Mechanism of the living lactide polymerization mediated by robust zinc guanidine complexes

Zinc bis(chelate) guanidine complexes promote living lactide polymerization at elevated temperatures. By means of kinetic and spectroscopic analyses the mechanism has been elucidated for these special initiators that make use of neutral N-donor ligands. The neutral guanidine function initiates the polymerization by a nucleophilic ring-opening attack on the lactide molecule. DFT calculations on the first ring-opening step show that the guanidine is able to act as a nucleophile. Three transition states were located for ligand rearrangement, nucleophilic attack, and ring-opening. The second ring-opening step was modeled as a representation for the chain growth because here, the lactate alcoholate opens the second lactide molecule via two transition states (nucleophilic attack and ring-opening). Additionally, the resulting reaction profile proceeds overall exothermically, which is the driving force for the reaction. The experimental and calculated data are in good agreement and the presented mechanism explains why the polymerization proceeds without co-initiators.     

Synthesis of 3-methoxyazetidines via an aziridine to azetidine rearrangement and theoretical rationalization of the reaction mechanism

The synthetic utility of N-alkylidene-(2,3-dibromo-2-methylpropyl)amines and N-(2,3-dibromo-2-methylpropylidene)benzylamines was demonstrated by the unexpected synthesis of 3-methoxy-3-methylazetidines upon treatment with sodium borohydride in methanol under reflux through a rare aziridine to azetidine rearrangement. These findings stand in contrast to the known reactivity of the closely related N-alkylidene-(2,3-dibromopropyl)amines, which are easily converted into 2-(bromomethyl)aziridines under the same reaction conditions. A thorough insight into the reaction mechanism was provided by both experimental study and theoretical rationalization.     

Isomer-Specific Vibrational Spectroscopy of Microhydrated Lithium Dichloride Anions: Spectral Fingerprint of Solvent-Shared Ion Pairs

The vibrational spectroscopy of lithium dichloride anions microhydrated with one to three water molecules, [LiCl₂(H₂O)_1–3]⁻, is studied in the OH stretching region (3800–2800 cm⁻¹) using isomer-specific IR/IR double-resonance population labelling experiments. The spectroscopic fingerprints of individual isomers can only be unambiguously assigned after anharmonic effects are considered, but then yield molecular level insight into the onset of salt dissolution in these gas phase model systems. Based on the extent of the observed frequency shifts Δν^OH of the hydrogen-bonded OH stretching oscillators solvent-shared ion pair motifs (<3200 cm⁻¹) can be distinguished from intact-core structures (>3200 cm⁻¹). The characteristic fingerprint of a water molecule trapped directly in-between two ions of opposite charge provides an alternative route to evaluate the extent of ion pairing in aqueous electrolyte solutions.     

Microphysiometric Measurement of PAF Receptor Responses to Ginkgolides

Microphysiometry was used to evaluate the effects of terpene trilactone and flavonoid constituents of Ginkgo biloba on human platelet‐activating‐factor receptor (PAFR). Inhibition of the platelet‐activating factor response by terpene trilactones was confirmed using this functional assay. Ginkgolide B (GB) and 10‐O‐benzyl‐GB showed the strongest inhibition (81 and 93%, resp.) of the PAFR response, while the flavonoids rutin, quercetin, and kaempferol showed negligible response inhibition. G. biloba extract mixtures were also tested, and results indicate possible synergistic effects among various components.     

Structural Aspects of Copper‐Mediated Atom Transfer Radical Polymerization with a Novel Tetradentate Bisguanidine Ligand

This contribution reports the synthesis of the novel tetradentate bisguanidine ligand 2′,2′‐[ethane‐1, 2‐diylbis(methylazanediyl)]bis(ethane‐2, 1‐diyl)bis(1, 1, 3, 3‐tetramethylguanidine) ( L1 , TMG₂dmtrien), which combines two weak amine and two strong guanidine donor functions. Two new copper(II) complexes were isolated and structurally characterized as complexes [Cu(TMG₂dmtrien)][Br]₂ · 3MeCN ( C1 [Br]₂ · 3MeCN) and [Cu(TMG₂dmtrien)][Cl]₂ · 3MeCN ( C2 [Cl]₂ · 3MeCN). The cations C1 and C2 [Cu(TMG₂dmtrien)]²⁺ show a square‐planar coordination environment and are chiral with both enantiomers being observed in the unit cell. We investigated the application of L1 in copper‐mediated styrene ATRP. L1 shows with CuBr and PEBr as initiator a high polymerization activity according to the polymerization rate. First order kinetics confirm the living character of the polymerization. However, the deviation of molecular weights from theoretical molecular weights and the broad molecular weight distributions hint for a low controlled ATRP. The ATRP with further copper(I) salts {CuCl, [Cu(MeCN)₄]BF₄ and [Cu(MeCN)₄]PF₆} and PECl and PEBr as initiators were investigated as well. Herein the use of [Cu(MeCN)₄]PF₆ with PECl led to promising results.     

