Class Of Substances Research Articles

Combination of Multidimensional Instrumental Analysis and the Ames Test for the Toxicological Evaluation of Mineral Oil Aromatic Hydrocarbons.

Mineral oil aromatic hydrocarbons (MOAHs) include mutagenic and carcinogenic substances and are considered a potential health risk. Current methods address the total MOAH content but cannot address the actual toxicological hazard of individual components. This work presents a combined methodology closing those gaps: high-performance liquid chromatography (HPLC) coupled to gas chromatography with flame ionization detection was used to determine the MOAH content. To characterize present substance classes, comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry was applied. Preparative HPLC separated MOAHs into subgroups, which were tested with a miniaturized Ames test evaluating DNA reactivity of isolated fractions. Combining these methods allowed a correlation between present subgroups and DNA reactivity. The developed approach was applied to a mineral oil and distinguished between not DNA-reactive mono- and diaromatics and DNA-reactive tri- and polyaromatics, providing a proof of concept. Hereinafter, it will be applied to diverse sample matrices including mineral oils, food, and food contact materials.

Off-target pharmacological profiling of synthetic cannabinoid receptor agonists including AMB-FUBINACA, CUMYL-PINACA, PB-22, and XLR-11.

Synthetic cannabinoid receptor agonists (SCRAs) are a diverse class of new psychoactive substances that have been associated with multiple instances and types of toxicity. Some SCRAs appear to carry a greater toxicological burden than others, or compared to the prototypical cannabis-derived agonist Δ9-tetrahydrocannabinol (Δ9-THC), despite a common primary mechanism of action via cannabinoid 1 (CB1) receptors. "Off-target" (i.e., non-CB1 receptor) effects could underpin this differential toxicity, although there are limited data around the activity of SCRAs at such targets. A selection of 7 SCRAs (AMB-FUBINACA, XLR11, PB-22, AKB-48, AB-CHMINICA, CUMYL-PINACA, and 4F-MDMB-BUTINACA), representing several distinct chemotypes and toxicological profiles, underwent a 30 μM single-point screen against 241 G protein-coupled receptor (GPCR) targets in antagonist and agonist mode using a cellular β-arrestin recruitment assay. Strong screening "hits" at specific GPCRs were followed up in detail using concentration-response assays with AMB-FUBINACA, a SCRA with a particularly notable history of toxicological liability. The single-point screen yielded few hits in agonist mode for any compound aside from CB1 and CB2 receptors, but many hits in antagonist mode, including a range of chemokine receptors, the oxytocin receptor, and histamine receptors. Concentration-response experiments showed that AMB-FUBINACA inhibited most off-targets only at the highest 30 μM concentration, with inhibition of only a small subset of targets, including H1 histamine and α2B adrenergic receptors, at lower concentrations (≥1 μM). AMB-FUBINACA also produced concentration-dependent CB1 receptor signaling disruption at concentrations higher than 1 μM, but did not produce overt cytotoxicity beyond CP55,940 or Δ9-THC in CB1 expressing cells. These results suggest that while some "off-targets" could possibly contribute to the SCRA toxidrome, particularly at high concentrations, CB1-mediated cellular dysfunction provides support for hypotheses concerning on-target, rather than off-target, toxicity. Further investigation of non-GPCR off-targets is warranted.

Highly efficient non-enzymatic electrochemical glucose sensor based on carbon nanotubes functionalized by molybdenum disulfide and decorated with nickel nanoparticles (GCE/CNT/MoS2/NiNPs)

Glucose detection using sensing materials has lately received interest due to the increased demand for sensitive and selective glucose sensors in pharmaceutical, clinical, and industrial settings. Carbon nanotubes (CNTs) are used intensively as a specific class of effective electrode substances in electrochemical sensing due to their large surface area and interesting physical and electrochemical characteristics. Nickel is an attractive transition metal for glucose electrooxidation with high catalytic activity. In this study, CNT/MoS2/NiNPs nanocomposites with different CNT/MoS2 ratios have been prepared by a hydrothermal reaction. The CNT/MoS2 nanocomposites were characterized by X-ray diffraction (XRD), Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR), and their morphology and composition were characterized by field emission scanning electron microscopy (FESEM). Electrocatalytic activity of the as-prepared nanomaterials towards glucose oxidation was investigated by cyclic voltammetry and amperometry in alkaline media. An excellent sensitivity value of 1212 μA·mM−1·cm−2 with a wide linear range (0.05–0.65 mM), a low detection threshold of 0.197 μM and a short response time (3 s) were achieved by the hybrid CNT/MoS2/NiNPs sensor. Its superior catalytic activity and low cost make this hybrid very promising for applications in the direct sensing of glucose.

