NMR of heparin API: investigation of unidentified signals in the USP-specified range of 2.12–3.00 ppm

This article addresses the identification and quantification of the chemical species resulting in resonances at 2.17 and 2.25 ppm in the ¹H nuclear magnetic resonance (NMR) spectrum of pharmaceutical-grade heparin sodium. The NMR signals in question were first confirmed to arise from chemical moieties covalently attached to the heparin molecule through NMR diffusion experiments as well as chemical treatment of heparin active pharmaceutical ingredient (API) containing the resonances. The material responsible for the extra NMR signals was then demonstrated by NMR spiking studies to be something other than oversulfated chondroitin sulfate and was finally identified as an O-acetylation product of heparin through ¹³C labeling experiments with subsequent NMR analysis. The extent of O-acetylation was quantified using three orthogonal techniques: ¹H NMR, ion chromatography, and headspace gas chromatography/mass spectrometry. The results of this work showed good agreement between the three quantitative methods developed to analyze the signals in the United States Pharmacopeia-specified region of 2.12–3.00 ppm for heparin API.     

Pore size analysis of >250,000 hypothetical zeolites

Computational methods have been used in the past to generate large libraries of hypothetical zeolite structures, but to date analysis of these structures has typically been limited to relatively simple physical properties such as density. We use efficient methods to analyze the adsorption and diffusion properties of simple adsorbate molecules in a library of >250,000 hypothetical silica zeolites that was generated previously by Deem and co-workers (J. Phys. Chem. C, 2009, 113, 21353). The properties of this library of materials are compared to the complete set of ～190 zeolites that have been identified experimentally. Our calculations provide information on the largest cavities available in each material for adsorption, and the size of the largest molecules that can diffuse through each material. For a subset of ～8000 materials, we computed the Henry's constant and diffusion activation energy for adsorbed CH(4) and H(2). We show that these calculations provide a useful screening tool for considering large collections of nanocrystalline materials and choosing materials with particular promise for more detailed modeling.     

Structural and mechanistic insights into C-P bond hydrolysis by phosphonoacetate hydrolase

Bacteria have evolved pathways to metabolize phosphonates as a nutrient source for phosphorus. In Sinorhizobium meliloti 1021, 2-aminoethylphosphonate is catabolized to phosphonoacetate, which is converted to acetate and inorganic phosphate by phosphonoacetate hydrolase (PhnA). Here we present detailed biochemical and structural characterization of PhnA that provides insights into the mechanism of C-P bond cleavage. The 1.35?? resolution crystal structure reveals a catalytic core similar to those of alkaline phosphatases and nucleotide pyrophosphatases but with notable differences, such as a longer metal-metal distance. Detailed structure-guided analysis of active site residues and four additional cocrystal structures with phosphonoacetate substrate, acetate, phosphonoformate inhibitor, and a covalently bound transition state mimic provide insight into active site features that may facilitate cleavage of the C-P bond. These studies expand upon the array of reactions that can be catalyzed by enzymes of the alkaline phosphatase superfamily.     

Course of poly(4-aminodiphenylamine)/Ag nanocomposite formation through UV-vis spectroscopy

Kinetics of chemical oxidative polymerization of 4-aminodiphenylamine (4ADPA) was followed in aqueous 1 M p-toluene sulfonic acid (p-TSA) using silver nitrate (AgNO3) as an oxidant by UV-vis spectroscopy. The medium was found to be clear and homogeneous during the course of polymerization. The absorbances corresponding to the intermediate and the polymer were followed for different concentrations of 4ADPA and AgNO3 and at different reaction time. The appearance of a band around 450 nm during the initial stages of polymerization corresponds to the plasmon resonance formed by the reduction of Ag+ ions. Rate of poly(4-aminodiphenylamine)/Ag nanocomposite (RP4ADPA/AgNC) was determined for various reaction conditions. R(P4ADP/AgNC) showed second order power dependence on 4ADPA and first order dependence on AgNO3. The observed order dependences of 4ADPA and AgNO3 on the formation of P4ADPA/AgNC were used to deduce a rate equation for the reaction. Rate constant for the reaction was determined through different approaches. The good agreement between the rate constants obtained through different approaches justifies the selection of rate equation.     