Development and validation of a cost-effective,efficient, and robust liquid chromatographic method for the simultaneous determination of the acetyl and succinoyl content in hydroxypropyl methylcellulose acetate succinate polymer

A reversed-phase liquid chromatographic method was developed and validated for the determination of the content of free acetic acid, free succinic acid, acetyl substituents, and succinoyl substituents in hydroxypropyl methylcellulose acetate succinate (HPMCAS; Chemical Abstracts Service Registry No. 71138-97-1) polymer. This single new method gave accurate and precise measurement of both acetyl and succinoyl substituents, which had previously required 3 Japanese Pharmaceutical Excipients (JPE) methods to accomplish. Consequently, analysis time and turnaround time are decreased significantly. Furthermore, this method can also separate and determine the free acetic and succinic acids in HPMCAS polymer, a task that the corresponding JPE method cannot achieve. The values for accuracy (average recovery from 12 standard samples) were 99.9% for acetic acid and 99.8% for succinic acid. The values for injection precision (relative standard deviation [RSD]) were 0.11% for acetic acid and 0.28% for succinic acid. The values for intermediate precision (RSD) were 1.25% for determination of the acetyl content at the 8.78% (w/w) level and 1.33% for determination of the succinoyl content at the 10.9% (w/w) level. The values for intermediate precision (RSD) were 5.98% for determination of free acetic acid at the 0.12% (w/w) level and 5.13% for determination of free succinic acid at the 0.029% (w/w) level. The method was proven to be robust with respect to variation in the pH of the mobile phase, the concentration of potassium dihydrogen phosphate, and the flow rate. The method is well suited for quality control in today's fast-paced pharmaceutical laboratories.     

Rheological studies of concentrated guar gum

Polymers and surfactants are essential ingredients of the printing paste. Polysaccharides are used commercially to thicken, suspend or stabilise aqueous systems. Also they are used to produce gels and to act as flocculates, binders, lubricants, to serve as modifiers of film properties, and have a function as adjusters of rheological parameters. Surfactants, on the other hand, perform numerous functions acting as dispersants, wetting agents, emulsifiers and antifoaming agents. The rheological properties of polysaccharide thickeners (guar gums with different substitution levels and different producers) at different concentrations and temperatures and, second, the effects produced by the addition of nonionic surfactants (polyoxyethylene stearyl alcohols with different numbers of EO groups) have been studied under linear and nonlinear shear conditions. Experimental data have been correlated with the different models: flow curves with the Cross, Carreau and Meter-Bird model, and mechanical spectra with the generalized Maxwell model and Friedrich-Braun model. The surface tensions of aqueous systems containing polysaccharide and/or surfactants have been determined over extended concentration ranges in order to detect the CMC conditions and to provide a better understanding about the polysaccharide-surfactant interactions.     

Analysis of acrylamide in food by isotope-dilution liquid chromatography coupled with electrospray ionization tandem mass spectrometry

A confirmatory method for the determination of low levels of acrylamide in different food products is presented. The method entails extraction of acrylamide with water, precipitation of matrix constituents with acetonitrile, and two clean-up steps consecutively over Isolute Multimode and cation-exchange cartridges. The final extract is analyzed by liquid chromatography (LC) coupled to positive electrospray ionization tandem mass spectrometry employing [13C3]-acrylamide as internal standard. For the chromatographic step, a LC column based on a polymethacrylate gel is employed which shows good retention of acrylamide under isocratic flow conditions (k' = 1.2). Mass spectral acquisition is done by selected reaction monitoring, choosing the characteristic transitions m/z 72-->55, 72-->54 and 72-->27. In-house validation data for breakfast cereals and crackers show good precision of the method, with intra- and interassay variation below 10%. The limits of detection for crackers and breakfast cereals, respectively are estimated at 15 and 20 microg/kg, and recoveries of fortified samples ranged between 58 and 76%. Furthermore, the method is applicable to a number of different food products, including biscuits, crisp bread, wafers, confectionery cocoa liquor, and nuts. Finally, the good results obtained in several small-scale interlaboratory tests provided additional confidence in the performance of the method.