Mild Friedel–Crafts Reactions inside a Hexameric Resorcinarene Capsule: C−Cl Bond Activation through Hydrogen Bonding to Bridging Water Molecules

A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self‐assembled cage was exploited to promote the Friedel–Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen‐bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C?Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N‐methylpyrrole is preferentially benzylated in the unusual β‐position while mesitylene reacts faster than 1,3‐dimethoxybenzene despite the greater π‐nucleophilicity of the latter compound.     

Comparative Study of Reversed-Phase High-Performance Liquid Chromatography and Ultraviolet–Visible Spectrophotometry to Determine Doxorubicin in pH-Sensitive Nanoparticles

Analytical methods by reversed-phase high-performance liquid chromatography (HPLC) and ultraviolet–visible spectrophotometry were developed and validated to determine doxorubicin in pH-sensitive chitosan nanoparticles. Chromatographic separation was performed on a reversed-phase C₁₈ column, with ultraviolet detection at 254?nm and a mobile phase composed by 90% (v/v) acetonitrile in water and water pH 3.0 (33:67, v/v). The spectrophotometry method had the wavelength set at 480?nm and pH 3.0 water was used as a diluent. Calibration curves were linear from 1 to 30?µg/?mL (r?>?0.9995) and the specificity was demonstrated by verifying the absence of interferences from nanoparticle components. The values of accuracy and precision were within the acceptable limits, and robustness studies were performed by a two-level full factorial design. The validated methods were further tested to assess doxorubicin content in six different batches of pH-sensitive chitosan nanoparticles. The comparative analyses showed nonsignificant differences (p?>?0.05). Likewise, the HPLC method was successfully applied to determine the drug encapsulation efficiency as well as to measure doxorubicin during in vitro release assays and degradation kinetic studies under ultraviolet light C irradiation. Both methods fulfilled all validation parameters and were shown to be suitable for the characterization of doxorubicin-loaded pH-sensitive chitosan nanoparticles, without interferences from nanoparticle matrix.     

Polymerization by phase-transfer catalysis 3: Poly(1,4-oxylylene thioethers) synthesis

Poly(1,4-oxylylenethioethers) were synthesized from 2,5-disubstituted-1,4-bis(chloromethyl)-benzenes and sodium sulfide under phase-transfer conditions. The polythioethers were characterized by elemental analysis and infrared spectroscopy. The effect of the catalyst, solvent, and temperature were studied. Their glass transition temperature and thermal decomposition were determined.     

Synthesis of arylsulfonyl substituted pyrroles

The cycloaddition reaction of symmetrically and unsymmetrically substituted munchnones with arylsulfonyl alkynes has been studied. The reaction affords pyrrole derivatives whose structures were assigned on the basis of spectroscopic data. The distribution of regioisomers observed in the case of unsymmetrically substituted munchnones is discussed.     

Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in β-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R–avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [⁶⁸Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a ⁶⁸Ge/⁶⁸Ga Generator (GalliaPharma^®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP^®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 μg/mL) and [⁶⁸Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [⁶⁸Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5–0.75 μg/mL for both the analytes (NODAGA-exendin-4 and ⁶⁸Ga-NODAGA-exendin-4), with a correlation coefficient (R²) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [⁶⁸Ga]Ga-NODAGA-exendin-4 was linear with a R² of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 μg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [⁶⁸Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [⁶⁸Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [⁶⁸Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.     

Nutraceutical Content and Genetic Diversity Share a Common Pattern in New Pomegranate Genotypes

The nutraceutical value of pomegranate in the treatment of many diseases is well-documented and is linked to its richness in phenolic compounds. This study aims to evaluate the nutraceutical and genetic diversity of novel pomegranate genotypes (G1–G5) in comparison to leading commercial pomegranate varieties, i.e., ‘Wonderful’, ‘Primosole’, ‘Dente di Cavallo’ and ‘Valenciana’. Morphometric measurements were carried out on fruits, accompanied by chemical characterization (total phenolic content, antioxidant activity, carbohydrates and minerals) and the development of four new polymorphic SSR markers involved in the flavonoid pathway. The cultivars displayed a marked variability in the weight and shape of the fruits, as well as in the weight of the arils and juice yield. The highest level of total phenolic content and antioxidant activity was found in ‘Wonderful’ and G4, while the lowest was in ‘Dente di Cavallo’. Furthermore, the results showed that pomegranate juice is an excellent source of minerals, especially potassium, which plays a key role in organ functioning. The new flavonoid-related markers effectively differentiated the cultivars with the same diversity pattern as morpho-chemical characterization, so the SSRs developed in the present study can be used as a rapid tool for the identification of pomegranate cultivars with relevant nutraceutical traits, such as the new genotypes investigated.     

Supramolecular Enhancement of Electrochemical Nitrate Reduction Catalyzed by Cobalt Porphyrin Organic Cages for Ammonia Electrosynthesis in Water**

The electrochemical nitrate (NO₃⁻) reduction reaction (NO₃RR) to ammonia (NH₃) represents a sustainable approach for denitrification to balance global nitrogen cycles and an alternative to traditional thermal Haber-Bosch processes. Here, we present a supramolecular strategy for promoting NH₃ production in water from NO₃RR by integrating two-dimensional (2D) molecular cobalt porphyrin ( CoTPP ) units into a three-dimensional (3D) porous organic cage architecture. The porphyrin box CoPB-C8 enhances electrochemical active site exposure, facilitates substrate–catalyst interactions, and improves catalyst stability, leading to turnover numbers and frequencies for NH₃ production exceeding 200,000 and 56 s⁻¹, respectively. These values represent a 15-fold increase in NO₃RR activity and 200-mV improvement in overpotential for the 3D CoPB-C8 box structure compared to its 2D CoTPP counterpart. Synthetic tuning of peripheral alkyl substituents highlights the importance of supramolecular porosity and cavity size on electrochemical NO₃RR activity. These findings establish the incorporation of 2D molecular units into 3D confined space microenvironments as an effective supramolecular design strategy for enhancing electrocatalysis.     

Estimation of reactivity ratios using emulsion copolymerization data

An approach for the estimation of reactivity ratios using cumulative copolymer composition–overall conversion data obtained in batch emulsion copolymerization is presented. The approach is based on an algorithm for parameter estimation in ordinary differential equations and takes into account the partition of the comonomers between the different phases present in the system. Both copolymer composition and conversion were considered to be affected by experimental errors. The method was first checked by using simulated data that included random errors. The effect of the initial guess and level of errors on the values of the estimated reactivity ratios was investigated. Once the approach was checked, it was used to estimate the reactivity ratios of the styrene–acrylonitrile system based on data obtained in unseeded batch emulsion copolymerizations of these monomers.     

Two competing species in super-diffusive dynamical regimes

The dynamics of two competing species within the framework of the generalized Lotka-Volterra equations, in the presence of multiplicative α-stable Lévy noise sources and a random time dependent interaction parameter, is studied. The species dynamics is characterized by two different dynamical regimes, exclusion of one species and coexistence of both, depending on the values of the interaction parameter, which obeys a Langevin equation with a periodically fluctuating bistable potential and an additive α-stable Lévy noise. The stochastic resonance phenomenon is analyzed for noise sources asymmetrically distributed. Finally, the effects of statistical dependence between multiplicative noise and additive noise on the dynamics of the two species are studied.