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.     

Anticancer Aminoferrocene Derivatives Inducing Production of Mitochondrial Reactive Oxygen Species

Elevated levels of reactive oxygen species (ROS) and deficient mitochondria are two weak points of cancer cells. Their simultaneous targeting is a valid therapeutic strategy to design highly potent anticancer drugs. The remaining challenge is to limit the drug effects to cancer cells without affecting normal ones. We have previously developed three aminoferrocene (AF)-based derivatives, which are activated in the presence of elevated levels of ROS present in cancer cells with formation of electron-rich compounds able to generate ROS and reduce mitochondrial membrane potential (MMP). All of them exhibit important drawbacks including either low efficacy or high unspecific toxicity that prevents their application in vivo up to date. Herein we describe unusual AF-derivatives lacking these drawbacks. These compounds act via an alternative mechanism: they are chemically stable in the presence of ROS, generate mitochondrial ROS in cancer cells, but not normal cells and exhibit anticancer effect in vivo.     

A Comparison of Four Different Electrode Matrices on the Performance of Amperometric Hydrogen Peroxide (Bio)Sensors

A comparison of the analytical performances of four different (bio)sensor designs in H₂O₂ determination is discussed. The (bio)sensor designs developed were based on the use of (i) multiwalled carbon nanotubes (MWCNT), zinc oxide nanoparticles (ZnONP), prussian blue (PB); (ii) MWCNT, ZnONP, PB and ionic liquid (IL); (iii) MWCNT, ZnONP and horseradish peroxidase (HRP) and (iv) MWCNT, ZnONP, HRP and IL modified glassy carbon electrode (GCE). A performance comparison of (bio)sensors showed that the one based on HRP/IL-MWCNT-ZnONP/GCE showed the best analytical characteristics with a linear dynamic range of 9.99×10⁻⁸–7.55×10⁻⁴ M, detection limit of 1.37×10⁻⁸ M and sensitivity of 17.00 μA mM⁻¹.     

Reactivities of mixed organozinc and mixed organocopper reagents. Part 13 Kinetic study for phosphine‐catalyzed acylation of alkylarylzincs and effect of residual group on the transfer rate of alkyl group

Kinetics of reactions of di‐n‐butylzinc, n‐Bu₂Zn, and mixed n‐butyl(substituted phenyl)zinc reagents and n‐Bu(functional group (FG)?C₆H₄)Zn with benzoyl chloride in the presence of tri‐n‐butylphosphine have been investigated. Reaction rates of transferable n‐butyl group have been determined in tetrahydrofuran at 0 °C to compare the transfer rate of n‐butyl group in homo and mixed diorganozincs. Rate law is consistent with a third‐order reaction, which is first order in diorganozinc, benzoyl chloride, and n‐Bu₃P, and a mechanism was proposed. The lower reaction rate of n‐BuPhZn than that of n‐Bu₂Zn and negative reaction constant in Hammett plot are in accordance with the carbanionic charge of transferable n‐butyl group in the acylation reaction. These findings support the hypothesis that the reaction rate of transferable group, R_T, changes depending upon the residual group, R_R, in R_RR_TZn reagents. Copyright © 2016 John Wiley & Sons, Ltd.     

The first use of [PdBr2(imidazolidin-2-ylidene)(pyridine)] catalysts in the direct C-H bond arylation of C2-substituted furan and thiophene

Research on Chemical Intermediates - N-Heterocyclic carbene (NHC)-linked PEPPSI-type palladium complexes have recently been used in the direct C-H bond arylation of heteroarenes. However, in most...     

Probing the Local Reaction Environment During High Turnover Carbon Dioxide Reduction with Ag-Based Gas Diffusion Electrodes

Discerning the influence of electrochemical reactions on the electrode microenvironment is an unavoidable topic for electrochemical reactions that involve the production of OH⁻ and the consumption of water. That is particularly true for the carbon dioxide reduction reaction (CO₂RR), which together with the competing hydrogen evolution reaction (HER) exert changes in the local OH⁻ and H₂O activity that in turn can possibly affect activity, stability, and selectivity of the CO₂RR. We determine the local OH⁻ and H₂O activity in close proximity to a CO₂-converting Ag-based gas diffusion electrode (GDE) with product analysis using gas chromatography. A Pt nanosensor is positioned in the vicinity of the working GDE using shear-force-based scanning electrochemical microscopy (SECM) approach curves, which allows monitoring changes invoked by reactions proceeding within an otherwise inaccessible porous GDE by potentiodynamic measurements at the Pt-tip nanosensor. We show that high turnover HER/CO₂RR at a GDE lead to modulations of the alkalinity of the local electrolyte, that resemble a 16 m KOH solution, variations that are in turn linked to the reaction selectivity.     