Alcohol and Substance Use Disorders Diagnostic Criteria Changes and Innovations in ICD-11: An Overview.

The new revision of the ICD came into effect on January 1st, 2022, and significant changes have been introduced in the section related to substance use disorders. In the present work we describe the new ICD-11 section "Disorders due to Substance Use and Addictive Behaviors" and outline the innovations in classification and diagnosis introduced, with a view to addressing the most important issues in terms of new opportunities for identifying and caring for people in need of treatment. The main innovations introduced in the ICD-11 chapter of interest are the expanded classes of psychoactive substances, the introduction of single episodes of substance use, the introduction of harmful patterns of substance use and severity qualifiers for substance intoxication. Furthermore, the new category "Disorders due to addictive behaviors" has been added, including "Gambling disorder" and the new diagnostic category "Gaming disorder". ICD-11 calls for renewed public health response and policies fostering the multi-professional and multidisciplinary management of alcohol and substance abuse treatment, giving to these forms of addiction new chances also towards the reaching of the UN 2030 Agenda Sustainable Development Goals.

Design, Synthesis, Molecular Docking and Antioxidant Evaluation of Benzimidazole-1,3,4 oxadiazole Derivatives

In this research, we synthesised novel benzimidazole-1,3,4 oxadiazole derivatives and studied their antioxidant properties using the DPPH Radical Scavenging Assay. A significant class of substances with a broad range of biological activities is the 1,3,4-benzimidazole family. Furthermore, enabling for various biological activities are the five-membered heterocyclic moieties. Thus, a number of benzimidazole derivatives have been created, there in vitro antioxidant activity has been evaluated, and they have been characterized by FTIR and 1H NMR spectral studies. Compounds 1A, 2A and 3A have the highest G-score i.e., - 7.575 kcal/mol, -6.932 kcal/mol, -6.911 kcal/mol, as compared to standards propyl gallate and Ascorbic acid, which had glide scores of -4.757 kcal/mol and -4.50 kcal/mol respectively. The benzimidazole-1,3,4 oxadiazole containing compounds that were created demonstrated impressive antioxidant activity. When compared to the reference standard, ascorbic acid, (IC50-11.51±0.31 µg/ml) Compound 2A demonstrated the strongest antioxidant activity with an IC50 value (53.00±1.31 µg/ml) respectively.

GC-FID and GC-MS profiling and <i>in vitro</i> antidiabetic and antioxidant activities of <i>Chenopodium ambrosioides</i> L.

<i>Chenopodium ambrosioides</i> is widely used in traditional medicines to manage several health conditions. This study aimed to investigate the chemical composition of the <i>n</i>-hexane fraction and the <i>in vitro</i> antidiabetic and antioxidant properties of <i>C. ambrosioides</i> L. The chemical composition was determined using Gas Chromatography-Flame Ionization Detection and Gas Chromatography-Mass Spectrometry. <i>In vitro</i> evaluations were assessed by evaluating the inhibitory potentials on the activities of α-glucosidase and antioxidants. A total of 58 phytochemicals were identified belonging to 11 classes of substances, of which aliphatic hydrocarbons (38.25%), diterpenes (20.54%), esters (16.33%), triterpenes (11.91%), diverse functional groups (3.74%), aromatic hydrocarbons (2.64%), sesquiterpenes (2.31%), alcohols (1.41%), ketones (0.29%), monoterpenes (0.16%), and fatty acids (0.14%). The major compounds were heptacosane (30.48%) (<b>46</b>), phytol (20.94) (<b>35</b>), and squalene (11.07%) (<b>56</b>). The methanol extract and its fractions showed moderate α-glucosidase activity, but their IC<sub>50</sub> values were lower than the positive control 1-deoxynojirimycin. However, the methanol and methanol-water fractions exhibited more scavenging activity on 2,2-diphenyl-1-picrylhydrazyl with IC<sub>50</sub> values similar to butylated hydroxyanisole (BHA). The plant is rich in various phytoconstituents, and its α-glucosidase and antioxidant status may justify its use in traditional medicine, especially for preventing complications of diabetes.