Controlling job arrivals with processing time windows into Batch Processor Buffer

We consider a two-stage manufacturing system composed of a batch processor and its upstream processor. Jobs exit the upstream processor and join a queue in front of the batch processor, where they wait to be processed. The batch processor has a finite capacity Q, and its processing time is independent of the number of jobs loaded into the batch processor. In certain manufacturing systems (including semiconductor wafer fabrication), a processing time window exists from the time instance the job exits the upstream processor till the time instance it enters the batch processor. If a job is not processed before reaching the end of its processing time window, job rework or validation is required. We model this drawback by assigning a reward R for each successfully processed job by the upstream processor, and a penalty C for each job that reaches the end of its processing time window without being processed by the batch processor. We initially assume an infinite job source in front of the serial processor and also assume that the batch processor is operated under a threshold policy. We provide a method for controlling the production of the serial processor, considering the processing time window between the upstream processor and the downstream batch processor. We then show how the serial processor control policy can be modified when the serial processor also experiences intermittent job arrival.     

Dihydrogen phosphate mediated supramolecular frameworks in 2‐ and 4‐chloroanilinium dihydrogen phosphate salts

The title compounds, 2‐chloroanilinium dihydrogen phosphate (2CADHP) and 4‐chloroanilinium dihydrogen phosphate (4CADHP), both C₆H₇NCl⁺·H₂PO₄⁻, form two‐dimensional supramolecular organic–inorganic hybrid frameworks. In 2CADHP, the dihydrogen phosphate anions form a double‐stranded anionic chain generated parallel to the [010] direction through O—H...O hydrogen bonds, whereas in 4CADHP they form a two‐dimensional supramolecular net extending parallel to the crystallographic (001) plane into which the cations are linked through strong N—H...O hydrogen bonds.     

Carbamic acid 2-trimethylsilylethyl ester as a new ammonia equivalent for palladium-catalyzed amination of aryl halides

Carbamic acid 2-trimethylsilylethyl ester (Teoc-NH₂) serves as an ammonia equivalent in the palladium-catalyzed amination of aryl bromides and aryl chlorides. Anilines with sensitive functional groups can be readily prepared using these amine derivatives.     

Luminescent Quantum Clusters of Gold in Bulk by Albumin‐Induced Core Etching of Nanoparticles: Metal Ion Sensing,Metal‐Enhanced Luminescence,and Biolabeling

The synthesis of a luminescent quantum cluster (QC) of gold with a quantum yield of ～4 % is reported. It was synthesized in gram quantities by the core etching of mercaptosuccinic acid protected gold nanoparticles by bovine serum albumin (BSA), abbreviated as Au_QC@BSA. The cluster was characterized and a core of Au₃₈ was assigned tentatively from mass spectrometric analysis. Luminescence of the QC is exploited as a “turn‐off” sensor for Cu²⁺ ions and a “turn‐on” sensor for glutathione detection. Metal‐enhanced luminescence (MEL) of this QC in the presence of silver nanoparticles is demonstrated and a ninefold maximum enhancement is seen. This is the first report of the observation of MEL from QCs. Folic acid conjugated Au_QC@BSA was found to be internalized to a significant extent by oral carcinoma KB cells through folic acid mediated endocytosis. The inherent luminescence of the internalized Au_QC@BSA was used in cell imaging.     

Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance

Both known and new CC3‐based porous organic cages are prepared and exposed to acidic SO₂ in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3‐R and CC3‐S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3‐R and CC3‐S, allowing facile access of aqueous SO₂ throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers.     

Synthesis of a Novel bis-Gluco-crown Ether Derivative

An efficient synthesis of a novel bis-gluco-22-crown-6 derivative 1 from allyl-α-D-glucopyranoside is described