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A novel type of phosphazene containing an additive that acts both as a catalyst and as a flame retardant for benzoxazine binders is presented in this study. The synthesis of a derivative of hexachlorocyclotriphosphazene (HCP) and meta-toluidine was carried out in the medium of the latter, which made it possible to achieve the complete substitution of chlorine atoms in the initial HCP. Thermal and flammability characteristics of modified compositions were investigated. The modifier catalyzes the process of curing and shifts the beginning of reaction from 222.0 °C for pure benzoxazine to 205.9 °C for composition with 10 phr of modifier. The additive decreases the glass transition temperature of compositions. Achievement of the highest category of flame resistance (V-0 in accordance with UL-94) is ensured both by increasing the content of phenyl residues in the composition and by the synergistic effect of phosphorus and nitrogen. A brief study of the curing kinetics disclosed the complex nature of the reaction. An accurate two-step model is obtained using the extended Prout–Tompkins equation for both steps. [ABSTRACT FROM AUTHOR]

In this work, we report a novel method of label-free detection of small molecules based on direct observation of interferometric signal change in graphene-modified glasses. The interferometric sensor chips are fabricated via a conventional wet transfer method of CVD-grown graphene onto the glass coverslips, lowering the device cost and allowing for upscaling the sensor fabrication. For the first time, we report the use of graphene functionalized by the aptamer as the bioreceptor, in conjunction with Spectral-Phase Interferometry (SPI) for detection of ochratoxin A (OTA). In a direct assay with an OTA-specific aptamer, we demonstrated a quick and significant change of the optical signal in response to the maximum tolerable level of OTA concentration. The sensor regeneration is possible in urea solution. The developed platform enables a direct method of kinetic analysis of small molecules using a low-cost optical chip with a graphene-aptamer sensing layer. [ABSTRACT FROM AUTHOR]

Thyroid stimulating hormone (TSH) is the first-line marker for initial evaluation of the thyroid gland function. We present a lateral flow immunoassay based on superparamagnetic nanolabels for rapid (<25 min) quantitative determination of TSH at a point of care. The demonstrated limit of detection (LOD) of 0.017 μIU/mL in human serum is on the level of third-generation TSH laboratory tests. The wide linear dynamic range of more than 3 orders covers the whole range of clinically relevant TSH concentrations for confident quantitative diagnostics of the gland function from hyper- to hypothyroidism, and different states in-between. The attractive values of LOD and linear dynamic range are due to counting of the superparamagnetic nanolabels over the whole reaction volume by their non-linear magnetization at two frequencies of an alternating magnetic field and detecting the response at combinatorial frequencies. The developed cost-efficient and user-friendly immunoassay can be used for express in vitro diagnostics and long-term quantitative monitoring of thyroid dysfunctions, especially in distant regions, developing countries, and sparsely populated areas. Image 1 • Highly sensitive and rapid (25-min) assay for quantitative measurements of TSH in human serum. • Limit of detection – 0.017 μIU/mL suitable for diagnostics of hyperthyroidism. • Steep slope of calibration plot within 3-order linear dynamic range. • Accurate discrimination of virtually all TSH concentrations, pivotal for treatment strategy. • Easy-to-use, can be implemented on site and cost-efficient even for a single test. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are promising agents for liquid biopsy—a non-invasive approach for the diagnosis of cancer and evaluation of therapy response. However, EV potential is limited by the lack of sufficiently sensitive, time-, and cost-efficient methods for their registration. This research aimed at developing a highly sensitive and easy-to-use immunochromatographic tool based on magnetic nanoparticles for EV quantification. The tool is demonstrated by detection of EVs isolated from cell culture supernatants and various body fluids using characteristic biomarkers, CD9 and CD81, and a tumor-associated marker—epithelial cell adhesion molecules. The detection limit of 3.7 × 105 EV/µL is one to two orders better than the most sensitive traditional lateral flow system and commercial ELISA kits. The detection specificity is ensured by an isotype control line on the test strip. The tool's advantages are due to the spatial quantification of EV-bound magnetic nanolabels within the strip volume by an original electronic technique. The inexpensive tool, promising for liquid biopsy in daily clinical routines, can be extended to other relevant biomarkers. [ABSTRACT FROM AUTHOR]

