First example of a di-cadmium tris-phthalocyanine triple-decker sandwich complex

An unprecedented M(II)2Pc3 (M = Cd) triple-decker sandwich complex has been synthesized and characterised by single crystal X-ray crystallography; cyclic voltammetry shows an unusually large range of redox states and EPR spectroscopy indicates that the material exists in at least two redox states, one having spin (1/2).     

Evaluation of direct analysis in real time mass spectrometry for onsite monitoring of batch slurry reactions

Batch slurry reactions are widely used in the industrial manufacturing of chemicals, pharmaceuticals, petrochemicals and polymers. However, onsite monitoring of batch slurry reactions is still not feasible in production plants due to the challenge in analyzing heterogeneous samples without complicated sample preparation procedures. In this study, direct analysis in real time mass spectrometry (DART-MS) has been evaluated for the onsite monitoring of a model batch slurry reaction. The results suggested that automation of the sampling process of DART-MS is important to achieve quantitative results. With a sampling technique of manual sample deposition on melting point capillaries followed by automatic sample introduction across the helium beam, relative standard deviation (RSD) of the protonated molecule signals from the reaction product of the model batch slurry reaction ranged from 6 to 30%. This RSD range is improved greatly over a sampling technique of manual sample deposition followed by manual sample introduction where the RSDs are up to 110%. Furthermore, with the semi-automated sampling approach, semi-quantitative analysis of slurry samples has been achieved. Better quantification is expected with a fully automated sampling approach.     

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.     

Micromechanical models of young's modulus of NR/organoclay nanocomposites

Small strain Young's moduli of natural rubber (NR)/organoclay nanocomposites were estimated using the Guth–Gold, Halpin–Tsai (HT), and Krieger–Dougherty (KD) models, and compared with experimental measurements of NR vulcanizates containing organo‐montmorillonite (OM) or organo‐sepiolite (OS). To account for the effect on modulus of the NR matrix of the vulcanization‐active modifier in the organoclay, a matrix modulus correction (MMC) term was derived from the vulcanization parameters of the nanocomposites. The KD model gave a better empirical fit with the experimental data than the Guth–Gold model, with both giving good agreement with particle shape factors estimated from transmission electron microscope (TEM) images. The HT model gave the best fit with experiment for both types of nanocomposite, and use of the MMC term meant that the empirical shape factor was sufficiently close to that estimated from TEM images that the model could potentially be used to accurately predict the Young's moduli of NR/OM and NR/OS nanocomposites. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 49: 1621–1627, 2011     

Polymerization kinetics of phosphonic acids and esters using an iodonium initiator

Phosphonic acids are known to be useful monomers in dental restorative materials because of their good potential to provide enhanced adhesion to hydroxyapatite and their high hydrolytic stability. In this study, the photopolymerization of phosphonic acid‐based monomer via the camphorquinone (CQ)/ethyl‐4‐(dimethylaminobenzoate) (EDAB) photoredox system is compared with a ternary system composed of iodonium hexafluorophosphate and CQ/EDAB. Photocalorimetry shows that the ternary system does not provide a significant acceleration of the polymerization with either acrylamide or methacrylate phosphonic acids. The complexation of the iodonium by the phosphonic moiety of the acidic monomers leads to a lowered iodonium reactivity and reduced polarizability of the medium and as a consequence limits the rate enhancement effect normally observed by phosphonic acids on the polymerization rate. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013 , 51, 5046–5055     

Use of xenon as a mobile phase for on–line capillary supercritical fluid chromatography–fourier transform infrared spectrometry

Xenon is investigated as a mobile phase for on-line capillary supercritical fluid chromatography-Fourier transform infrared spectrometry (SFC-FTIR). Polycyclic aromatic hydrocarbons, aromatic isocyanates, and epoxy acrylate oligomers are analyzed as examples to show that xenon has similar selectivities and solvating powe to CO₂. Its optical transparency makes it ideal for IR detection. A stop flow system is constructed to increase the sensitivity of spectra measured from compounds which are weak IR absorbers.     

Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging

Glycogen synthase kinase‐3 (GSK‐3) regulates multiple cellular processes in diabetes, oncology, and neurology. N‐(3‐(1H‐1,2,4‐triazol‐1‐yl)propyl)‐5‐(3‐chloro‐4‐methoxyphenyl)oxazole‐4‐carboxamide (PF‐04802367 or PF‐367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK‐3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF‐367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF‐367 is ideal for discovery of radiopharmaceuticals for GSK‐3 in the central nervous system. A ¹¹C‐isotopologue of PF‐367 was synthesized and preliminary PET imaging studies in non‐human primates confirmed that we have overcome the two major obstacles for imaging GSK‐3, namely, reasonable brain permeability and displaceable binding.     

An efficient palladium-catalyzed Negishi cross-coupling reaction with arylvinyl iodides: facile regioselective synthesis of E-stilbenes and their analogues

A general synthetic route for the Pd-catalyzed cross-coupling of an arylzinc reagent with arylvinyl iodides (Negishi cross-coupling) has been developed. The system permits efficient and selective preparation of E-stilbenes and their analogues. It also functions effectively at low levels of catalyst loading without the need for an additional ligand and tolerates a wide range of functional groups including heteroaromatic substrates. A systematic study of various parameters was performed and correlated with catalyst-substrate activity.