Classification of Graeco‐Latin Cubes

A q‐ary code of length n, size M, and minimum distance d is called an code. An code with is said to be maximum distance separable (MDS). Here one‐error‐correcting () MDS codes are classified for small alphabets. In particular, it is shown that there are unique (5, 5³, 3)₅ and (5, 7³, 3)₇ codes and equivalence classes of (5, 8³, 3)₈ codes. The codes are equivalent to certain pairs of mutually orthogonal Latin cubes of order q, called Graeco‐Latin cubes.     

Synergistic Effect of Lithium Perchlorate and Sodium Hydroxide in the Preparation of Electrochemically Treated Pencil Graphite Electrodes for Selective and Sensitive Bisphenol A Detection in Water Samples

In this study, pencil graphite electrodes were activated electrochemically in the presence of different supporting electrolytes and used for the selective and sensitive determination of bisphenol A (BPA) in water samples. Synergistic effects of both LiClO₄ and NaOH supporting electrolytes on the performance of the electrochemically treated pencil graphite electrode (ETPGE) were demonstrated in the oxidation of BPA. The electrochemical behavior of BPA on the ETPGE showed two irreversible oxidation peaks at 0.744 V and 0.877 V (vs. SCE). The detection limit was determined to be 3.1 nM. This single‐use electrode is a very promising candidate to overcome the passivation problems arising from the oxidation of BPA. The analytical application of the ETPGE was performed in tap and river water samples.     

Strong ionic interactions in noncovalent complexes between poly(ethylene imine), a cationic electrolyte,and Cibacron Blue,a nucleotide mimic – implications for oligonucleotide vectors

Cationic polymers can bind DNA to form polyplexes, which are noncovalent complexes used for gene delivery into the targeted cells. For more insight on such biologically relevant systems, the noncovalent complexes between the cationic polymer poly(ethylene imine) (PEI) and the nucleotide mimicking dye Cibacron Blue F3G‐A (CB) were investigated using mass spectrometry methods. Two PEIs of low molecular weight were utilized (M_n ≈ 423 and 600 Da). The different types of CB anions produced by Na⁺/H⁺ exchanges on the three sulfonic acid groups of CB and their dehydrated counterparts were responsible for complex formation with PEI. The CB anions underwent noncovalent complex formation with protonated, but not with sodiated PEI. A higher proportion of cyclic oligomers were detected in PEI423 than PEI600, but both architectures formed association products with CB. Tandem mass spectrometry studies revealed a significantly stronger noncovalent interaction between PEI and dehydrated CB than between PEI and intact CB. Copyright © 2014 John Wiley & Sons, Ltd.     

Dyeing of cotton with thyme and pomegranate peel

Application of natural dyes for textiles is increasing due to awareness of environment, ecology, and pollution control. The purpose of this study is to determine the color, antimicrobial, and fastness properties of cotton fabrics dyed with thyme and pomegranate peel without a mordanting process. In this way, it was planned to avoid use of metallic mordants (heavy-metal salts) and prevent heavy-metal pollution for ecological production. Additionally, a variety of the most commonly used mordants, namely potassium aluminum sulfate, copper(II) sulfate, iron(II) sulfate, and tin(II) chloride, were used for mordanting of cotton fabrics in order to compare the differently mordanted and unmordanted dyed fabrics’ color efficiencies (K/S) and CIE L ^* a ^* b ^* color values. It was found that mordant type had an effect on color efficiency and the color coordinates of fabrics dyed with both thyme and pomegranate fruit peel. Moreover, the antimicrobial properties of the fabrics only dyed directly with thyme and pomegranate peel without any mordanting process were determined to demonstrate the usability of these natural dye sources without use of any mordanting agents. The obtained antimicrobial activities were compared with undyed samples. Undyed samples showed no antimicrobial activity, whereas significant antimicrobial activity was obtained after the dyeing procedure using thyme and pomegranate peel on unmordanted fabrics. Washing, rubbing, perspiration, and lightfastness properties of dyed fabrics were also evaluated. Thyme and pomegranate fruit peel as natural dye sources revealed sufficient results even for unmordanted samples.