A rapid lateral flow immunoassay is presented that uses carboxyl-modified superparamagnetic nanoparticles as labels that can be quantified by highly sensitive multi-channel electronic readers. The approach is generic in that it is likely to be applicable to numerous small molecules. The method permits both single- and multiplex assays at a point-of-need without sample pretreatment. It is user-friendly and offers attractive characteristics demonstrated here for detection of morphine, fentanyl and methamphetamine in urine. The competitive immunoassay uses commercially available reagents that do not require special permissions. After migration of sample, the lateral flow test strips are subjected to an alternating magnetic field at two frequencies. The response from the nanolabels is readout at a combinatorial frequency from the entire volume of a porous immunochromatographic membrane by the magnetic particle quantification technique. Even trace concentrations can be quantified within ≤20 min with the limits of detection (LOD) of 0.20 ng·mL−1, 0.36 ng·mL−1 and 1.30 ng·mL−1 for morphine, fentanyl and methamphetamine, respectively. The second variant presented here features highly sensitive quantification of haptens (LOD for fentanyl - 0.05 ng·mL−1). This is due to high-affinity trapping of magnetic nanolabels in a universal streptavidin-based test strip, which can be also used for detection of virtually any other small molecule. The third variant is of the multiplexed type and intended for rapid and simultaneous detection of the drugs of abuse in human urine with LODs equal to 0.60 ng·mL−1 and 3.0 ng·mL−1 for morphine and methamphetamine, respectively. In addition to the low LODs, the RSDs did not exceed 7%, 9%, and 11% for methamphetamine, morphine and fentanyl, respectively. [ABSTRACT FROM AUTHOR]

Evolutionary potential of viruses can result in outbreaks of well‐known viruses and emergence of novel ones. Pharmacological methods of intervening the reproduction of various less popular, but not less important viruses are not available, as well as the spectrum of antiviral activity for most known compounds. In the framework of chemical biology paradigm, characterization of antiviral activity spectrum of new compounds allows to extend the antiviral chemical space and provides new important structure–activity relationships for data‐driven drug discovery. Here we present a primary assessment of antiviral activity of spiro‐annulated derivatives of seven‐membered heterocycles, oxepane and azepane, in phenotypic assays against viruses with different genomes, virion structures, and genome realization schemes: orthoflavivirus (tick‐borne encephalitis virus, TBEV), enteroviruses (poliovirus, enterovirus A71, echovirus 30), adenovirus (human adenovirus C5), hantavirus (Puumala virus). Hit compounds inhibited reproduction of adenovirus C5, the only DNA virus in the studied set, in the yield reduction assay, and did not inhibit reproduction of RNA viruses. [ABSTRACT FROM AUTHOR]