Synthesis of emerging cathinones and validation of a SPE GC-MS method for their simultaneous quantification in blood.

Over the past 15years, synthetic cathinones have emerged as an important class of new psychoactive substances (NPS) worldwide. The proliferation of these psychostimulants and their sought-after effects among recreational drug users pose a serious threat to public health and enormous challenges to forensic laboratories. For forensic institutions, it is essential to be one step ahead of covert laboratories, foreseeing the structural changes possible to introduce in the core skeleton of cathinones while maintaining their stimulating activity. In this manner, it is feasible to equip themselves with standards of possible new cathinones and validated analytical methods for their qualitative and quantitative detection. Therefore, the aim of the work herein described was to synthesize emerging cathinones based on the evolving patterns in the illicit drug market, and to develop an analytical method for their accurate determination in forensic situations. Five so far unreported cathinones [4'-methyl-N-dimethylbuphedrone (4-MDMB), 4'-methyl-N-ethylbuphedrone (4-MNEB), 4'-methyl-N-dimethylpentedrone (4-MDMP), 4'-methyl-N-dimethylhexedrone (4-MDMH), and 4'-methyl-N-diethylbuphedrone (4-MDEB)] and a sixth one, 4'-methyl-N-ethylpentedrone, already reported to EMCDDA and also known as 4-MEAP, were synthesized and fully characterized by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). An analytical method for the simultaneous quantification of these cathinones in blood, using solid phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS) was developed and validated. The results prove that this methodology is selective, linear, precise, and accurate. For all target cathinones, the extraction efficiency was higher than 73%, linearity was observed in the range of 10 (lower limit of quantification, LLOQ) to 800ng/mL, with coefficients of determination higher than 0.99, and the limits of detection (LODs) were 5ng/mL for all target cathinones. The stability of these cathinones in blood matrices is dependent on the storage conditions; 4-MNEBis the most stable compound and 4-MDMH isthe least stable compound. The low limits obtained allow the detection of the compounds in situations where they are involved, even if present at low concentrations.

Voltammetric Detection of Irbesartan by Molecularly Imprinted Polymer (MIP)-Modified Screen-Printed Electrodes

Irbesartan is a drug used to treat hypertension and high blood pressure. Recent studies associated sartans with several forms of cancer, making removing this class of substances from the environment a high priority. The EU has categorized drugs as emerging pollutants, and they can be more potent than other substances because they were designed to operate at low concentrations. Thus, effective and sensitive methods of determining Irbesartan selectively and accurately in environmental samples are necessary. MIPs have already been used to remove pollutants from complex matrixes, so they were also chosen for this work. In particular, a polyacrylate-based MIP was used to functionalize the graphite working electrode of screen-printed cells (SPCs), aiming to develop a voltammetric method for Irbesartan sensing. The MIP composition and the experimental conditions for the electrochemical determination were optimized through a Design of Experiments (DoE) approach. The whole analysis was replicated with different SPCs obtaining similar results, which highlight the good reproducibility potential. MIP-based electrodes were also applied to determine Irbesartan in fortified tap water samples, obtaining high recovery percentages. Given the good results, the electrochemical method based on MIP-modified screen-printed electrodes is promising for quantifying Irbesartan at a trace level.

The Global Landscape of Manufacturers of Follow-on Biologics: An Overview of Five Major Biosimilar Markets and 15 Countries.

