Continuous Consecutive Reactions with Inter‐Reaction Solvent Exchange by Membrane Separation

Pharmaceutical production typically involves multiple reaction steps with separations between successive reactions. Two processes which complicate the transition from batch to continuous operation in multistep synthesis are solvent exchange (especially high‐boiling‐ to low‐boiling‐point solvent), and catalyst separation. Demonstrated here is membrane separation as an enabling platform for undertaking these processes during continuous operation. Two consecutive reactions are performed in different solvents, with catalyst separation and inter‐reaction solvent exchange achieved by continuous flow membrane units. A Heck coupling reaction is performed in N,N‐dimethylformamide (DMF) in a continuous membrane reactor which retains the catalyst. The Heck reaction product undergoes solvent exchange in a counter‐current membrane system where DMF is continuously replaced by ethanol. After exchange the product dissolved in ethanol passes through a column packed with an iron catalyst, and undergoes reduction (>99 % yield).     

29Si-13C spin-spin couplings over an Si-O-Csp3 link

(29)Si-(13)C spin-spin couplings over one, two, and three bonds as well as other NMR parameters [delta((29)Si), delta((13)C), delta((1)H), (1)J((13)C-(1)H), and (2)J((29)Si-C-(1)H)] were calculated and measured for a series of trimethylsilylated alcohols of the types Me(3)Si-O-(CH(2))(n)CH(3) and Me(3)Si-O-CH(3-n)R(n)(n = 0-3; R = Me, Ph, or Vi). The signs of the coupling constants determined for selected compounds can likely be extended to all such compounds, as supported by theoretical calculations. Similar to couplings between other pairs of nuclei, the 2-bond and 3-bond (29)Si-O-(13)C couplings are of opposite signs ((2)J > 0 and (3)J < 0), and their relative magnitudes depend on the extent of branching at the alpha-carbon.     

Study of the slow electrolyte-induced changes in the TiO<Subscript>2</Subscript> hydrosol structure

Slow changes in the TiO₂ hydrosol structure induced by a small KCl additive were studied using the small-angle X-ray scattering. The initial sol of anisometric anatase nanocrystals stabilized by HCl was prepared. After addition of KCl scattering curves were measured regularly for 2 years. It was established the formation and the accumulation of small dense aggregates. A model of the slow structural changes in the TiO₂ sols with electrolyte additives comprising the two steps of aggregation was proposed. At first the larger anatase nanocrystals combine slowly forming the small dense aggregates through the oriented attachment mechanism. Then, at the critical size of such aggregates, they coagulate quickly forming the looser particles.     

2,6-Di(1H-tetrazol-1-yl)pyridine and its cupric chloride complex

2,6-Di(1H-tetrazol-1-yl)pyridine (DTP) was prepared by a four-stage procedure, including step-by-step heterocyclization of both amino groups of 2,6-diaminopyridine with triethyl orthoformate and sodium azide. According to quantum-chemical calculations and single crystal X-ray diffraction data, DTP crystallizes in the form of the thermodynamically most stable conformer and has an almost flat molecular geometry. DTP was found to react with CuCl₂ ⋅ 2H₂O in ethanol to give the [Cu(DTP)Cl₂(H₂O)]_n complex, which is a 1D coordination polymer, formed at the expense of bridging DTP ligand via the tetrazole ring nitrogen atoms N⁴. Possible coordination cites in DTP molecule are discussed using the data of quantum chemical calculations. The pyridine ring nitrogen atom of DTP does not participate in the formation of either coordination or intermolecular hydrogen bonds. This is explained by the results of quantum chemical calculations showing that this atom is less basic than N3 and N4 atoms of DTP molecule.     

Synthesis and Structures of Two Isomeric 4‐Diazo‐2,3,4,5‐tetrahydrofuran‐3‐ones

The two regioisomeric 4‐diazo‐2,3,4,5‐tetrahydrofuran‐3‐ones 6 and 7 were prepared via the common intermediate 2,3,4,5‐tetrahydro‐2,2‐dimethyl‐5,5‐diphenylfuran‐3‐one ( 8 ). Diazo transfer with 2,4,6‐triisopropylbenzenesulfonyl azide yielded 6 , whereas 7 was obtained via oxidation of the monohydrazone 12 , which was prepared selectively from tetrahydrofuran‐3,4‐dione 11 . The crystal structures of 6 and 7 have been established by X‐ray crystallography.     