Super-enhancers (SEs) are regions of the genome that play a crucial regulatory role in gene expression by promoting large-scale transcriptional responses in various cell types and tissues. Recent research suggests that alterations in super-enhancer activity can contribute to the development and progression of various disorders. The aim of this research is to explore the multifaceted roles of super-enhancers in gene regulation and their significant implications for understanding and treating complex diseases. Here, we study and summarise the classification of super-enhancer constituents, their possible modes of interaction, and cross-regulation, including super-enhancer RNAs (seRNAs). We try to investigate the opportunity of SE dynamics prediction based on the hierarchy of enhancer single elements (enhancers) and their aggregated action. To further our understanding, we conducted an in silico experiment to compare and differentiate between super-enhancers and locus-control regions (LCRs), shedding light on the enigmatic relationship between LCRs and SEs within the human genome. Particular attention is paid to the classification of specific mechanisms and their diversity, exemplified by various oncological, cardiovascular, and immunological diseases, as well as an overview of several anti-SE therapies. Overall, the work presents a comprehensive analysis of super-enhancers across different diseases, aiming to provide insights into their regulatory roles and may act as a rationale for future clinical interventions targeting these regulatory elements. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Three types of polymer-coated glass slides were prepared by acylation of their γ–aminopropyl derivatives with succinic anhydride or poly(p -nitrophenyl acylate) (PNPA) at various reaction times. The variations in duration of chemical adsorption of PNPA allowed control over nano-corrugation of the reactive surfaces employed for biosensing. The visually smooth and optically clear polymer-coated slides were used for immobilization of a conjugate of bovine serum albumin with chloramphenicol (CAP) and label-free measurement of concentration of this antibiotic. The sensor chips prepared in this way provided strong biosensing response due to fast biomolecular interactions and efficient competition of the target analyte during indirect immunoassay. The kinetics of formation and dissociation of immune complexes "conjugate-antibody" on the sensor chip surface was registered by the label-free methods of spectral-correlation and spectral-phase interferometry. The average thickness of immune complex adsorption layers was in the range of 5–12 nm. The highest value of kinetic association constant (k on = 5 × 104 M−1s−1) and the lowest equilibrium dissociation constant (K diss = 2 × 10-8 M−1) were achieved with the chips originated in the PNPA-coated slides, which were produced under short (2 min) polymer chemisorption and exhibited nano-corrugation almost unchanged with respect to the parent glass, according to the atomic-force microscopy. The detection limit for CAP detection was 80 pg/mL, and the dynamic range was 5 orders. The proposed methods for fabrication of sensor chips with nano-corrugated surface, the results of their characterization, as well as the developed assay can be employed for high-throughput recording of multiple molecular interactions by spectral interferometry and in a wide range of biosensing platforms for registration of biologically active compounds in medicine, veterinary, food control and ecological monitoring. [ABSTRACT FROM AUTHOR]

Abstract The phenoxazine scaffold is widely used to stabilize nucleic acid duplexes, as a part of fluorescent probes for the study of nucleic acid structure, recognition, and metabolism, etc. Here we present the synthesis of phenoxazine-based nucleoside derivatives and their antiviral activity against a panel of structurally diverse viruses: enveloped DNA herpesviruses varicella zoster virus (VZV) and human cytomegalovirus, enveloped RNA tick-borne encephalitis virus (TBEV), and non-enveloped RNA enteroviruses. Studied compounds were effective against DNA and RNA viruses reproduction in cell culture. 3-(2′-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication with superior activity against wild type than thymidine kinase deficient strains (EC 50 0.06 and 10 μM, respectively). This compound did not show cytotoxicity on all the studied cell lines. Several compounds showed promising activity against TBEV (EC 50 0.35–0.91 μM), but the activity was accompanied by pronounced cytotoxicity. These compounds may be considered as a good starting point for further structure optimization as antiherpesviral or antiflaviviral compounds. Highlights • 1,3-Diaza-2-oxophenoxazine nucleoside derivatives were synthesized. • These compounds were evaluated against DNA and RNA viruses in vitro. • 3-(2′-Deoxy-β-D-ribofuranosyl)-1,3-diaza-2-oxophenoxazine proved to be a potent inhibitor of VZV replication. • Several derivatives showed promising activity against TBEV, but the activity was accompanied with pronounced cytotoxicity. [ABSTRACT FROM AUTHOR]

1-Substituted 4-perylen-2(3)-yl-1,2,3-triazoles, easily accessible by ‘click’ reaction and combining in one molecule a polyaromatic unit and a nitrogen heterocycle, were found to strongly inhibit the reproduction of enveloped viruses. 5-[4-(Perylen-3-yl)-1,2,3-triazol-1-yl]-uridine and 2-[1-(2-hydroxyethyl)-1,2,3-triazol-4-yl]perylene show EC 50 of 0.031 and 0.023 μM, respectively, against tick-borne encephalitis virus (TBEV). Remarkably, the nucleoside unit appears to be not essential for antiviral activity. These results provide deeper understanding of structural basis of activity for this new class of antivirals. [ABSTRACT FROM AUTHOR]