Current knowledge is limited about which manufacturers are active in the global field of biopharmaceutical product development and how many unique follow-on biologics are approved in global markets. This study aimed to provide a cross-sectional overview of manufacturers of follow-on biologics approved in 15 large countries from different regions of the world, as well as in five major biosimilar markets with long established biosimilar frameworks. We screened national drug databases to identify follow-on biologics and their manufacturers approved in 15 countries in Asia, Africa, Latin America and the rest of the world, as well as five major biosimilar markets: the European Union (including the UK), USA, Canada, Australia and Japan. This study identified a total of 304 follow-on biologics from different manufacturers for 18 active substance classes included in the analysis. Of these, 67 products are approved as biosimilars in at least one of the five major biosimilar markets. A total of 140 (46%) follow-on biologics are manufactured in India or China, of which only eight (seven from India and one from China) are approved as biosimilars in any of the five major biosimilar markets. This study found that the majority of follow-on biologics are only approved in the respective country of manufacturing. A small number of manufacturers, primarily from India and Argentina, supply their products to other regions in the world. As some countries have less stringent regulatory approaches for biosimilars, or have only recently implemented biosimilar guidance in line with World Health Organization standards, follow-on biologics could have been approved that would not be considered biosimilars according to the World Health Organization standards. With this study, we try to contribute to discussions on creating more transparency about global approvals of follow-on biologics and promoting access to high-quality biosimilars in countries around the world.

Nanoscale friction characteristics of layered-structure materials in dry and wet environments

Bulk layered materials, such as graphite and molybdenum disulfide, have long been used as solid lubricants in various industrial applications. The weak interlayer van der Waals interactions in these materials generate a low shear slip-plane, which reduces the interfacial friction. The cumulative trends toward device miniaturization have increased the need for basic knowledge of the nanoscale friction of contact-mode devices containing layered materials. Further, the decomposition and degradation of bulk layered solids subjected to shear forces are detrimental to their lubricating characteristics. Layered-structure materials, such as graphene, hexagonal boron nitride, and MXenes consisting of single or few atomic layers, behave as a new class of lubricious substances when deposited at a sliding interface. The exceptional mechanical strength, thermal conductivity, electronic properties, large theoretical specific area, and chemical inertness of these materials make them ideal antifriction materials for continuous sliding interfaces, especially when operated at elevated temperatures. These properties hold great promise for widespread applications both in dry environments, such as solid film lubrication for micro/nano-electromechanical systems, nanocomposite materials, space lubrication, and optical devices, as well as in wet environments, such as desalination membranes, lubricant additives, and nanofluidic transporters. However, accurate and reliable prediction of the frictional behavior of layered-structure materials is challenging due to the complex physicochemical transformations encountered under tribostress. The presence of a liquid in the vicinity of a surface in wet-environment applications further complicates the lubrication behavior of layered-structure materials. Furthermore, insight into the origins of interfacial friction and adhesion due to localized contact interactions can be accomplished by atomic-level experimental techniques and computational methods, such as atomic force microscope (AFM) in combination with molecular dynamics (MD) and density functional theory (DFT). The AFM setup mimics asperity-asperity contact at the atomic level and can measure the friction force of layered-structure materials, whereas MD and DFT can provide insight into the chemomechanical transformations commencing at hidden interfaces, which cannot be detected by experimental methods. The objective of this review article is threefold. First, the relationship between friction and potential energy surface is examined for different layered-structure material systems, and the parameters that mainly affect the energy corrugation are interpreted in the context of reported results. Second, the atomic-scale friction mechanisms of layered-structure materials in dry or vacuum environments are discussed in light of experimental and theoretical findings, focusing on the most crucial frictional energy dissipation mechanisms. Third, the complex mechanisms affecting the nanosccale friction of layered-structure materials incorporated in liquid media are introduced for ionic, polar, and non-polar solutions.

Pharmaceuticals and Personal Care Products in the Environment with Emphasis on Horizontal Transfer of Antibiotic Resistance Genes

Abstract Pharmaceuticals and personal care products (PPCPs) discharged into environment has several adverse impacts. PPCPs are widely utilised for veterinary as well as cosmetic and personal health reasons. These are members of the expanding class of substances known as Contaminants of Emerging Concern (CECs). Antibiotic resistance in the environment and garbage generated by PPCP endanger life. The World Health Organisation (WHO) now recognises antibiotic resistance as a significant global health problem due to the expected increase in mortality caused by it. In the past ten years, mounting data has led experts to believe that the environment has a significant impact on the development of resistance. For human diseases, the external environment serves as a source of resistance genes. It also serves as a major pathway for the spread of resistant bacteria among various habitats and human populations. Large-scale DNA sequencing methods are employed in this thesis to better comprehend the dangers posed by environmental antibiotic resistance. The quantification of the number is an important step in this process. Metagenomic measurement of the number of antibiotic resistance genes in various contexts is a crucial step in this process. However, it’s also crucial to put this data into a broader context by integrating things like taxonomic information, antibiotic concentrations, and the genomic locations of found resistance genes.

