Molecular design of ambipolar redox-active molecules II: closed-shell systems

This mini-review highlights key structural features that should be taken into account when creating ambipolar redox-active closed-shell metal-free molecules. This type of compound is strongly required for the fabrication of all-organic ‘poleless’ batteries and semiconductors. The suggested strategies aimed at stabilization of both oxidized (cationic) and reduced (anionic) redox-states are based on the comprehensive analysis of the most successful structures taken from the recent publications.     

Response surface methodology toward the optimization of high-energy carotenoid extraction from Aristeus antennatus shrimp

High-energy assisted extraction techniques, like ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), are widely applied over the last years for the recovery of bioactive compounds such as carotenoids, antioxidants and phenols from foods, animals and herbal natural sources. Especially for the case of xanthophylls, the main carotenoid group of crustaceans, they can be extracted in a rapid and quantitative way with the use of UAE and MAE.     

Effect of impeller design on homogeneity,size and strength of pharmaceutical granules produced by high-shear wet granulation

Small mixer impeller design is not tailored for granulation because impellers are intended for a wide range of processes. The aim of this research was to evaluate the performances of several impellers to provide guidance on the selection and design for the purposes of granulation. Lactose granules were produced using wet granulation with water as a binder. A Kenwood KM070 mixer was used as a standard apparatus and five impeller designs with different shapes and surface areas were used. The efficacy of granulate formation was measured by adding an optically sensitive tracer to determine variations in active ingredient content across random samples of granules from the same size classes. It was found that impeller design influenced the homogeneity of the granules and therefore can affect final product performance. The variation in active ingredient content across granules of differing size was also investigated. The results show that small granules were more potent than larger granules.     

D3h‐Symmetric Porphyrin‐Based Rigid Macrocyclic Ligands for Multicofacial Multinuclear Complexes in a One‐Nanometer‐Sized Cavity

The one‐step synthesis of D_3h‐symmetric cyclic porphyrin trimers 1 composed of three 2,2′‐[4,4′‐bis(methoxycarbonyl)]bipyridyl moieties and three porphyrinatozinc moieties was achieved from a nickel‐mediated reductive coupling of meso‐5,15‐bis(6‐chloro‐4‐methoxycarbonylpyrid‐2‐yl)porphyrinatozinc. Although cyclic trimers 1 were obtained as a mixture that included other cyclic and acyclic porphyrin oligomers, an extremely specific separation was observed only for cyclic trimers 1 when using columns of silica gel modified with pyrenylethyl, cyanopropyl, and other groups. Structural analysis of cyclic trimers 1 was carried out by means of NMR spectroscopy and X‐ray crystallography. Treatment of an η³‐allylpalladium complex with a cyclic trimer gave a tris(palladium) complex containing three η³‐allylpalladium groups inside the space, which indicated that the bipyridyl moieties inside the ring could work as bidentate metalloligands.     

Bio‐Inspired Transition Metal–Organic Hydride Conjugates for Catalysis of Transfer Hydrogenation: Experiment and Theory

Taking inspiration from yeast alcohol dehydrogenase (yADH), a benzimidazolium (BI⁺) organic hydride‐acceptor domain has been coupled with a 1,10‐phenanthroline (phen) metal‐binding domain to afford a novel multifunctional ligand ( L ^BI+) with hydride‐carrier capacity ( L ^BI++H^?? L ^BIH). Complexes of the type [Cp*M( L ^BI)Cl][PF₆]₂ (M=Rh, Ir) have been made and fully characterised by cyclic voltammetry, UV/Vis spectroelectrochemistry, and, for the Ir^III congener, X‐ray crystallography. [Cp*Rh( L ^BI)Cl][PF₆]₂ catalyses the transfer hydrogenation of imines by formate ion in very goods yield under conditions where the corresponding [Cp*Ir( L ^BI)Cl][PF₆] and [Cp*M(phen)Cl][PF₆] (M=Rh, Ir) complexes are almost inert as catalysts. Possible alternatives for the catalysis pathway are canvassed, and the free energies of intermediates and transition states determined by DFT calculations. The DFT study supports a mechanism involving formate‐driven Rh?H formation (90 kJ mol^?1 free‐energy barrier), transfer of hydride between the Rh and BI⁺ centres to generate a tethered benzimidazoline (BIH) hydride donor, binding of imine substrate at Rh, back‐transfer of hydride from the BIH organic hydride donor to the Rh‐activated imine substrate (89 kJ mol^?1 barrier), and exergonic protonation of the metal‐bound amide by formic acid with release of amine product to close the catalytic cycle. Parallels with the mechanism of biological hydride transfer in yADH are discussed.     