The therapeutic potential of short interfering RNA (siRNA) to treat many diseases that are incurable with traditional preparations is limited by the extensive metabolism of serum nucleases, low permeability through biological membrane barriers because of a negative charge, and endosomal trapping. Effective delivery vectors are required to overcome these challenges without causing unwanted side effects. Here, we present a relatively simple synthetic protocol to obtain positively charged gold nanoparticles (AuNPs) with narrow size distribution and the surface modified with Tat-related cell-penetrating peptide. The AuNPs were characterized using TEM and the localized surface plasmon resonance technique. The synthesized AuNPs showed low toxicity in experiments in vitro and were able to effectively form complexes with double-stranded siRNA. The obtained delivery vehicles were used for intracellular delivery of siRNA in an ARPE-19 cell line transfected with secreted embryonic alkaline phosphatase (SEAP). The delivered oligonucleotide remained intact and caused a significant knockdown effect on SEAP cell production. The developed material could be useful for delivery of negatively charged macromolecules, such as antisense oligonucleotides and various RNAs, particularly for retinal pigment epithelial cell drug delivery. [ABSTRACT FROM AUTHOR]

Super-enhancers (SEs) are cis-regulatory elements of the human genome that have been widely discussed since the discovery and origin of the term. Super-enhancers have been shown to be strongly associated with the expression of genes crucial for cell differentiation, cell stability maintenance, and tumorigenesis. Our goal was to systematize research studies dedicated to the investigation of structure and functions of super-enhancers as well as to define further perspectives of the field in various applications, such as drug development and clinical use. We overviewed the fundamental studies which provided experimental data on various pathologies and their associations with particular super-enhancers. The analysis of mainstream approaches for SE search and prediction allowed us to accumulate existing data and propose directions for further algorithmic improvements of SEs' reliability levels and efficiency. Thus, here we provide the description of the most robust algorithms such as ROSE, imPROSE, and DEEPSEN and suggest their further use for various research and development tasks. The most promising research direction, which is based on topic and number of published studies, are cancer-associated super-enhancers and prospective SE-targeted therapy strategies, most of which are discussed in this review. [ABSTRACT FROM AUTHOR]

The reaction of β-diketophosphazene with the europium (III) salt synthesized the corresponding metal complex which was structured with (3-aminopropyl)triethoxysilane and treated with dibenzoylmethane for additional coordination of europium atoms. The polymer thus obtained exhibits luminescence with a maximum of 615 nm, which is characteristic of europium. The polymer is thermally stable up to 300 °C, the coating based on it has a contact angle of 101°, and the adhesive strength of the coating to non-finished glass (according to ISO 2409: 2013) is 1 point. [ABSTRACT FROM AUTHOR]

[Display omitted] Using a mouse model, an organ distribution for microgels of carboxymethyl cellulose cross-linked with 67Cu2+ ions was investigated and compared with the distribution of free 67Cu2+ ions from 67CuCl 2. The clearance of the microgels through both liver and kidneys was demonstrated. An additional examination of distribution for [3H]CMC microparticles and [3H]CMC–Cu microgels revealed no copper release from the microgels in vivo. [ABSTRACT FROM AUTHOR]