Effect of Surfactants on the Binding Properties of a Molecularly Imprinted Polymer.

In molecularly imprinted polymers, non-specific interactions are generally based on weak forces between the polymer surface and the sample matrix. Thus, additives able to interfere with such interactions should be able to significantly reduce any non-specific binding effect. Surfactants represent an interesting class of substances as they are cheap and easily available. Here, we present a study of the effect of three surfactants (the anionic sodium dodecylsulphate, SDS, the cationic cetyltrimethylammonium bromide (CTAB) and the non-ionic polyoxyethylene-(20)-sorbitan monolaurate Tween 20) on the binding affinity of a 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)-imprinted polymer for the template and its analogue 2,4-dichlorophenoxyacetic acid (2,4-D). The experimental results indicate that increasing amounts of surfactant decrease the binding affinity for the ligands strongly for the ionic ones, and more weakly for the non-ionic one. This effect is general, as it occurs for both 2,4,5-T and 2,4-D and for both the imprinted and the not-imprinted polymers. It also proves that the magnitude of this effect mainly depends on the presence or absence of an ionic charge, and that the hydrophobic "tail" of surfactants plays only a minor role.

Molecular characterization of humic-like substances (HULIS) in atmospheric particles (PM2.5) in offshore Eastern China Sea (OECS) using solid-phase extraction coupled with ESI FT-ICR MS

Humic-like substances (HULIS) are organic macromolecular compounds (water-soluble brown carbon) that have an important effect on climate change due to their strong light absorption. However, the molecular composition of HULIS in atmospheric particles in the offshore Eastern China Sea (OECS) has scarcely been investigated. In this study, solid-phase extraction (SPE) was performed to collect HULIS from water extracts. The molecular compositions of samples were characterized by negative-ion electrospray ionization (ESI) Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). A total of 1197–1828 molecular formulas of HULIS were identified in collected samples, and three of them with higher intensities near Shanghai city, Zhejiang province, and Fujian province were discussed in detail. The identified molecular formulas were classified into four major subgroups, including CHO, CHNO, CHOS, and CHNOS compounds. S-containing formulas (CHOS and CHNOS) represented the dominant components (21.0–76.7% relative abundance), followed by CHO (16.5–64.3%), while CHNO compounds constituted 6.1–18.1% of the identified formulas. High fractions of CHO formulas were found in the list of α-pinene ozonolysis yields and S-containing formulas with olefinic structures were abundant in atmospheric particles, suggesting enhanced SOA formation. The samples had a relative abundance-weighted average O/C of 0.25–0.67 and a double bond equivalent of 3.49–4.96. Most identified formulas (>89%) were assigned to aliphatic and olefinic species. The CHNO and S-containing formulas identified in the samples were primarily contributed by –ONO2 functional groups and organosulfates. Biogenic volatile organic compounds (α-pinene or monoterpene) were the dominant precursors of HULIS in the samples. Lignin-like species (41–46%) and protein/amino sugars (28–30%) were the major species among substance classes. The results provide an improved understanding of the molecular composition of HULIS in the Eastern China Sea.

2022 ESC guidelines on cardio-oncology : Understanding and treating cardiovascular side effects from cancer therapy

The continuous improvement in cancer treatment leads to agrowing number of long-term survivors. Arguably, the treatment of cardiovascular side effects from cancer therapy is therefore of major importance for the morbidity and mortality affected patients. The 2022 ESC guidelines on cardio-oncology of the European Society of Cardiology (ESC) aim to improve the treatment of affected patients across the entire continuum of therapy and in the long term by establishing standardized procedures for prevention, diagnostics, and treatment of cardiovascular side effects. Suitable diagnostic and therapeutic measures for specific substance classes are defined on the basis of fundamental recommendations for cardio-oncological care in individual therapy phases. Furthermore, the guidelines provide acomprehensive focus on individual risk assessment before the start of therapy as the basis for determining the type and intensity of cardio-oncological care in the further course. In addition, the risk assessment serves as abasis for the initiation of suitable preventive measures to avoid or minimize the development of cardiovascular side effects during therapy. The present article provides an overview of the most important innovations of the 2022 ESC guidelines on cardio-oncology with respect to general definitions and recommendations as well as asummary of the most important recommendations for some specific forms of therapy with relevance for cardio-oncology in the future.