Cyanide Bridged Platinum-Iron Complexes as Cisplatin Prodrug Systems: Design and Computational Study

The potential role of cyanide-bridged platinum-iron complexes as an anti-cancer Pt(IV) prodrug is studied. We present design principles of a dual-function prodrug that can upon reduction dissociate and release concurrently six cisplatin units and a ferricyanide anion per prodrug unit. The prodrug molecule is a unique complex of hepta metal centers consisting of a ferricyanide core with six Pt(IV) centers each bonded to the Fe(III) core through a cyano ligand. The functionality of the prodrug is addressed through density functional theory (DFT) calculations.     

CRISPR-Cas12a System for Biosensing and Gene Regulation

Clustered regularly interspaced short palindromic repeats (CRISPR) is a promising technology in the biological world. As one of the CRISPR-associated (Cas) proteins, Cas12a is an RNA-guided nuclease in the type V CRISPR-Cas system, which has been a robust tool for gene editing. In addition, due to the discovery of target-binding-induced indiscriminate single-stranded DNase activity of Cas12a, CRISPR-Cas12a also exhibits great promise in biosensing. This minireview not only gives a brief introduction to the mechanism of CRISPR-Cas12a but also highlights the recent developments and applications in biosensing and gene regulation. Finally, future prospects of the CRISPR-Cas12a system are also discussed. We expect this minireview will inspire innovative work on the CRISPR-Cas12a system by making full use of its features and advantages.     

Stability-indicating RP-HPLC method development and validation for determination of nine impurities in apixaban tablet dosage forms. Robustness study by quality by design approach

A quality by design (QbD) based high-resolution HPLC method is described for determination of impurities in apixaban (APX) in the tablet dosage form. Employing a simple and stability-indicating HPLC method, nine known impurities were quantified with good peak resolution. Mobile phase A (MP-A) was prepared with buffer and acetonitrile 90:10 v/v, while mobile phase B (MP-B) contained water and acetonitrile 10:90 v/v. The gradient program was 0 min, MP-A 75%, B 25%; 20 min, MP-A 65%, B 35%; 30 min, MP-A 40%, B 60%; 40min, MP-A 40%, B 60%; 42 min, MP-A 75%, B 25%; and 50 min, MP-A 75%, B 25%. The chromatographic separation was achieved using a Zorbax RX C₁₈ 250 × 4.6 mm column, 5 μm (1.0 ml min⁻¹, 280 nm, 50 μl) and a column temperature of 40°C. Several separation studies were carried out using design of experiments to optimize the method. Validation results confirm the applicability of the developed method for quality analysis and stability studies of the regular product on the manufacturing stream.     

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design

Developing optimized hydrogel products requires an in-depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl₂ concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl₂ concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power-law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl₂ concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.     

Copper Bis(oxazoline)-Catalyzed Enantioselective Alkynylation of Benzopyrylium Ions

The stereocontrolled construction of biologically relevant chromanones and tetrahydroxanthones has been achieved through the addition of alkynes to benzopyrylium trilfates under the influence of copper bis(oxazoline) catalysis. Excellent levels of enantiocontrol (63–98 % ee) are achieved in the addition of a variety of alkynes to an array of chromenones with a hydrogen in the 2-position. Promising levels of enantiocontrol (54–67 % ee) are achieved in the alkynylation of chromenones with esters in the 2-position, generating tertiary ether stereocenters resembling those frequently found in naturally occurring metabolites.