Five-fold-symmetric macrocyclic aromatic pentamers: high-affinity cation recognition, ion-pair-induced columnar stacking, and nanofibrillation

Described in this study is a conceptually new class of five-fold-symmetric cavity-containing planar pentameric macrocycles with their interior decorated by five convergently aligned, properly spaced carbonyl oxygen atoms. These cation-binding oxygens enclose a hydrophilic lumen of 2.85 ? in radius and thus display high-affinity binding toward alkali metal cations, and possibly many other cations, too. Arising from their high-affinity recognition of metal ions, these planar macrocycles form cation- or ion-pair-induced one-dimensional columnar aggregates, and subsequently fascinating fibrillation results.     

A novel kernel Fisher discriminant analysis: constructing informative kernel by decision tree ensemble for metabolomics data analysis

Large amounts of data from high-throughput metabolomics experiments become commonly more and more complex, which brings an enormous amount of challenges to existing statistical modeling. Thus there is a need to develop statistically efficient approach for mining the underlying metabolite information contained by metabolomics data under investigation. In the work, we developed a novel kernel Fisher discriminant analysis (KFDA) algorithm by constructing an informative kernel based on decision tree ensemble. The constructed kernel can effectively encode the similarities of metabolomics samples between informative metabolites/biomarkers in specific parts of the measurement space. Simultaneously, informative metabolites or potential biomarkers can be successfully discovered by variable importance ranking in the process of building kernel. Moreover, KFDA can also deal with nonlinear relationship in the metabolomics data by such a kernel to some extent. Finally, two real metabolomics datasets together with a simulated data were used to demonstrate the performance of the proposed approach through the comparison of different approaches.     

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.     

Two-dimensional supercritical fluid chromatography/mass spectrometry for the enantiomeric analysis and purification of pharmaceutical samples

A new analytical two-dimensional supercritical fluid chromatography/mass spectrometry system (2D SFC/SFC/MS) has been designed and implemented to enhance the efficiency and quality of analytical support in drug discovery. The system consists of a Berger analytical SFC pump and a modifier pump, a Waters ZQ 2000 mass spectrometer, a set of switching valves, and a custom software program. The system integrates achiral and chiral separations into a single run to perform enantiomeric analysis and separation of a racemic compound from a complex mixture without prior clean up. The achiral chromatography in the first dimension separates the racemate from all other impurities, such as un-reacted starting materials and by-products. Mass-triggered fractionation is used to selectively fractionate the targeted racemic compound based on its molecular weight. The purified racemate from the achiral chromatography in the first dimension is then transferred to the chiral column in the second dimension to conduct the enantiomeric separation and analysis. A control software program, we coined SFC2D, was developed and integrated with MassLynx to retrieve acquisition status, current sample information, and real time mass spectrometric data as they are acquired. The SFC2D program also monitors the target ion signal to carry out mass-triggered fractionation by switching the valve to fractionate the desired peak. The 2D SFC/SFC/MS system uses one CO(2) pump and one modifier pump for both first and second dimension chromatographic separations using either gradient or isocratic elution. Similarly, a preparative 2D SFC/SFC/MS system has been constructed by modifying an existing Waters preparative LC/MS system. All components except the back pressure regulator are from the original LC/MS system. Applications of the 2D SFC/SFC/MS methods to the separation and the analysis of racemic pharmaceutical samples in complex mixtures demonstrated that an achiral separation (in first dimension) and a chiral separation (in second dimension) can be successfully combined into a single, streamlined process both in analytical and preparative scale.     

Synthesis, characterization and adsorption performance of a novel post-crosslinked adsorbent

In this paper a post-crosslinked polymeric adsorbent PDHT-2 with high specific surface area was prepared by Friedel-Crafts reaction of the pendant vinyl groups without an externally added crosslinking agent. It was obvious that both the specific surface area and the pore volume of starting copolymer PDHT-1 increased significantly after post-crosslinking. Batch adsorption runs of phenol from aqueous solution onto adsorbent PDHT-1 and PDHT-2 were researched, and commercial macroporous resin XAD-4 was chosen for comparison purpose. Experimental results showed that the adsorption isotherms could be fitted by Langmuir model and Freundlich model and the adsorption capacity onto PDHT-2 was much larger than that onto PDHT-1 and XAD-4 with respect to phenol and phenolic compound, which possibly resulted from its larger specific surface area. The adsorption process for phenol onto the three adsorbents was proved to be exothermic and spontaneous in nature. The thermodynamic parameters such as Gibb's free energy (ΔG), change in enthalpy (ΔH) and change in entropy (ΔS) had been calculated. The adsorption kinetic curves obeyed the pseudo-second order model and the intraparticle diffusion process was the rate-controlling step.     