[Display omitted] • Aptamer-conjugated rGO-FET biosensor on commercially available IDE chip was developed. • Proper choice of solution ionic strength improves the performance of aptasensor to NT-proBNP. • Realistic model of biosensing considering the size of aptamer and analyte molecule is suggested. • Correlation analysis of independent aptasensor parameters was proposed to increase its reliability. • Aptasensor enables on-site detection of NT-proBNP in artificial saliva with LOD 41 fg/mL. Measuring NT-proBNP biomarker is recommended for preliminary diagnostics of the heart failure. Recent studies suggest a possibility of early screening of biomarkers in saliva for non-invasive identification of cardiac diseases at the point-of-care. However, NT-proBNP concentrations in saliva can be thousand time lower than in blood plasma, going down to pg/mL level. To reach this level, we developed a label-free aptasensor based on a liquid-gated field effect transistor using a film of reduced graphene oxide monolayer (rGO-FET) with immobilized NT-proBNP specific aptamer. We found that, depending on ionic strength of tested solutions, there were different levels of correlation in responses of electrical parameters of the rGO-FET aptasensor, namely, the Dirac point shift and transconductance change. The correlation in response to NT-proBNP was high for 1.6 mM phosphate-buffered saline (PBS) and zero for 16 mM PBS in a wide range of analyte concentrations, varied from 1 fg/mL to 10 ng/mL. The effects of transconductance and Dirac point shift in PBS solutions of different concentrations are discussed. The biosensor exhibited a high sensitivity for both transconductance (2 µS/decade) and Dirac point shift (2.3 mV/decade) in diluted PBS with the linear range from 10 fg/mL to 1 pg/mL. The aptasensor performance has been also demonstrated in undiluted artificial saliva with the achieved limit of detection down to 41 fg/mL (∼4.6 fM). [ABSTRACT FROM AUTHOR]

[Display omitted] A new peptidomimetic conjugate of natural methionine and pyridine-2,6-dicarboxylate was synthesized and evaluated as a potential ligand for 97Ru radiopharmaceuticals. The distribution of this radiopharmaceutical in mice was investigated. A fundamental difference was found in the distribution and excretion of ruthenium complex and free ruthenium ion in the body, which suggests a difference in their transport pathways due to the stability of the complex in the body. [ABSTRACT FROM AUTHOR]

Graphical abstract Novel N -(1-oxidopyrimidin-4-yl)- and N , N ′-bis(1-oxidopyrimidin-4-yl)diamines were prepared from 4-fluoropyrimidine N -oxides and diamines basing on S N Ar reaction. One compound from this series possessed antiviral activity against tick-borne encephalitis virus (TBEV). [ABSTRACT FROM AUTHOR]

A 3-channel biosensor based on spectral correlation interferometry (SCI) has been adapted for direct optical detection of antigens by measuring changes in thickness of a biolayer on functionalized glass slips employed as affordable single-use sensor chips. The instrument is insensitive to the bulk refractive index of a solution under test and provides signals in metrological units (pm or nm). Using real-time monitoring with the SCI, protocols for fabrication of sensor chips with different functional (epoxylated, carboxylated, and biotinylated) surfaces for antibody immobilization have been developed and optimized to minimize chip-to-chip variations and achieve better limit of detection (LOD), shorter assay time, and longer shelf life. The optimized coupling surfaces have been compared for detection of human serum albumin (HSA) used as a model agent of medical significance. The dynamic ranges for measuring the HSA concentration were 0.07–20, 0.12–30, and 0.25–10 μg/ml, and the assay durations were less than 20, 15, and 30 min for the epoxylated, carboxylated, and biotinylated chips, respectively. The advantages of each type of sensor chip have been shown, namely, the carboxylated chips feature the shortest assay time, the epoxylated ones demonstrate the best LOD, and the biotinylated chips exhibit the longest shelf life in an unprotected environment. The developed protocols of antibody immobilization can be used in different biosensors and assay techniques including those based on fluorescent, magnetic or plasmonic labels, etc. The SCI is well compatible with various partially transparent layers used in biosensing and with microarrays for multi-analyte detection. [ABSTRACT FROM AUTHOR]