A two‐step protocol for isolation of influenza A (H7N7) virions and their RNA for PCR diagnostics based on modified paramagnetic particles

Annual epidemics of influenza cause death of hundreds of thousands people and they also have a significant economic impact. Hence, a need for fast and cheap influenza diagnostic method is arising. The conventional methods for an isolation of the viruses are time‐consuming and require expensive instrumentation as well as trained personnel. In this study, we modified the surface of nanomaghemite (γ‐Fe₂O₃) paramagnetic core with tetraethyl orthosilicate and (3‐aminopropyl)triethoxysilane and the resulting particles were utilized for the isolation of H7N7 influenza virions. Consequently, we designed γ‐Fe₂O₃ paramagnetic core modified with calcium tripolyphosphate which was employed for the isolation of viral nucleic acid after virion's lysis. Both of these procedures can be performed rapidly in less than 10 min and, in combination with the RT‐PCR, the whole influenza detection can be shortened to few hours. Moreover, the whole protocol could be easily automated and/or miniaturized, and thus can serve as a basis for use in a lab‐on‐a‐chip device. We assume that magnetic isolation is an exceptional procedure which can significantly accelerate the diagnostic possibilities of a broad spectrum of diseases.     

Itaconamide derivatives as organic stabilizers for poly(vinyl chloride) against photodegradation

Itaconamide derivatives have been prepared and investigated as photo-stabilizers for rigid PVC. We investigated their stabilizing efficiencies by testing the weight loss (%) with the amount of formed gel. The results indicated a reasonable stabilizing efficiency of these derivatives compared with commercial UV absorber; phenyl salicylate. The extent of discoloration of the photodegraded polymer was also improved in the presence of the prepared compounds. Rheological properties were studied to investigate the flow behavior with providing a vision into the mechanical behavior for the tested materials. Employing the evaluated photostabilizers reflects the reduction in the extent of cross-linking of the polymer. This implies preserving the mechanical properties of PVC. A radical mechanism is proposed to account for the stabilizing action of the investigated materials. The prepared itaconamide derivatives provide appropriate photostability and mechanical properties for a durable poly(vinyl chloride).     

Step gradients in 3-zone simulated moving bed chromatography. Application to the purification of antibodies and bone morphogenetic protein-2

The simulated moving bed (SMB) technology is a proven tool for efficient separation of binary mixtures. However, relying on isocratic conditions limits the applicability of the classical SMB approach when considering the field of bioseparations. Here, the use of gradients opens up new possibilities. A gradient in a SMB process can be established by using different solvent strengths in the incoming feed and desorbent streams, resulting in two internal plateaus of elution strength. Thus, compared to the conventional process, the overall amount of solvent needed can be reduced, productivity can be increased and more concentrated product streams can be obtained. In this contribution, two case studies will be presented. At first, the separation of bovine IgG from lysozyme will be analyzed as a model system. Antibodies are a common target substance in bio-chromatography, as therapeutic monoclonal antibodies are among the most promising biopharmaceuticals. Using adsorption data obtained from single-column experiments, an appropriate SMB process was designed and implemented. The second target component is the active dimeric form of the bone morphogenetic protein-2 (BMP-2). This protein was isolated from a renaturation solution, which also contained its inactive monomeric form as well as other undefined proteins from the bacterial production strain. A 3-zone open-loop gradient-SMB approach was used successfully for both separations.     

Synthesis and evaluation of a pseudocyclic tristhiourea-based anion host

A novel methodology for the evaluation of receptor arrangement in structurally flexible anion chemosensors was developed and applied to map the binding site of a new pseudocyclic tristhiourea chemosensor (6). The syntheses of 6 and related macrocyclic chemosensor 10 (a model of the folded monomeric structure of 6) are reported. Both chemosensors were evaluated by titration with a variety of structurally different anions in CH3Cl and DMSO, showing a common preference for F-, CH3CO2-, and H2PO4-. However, within this group of anions, the binding patterns of the chemosensors differed, indicating dissimilarity in the arrangement of the binding sites of 6 and 10.     

Hybrid Minimal Core Streptavidin–Obelin as a Versatile Reporter for Bioluminescence‐based Bioassay

Ca²⁺‐regulated photoprotein obelin was genetically fused with a minimum‐sized core streptavidin. Hybrid protein (SAV–OL) was produced by bacterial expression and applied as a specific bioluminescent probe in diverse solid‐phase assays. The obtained results clearly demonstrate specific activity of each domain indicating its proper folding with favorable space orientation. SAV–OL has been shown to be a much more sensitive label than the chemical conjugate of a full‐length streptavidin with obelin.