Radiolyo-chemiluminescence of bones and seafood shells – a new,promising method for the detection of food irradiation?

Biomineral substances are dissolved in an alkaline mixture of luminol solution and EDTA. Light emission is observed upon dissolution of irradiated calcium carbonate in mollusk and crustacean shells and calcium hydroxyapatite in bones, showing a significantly increased chemiluminescence compared to unirradiated samples. This enables the determination of exposure to ionizing radiation and in some cases even dosimetry. The method described is simple in sample preparation and fast for the detection of irradiated seafood and poultry.     

Development of a novel quality by design–enabled stability-indicating HPLC method and its validation for the quantification of nirmatrelvir in bulk and pharmaceutical dosage forms

A systematic and novel quality by design–enabled, rapid, simple, and economic stability–indicating HPLC method for quantifying nirmatrelvir (NMT) was successfully developed and validated. An analytical target profile (ATP) was established, and critical analytical attributes (CAAs) were allocated to meet the ATP requirements. The method used chromatographic separation using a Purosphere column with a 4.6 mm inner diameter × 250 mm (2.5 μm). The analysis occurred at 50°C with a flow rate of 1.2 mL/min and detection at 220 nm. A 10 μL sample was injected, and the mobile phase consisted of two components: mobile phase A, containing 0.1% formic acid in water (20%), and mobile phase B, containing 0.1% formic acid in acetonitrile (80%). The diluent was prepared by mixing acetonitrile and water at a 90:10 v/v ratio. The retention time for the analyte was determined to be 2.78 min. Accuracy exceeded 99%, and the correlation coefficient was greater than 0.999. The validated HPLC method was characterized as precise, accurate, and robust. Significantly, NMT was found to be susceptible to alkaline, acidic, and peroxide conditions during forced degradation testing. The stability-indicating method developed effectively separated the degradation products formed during stress testing, underlining its effectiveness in stability testing and offering accuracy, reliability, and sensitivity in determining NMT.     

A label-free MALDI TOF MS-based method for studying the kinetics and inhibitor screening of the Alzheimer’s disease drug target β-secretase

Analytical and Bioanalytical Chemistry - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) is a well-established method with a unique set of qualities...     

Development and Box–Behnken design optimization of a green extraction method natural deep eutectic solvent-based for phenolic compounds from barley malt rootlets

In recent years, attention has been turned finding new sources of phenolic compounds, antioxidant molecules, main by-products from the agri-food chain like barley malt rootlets (BMRs). Traditionally, phenolic compounds are extracted from food matrices using different procedures, for example, solid–liquid, liquid–liquid, or solid-phase extraction techniques employing organic solvents. With the advent of green chemistry, attention has been paid to the search for green, nontoxic, inexpensive, and nonflammable solvents and the natural deep eutectic solvents (NADESs) respect these characteristics. The aim of this project was to develop and optimize an environmentally friendly, inexpensive, and rapid extraction method for phenolic compounds from BMRs using natural DESs as extractive solvents. Several natural DESs were tested as extractive solvents and, among them, the best results in terms of total phenolic content were obtained using a choline chloride-malic acid (1:2 molar ratio)-based mixture. Box–Behnken experimental design guaranteed the extraction of 9.51 ± 0.83 gallic acid equivalent/g of BMRs, under the following optimal extraction conditions: 1:21 solid-to-liquid ratio, 80°C as extraction temperature, 43 min as the time of extraction, and 29% as a percentage of added water in the NADESs. Phenolic acids and flavonoids were detected in the BMRs extract through HPLC-PDA/MS analysis.     

Theoretical studies on organic transition-metal complexes—I. Parameterization and calibration of an extended CNDO/2 method for the calculation of stability constants

An extended CNDO/2 method has been developed for the calculation of stability constants of organic transition-metal complexes. An atom parameterization scheme is described for Mn to Zn using Slater exponents which is found to give a reasonable correlation with the ionization potential of the respective metal. The corresponding bonding parameters have been evaluated by initially deriving the best correlation between the calculated and experimental stability constants of a series of substituted copper bis(salicylaldehydes) and then relating these values to the other transition metals using the bond dissociation energies of simple diatomics as the essential criteria.     