A porous coordination polymer assembled from 8-connected {Co(II)3(OH)} clusters and isonicotinate: multiple active metal sites, apical ligand substitution, H2 adsorption, and magnetism

A microporous coordination polymer, namely, [Co(3)(ina)(4)(OH)(C(2)H(5)OH)(3)](NO(3))·C(2)H(5)OH·(H(2)O)(3) (1, or MCF-38, ina = isonicotinate), with 8-connected {Co(3)(OH)} clusters as the structural secondary building units, has been solvothermally synthesized. The hydroxo-centered Co(II) cluster involves multiple active metal sites. The interesting apical ligand substitutions have been directly observed, and the corresponding products of [Co(3)(ina)(4)(OH)(G)(x)(H(2)O)(n)](NO(3))·G·(H(2)O)(m) (1 ? PrOH, G = PrOH, x = 2, n = 1, m = 3; 1 ? BuOH, G = BuOH, x = 2, n = 1, m = 1, and 1 ? MeOH, G = MeOH, x = 3, n = 0, m = 7) have also been obtained by solvothermal syntheses or crystal-to-crystal transformations. High-pressure H(2) adsorption measurement at 77 K reveals that activated 1 can absorb 2.2 wt % H(2) at 5 bar. The relative H(2) absorption at low pressure (86% of the storage capacity at 1 bar) is higher than the corresponding values reported for some typical porous coordination polymers. The magnetic studies of 1 show a dominant antiferromagnetic coupling between Co(II) ions of intra- and inter-cluster.     

Theoretical study on two types of weak interactions between methylenecyclopropane and XY (X,Y = H,F, Cl,and Br)

We present theoretical evidence that the two types of interactions exist in the complexes formed between methylenecyclopropane (MECP) and XY (X, Y = H, F, Cl, and Br). Two seats of XY interacted with MECP are located: (a) is via the pseudo‐π bonding electron pair associated with a C? C bond of the cyclopropane ring and (b) is via the typical‐π bonding of electron pair of the C?C bond of MECP. These two types of weak interactions are compared based on the calculated geometries, interaction energies, frequency changes, and topological properties of electron density. The integration of electron density over the interatomic surface is found to be a good measure for the strength of weak interaction. Furthermore, the total electron density and separated σ and π electron densities are also computed and discussed in this article. The separated electron density shows σ electron density determined the strength and π electron density influenced the direction of the hydrogen/halogen bond. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

"Adiabatic-hindered-rotor" treatment of the parahydrogen-water complex

Inspired by a recent successful adiabatic-hindered-rotor treatment for parahydrogen pH(2) in CO(2)-H(2) complexes [H. Li, P.-N. Roy, and R. J. Le Roy, J. Chem. Phys. 133, 104305 (2010); H. Li, R. J. Le Roy, P.-N. Roy, and A. R. W. McKellar, Phys. Rev. Lett. 105, 133401 (2010)], we apply the same approximation to the more challenging H(2)O-H(2) system. This approximation reduces the dimension of the H(2)O-H(2) potential from 5D to 3D and greatly enhances the computational efficiency. The global minimum of the original 5D potential is missing from the adiabatic 3D potential for reasons based on solution of the hindered-rotor Schro?dinger equation of the pH(2). Energies and wave functions of the discrete rovibrational levels of H(2)O-pH(2) complexes obtained from the adiabatic 3D potential are in good agreement with the results from calculations with the full 5D potential. This comparison validates our approximation, although it is a relatively cruder treatment for pH(2)-H(2)O than it is for pH(2)-CO(2). This adiabatic approximation makes large-scale simulations of H(2)O-pH(2) systems possible via a pairwise additive interaction model in which pH(2) is treated as a point-like particle. The poor performance of the diabatically spherical treatment of pH(2) rotation excludes the possibility of approximating pH(2) as a simple sphere in its interaction with H(2)O.     

Insights into dehydrogenative coupling of alcohols and amines catalyzed by a (PNN)-Ru(II) hydride complex: unusual metal-ligand cooperation

Density functional theory calculations were performed to elucidate the mechanism of dehydrogenative coupling of primary alcohols and amines mediated by a PNN-Ru(II) hydride complex (PNN = (2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine)). A plausible reaction pathway was proposed which contains three stages: (1) The alcohol dehydrogenation reaction to generate the aldehyde and H(2); (2) The aldehyde-amine condensation reaction to form the hemiaminal intermediate; (3) The dehydrogenation process of the hemiaminal intermediate to yield the final amide product with the liberation of H(2). The first and third stages occur via a similar pathway: (a) Proton transfer from the substrate to the PNN ligand; (b) Intramolecular rearrangement of the deprotonated substrate to form an anagostic complex; (c) Hydride transfer from the deprotonated substrate to the Ru center to yield the trans-dihydride intermediate and the aldehyde (or amide); (d) Benzylic proton migration from the PNN ligand to the metal center forming a dihydrogen complex and subsequent H(2) liberation to regenerate the catalyst. In all these steps, the metal-ligand cooperation plays an essential role. In proton transfer steps (a) and (d), the metal-ligand cooperation is achieved through the aromatization/dearomatization processes of the PNN ligand. While in steps (b) and (c), their collaboration are demonstrated by the formation of an anagostic interaction between Ru and the C-H bond and two ionic hydrogen bonds supported by the PNN ligand.     

Synthesis and characterization of sulfuryl diazide, O2S(N3)2

Sulfuryl diazide, O(2)S(N(3))(2), previously described as an "exceedingly explosive" compound, has been isolated and characterized by IR (Ar matrix, gas) and Raman (solid) spectroscopy, and its structure has been determined by X-ray crystallography. It has a melting point of -15 °C and can be handled in small quantities in gas, liquid, and solid states. Vibrational spectroscopic studies suggest the presence of only one conformer in both gas and solid states, and the X-ray crystallography revealed an anti conformation of the two azido groups with respect to the NSN plane. Calculations predict the anti (C(2)) conformer to be 6.6 kJ mol(-1) lower in energy than the syn (C(s)) one at the CBS-QB3 level of theory. The related chlorosulfuryl azide, ClSO(2)N(3), has also been prepared and characterized by IR and Raman spectroscopy.