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Manfred Keller

Publications and source records attributed to Manfred Keller.

9 recordsLinked to original sources
PubMed2006

Phosphabarrelenes as ligands in rhodium-catalyzed hydroformylation of internal alkenes essentially free of alkene isomerization.

Despite significant research efforts in the past, one of the remaining problems to be solved in industrially important hydroformylation is the chemoselective low-pressure hydroformylation of internal alkenes. We report here on a new class of phosphabarrelene/rhodium catalysts 2 that display very high activity towards hydroformylation of internal alkenes with an unusually low tendency towards alkene isomerization. Preparation of new phosphabarrelene ligands, studies of their coordination properties, as well as results obtained in the rhodium-catalyzed hydroformylation of cyclic and acyclic internal alkenes are reported.

Alkenes↗
PubMed2006

o-DPPB-directed copper-mediated and -catalyzed allylic substitution with Grignard reagents.

The ortho-diphenylphosphanylbenzoyl (o-DPPB) group was explored as a directing leaving group in copper-mediated and copper-catalyzed allylic substitution with Grignard reagents. Complete control of chemo-, regio- and stereoselectivity with complete syn-1,3-chirality transfer was observed as a result of the directed nature of the reaction. No excess of organometallic reagent is required and the directing group can be recovered quantitatively. Coordination studies in the solid state and in solution have shown that two substrates are bound via the phosphine function of the directing group at copper. Dynamic NMR experiments in solution are in agreement with a ligand-exchange process at copper, a prerequisite for the development of a substoichiometric process.

Journal Article↗
PubMed2006

Bromination of unsaturated dodecahedranes--en route to C20 fullerene.

As part of a study to achieve selective oligo(poly)bromination-ultimately perbromination-of the dodecahedral C(20) skeleton, the extent and direction of the ionic bromination of dodecahedrene and 1,16-dodecahedradiene were explored. Along sequences of Br(+) additions/deprotonations and allylic rearrangements, up to ten hydrogen atoms were substituted (traces of C(20)H(x)Br(10)). Tetrabromododecahedrenes obtained under defined conditions in up to 50 % total yield with three and four allylic bromine substituents protecting the extremely bent C==C bonds, proved highly unreactive even towards oxygen but reacted rapidly with CH(2)N(2). Upon electron impact ionization (MS) of the newly secured oligo(poly)bromododecahedra(e)nes, sequential loss of the substituents ended generally in polyunsaturated dodecahedranes (in the extreme C(20)H(4), "tetrahydro-C(20) fullerenes"). Only subsequently did skeletal fragmentations occur. From X-ray crystal-structure analyses, more information was obtained on the structural response of the dodecahedral skeleton to the strain induced by the voluminous substituents. As Appendix, the forcing radical bromination of 1,6-dibromododecahedrane and exploratory cis-beta-HBr/cis-beta-Br(2) eliminations in bromododecahedranes with [Fe(2)(CO)(9)], P(2)F/[FeCp(2)] and [Fe(tmeda)Cp*Cl] (in situ protection) are presented.

Journal Article↗
PubMed2005

Extremely base-resistant organic phosphazenium cations.

A series of peralkylated polyaminophosphazenium cations exhibiting extraordinary base resistance under phase-transfer conditions were efficiently synthesized from readily available starting materials. Their half lives under these conditions exceed those of the most stable conventional organic cations by factors of up to 3000.

Journal Article↗
PubMed2005

In vitro determination of the optimal particle size for nebulized aerosol delivery to infants.

We investigated the in vitro influence of breathing patterns on lung dose (LD) and particle size distribution in an infant upper airway cast model in order to determine the optimal particle size for nebulized aerosol delivery to infants. Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200 mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm, respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8-30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p < 0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4 microm) through the upper airway cast showed a negative correlation with increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available as LD for all simulated breathing pattern showed a particle size distribution with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From our in vitro study, we conclude that the optimal particle size for nebulized aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.

Administration, Inhalation↗
PubMed2005

The customised electronic nebuliser: a new category of liquid aerosol drug delivery systems.

Inhalation of aerosols is the preferred route of administration of pharmaceutical compounds to the lungs when treating various respiratory diseases. Inhaled antibiotics, hormones, peptides and proteins are potential candidates for direct targeting to the site of action, thus minimising systemic absorption, dilution and undesired side effects, as much lower doses (as low as a fiftieth) are sufficient to achieve a similar therapeutic effect, compared with oral administration. A quick relief from the symptoms and a good tolerance are the main advantages of aerosol therapy. A new class of electronic delivery device is now starting to enter the market. The eFlow electronic nebuliser (PARI GmbH, Germany) provides improved portability and, in some instances, cuts treatment time to only a fraction of what has been experienced with current nebulised therapy. Drug formulations and the device can be mutually adapted and matched for optimal characteristics to meet the desired therapeutic target. Reformulation of known and proven compounds in a liquid format are commercially attractive as they present a relatively low development risk for potential drug candidates and, thus, have become a preferred pathway for the development of new inhalation products.

Administration, Inhalation↗
PubMed2004

Internal motility in stiffening actin-myosin networks.

We present a study on filamentous actin solutions containing heavy meromyosin subfragments of myosin II motor molecules. We focus on the viscoelastic phase behavior and internal dynamics of such networks during adenosine-triphosphate depletion. By combining microrheology and fluorescence microscopy, we observed a sol-gel transition accompanied by a sudden onset of directed filament motion. We interpret the sol-gel transition in terms of myosin II enzymology, and suggest a "zipping" mechanism to explain the filament motion in the vicinity of the sol-gel transition.

Actins↗
PubMed2003

Slow filament dynamics and viscoelasticity in entangled and active actin networks.

This paper deals with correlations between the viscoelastic impedance of entangled actin networks and the slow conformational dynamics and diffusive motions of single filaments. The single filament dynamics is visualized and analysed by analysing the Brownian motion of attached colloidal beads, which enables independent measurements of characteristic viscoelastic response times such as the entanglement and reptation times. We further studied the frequency-dependent viscoelastic impedance of active actin-heavy-meromyosin II networks by magnetic-tweezers microrheometry to gain insight into the effect of such highly dynamic and force-generating crosslinkers (exhibiting bond lifetimes of less than 1 s) on the rheological properties. We show that at high frequencies (higher than 1 Hz) the viscoelastic loss modulus is slightly increased relative to the entangled network (associated with an increase in the energy dissipated during mechanical excitations), while at low frequencies the plateau of the impedance spectrum becomes more pronounced as a consequence of the cross-linking of the network and the suppression of the terminal regime. Our data provide evidence that the myosin motor protein may play a role as softener of the actin cortex, enabling the adaptive reduction of the yield stress of cells and thus facilitating cellular deformations.

Actin Cytoskeleton↗