Reactive supramolecular assemblies of mucopolysaccharide,polypyrrole and protein as controllable biocomposites for a new generation of ‘intelligent biomaterials’

A method for the simple synthesis of supramolecular composites of polypyrrole, complex mucopolysaccharides and protein is described. These materials have interesting hydrogel-like properties such as high water content and biocompatibility. In addition they are capable of trapping protein in their structure during synthesis and releasing this protein in response to electrical stimuli. The materials are also electroconductive and electroactive. The improved mechanical properties of polypyrrole films over hydrogels and the facile control of their properties by the application of small electrical potentials make them interesting candidates for the design and synthesis of a new generation of ‘smarter’ biomaterials.     

Design and electrochemical characterization of a new cobalt(II)–cyclodextrin complex. Evidence for a supramolecular stabilization of the Co(I) state

The electrochemical behavior of a new cobalt–cyclodextrin (CD) complex was investigated, in dimethylformamide, from CoX₂ (X = Br and BF₄) in the presence of 1 equiv. 6-Deoxy-6-N-(2-methyliminopyridine)-β-cyclodextrin as ligand. Under these conditions, it was demonstrated for the first time, that the electrogenerated cobalt(I) species can be kinetically and thermodynamically stabilized. The electrochemical study of CoX₂ in the presence of a related iminopyridine ligand (2-pyridyl-N-benzylmethylimine), in which the cyclodextrin (CD) group was replaced by a simple aryl moiety, allowed to highlight the crucial role of the CD in this unexpected stabilization. Importantly, this unprecedented result was only observed when both the iminepyridine and the CD moieties were together covalently attached. Importantly, the supramolecular stabilized low-valent cobalt species remained fairly reactive towards aromatic halides despite its intrinsic stability. This original work opens new opportunities for the development of more selective catalytic processes both in organic and aqueous media.     

Application of natural compounds–based gold nanoparticles for the treatment of hemolytic anemia in an anemic mouse model: Formulation of a novel drug from relationship between the nanotechnology and hematology sciences

From time immemorial, people have tried to treat several diseases using natural compounds, including plants. Recently, researchers proposed that plants and herbal nanoparticles possess many remedial potentials. The results of this study confirmed the ability of an aqueous extract of Allium eriophyllum Boiss leaf grown under in vitro conditions for the biosynthesis of gold nanoparticles (AuNPs) and also revealed the anti-hemolytic anemia activity of AuNPs in an anemic rodent model. These nanoparticles were characterized using Fourier-transform infrared spectroscopy (FT-IR) spectroscopy, ultraviolet–visible spectroscopy, X-ray diffraction, field-emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). TEM and FE-SEM images showed the biosynthesized nanoparticles as having a uniform spherical morphology and diameters in the range of 5–30 nm. In vivo design, the induction of hemolytic anemia, was done using phenylhydrazine in 40 mice. Then, the mice were randomly divided into five groups: HAuCl₄, A. eriophyllum, AuNPs, untreated, and control. AuNPs significantly (p ≤ 0.01) decreased the concentration of glucocorticoid receptors in the serum, liver, and spleen, and also alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, total and conjugated bilirubin, cholesterol, triglyceride, low-density lipoprotein, urea, creatinine, ferrous, ferritin, and erythropoietin in the serum increased the concentrations of superoxide dismutase, catalase, and glutathione peroxidase (GPx) in the serum, liver, and spleen and also total protein, high-density lipoprotein, and albumin in serum in the control mice as compared to the anemic mice. Also, AuNPs significantly (p ≤ 0.01) increased the body weight; anti-inflammatory cytokine (IL4, IL5, IL10, IL13, and IFNα) concentration; and the total platelet, white blood cells, lymphocyte, neutrophil, monocyte, eosinophil, and basophil counts and red blood cell parameters but decreased the weight and volume of the liver and spleen and their subcompartments and decreased the concentration of pro-inflammatory cytokines (IL1, IL6, IL12, IL18, IFNY, and TNFα) compared to the untreated mice. In vitro design, using 2,2-diphenyl-1-picrylhydrazyl test, revealed similar antioxidant potentials for A. eriophyllum, AuNPs, and butylated hydroxytoluene. In addition, AuNPs were similar to A. eriophyllum and had a high cell viability dose dependently against the human umbilical vein endothelial cell line. In conclusion, the results of the chemical characterization confirm that the leaves of A. eriophyllum can be used to produce AuNPs with a remarkable amount of anti-hemolytic anemia property.     

