains its functionality after the biodegradable films have completely degraded. The versatility of these PEM films and their ability to prevent biofilm formation make them attractive as coatings for implantable devices.     

Synthesis and characterisation of the water soluble bis-phosphine complex [Ru(η6-cymene)(PPh2(o-C6H4O)-κ2-P,O)(pta)]+ and an investigation of its cytotoxic effects

Metal complexes bearing phosphine ligands are attracting increasing attention for their applications in medicinal chemistry. In particular, organometallic ruthenium-phosphine complexes have been found to exhibit promising antitumour activity. The synthesis, anticancer activity and reactivity of a novel bis-phosphine complex, [Ru(η⁶-cymene)(PPh₂(o-C₆H₄O)-κ²-P,O)(pta)]Cl (pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1.]decane), is presented. The complex appears to exhibit its anticancer effect via a different mechanism to other ruthenium-arene pta complexes with labile co-ligands.