Synthesis of chiral titanium-containing phosphinoamide ligands for enantioselective heterobimetallic catalysis

The synthesis of six chiral titanium-containing phosphinoamide ligands is discussed. These ligands assemble chiral heterobimetallic Pd–Ti complexes, enable enantioselective intramolecular allylic aminations with hindered amine nucleophiles and achieve selectivity up to 53% ee. Mechanistic studies demonstrate the reversibility of the enantio-determining C–N bond forming step, which leads to a gradual increase in the % ee of the reaction over time. These results represent a rare example of enantioselective heterobimetallic catalysis and suggest that these new ligands could find broad application in enantioselective transition metal catalysis.     

Copper‐Catalyzed Electrophilic Amination of Heteroarenes and Arenes by CH Zincation

Direct amination of heteroarenes and arenes has been achieved in a one‐pot C? H zincation/copper‐catalyzed electrophilic amination procedure. This amination method provides an efficient and rapid approach to access a diverse range of heteroaromatic and aromatic amines including those previously inaccessible using C? H amination methods. The mild reaction conditions and good functional‐group compatibility demonstrate its great potential for the synthesis of important and complex amines.     

Biomimetic growth of gallic acid–ZnO hybrid assemblies and their applications

In this study, we probed the biomimetic formation of gallic acid (GA)–ZnO nanoparticle hybrids. It was found that the morphologies formed were dependent upon pH values, resulting in GA–ZnO hybrids of varying shapes such as micro or nanoplates or fibers. The formed supramolecular GA–ZnO hybrids were found to be luminescent as indicated by confocal microscopy and were utilized for the photocatalytic degradation of the organic dye methylene blue. We also explored the bactericidal effects of the hybrids on Staphylococcus aureus (S. aureus) as well as Escherichia Coli (E. Coli). Thus, we have developed a new class of shape-controlled nanohybrid assemblies via mild, green synthetic methods that may be utilized for photocatalytic degradation for environmental remediation as well as for antibacterial applications.     

Universal minimal total dominating functions of trees

We show that any tree that has a universal minimal total dominating function has one which only takes 0–1 values. K₃ demonstrates that this fails for graphs in general.     

Delamination of layered zeolite precursors under mild conditions: synthesis of UCB-1 via fluoride/chloride anion-promoted exfoliation

New material UCB-1 is synthesized via the delamination of zeolite precursor MCM-22 (P) at pH 9 using an aqueous solution of cetyltrimethylammonium bromide, tetrabutylammonium fluoride, and tetrabutylammonium chloride at 353 K. Characterization by powder X-ray diffraction, transmission electron microscopy, and nitrogen physisorption at 77 K indicates the same degree of delamination in UCB-1 as previously reported for delaminated zeolite precursors, which require a pH of greater than 13.5 and sonication in order to achieve exfoliation. UCB-1 consists of a high degree of structural integrity via (29)Si MAS NMR and Fourier transform infrared spectroscopies, and no detectable formation of amorphous silica phase via transmission electron microscopy. Porosimetry measurements demonstrate a lack of hysteresis in the N(2) adsorption/desorption isotherms and macroporosity in UCB-1. The new method is generalizable to a variety of Si:Al ratios and leads to delaminated zeolite precursor materials lacking amorphization.     

Surface plasmon resonance biosensor for determination of tetrodotoxin: prevalidation study

A label-free surface plasmon resonance biosensor method was applied to determine tetrodotoxin (TTX) in pufferfish matrixes using an antibody inhibition assay format. A prevalidation study was conducted to demonstrate the assay performance characteristics, such as selectivity, LOD, LOQ, repeatability, reproducibility, and accuracy. Three participating laboratories reported standard curves in buffer and pufferfish matrix. A set of blind samples with TTX spiked into buffer as well as in 10% pufferfish extract were analyzed. Additionally, three blind naturally contaminated samples were analyzed, and the results were compared to those obtained using a reference method (HPLC/electrospray ionization-selected reaction monitoring-MS). The developed method was demonstrated to be capable of detecting TTX in pufferfish matrix standard samples in a broad concentration range (2-9000 ng/mL) with an LOD of 1.5 ng/mL. Between-laboratory recovery values were in the range of 51-190% with a mean of 107%, and 64-180% with a mean of 103% for TTX-spiked samples in buffer and pufferfish matrix, respectively. Between-laboratory recoveries were in the satisfactory range of 101-119% for naturally contaminated samples. This robust, rapid, and noninvasive method may serve as an attractive alternative to established methods for detection of TTX in pufferfish extracts.     

Intercompany Study to Evaluate the Robustness of Capillary Isoelectric Focusing Technology for the Analysis of Monoclonal Antibodies

Interlaboratory comparisons are essential to bringing emerging technologies into biopharmaceutical industry practice and regulatory acceptance. As a result, an international team including 12 laboratories from 10 independent biopharmaceutical companies in the United States and Switzerland was formed to evaluate the precision and robustness of capillary isoelectric focusing (CIEF) to assess the charge heterogeneity of monoclonal antibodies. The different laboratories determined the apparent pI and the relative distribution of the charge isoforms of a representative monoclonal antibody (rMAb) sample using the same CIEF method. Statistical evaluation of the data was performed to determine within and between-laboratory consistencies and outlying information. The apparent pI data generated for each charge variant peak showed very good precision between laboratories with percentage of RSD values of ??0.5%. Similarly, the percentage of RSD for the rMAb charge variants percent peak area values are ??4.4% across different laboratories with different analysts using different lots of ampholytes and multiple instruments. Taken together, these results validate the appropriate use of CIEF in the biopharmaceutical industry in support of regulatory submissions.     

Enzyme mediated incorporation of zirconium-89 or copper-64 into a fragment antibody for same day imaging of epidermal growth factor receptor

Identification of tumors which over-express Epidermal Growth Factor Receptor (EGFR) is important in selecting patients for anti-EGFR therapies. Enzymatic bioconjugation was used to introduce positron-emitting radionuclides (⁸⁹Zr, ⁶⁴Cu) into an anti-EGFR antibody fragment for Positron Emission Tomography (PET) imaging the same day as injection. A monovalent antibody fragment with high affinity for EGFR was engineered to include a sequence that is recognized by the transpeptidase sortase A. Two different metal chelators, one for ⁸⁹Zr^IV and one for ⁶⁴Cu^II, were modified with a N-terminal glycine to enable them to act as substrates in sortase A mediated bioconjugation to the antibody fragment. Both fragments provided high-quality PET images of EGFR positive tumors in a mouse model at 3 hours post-injection, a significant advantage when compared to radiolabeled full antibodies that require several days between injection of the tracer and imaging. The use of enzymatic bioconjugation gives reproducible homogeneous products with the metal complexes selectively installed on the C-terminus of the antibody potentially simplifying regulatory approval.

Enzymatic bioconjugation to introduce positron-emitting radionuclides (⁸⁹Zr, ⁶⁴Cu) into an anti-EGFR antibody fragment allows same day imaging with positron emission tomography.