Facile Method for 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylides: Highly Stereoselective Synthesis of Substituted Pyrrolidine Derivatives

The substituted pyrolidine derivatives with high stereoselectivity were obtained through cycloaddition reaction in the presence of a Lewis acid namely diethylzinc by solvent‐free grinding method.     

Cone motion viscosity and optical second harmonic generation of ferroelectric liquid crystalline dendrimers

We report second harmonic generation in a ferroelectric liquid crystalline trimer and ferroelectric liquid crystalline dendrimers of first, second and third generation. Thin cells were filled with the compounds by capillary forces at elevated temperature, and cooled from the surface stabilized ferroelectric state to below the glass transition temperature, while kept in an electric field. The cone motion viscosity and the threshold electric field for unwinding of the helix axis of the chiral tilted smectic mesophases were studied separately at elevated temperature, and these data were used to optimize the preparation of the films. The measured response time was between 0.3 and 3ms, which corresponds to a cone motion viscosity between 0.5 and 50 Pa s. Second harmonic generation was studied both at elevated temperature with an electric field and at room temperature with and without electric field. The first generation dendrimer exhibited a strong increase in the second order non-linear optical response with time at room temperature. The d ₂₃-coefficient of this dendrimer was approximately four times larger than for the other macromolecules and was 0.045 pm V^-1. The relatively large d-coefficient of the first generation dendrimer is ascribed to crystallization, which improved the orientation of the molecular dipoles.     

Preparation of Methyl 6‐O‐p‐Nitrobenzoyl‐β‐d‐Glucoside

Methyl 6‐O‐p‐nitrobenzoyl‐β‐d‐glucoside was synthesized by reacting methyl 4,6‐O‐p‐nitrobenzylidine‐β‐d‐glucoside with N‐bromosuccinimide (NBS). First, methyl β‐d‐glucoside was converted into methyl 4,6‐O‐p‐nitrobenzylidine‐β‐d‐glucoside with p‐nitrobenzaldehyde. Later, methyl 4,6‐O‐p‐nitrobenzylidine‐β‐d‐glucoside was opened oxidatively with NBS to give methyl 6‐O‐p‐nitrobenzoyl‐β‐d‐glucoside.     

Lyotropic Liquid Crystal to Soft Mesocrystal Transformation in Hydrated Salt–Surfactant Mixtures

Hydrated CaCl₂, LiI, and MgCl₂ salts induce self‐assembly in nonionic surfactants (such as C₁₂H₂₅(OCH₂CH₂)₁₀OH) to form lyotropic liquid‐crystalline (LLC) mesophases that undergo a phase transition to a new type of soft mesocrystal (SMC) under ambient conditions. The SMC samples can be obtained by aging the LLC samples, which were prepared as thin films by spin‐coating, dip‐coating, or drop‐casting of a clear homogenized solution of water, salt, and surfactant over a substrate surface. The LLC mesophase exists up to a salt/surfactant mole ratio of 8, 10, and 4 (corresponding to 59, 68, and 40 wt % salt/surfactant) in the CaCl₂, LiI, and MgCl₂ mesophases, respectively. The SMC phase can transform back to a LLC mesophase at a higher relative humidity. The phase transformations have been monitored using powder X‐ray diffraction (PXRD), polarized optical microscopy (POM), and FTIR techniques. The LLC mesophases only diffract at small angles, but the SMCs diffract at both small and wide angles. The broad surfactant features in the FTIR spectra of the LLC mesophases become sharp and well resolved upon SMC formation. The unit cell of the mesophases expands upon SMC transformation, in which the expansion is largest in the MgCl₂ and smallest in the CaCl₂ systems. The POM images of the SMCs display birefringent textures with well‐defined edges, similar to crystals. However, the surface of the crystals is highly patterned, like buckling patterns, which indicates that these crystals are quite soft. This unusual phase behavior could be beneficial in designing new soft materials in the fields of phase‐changing materials and mesostructured materials, and it demonstrates the richness of the phase behavior in the salt–surfactant mesophases.     

Clean and reactive nanostructured cellulose surface

A simple, solvent-free and low cost method to activate the surface of nanofibrillated cellulose films for further functionalization is presented. The method is based on the oxidative properties of UV radiation and ozone, to effectively remove contaminants from nanocellulosic surface, which remains clean and reactive for at least a week. The efficiency of the method is demonstrated by X-ray photoelectron spectroscopy (XPS) and contact angle measurements. In clear contrast to previous results on nanoscaled cellulose the relative atomic concentration of non-cellulosic carbon atoms was only 4 %, and water completely wetted the surface within seconds. After activation, neither chemical degradation nor morphological changes on cellulose were observed. This surface activation is essential for further functionalization of the film in dry state or nonpolar media. The surface activation was confirmed by silylation and a four times higher degree of substitution was achieved on the activated sample compared to non-activated reference film, as monitored with XPS.     

A quantitative LC/MS method targeting urinary 1-methyl-4-imidazoleacetic acid for safety monitoring of the global histamine turnover in clinical studies

Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-imidazoleacetic acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC–ESI–MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-imidazoleacetic acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3 %, respectively, at the mean urinary concentration level, while method accuracy was between ?16.2 and 8.0 % across the linear concentration range of 22–1,111 ng mL^?1. Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 μmol mmol^?1 of creatinine, and for male subjects, it was 2.1 μmol mmol^?1 of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.

Quinolines in clothing textiles—a source of human exposure and wastewater pollution?

A production process in which the use of various types of chemicals seems to be ubiquitous makes the textile industry a growing problem regarding both public health as well as the environment. Among several substances used at each stage, the present study focuses on the quinolines, a class of compounds involved in the manufacture of dyes, some of which are skin irritants and/or classified as probable human carcinogens. A method was developed for the determination of quinoline derivatives in textile materials comprising ultrasound-assisted solvent extraction, solid phase extraction cleanup, and final analysis by gas chromatography/mass spectrometry. Quinoline and ten quinoline derivatives were determined in 31 textile samples. The clothing samples, diverse in color, material, brand, country of manufacture, and price, and intended for a broad market, were purchased from different shops in Stockholm, Sweden. Quinoline, a possible human carcinogen, was found to be the most abundant compound present in almost all of the samples investigated, reaching a level of 1.9 mg in a single garment, and it was found that quinoline and its derivatives were mainly correlated to polyester material. This study points out the importance of screening textiles with nontarget analysis to investigate the presence of chemicals in an unbiased manner. Focus should be primarily on clothing worn close to the body.     

You cannot fight the pressure: Structural rearrangements of active pharmaceutical ingredients under magic angle spinning

Although solid-state nuclear magnetic resonance (NMR) is a versatile analytical tool to study polymorphs and phase transitions of pharmaceutical molecules and products, this work summarizes examples of spontaneous and unexpected (and unwanted) structural rearrangements and phase transitions (amorphous-to-crystalline and crystalline-to-crystalline) under magic angle spinning (MAS) conditions, some of them clearly being due to the pressure experienced by the samples. It is widely known that such changes can often be detected by X-ray powder diffraction (XRPD); here, the capability of solid-state NMR experiments with a special focus on ¹H-¹³C frequency-switched Lee–Goldburg heteronuclear correlation (FSLG HETCOR)/MAS NMR experiments to detect even subtle changes on a molecular level not observable by conventional 1D NMR experiments or XRPD is presented. Furthermore, it is shown that a polymorphic impurity combined with MAS can induce a crystalline-to-crystalline phase transition. This showcases that solid-state NMR is not always noninvasive and such changes upon MAS should be considered in particular when compounds are studied over longer time spans.