Adsorption and recovery issues of recombinant monoclonal antibodies in reversed‐phase liquid chromatography†

The poor recovery of large biomolecules is a well‐known issue in reversed‐phase liquid chromatography. Several papers have reported this problem, but the reasons behind this behavior are not yet fully understood. In the present study, state‐of‐the‐art reversed‐phase wide‐pore stationary phases were used to evaluate the adsorption of therapeutic monoclonal antibodies. These biomolecules possess molar mass of approximately 150 000 g/mol and isoelectric points between 6.6 and 9.3. Two types of stationary phases were tested, the Phenomenex Aeris Widepore (silica based), with 3.6 μm superficially porous particles, and the Waters Acquity BEH300 (ethylene‐bridged hybrid), with 1.7 μm fully porous particles. A systematic investigation was carried out using 11 immunoglobulin G1, G2, and G4 antibodies, namely, panitumumab, natalizumab, cetuximab, bevacizumab, trastuzumab, rituximab, palivizumab, belimumab, adalimumab, denosumab, and ofatumumab. All are approved by the Food and Drug Administration and the European Medicines Agency in various therapeutic indications and are considered as reference antibodies. Several test proteins, such as human serum albumin, transferrin, apoferritin, ovalbumin, and others, possessing a molar mass between 42 000 and 443 000 g/mol were also evaluated to draw reliable conclusions. The purpose of this study was to find a correlation between the adsorption of monoclonal antibodies and their physicochemical properties. Therefore, the impact of isoelectric point, molar mass, protein glycosylation, and hydrophobicity was investigated. The adsorption of intact antibodies on the stationary phase was significantly higher than that of proteins of similar size, isoelectric point, or hydrophobicity. The present study also demonstrates the unique behavior of monoclonal antibodies, contributing some unwanted and unpredictable strong secondary interactions.     

Synthesis of hemilabile P,N-ligands with a pentane-2,4-diyl backbone

A general and convenient two-step synthetic method has been developed for the preparation of a novel class of aminoalkyl-phosphine type compounds, which involves nucleophilic ring-opening of cyclic sulfate esters. The ring-opening step was performed using several different aliphatic and aromatic amines to produce aminoalkyl sulfates that were reacted with LiPPh₂ to give the corresponding P,N-ligands. The desymmetrization procedure affords an easy route to synthesize enantiomerically pure pentane-2,4-diyl based P,N-ligands with a highly tunable structure. The ligands derived from primary amines have a stereogenic N-atom that can be useful in asymmetric catalytic syntheses.     

Matrix Models from Operators and Topological Strings, 2

The quantization of mirror curves to toric Calabi–Yau threefolds leads to trace class operators, and it has been conjectured that the spectral properties of these operators provide a non-perturbative realization of topological string theory on these backgrounds. In this paper, we find an explicit form for the integral kernel of the trace class operator in the case of local \({{\mathbb{P}}^1 \times {\mathbb{P}}^1}\), in terms of Faddeev’s quantum dilogarithm. The matrix model associated to this integral kernel is an \({O(2)}\) model, which generalizes the ABJ(M) matrix model. We find its exact planar limit, and we provide detailed evidence that its \({1/N}\) expansion captures the all genus topological string free energy on local \({{\mathbb{P}}^1 \times {\mathbb{P}}^1}\).     

The structure of aqueous sodium hydroxide solutions: a combined solution x-ray diffraction and simulation study

To determine the structure of aqueous sodium hydroxide solutions, results obtained from x-ray diffraction and computer simulation (molecular dynamics and Car-Parrinello) have been compared. The capabilities and limitations of the methods in describing the solution structure are discussed. For the solutions studied, diffraction methods were found to perform very well in describing the hydration spheres of the sodium ion and yield structural information on the anion's hydration structure. Classical molecular dynamics simulations were not able to correctly describe the bulk structure of these solutions. However, Car-Parrinello simulation proved to be a suitable tool in the detailed interpretation of the hydration sphere of ions and bulk structure of solutions. The results of Car-Parrinello simulations were compared with the findings of diffraction experiments.     

GC-MS Identification and GC-FID Quantitation of Terpenoids in Ononidis spinosae Radix

A GC-MS method has been developed for the qualitative analysis of sterol and triterpene (terpenoid) constituents of Ononis spinosa L. (spiny restharrow) root without derivatization. β-Sitosterol, campesterol, stigmasterol, stigmastan-3,5-diene sterol compounds and the triterpene derivatives β-amyrin and α-onocerin were identified. A validated GC-FID quantitative method was developed for measuring β-sitosterol, the main sterol component, in various extracts of this plant, obtained with organic solvents and by supercritical fluid extraction. The extracts were cleaned by saponifying and then the β-sitosterol was quantified in the non-saponifiable fractions by GC-FID with an internal standard. In addition, the relative concentrations of the other terpenoids were also determined. The β-sitosterol content in the non-saponifiable solvent extraction fractions was 0.19–5.5%, that of the supercritical fractions were 4.8–9.2%, depending on the experimental conditions. The hexane and the pilot scale SFE extracts were considered as main sources of terpenoids (71.8%; 93.3%, respectively).     

Iron‐Catalyzed Ring‐Closing C−O/C−O Metathesis of Aliphatic Ethers

Among all metathesis reactions known to date in organic chemistry, the metathesis of multiple bonds such as alkenes and alkynes has evolved into one of the most powerful methods to construct molecular complexity. In contrast, metathesis reactions involving single bonds are scarce and far less developed, particularly in the context of synthetically valuable ring‐closing reactions. Herein, we report an iron‐catalyzed ring‐closing metathesis of aliphatic ethers for the synthesis of substituted tetrahydropyrans and tetrahydrofurans, as well as morpholines and polycyclic ethers. This transformation is enabled by a simple iron catalyst and likely proceeds via cyclic oxonium intermediates.     

One-pot synthesis of α-aminonitriles from alkyl and aryl cyanides: a Strecker reaction via aldimine alanes

A one-pot Strecker reaction using various alkyl, arylalkyl and arylnitriles is developed. Aldimine alanes were generated in situ from nitriles by the addition of diisobutylaluminium hydride, and were converted into the corresponding imines on reaction with (S)-(−)-1-phenylethylamine. Nucleophilic addition to the imines in the presence of catalytic triethylamine, using acetone cyanohydrin as a cyanide source, provided α-aminonitriles.     

Rotation Planar Extraction (RPE)–A New Exhaustive,Preparative Forced-Flow Technique. Part 1: Description of the Method and Practical Aspects

JPC – Journal of Planar Chromatography – Modern TLC -     

The Minimal Occupancy Level of the Clathrate Hydrate Host Lattice and the Intercalation Heat of the Guest Molecules in the Chlorine Hydrates

The minimal occupancy level (θ_min) of the clathrate lattice of gas molecules is defined as the number of guest molecules in the host clathrate lattice, which can stabilize the thermodynamically unstable empty cage by covering the energy demand of the transformation of hexagonal ice into empty clathrate lattice (ΔH_trans). The θ_min values for chlorine hydrate were determined from the n = f(p)_T=const. relationship and the average molar intercalation heat of chlorine in the type I clathrate lattice was also calculated for both type of cavities.