Mycotoxins comprise a frequent type of toxins present in food and feed. The problem of mycotoxin contamination has been recently aggravated due to the increased complexity of the farm-to-fork chains, resulting in negative effects on human and animal health and, consequently, economics. The easy-to-use, on-site, on-demand, and rapid monitoring of mycotoxins in food/feed is highly desired. In this work, we report on an advanced mycotoxin biosensor based on an array of graphene field-effect transistors integrated on a single silicon chip. A specifically designed aptamer against ochratoxin A (OTA) was used as a recognition element, where it was covalently attached to graphene surface via pyrenebutanoic acid, succinimidyl ester (PBASE) chemistry. Namely, an electric field stimulation was used to promote more efficient π-π stacking of PBASE to graphene. The specific G-rich aptamer strand suggest its π-π stacking on graphene in free-standing regime and reconfiguration in G-quadruplex during binding an OTA molecule. This realistic behavior of the aptamer is sensitive to the ionic strength of the analyte solution, demonstrating a 10-fold increase in sensitivity at low ionic strengths. The graphene-aptamer sensors reported here demonstrate fast assay with the lowest detection limit of 1.4 pM for OTA within a response time as low as 10 s, which is more than 30 times faster compared to any other reported aptamer-based methods for mycotoxin detection. The sensors hold comparable performance when operated in real-time within a complex matrix of wine without additional time-consuming pre-treatment. • Biosensor based on an microarray of aptamer-conjugated graphene field-effect transistors was developed. • Real-time highly responsive and rapid detection of Ochratoxin A is achieved. • Ionic strength effect on sensitivity to OTA in buffer is demonstrated. • Realistic scheme of aptamer G-quadruplex conformation upon small toxin molecules binding is proposed. • On-chip device enables in-field detection of OTA trace in wine within 50 s. [ABSTRACT FROM AUTHOR]

This work is devoted to the influence of phosphazene modifiers with different substituents on the curing process, thermal properties and flammability of benzoxazine resin. Novel catalysts with m-toluidine substituents were introduced. The catalytic activity of studied phosphazene compounds decreased in the row: hexachlorocyclotriphosphazene (HCP) > tetra m-toluidine substituted phosphazene PN-mt (4) > hexa m-toluidine substituted phosphazene PN-mt (6) > hexaphenoxycyclotriphosphazene (HPP), where HPP is totally inactive. Two types of catalysis: basic and acid were proposed. A brief study of resulting properties of polybenzoxazines was presented. The addition of any studied modifier caused the decrease of glass transition temperature and thermal stability of polymers. The morphology of cured compositions was characterized by matrix-dispersion phase structure. All phosphazene containing polybenzoxazines demonstrated the improved flame resistance. [ABSTRACT FROM AUTHOR]

Natural products, such as humic substances (HS) and shilajit, are known to possess antiviral activity. Humic-like components are often called as carriers of biological activity of shilajit. The goal of this study was to evaluate anti-HIV activity of well characterized HS isolated from coal, peat, and peloids, and compare it to that of water-soluble organic matter (OM) isolated from different samples of Shilajit. The set of humic materials included 16 samples of different fractional composition: humic acid (HA), hymatomelanic acid (HMA), fulvic acid (FA). The set of shilajit OM included 19 samples of different geographic origin and level of alteration. The HIV-1 p24 antigen assay and cell viability test were used for assessment of antiviral activity. The HIV-1 Bru strain was used to infect CEM-SS cells. The obtained EC50 values varied from 0.37 to 1.4 mg L−1 for the humic materials, and from 14 to 142 mg L−1 for the shilajit OM. Hence, all humic materials used in this study outcompeted largely the shilajit materials with respect to anti-HIV activity: For the humic materials, the structure-activity relationships revealed strong correlation between the EC50 values and the content of aromatic carbon indicating the most important role of aromatic structures. For shilajit OM, the reverse relationship was obtained indicating the different mechanism of shilajit activity. The FTICRMS molecular assignments were used for ChEMBL data mining in search of the active humic molecules. As potential carriers of antiviral activity were identified aromatic structures with alkyl substituents, terpenoids, N-containing analogs of typical flavonoids, and aza-podophyllotoxins. The conclusion was made that the typical humic materials and Shilajit differ greatly in molecular composition, and the humic materials have substantial preferences as a natural source of antiviral agents as compared to shilajit. • Comparison of anti-HIV activity measured for the two large sets of humic materials and Shilajit water extracts demonstrated much higher activity of the humic materials. • Structure-activity relationships revealed leading role of aromatic structures in anti-HIV activity of humic substances, and the opposite trend was observed for shilajit. • 13C NMR and FTICR MS studies revealed structural similarity of shilajit extract to fulvic acid. • Different mode of antiviral action is suggested for aromatics-rich humic materials (humic acids, hymatomelanic acids) and N-rich shilajit. [ABSTRACT FROM AUTHOR]

Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophilic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxylic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as antibiotic heliomycin, still showed pronounced activity against tick-borne encephalitis virus (TBEV) with limited toxicity in porcine embryo kidney (PEK) cell line. 5-(Perylen-3-yl)-2-thiophenecarboxylic acid (5a) showed the highest antiviral activity with 50% effective concentration of approx. 1.6 nM. [ABSTRACT FROM AUTHOR]

Convenient synthesis path of nanostructured water-soluble microgels (PMG) based on carboxymethylcellulose cross-linked with zinc and ligand N -(5,6-dihydro-4H-1,3-thiazine-2 yl) benzamide and N -(4- isopropyl-phenyl)- N -(1-iminoethyl)piperidine-1-carbothioamide hydrobromides is described. Being insoluble in aqueous solutions the complex of zinc with the ligand acquires the solubility in water when dispersed in nanocontainers of PMG. Microgels were obtained by varying the content of zinc-ions in the reaction mixture. A new method for the determination of zinc in PMG composite using sulfarsazene is proposed. The resulting nanoparticles have been tested for cytotoxicity. It was established cytotoxicity of nanocontainers strongly depends on the concentration of zinc and ligand in composition of PMG. [ABSTRACT FROM AUTHOR]

Dimensionality reduction is an important exploratory data analysis method that allows high-dimensional data to be represented in a human-interpretable lower-dimensional space. It is extensively applied in the analysis of chemical libraries, where chemical structure data - represented as high-dimensional feature vectors-are transformed into 2D or 3D chemical space maps. In this paper, commonly used dimensionality reduction techniques - Principal Component Analysis (PCA), t-Distributed Stochastic Neighbor Embedding (t-SNE), Uniform Manifold Approximation and Projection (UMAP), and Generative Topographic Mapping (GTM) - are evaluated in terms of neighborhood preservation and visualization capability of sets of small molecules from the ChEMBL database., (© 2024 The Author(s). Molecular Informatics published by Wiley-VCH GmbH.)

Carbon capture and storage technologies are projected to increasingly contribute to cleaner energy transitions by significantly reducing CO 2 emissions from fossil fuel-driven power and industrial plants. The industry standard technology for CO 2 capture is chemical absorption with aqueous alkanolamines, which are often being mixed with an activator, piperazine, to increase the overall CO 2 absorption rate. Inefficiency of the process due to the parasitic energy required for thermal regeneration of the solvent drives the search for new tertiary amines with better kinetics. Improving the efficiency of experimental screening using computational tools is challenging due to the complex nature of chemical absorption. We have developed a novel computational approach that combines kinetic experiments, molecular simulations and machine learning for the in silico screening of hundreds of prospective candidates and identify a class of tertiary amines that absorbs CO 2 faster than a typical commercial solvent when mixed with piperazine, which was confirmed experimentally., (© 2022. The Author(s).)

