A Hybrid Ring‐Opening Metathesis Polymerization Catalyst Based on an Engineered Variant of the β‐Barrel Protein FhuA

A β‐barrel protein hybrid catalyst was prepared by covalently anchoring a Grubbs–Hoveyda type olefin metathesis catalyst at a single accessible cysteine amino acid in the barrel interior of a variant of β‐barrel transmembrane protein ferric hydroxamate uptake protein component A (FhuA). Activity of this hybrid catalyst type was demonstrated by ring‐opening metathesis polymerization of a 7‐oxanorbornene derivative in aqueous solution.     

The Role of 2,6‐Diaminopyridine Ligands in the Isolation of an Unprecedented,Low‐Valent Tin Complex

Stabilization of the central atom in an oxidation state of zero through coordination of neutral ligands is a common bonding motif in transition‐metal chemistry. However, the stabilization of main‐group elements in an oxidation state of zero by neutral ligands is rare. Herein, we report that the transamination reaction of the DAMPY ligand system (DAMPY=2,6‐[ArNH‐CH₂]₂(NC₅H₃) (Ar=C₆H₃‐2,6‐iPr₂)) with Sn[N(SiMe₃)₂]₂ produces the DIMPYSn complex (DIMPY=(2,6‐[ArN?CH]₂(NC₅H₃)) with the Sn atom in a formal oxidation state of zero. This is the first example of a tin compound stabilized in a formal oxidation state of zero by only one donor molecule. Furthermore, three related low‐valent Sn^II complexes, including a [DIMPYSn^IICl]⁺[SnCl₃]^? ion pair, a bisstannylene DAMPY{Sn^II[N(SiMe₃)₂]₂}₂, and the enamine complex MeDIMPYSn^II, were isolated. Experimental results and the conclusions drawn are also supported by theoretical studies at the density functional level of theory and ¹¹⁹Sn Mössbauer spectroscopy.     

A Microgel Construction Kit for Bioorthogonal Encapsulation and pH‐Controlled Release of Living Cells

pH‐Cleavable cell‐laden microgels with excellent long‐term viabilities were fabricated by combining bioorthogonal strain‐promoted azide–alkyne cycloaddition (SPAAC) and droplet‐based microfluidics. Poly(ethylene glycol)dicyclooctyne and dendritic poly(glycerol azide) served as bioinert hydrogel precursors. Azide conjugation was performed using different substituted acid‐labile benzacetal linkers that allowed precise control of the microgel degradation kinetics in the interesting pH range between 4.5 and 7.4. By this means, a pH‐controlled release of the encapsulated cells was achieved upon demand with no effect on cell viability and spreading. As a result, the microgel particles can be used for temporary cell encapsulation, allowing the cells to be studied and manipulated during the encapsulation and then be isolated and harvested by decomposition of the microgel scaffolds.     

Optimizing control of simulated moving beds--linear isotherm

A new optimization based adaptive control strategy for simulated moving beds (SMBs) is proposed. A linearized reduced order model, which accounts for the periodic nature of the SMB process, is used for online optimization and control. The manipulated variables are the four inlet flow rates, the outputs are the raffinate and extract concentrations. Concentration measurements at the raffinate and extract outlets are used as the feedback information. The state estimate from the periodic Kalman filter is used for the prediction of the outlet concentrations over a chosen horizon. Predicted outlet concentrations are the basis for the calculation of the optimal input adjustments, which maximize the productivity and minimize the desorbent consumption subject to constraints on product purities. The realization of this concept is discussed and the implementation on a virtual eight column SMB platform is assessed, in the case of binary linear systems. For a whole series of typical plant disturbances it is shown that the proposed approach is effective in minimizing off-spec products and in achieving optimal SMB operation, also in the case where there are significant model uncertainties.     

Quantification of mephenytoin and its metabolites 4'-hydroxymephenytoin and nirvanol in human urine using a simple sample processing method

A reliable and easy to use liquid chromatography/tandem mass spectrometry (LC/MS/MS) method without the use of sample extraction was developed for the simultaneous quantification of urinary concentrations of mephenytoin, a standard phenotyping substrate for the cytochrome P450 enzyme CYP2C19, and its phase I metabolites 4'-hydroxymephenytoin and nirvanol. Fifty microL of urine were diluted with a buffered beta-glucuronidase solution and incubated at 37 degrees C for 6 h followed by addition of methanol, containing the internal standard 4'-methoxymephenytoin. The chromatographic separation was achieved using a 100 x 3 mm, 5 micro Thermo Electron Aquasil C18 column with a gradient flow, increasing the organic fraction (acetonitrile/methanol 50:50) of the mobile phase from 10 to 90%. Quantification by triple-stage mass spectrometry (TSQ Quantum, Thermo Electron) was accomplished by negative electrospray ionization in the selected reaction monitoring mode. Linearity was observed for all substances in the concentration range 15-10 000 ng/mL. The lower limit of quantification (LLOQ) was 20 ng/mL for 4'-hydroxymephenytoin and 30 ng/mL for nirvanol and mephenytoin, respectively. Intra- and inter-day inaccuracy did not exceed 9.5% for all substances from LLOQ to 10 000 ng/mL. Intra- and inter-day precision were in the range of 0.8-10.5%. The method was validated according to international ICH and FDA guidelines and successfully applied for phenotyping of Caucasian male volunteers who received an oral dose of 50 mg mephenytoin.     

The effect of mixing methods on the dispersion of carbon nanotubes during the solvent-free processing of multiwalled carbon nanotube/epoxy composites

Several solvent-free processing methods to disperse multiwalled carbon nanotubes (MWCNTs) in bisphenol F-based epoxy resin were investigated, including the use of a microfluidizer (MF), planetary shear mixer (PSM), ultrasonication (US) and combinations. The processed mixture was cured with diethyl toluene diamine. Three complimentary techniques were used to characterize the dispersion of the MWCNTs in cured composite samples: optical microscopy, micro Raman spectroscopy, and scanning electron microscopy (SEM). For sample MF + PSM, optical micrographs and Raman images showed reduced agglomeration and a homogeneous distribution of MWCNTs in the epoxy matrix. SEM analysis of fractured specimen after tensile testing revealed breakage of nanotubes along the fracture surface of the composite. A comparison of the MWCNT dispersion in the epoxy samples processed using different methods showed that a combination of MF and PSM processing yields a more homogeneous sample than the PSM or US + PSM processed samples. Mechanical testing of the composites showed about 15% improvement in the tensile strength of samples processed by the MF + PSM method over other methods. Thermogravimetric analysis (TGA) results showed a small decrease in the onset degradation temperature for poorly dispersed samples produced by PSM compared with the well-mixed samples (MF + PSM). These results strongly suggest that the MF + PSM processing method yield better-dispersed and stronger MWCNT/epoxy composites. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2013     

Cyclization of Propargylic Amides: Mild Access to Oxazole Derivatives

The substrate scope, the mechanistic aspects of the gold‐catalyzed oxazole synthesis, and substrates with different aliphatic, aromatic, and functional groups in the side chain were investigated. Even molecules with several propargyl amide groups could easily be converted, delivering di‐ and trioxazoles with interesting optical properties. Furthermore, the scope of the gold(I)‐catalyzed alkylidene synthesis was investigated. Further functionalizations of these isolable intermediates of the oxazole synthesis were developed and chelate ligands can be obtained. The use of Barluenga’s reagent offers a new and mild access to the synthetically valuable iodoalkylideneoxazoles from propargylic amides, this reagent being superior to other sources of halogens.