Application of dispersive liquid–liquid microextraction with alcoholic solvents followed by HPLC–UV as a sensitive and efficient method for the extraction and determination of citalopram in biological samples using an experimental design

A sensitive and rapid method based on alcoholic-assisted dispersive liquid–liquid microextraction followed by high-performance liquid chromatography for determination of citalopram in human plasma and urine samples was developed. The effects of six parameters (extraction time, stirring speed, pH, volume of extraction and disperser solvents, and ionic strength) on the extraction recovery were investigated and optimized utilizing Plackett–Burman design and Box–Behnken design, respectively. According to Plackett–Burman design results, the volume of disperser solvent, stirring speed, and extraction time had no effect on the recovery of citalopram. The optimized condition was a mixture of 172 µL of 1-octanol as extraction solvent and 400 µL of methanol as disperser solvent, pH of 10.3 and 1% w/v of salt in the sample solution. Replicating the experiment in optimized condition for five times, gave the average extraction recoveries equal to 89.42%. The detection limit of citalopram in human plasma was obtained 4 ng/mL, and the linearity was in the range of 10–1200 ng/mL. The corresponding values for human urine were 5.4 ng/mL with the linearity in the range of 10–2000 ng/mL. Relative standard deviations for inter- and intraday extraction of citalopram were less than 7% for five measurements. The proposed method was successfully implemented for the determination of citalopram in human plasma and urine samples.     

Synthesis of novel PPARα/γ dual agonists as potential drugs for the treatment of the metabolic syndrome and diabetes type II designed using a new de novo design program PROTOBUILD

Peroxisome proliferator activated receptors (PPARs) have been shown to have critical roles in fatty acid oxidation, triglyceride synthesis, and lipid metabolism - making them an important target in drug discovery. Here we describe the in silico design, synthesis and in vitro characterisation of a novel series of 2,5-disubstituted indoles as PPARα/γ dual agonists. PPAR activation assays are performed with known agonists diazabenzene (WY14.643), aminopyridine (BRL49653) and bisaryl (L165.041), as positive controls. All the indole compounds synthesized are found to be active PPARα and PPARγ agonists, with particular efficacy from those with 2-naphthylmethyl substitution. This is a useful demonstration of a new de novo design methodology implemented by the protobuild program and its ability to rapidly produce novel modulators for a well characterized drug target.     

Ultrahigh performance liquid chromatography–triple quadrupole mass spectrometry inhibitors fishing assay: A novel method for simultaneously screening of xanthine oxidase inhibitor and superoxide anion scavenger in a single analysis

Xanthine oxidase (XOD) inhibitors and superoxide anion scavengers play an important role in the treatment of gout and the inhibition of many diseases related to superoxide anion. The respective quantitation of uric acid and superoxide anion by traditional spectroscopic methods is routine in XOD inhibitors and superoxide anion scavengers screening at laboratories worldwide. In the present study, we established an ultrahigh performance liquid chromatography and triple quadrupole mass spectrometry (UHPLC–TQ-MS) method of higher accuracy and speed that combines screening of superoxide anion scavenger and XOD inhibitor in a single analysis by adding WST-1 (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium sodium salt) to the enzymatic reaction. We applied the established method to determine the XOD inhibitory activities and superoxide scavenging activities of some herbal extracts and compounds from natural products, which could be classified into six groups based on the results of the assay. Our innovative protocol is fast, accurate and robust. Moreover, it can eliminate false positive and false negative results which may occur in the traditional spectroscopic methods.     

