Highly active catalyst systems for the ring-opening metathesis polymerization (ROMP) of strained (norbornene) and low-strain (cyclooctene) olefins are readily prepared from RuCl2(arene)(PR3) precursors (directly available by addition of a phosphine to the stable [(arene)RuCl2]2 dimers) after activation with (trimethylsilyl)diazomethane. Durene or p-cymene as arene ligands, together with a sterically demanding basic phosphine (typically tricyclohexylphosphine), promoted the formation of the most active polymerization catalysts. The effects of arene and phosphine ligands and of the solvent on polynorbornene and polyoctenamer molecular weight distributions and microstructures were investigated. The excellent functional group compatibility of the catalyst system was illustrated by the synthesis of a variety of polyoctenamers bearing epoxide, acid, ether, ester, acetal, and bromine functionalities. The polymers were isolated in quite good yields. The striking positional influence of the functional group on the polymerization was revealed by comparing two 4,5-substituted cyclooctenes with the corresponding allylic derivatives. Sulfide and azide functionalities in the monomers resulted in a deactivation of the catalyst. The characterization of the polymers by IR-and NMR-spectroscopies revealed a lack of high regio-and stereospecificity in the propagation step.

New, readily available catalyst systems based on [(arene)RuC12phosphinel complexes activated by addition of trimethylsilyldiazomethane are very active for promoting the ring opening metathesis polymerisation (ROMP) of functionalised norbornenes and cyclooctenes.

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ABSTRACT:We present the clinical and laboratory features of a boy with a new syndrome of mitochondrial depletion syndrome and T cell immunodeficiency. The child suffered from severe recurrent infectious diseases, anemia, and thrombocytopenia. Clinically, he presented with severe psychomotor retardation, axial hypotonia, and a disturbed pain perception leading to debilitating biting of the thumb, lower lip, and tongue. Brain imaging showed hypoplasia of corpus callosum and an impaired myelinization of the temporooccipital region with consecutive supratentorial hydrocephalus. Histologic examination of a skeletal muscle biopsy was normal. Biochemical investigation showed combined deficiency of respiratory chain complexes IIϩIII and IV. MtDNA depletion was found by real-time PCR. No pathogenic mutations were identified in the TK2, SUCLA2, DGUOK, and ECGF1 genes. A heterozygous missense mutation was found in POLG1. The pathogenic relevance of this mutation is unclear. Interestingly, a lack of CD8 ϩ T lymphocytes as well as NK cells was also observed. The percentage of CD45RO-expressing cells was decreased in activated CD8 ϩ T lymphocytes. Activation of T lymphocytes via IL-2 was diminished. The occurrence of the immunologic deficiency in our patient with mtDNA depletion is a rare finding, implying that cells of the immune system might also be affected by mitochondrial disease. with clinical manifestations, which may be caused by mutations of nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Due to diverse genetic causes and occurrence in various developmental stages, tissues, or systems, there is a wide variability in clinical phenotype that spans all age groups (1). As many of the RC disorders involve brain and skeletal muscle, these disorders are also known as mitochondrial encephalomyopathies (2). Nevertheless, given the essential role of oxidative phosphorylation in tissue function, virtually all tissues and organs can be involved, accounting for a diverse array of multisystem disorders with a large variety of clinical symptoms in both childhood and adulthood.MDS is defined as a reduction of mtDNA copy number compared with nDNA in different tissues, which leads to insufficient synthesis of RC complexes I, III, IV, and V (3). Autosomal recessive mutations of five nuclear genes have been identified in MDS patients with different clinical presentations (2,4 -7). The onset of symptoms usually occurs during the first year of life and most patients die in early childhood. Thymidine phosphorylase (ECGF1) defects are associated with leukodystrophy and gastrointestinal disorders (8). Mutations in deoxyguanosine kinase (DGUOK) (9) and polymerase gamma (POLG1) (10,11) were described in the hepatocerebral form of MDS, whereas thymidine kinase 2 (TK2) mutations are associated with a mostly myopathic phenotype and CK elevation (12). Most recently, mutations in the succinyl-CoA synthase (SUCLA2) were identified in four infants of a single family reported with severe psychomotor retardation, epilepsy, hearing loss, Leigh-like les...

Suitable as highly effective polymerization catalysts is the new class of donor/acceptor metallocenes in which the rotation of the two pi ligands is restricted through the formation of a dative D(+)-->A(-) bond (see picture). Specifically optimized substitution patterns yield excellent properties for the synthesis of high-melting, highly crystalline thermoplastic materials, amorphous thermoplastic materials with high glass transition temperatures as well as polyolefin elastomers with low glass T(g).

GENE-A, a Nav1.7 inhibitor compound with analgesic activity, was developed as a crystalline anhydrate, for which two polymorphic forms, I and II, were discovered. The two forms were found to possess very similar free energies as determined experimentally with Form II being thermodynamically stable above 25 °C based on solubility measurements. A detailed solid-state characterization was conducted to determine the relative stability of these solid forms, and both thermodynamic and kinetic pathways (slurry bridging and crystallization) were evaluated. Form II was obtained as the final form in competitive slurries at RT. The outcome of crystallization experiments in terms of the solid form obtained was complicated and yielded variable results depending on the form of the starting material and that of the seeds. Form II was reproducibly obtained as the end product in unseeded experiments and in those with Form II as seeds and starting material, while Form I was obtained in all other seeded experiments. On the basis of the experimental data, a controlled crystallization strategy was developed, wherein Form II was used both as starting material and seeds to reproducibly obtain the desired form upon scale-up.

Ruthenium-catalyzed asymmetric homogeneous hydrogenation (AHH) is used as the key step of a multi-kilogram scale synthesis of an enantiomeric fluoropiperidine. The AHH of a tetrasubstituted b-fluoroenamide is carried out under mild conditions using a Ru/Josiphos catalyst with high ee (98%).

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