Chemo- and enantioselective routes to chiral fluorinated hydroxyketones using ketoreductases

Chiral fluorinated hydroxyketones were synthesized with excellent ee (>98%) and yield by a chemo- and stereoselective reduction of prochiral methyl/trifluoromethyl diketones using commercially available ketoreductase enzymes. By using p- and m-trifluoroacetyl substituted acetophenones, we demonstrate that ketoreductases can selectively differentiate between methyl and trifluoromethyl ketones within the same molecule. As a result, useful catalysts were identified that eliminated the need for costly and time-consuming protection/deprotection of the ketone moiety, enabling a more convergent synthesis of hydroxyketones. Further, a route to chiral methyl hydroxyketones is provided where an enzyme selectively reduces the unactivated ketone.     

Synthesis of novel 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA) derivatives for chemoselective attachment to unprotected polyfunctionalized compounds

A convenient synthesis of novel bifunctional poly(amino carboxylate) chelating agents allowing chemoselective attachment to highly functionalized biomolecules is described. Based on the well known chelator 1,4,7,10-tetraazacyclodecane-1,4,7,10-tetraacetic acid (DOTA), we synthesized novel bifunctional chelating agents bearing additional functional groups by alkylating 1,4,7,10-tetraazacyclododecane (cyclen) with one equivalent of para-functionalized alkyl 2-bromophenyl-acetate and three equivalents of tert-butyl 2-bromoacetate. The resulting compounds, which contain an additional carbonyl or alkyne functionality, allow site specific labeling of appropriately functionalized unprotected biomolecules in a rapid manner via click reactions. This was demonstrated by the attachment of our new DOTA derivatives to the somatostatin analogue Tyr3-octreotate by chemoselective oxime ligation and CuI-catalyzed azide-alkyne cycloaddition. Initial biodistribution studies in mice with the radiometalated compound demonstrated the applicability of the described DOTA conjugation.     

Transfer of heterocyclic carbene ligands from chromium to gold, palladium and platinum

The reaction of pentacarbonyl(pyrazolin-3-ylidene)chromium complexes, (2a-c) (R = Ph (a), C₆H₄NMe₂-4 (b); (C₅H₄)FeCp (c)), with [AuCl(SMe₂)], H[AuCl₄], [PdCl₂(NCPh)₂] and [PtCl₂(NCPh)₂] gives, by transfer of the heterocyclic carbene ligand, new chloro pyrazolin-3-ylidene complexes of gold(I) and gold(III), dichloro bis(pyrazolin-3-ylidene) palladium and dichloro bis(pyrazolin-3-ylidene) platinum in high yield. The chloride ligand in (Fc = (C₅H₄)FeCp) is readily displaced by trifluoroacetate. The analogous substitution of iodide for the chloride ligands in (M = Pd, Pt) give the corresponding diiodo complexes although in a much slower reaction. In contrast, the reaction of silver trifluoroacetate with affords a binuclear Pd-Ag complex containing two pyrazolin-3-ylidene and three trifluoroacetate ligands two of whom occupy bridging positions between Pd and Ag. The reactions of the pyrazolidin-3-ylidene complex (R = C₆H₄NMe₂-4) with [AuCl(SMe₂)] and [PdCl₂(NCPh)₂] yield chloro pyrazolidin-3-ylidene gold and dichloro bis(pyrazolidin-3-ylidene) palladium complexes. The related dichloro bis(tetrahydropyrimidin-4-ylidene) palladium complex is formed in the reaction of with the palladium complex [PdCl₂(NCPh)₂]. The solid-state structures of several of these heterocyclic carbene complexes including the structure of the binuclear Pd-Ag complex are established by X-ray structure analyses.     

Enzyme activity control by responsive redoxpolymers

A new thermoresponsive poly-N-isopropylacrylamide (PNIPAM)-ferrocene polymer was synthesized and characterized. PNIPAMFoxy bears additional oxirane groups which were used for attachment by a self-assembly process on a cysteamine-modified gold electrode to create a thin hydrophilic film. The new redox polymer enabled electrical communication between the cofactor pyrrolinoquinoline quinone (PQQ) of soluble glucose dehydrogenase (sGDH) and the electrode for sensitive detection of this enzyme as a prospective protein label. The temperature influence on the redox polymer/enzyme complex was investigated. An inverse temperature response behavior of surface bound PNIPAMFoxy compared to the soluble polymer was found and is discussed in detail. The highest efficiency of mediated electron transfer for the immobilized PNIPAMFoxy with sGDH was observed at 24 degrees C, which was twice as high as that of its soluble counterpart. A steady-state electrooxidation current densitiy of 4.5 microA.cm-2 was observed in the presence of 10 nM sGDH and 5 mM glucose. A detection limit of 0.5 nM of soluble PQQ-sGDH was obtained.     

Migration of Additives from Poly(vinyl chloride) (PVC) Tubes into Aqueous Media

The stability and migration product of medical PVC tubes plasticized with polyadipates were investigated by ageing in phosphate buffer at pH 1.679 and water at different temperatures. Changes in the PVC tubes were studied by water absorption, weight loss, Fourier infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA). The low molecular weight migration product that was released was extracted and silylanized before gas chromatography/mass spectroscopy (GC/MS) identification and quantification. After 70 days, the weight loss was less than 0.5% and only a small amount of adipic acid migrated when a tube was aged at 37°C in water and phosphate buffer (pH 1.679), and at 70°C in water after 56 days. However, when aged at 70 and 110°C, gradual deactivation of heat stabilizer after 21 days of ageing in buffer solution and separation of plasticizer from PVC matrix occurred. When the tube was aged at 110°C, significant degradation of both polyadipates and PVC were observed. Adipic acid and 1,4-butanediol monomers and oligomers of polyadipate were the major migration products from polyadipates in the water ageing solution, while only a relatively high amount of adipic acid was identified as the main product in the buffer ageing solution.     

Numerical Investigation of Shock Wave Interference Heating in Chemical Nonequilibrium

A Navier‐Stokes solver is extended by a nonequlibrium gas model to investigate heat transfer rates in hypersonic flow. The nonequlibrium model is shortly discussed and results for a type IV interaction on a cylinder are presented and compared to experimental measurements. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)