Static mass spectrographs of a new type using Euler’s homogeneous electric and magnetic fields. II: Conditions of high-order double focusing for two-cascade schemes

Static mass spectrometers are masked by more modern and more sophisticated mass spectrometric instruments, but their potential nowhere is almost exhausted. One of the principle advantages of static mass spectrometers is that they are the only type of mass spectrometric instruments capable of operating in a spectrographic mode by measuring the whole range of masses per a single run. However, systems with good spectrographic properties significantly differ from the optical point of view from systems with good spectrometric properties, and the development of such devices leads to completely new optical problems and, accordingly, to novel methods of their solution. In this paper, we consider possibilities related to the application of electrostatic and magnetostatic fields, homogeneous in Euler’s terms, to the development of two-cascade mass spectrographs with double focusing.     

Results of a European interlaboratory method validation study for the quantitative determination of lipophilic marine biotoxins in raw and cooked shellfish based on high-performance liquid chromatography–tandem mass spectrometry. Part I: collaborative study

A European interlaboratory collaborative study was conducted to validate a method for the quantitative determination of lipophilic marine biotoxins based on high-performance liquid chromatography–tandem mass spectrometry. During this study, the diarrhetic shellfish poisoning toxins okadaic acid, dinophysis toxin1 and 2 including their esters, the azaspiracids 1-3, pectenotoxin2, and the yessotoxins were investigated at concentration levels near the limit of quantification and near the legal limit. Naturally contaminated blue mussels, both raw and cooked and spiked extracts of clams and oysters were studied and results were obtained for 16 test samples from 16 laboratories representing eight different countries. This article summarizes the study outcome concerning validation key parameters like specificity, linearity, limit of detection, accuracy/recovery, and precision. Further, influences of cooking of mussels before homogenization or hydrolysis on method robustness have been evaluated.     

Cholesteric bonded stationary phases for high-performance liquid chromatography: synthesis, physicochemical characterization, and chromatographic behavior of a phospho–cholesteric bonded support. A new way to mimic drug/membrane interactions?

Among the various methods exploitable to determine the bioavailability of drugs, reversed-phase liquid chromatography (RPLC) appears to be suited to creation of patterns of prediction. In this context a new stationary phase was designed in this work to reproduce, in terms of chemical structure, as accurately as possible, the main elements of cellular membranes; which include phospholipids and cholesterol molecules. An efficient synthetic pathway was developed to prepare ligands that contain a phosphate head, a long alkyl chain chemically bonded to silica, and a cholesteric moiety, in order to mimic both hydrophilic and hydrophobic interactions, and "membrane-like" organization, respectively. The new stationary phase was characterized by Fourier-transform infra red (FTIR) and (1)H-(13)C, (1)H-(31)P, and (1)H-(29)Si cross-polarization magic-angle-spinning nuclear magnetic resonance (CP MAS NMR) spectroscopy. Its chromatographic behavior has been studied by classical classification tests for RPLC columns. Despite its low surface coverage, the material produced exhibits high shape selectivity, possibly due to the organization of the grafted moieties.     

Cu(I)-catalyzed alkyne–azide ‘click’ cycloaddition (CuAAC): a clean,efficient, and mild synthesis of new 1,4-disubstituted 1H-1,2,3-triazole-linked 2-amino-4,8-dihydropyrano[3,2-b]pyran-3-carbonitrile–crystal structure

Research on Chemical Intermediates - Cu(I)-catalyzed alkyne–azide ‘click’ cycloaddition (CuAAC) is an important ‘‘click chemistry’’ reaction that is widely...