BIFLUOROPHORES BASED ON NAPHTHALIC ACID DERIVATIVES AS BIOLOGICALLY ACTIVE SUBSTANCES

A large number of organic compounds, capable to luminesce under influence of various types of radiation, are known nowadays. These substances are called luminophores. Features of the chemical structure of these compounds determine their luminescent properties and behavior of a specific luminophore molecules in one or another environment. Possessing a number of spectral properties, luminophores are widely used in many spheres of human a ctivity. Their usage in biology and medicine plays an important role. Number of new methods of biological research, developed on the basis of luminescent dyes, is growing very quickly. This explains the need for synthesis of new luminescent dyes. Bright and water-soluble fluorescent dyes, for example, are important for sensitive detection of DNA via fluorescent probes. Currently, search for new potential antiviral agents is divided in two main strategies. One trend concerns synthesis of new derivatives of already existing antiviral drugs; chemical synthesis of such compounds is aimed at creating a new, more effective drug. Another trend in work on new antiviral drugs is the search for natural compounds, mainly of plant origin, in order to obtain potential chemotherapeutic agents. An interesting object of synthesis is formazans -- a class of organic substances with various biological activities.Biological and industrial application of formazans begins with their use as analytical reagents and dyes, and ends, primarily interesting for us, with their usage in pharmacology. They found wide practical usage as dyes, indicators of redox reactions, etc. In medicine, formazans are used due to their antioxidant, antiviral, antimicrobial, analgesic, anthelmintic and other properties. Many formazans are used in medicine as indicators of cancer cells, drugs against tuberculosis, influenza, and fungal diseases. Important advantage in of formazans synthesis is fairly easy and cheap methods of their production, available starting materials and speed of synthesis processes. In addition, an interesting direction in search for effective substances is the synthesis of formazans with luminescent properties, which significantly expand areas of their application. In our case, such organic luminophores are formazanonaphthalimides and formazanoacenaphthenquinones, which are close to them in structure.

Chemical Emulation of the Biosynthetic Route to Anthrasteroids: Synthesis of Asperfloketal A.

The anthrasteroid rearrangement has been discussed for the formation of the eponymous substance class since its discovery. We here report its chemical emulation from a plausible biogenetic precursor and show how it accounts for the formation of asperfloketals A and B through a mechanistic bifurcation event. As a result, these natural products arise from double Wagner-Meerwein rearrangements and, thus, are 1(10→5),1(5→6)- and 1(10→5),4(5→6)diabeo-14,15-secosteroids, respectively. To establish an efficient route to a bioinspired precursor, we devised a sequence of orchestrated oxidative activation and rearrangement from ergosterol.

Comparison of column chromatography and solid-phase extraction on virgin and aged bituminous maltene phases

Bitumen is a complex mixture consisting of different hydrocarbons, which can be categorised into substance classes called SARA (saturates, aromatics, resins and asphaltenes) fractions. The saturates, aromatics and resins are further referred to as maltenes or maltene phase. To determine the SARA fractions the asphaltenes were separated from the maltenes in a first step. A standard method to further separate the maltenes is column chromatography (CC). Since column chromatography is a time-consuming and solvent-intensive process, an alternative method for separating maltenes using solid-phase extraction (SPE) was investigated. A total of nine bitumen samples of the same type in different ageing states but from different manufacturers were separated with both methods to determine the mass percentages of the fractions for investigating their comparability. The results show that both methods led to different mass percentages of the fractions. However, with the SPE, separating smaller amounts of maltenes is possible while saving a large amount of material, costs, and workload. Linear regression analyses between the colloidal indices with conventional and rheological parameters revealed that the fractions obtained from SPE led to higher coefficients of determination of the linear regression model. The obtained fractions were further structurally compared with FTIR spectroscopy, whereby the spectra of the SPE fractions and the CC fractions did not show any significant differences. The overall consideration of the results concludes that the SPE can replace the CC.

