Encapsulation of a magnesium hydroxide cubane by a bowl-shaped polypyrrolic Schiff base macrocycle

Hydrolysis of a Pacman-shaped binuclear magnesium complex of a polypyrrolic Schiff base macrocycle results in the formation of a new magnesium hydroxide cubane that is encapsulated by the macrocyclic framework through both coordinative and hydrogen-bonding interactions.     

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.     

Complete family of mono-, bi-, and trinuclear Re(I)(CO)3Cl complexes of the bridging polypyridyl ligand 2,3,8,9,14,15-hexamethyl-5,6,11,12,17,18-hexaazatrinapthalene: syn/anti isomer separation, characterization, and photophysics

The syn and anti isomers of the bi- and trinuclear Re(CO)(3)Cl complexes of 2,3,8,9,14,15-hexamethyl-5,6,11,12,17,18-hexaazatrinapthalene (HATN-Me(6)) are reported. The isomers are characterized by (1)H NMR spectroscopy and X-ray crystallography. The formation of the binuclear complex from the reaction of HATN-Me(6) with 2 equiv of Re(CO)(5)Cl in chloroform results in a 1:1 ratio of the syn and anti isomers. However, synthesis of the trinuclear complex from the reaction of HATN-Me(6) with 3 equiv of Re(CO)(5)Cl in chloroform produces only the anti isomer. syn-{(Re(CO)(3)Cl)(3)(μ-HATN-Me(6))} can be synthesized by reacting 1 equiv of Re(CO)(5)Cl with syn-{(Re(CO)(3)Cl)(2)(μ-HATN-Me(6))} in refluxing toluene. The product is isolated by subsequent chromatography. The X-ray crystal structures of syn-{(Re(CO)(3)Cl)(2)(μ-HATN-Me(6))} and anti-{(Re(CO)(3)Cl)(3)(μ-HATN-Me(6))} are presented both showing severe distortions of the HATN ligand unit and intermolecular π stacking. The complexes show intense absorptions in the visible region, comprising strong π → π* and metal-to-ligand charge-transfer (MLCT) transitions, which are modeled using time-dependent density functional theory (TD-DFT). The energy of the MLCT absorption decreases from mono- to bi- to trinuclear complexes. The first reduction potentials of the complexes become more positive upon binding of subsequent Re(CO)(3)Cl fragments, consistent with changes in the energy of the MLCT bands and lowering of the energy of relevant lowest unoccupied molecular orbitals, and this is supported by TD-DFT. The nature of the excited states of all of the complexes is also studied using both resonance Raman and picosecond time-resolved IR spectroscopy, where it is shown that MLCT excitation results in the oxidation of one rhenium center. The patterns of the shifts in the carbonyl bands upon excitation reveal that the MLCT state is localized on one rhenium center on the IR time scale.     

One-pot nitro-Mannich/hydroamination cascades for the direct synthesis of 2,5-disubstituted pyrroles using base and gold catalysis

An efficient, easy to perform, one-pot reaction cascade for the synthesis of 2,5-disubstituted pyrroles from p-toluenesulfonyl protected imines and 4-nitrobut-1-yne under a combination of base and gold(III) catalysis is reported.     

Linking [2]rotaxane wheels to create a new type of metal organic rotaxane framework

Three new [2]rotaxanes with aromatic nitrogen donors appended to the crown ether wheel have been synthesized and used as ligands to coordinate Cd(II) ions. One of these yields a new type of 2-periodic, metal organic rotaxane framework in which the wheel rather than the axle is used to link the metal nodes.     

Alkenenitrile Transmissive Olefination: Synthesis of the Putative Lignan "Morinol I"

Grignard reagents trigger an addition-elimination with α'-hydroxy acrylonitriles to selectively generate Z-alkenenitriles. The modular assembly of Z-alkenenitriles from a Grignard reagent, acrylonitrile, and an aldehyde is ideal for stereoselectively synthesizing alkenes as illustrated in the synthesis of the putative lignan "morinol I."     

Hierarchical ZnO/Cu "corn-like" materials with high photodegradation and antibacterial capability under visible light

A novel hierarchical ZnO/Cu "corn-like" material was successfully synthesized via facile low temperature hydrothermal and photo-deposition methods. This novel hierarchical material was well characterized by FESEM, XRD, EDS, UV-Vis. This novel material displayed high photodegradation and antibacterial capability under the irradiation of visible light. This is owing to its unique properties, including maximized light utilization rate via red-shifting the light absorption spectrum, enhanced specific surface area for mass transfer and reaction sites, and retarded recombination of photogenerated electrons and holes. Moreover, this novel hierarchical ZnO/Cu "corn-like" material demonstrated easy recovery from treated water for reuse. All these excellent properties indicate that this novel hierarchical ZnO/Cu "corn-like" material has a bright future in water purification applications.     

Multiplex digital PCR: breaking the one target per color barrier of quantitative PCR

Quantitative polymerase chain reactions (qPCR) based on real-time PCR constitute a powerful and sensitive method for the analysis of nucleic acids. However, in qPCR, the ability to multiplex targets using differently colored fluorescent probes is typically limited to 4-fold by the spectral overlap of the fluorophores. Furthermore, multiplexing qPCR assays requires expensive instrumentation and most often lengthy assay development cycles. Digital PCR (dPCR), which is based on the amplification of single target DNA molecules in many separate reactions, is an attractive alternative to qPCR. Here we report a novel and easy method for multiplexing dPCR in picolitre droplets within emulsions-generated and read out in microfluidic devices-that takes advantage of both the very high numbers of reactions possible within emulsions (>10(6)) as well as the high likelihood that the amplification of only a single target DNA molecule will initiate within each droplet. By varying the concentration of different fluorogenic probes of the same color, it is possible to identify the different probes on the basis of fluorescence intensity. Adding multiple colors increases the number of possible reactions geometrically, rather than linearly as with qPCR. Accurate and precise copy numbers of up to sixteen per cell were measured using a model system. A 5-plex assay for spinal muscular atrophy was demonstrated with just two fluorophores to simultaneously measure the copy number of two genes (SMN1 and SMN2) and to genotype a single nucleotide polymorphism (c.815A>G, SMN1). Results of a pilot study with SMA patients are presented.