Organocatalyzed Phospha-Michael Addition: A Highly Efficient Synthesis of Customized Bis(acyl)phosphane Oxide Photoinitiators.

Addition of the P-H bond in bis(mesitoyl)phosphine, HP(COMes)2 (BAPH), to a wide variety of activated carbon-carbon double bonds as acceptors was investigated. While this phospha-Michael addition does not proceed in the absence of an additive or catalyst, excellent results were obtained with stoichiometric basic potassium or caesium salts. Simple amine bases can be employed in catalytic amounts, and tetramethylguanidine (TMG) in particular is an outstanding catalyst that allows the preparation of bis(acyl)phosphines, R-P(COMes)2 , under very mild conditions in excellent yields after only a short time. All phosphines RP(COMes)2 can subsequently be oxidized to the corresponding bis(acyl)phosphane oxides, RPO(COMes)2 , a substance class belonging to the most potent photoinitiators for radical polymerizations known to date. Thus, a simple and highly atom economic method has been found that allows the preparation of a broad range of photoinitiators adapted to their specific field of application even on a large scale.

Pharmacognostic studies of Trifolium fragiferum L. flora of Southern Ukraine

The work is devoted to the study of herbs of the representative genus Clover Trifolium fragiferum L. from the south Ukrainian flora. The aim of this research is to investigate the representative of Southern Ukraine flora Trifolium fragiferum L. which has a sufficient raw material base and use in folk medicine. Materials and methods. Samples were grown in the suburbs of Zaporizhzhia and harvested during full flowering (May – June). Microscopic analysis was performed with temporary preparations of leaves and stems. Plant extracts were analyzed chromatographically using an Agilent Technologies 6890 gas chromatograph with mass spectrometric detection. Results. The leaf is covered with parenchymal cells with slightly thickened membranes with anocytic stomata. The main parenchyma is composed of rounded toxoid cells. Stem rounded, covered with elongated parenchymal cells with thin membranes with almost no stomata and pubescence. Central axial cylinder is of beam type. Beams are open collateral, large. Above the phloem of the bundles is a multilayered sclerenchyma. The core is partially filled, hollow in the center. 63 compounds were found in the native extract, of which 37 were identified: coumarins, fatty acids, diterpene alcohols, oxygenated hydrocarbons of terpenoid nature, higher hydrocarbons, representatives of phytosterols, and phytosterols. After acid hydrolysis with sulfuric acid, 58 compounds were found, of which 49 were identified: coumarins, alcohols and phenols, aldehydes and ketones, compounds of diterpene nature. Conclusions. Pharmacognostic analysis of the genus Clover Trifolium fragiferum L. revealed diagnostic microscopic signs of leaves and stems. The components of the native extract are compared, and after its acid hydrolysis. Certain regularities in the distribution of classes of substances that characterized certain types of extracts were revealed: monoterpenoids, aromatic, heterocyclic compounds characterized the hydrolyzed product. Sesquiterpenes and steroid compounds are found only in the native extract of strawberry clover herb. Alcohols, aldehydes, and ketones were the majority in the hydrolyzed extract, and hydrocarbons were observed more in the native. Only 5 components were identified in both extracts: nonacosan, 2-phenoxyethanol, loliolide, dihydroactinidiolide and coumarin with significant differences in amounts.

Cardiac amyloidosis - important differential diagnosis in heart failure

The systemic disease amyloidosis is caused by deposits of misfolded proteins and can cause very different symptoms depending on the organ involvement. The two most common forms are AL amyloidosis and ATTR amyloidosis. The determination of light chains and bone scintigraphy have a high priority in the diagnostic algorithm. New, causally effective substance classes are available for the therapy of AL and ATTR amyloidosis. The classic heart failure medication is often not well tolerated by patients with cardiac amyloidosis and must be adjusted in the presence of symptoms. This article shows which findings and symptom complexes should make you think of amyloidosis and how to arrive at the correct diagnosis in a targeted manner. Causal therapy options as well as special features of heart failure therapy in this patient collective are explained.