Antimicrobial resistance is a global threat. The use of biologically active natural products alone or in combination with the clinically proven antimicrobial agents might be a useful strategy to fight the resistance. The scientific hypotheses of this study were twofold: (1) the natural humic substances rich in dicarboxyl, phenolic, heteroaryl, and other fragments might possess inhibitory activity against β-lactamases, and (2) this inhibitory activity might be linked to the molecular composition of the humic ensemble. To test these hypotheses, we used humic substances (HS) from different sources (coal, peat, and soil) and of different fractional compositions (humic acids, hymatomelanic acids, and narrow fractions from solid-phase extraction) for inhibiting serine β-lactamase TEM-1. Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) was used to characterize the molecular composition of all humic materials used in this study. The kinetic assay with chromogenic substrate CENTA was used for assessment of inhibitory activity. The inhibition data have shown that among all humic materials tested, a distinct activity was observed within apolar fractions of hymatomelanic acid isolated from lignite. The decrease in the hydrolysis rate in the presence of most active fractions was 42% (with sulbactam-87%). Of particular importance is that these very fractions caused a synergistic effect (2-fold) for the combinations with sulbactam. Linking the observed inhibition effects to molecular composition revealed the preferential contribution of low-oxidized aromatic and acyclic components such as flavonoid-, lignin, and terpenoid-like molecules. The binding of single low-molecular-weight components to the cryptic allosteric site along with supramolecular interactions of humic aggregates with the protein surface could be considered as a major contributor to the observed inhibition. We believe that fine fractionation of hydrophobic humic materials along with molecular modeling studies on the interaction between humic molecules and β-lactamases might contribute to the development of novel β-lactamase inhibitors of humic nature., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Humic substances (HS) are complex natural mixtures comprising a large variety of compounds produced during decomposition of decaying biomass. The molecular composition of HS is extremely diverse as it was demonstrated with the use of high resolution mass spectrometry. The building blocks of HS are mostly represented by plant-derived biomolecules (lignins, lipids, tannins, carbohydrates, etc.). As a result, HS show a wide spectrum of biological activity. Despite that, HS remain a 'biological activity black-box' due to unknown structures of constituents responsible for the interaction with molecular targets. In this study, we investigated the antiviral activity of eight HS fractions isolated from peat and coal, as well as of two synthetic humic-like materials. We determined molecular compositions of the corresponding samples using ultra-high resolution Fourier-transform ion cyclotron resonance mass-spectrometry (FTICR MS). Inhibitory activity of HS was studied with respect to reproduction of tick-borne encephalitis virus (TBEV), which is a representative of Flavivirus genus, and to a panel of enteroviruses (EVs). The samples of natural HS inhibited TBEV reproduction already at a concentration of 1 µg/mL, but they did not inhibit reproduction of EVs. We found that the total relative intensity of FTICR MS formulae within elemental composition range commonly attributed to flavonoid-like structures is correlating with the activity of the samples. In order to surmise on possible active structural components of HS, we mined formulae within FTICR MS assignments in the ChEMBL database. Out of 6502 formulae within FTICR MS assignments, 3852 were found in ChEMBL. There were more than 71 thousand compounds related to these formulae in ChEMBL. To support chemical relevance of these compounds to natural HS we applied the previously developed approach of selective isotopic exchange coupled to FTICR MS to obtain structural information on the individual components of HS. This enabled to propose compounds from ChEMBL, which corroborated the labeling data. The obtained results provide the first insight onto the possible structures, which comprise antiviral components of HS and, respectively, can be used for further disclosure of antiviral activity mechanism of HS.

Rigid amphipathic fusion inhibitors (RAFIs) are potent antivirals based on a perylene core linked with a nucleoside moiety. Sugar-free analogues of RAFIs, 5-(perylen-3-ylethynyl)uracil-1-acetic acid 1 and its amides 2, were synthesized using combined protection group strategy. Compounds 1 and 2 appeared to have low toxicity on porcine embryo kidney (PEK) or rhabdomiosarcoma (RD) cells together with remarkable activity against enveloped tick-borne encephalitis virus (TBEV): EC 50 values vary from 0.077 μM to subnanomolar range. Surprisingly, 3-pivaloyloxymethyl (Pom) protected precursors 7 and 8 showed even more pronounced activity. All the compounds showed no activity against several non-enveloped enteroviruses, except 4-hydroxybutylamides 2d,g, which inhibited the reproduction of enterovirus A71 with EC 50 50-100 μM, with a non-specific mode of action. The results suggest that the carbohydrate moiety of RAFI nucleosides does not play a crucial role in their antiviral action, and biological activity of the 5-(perylen-3-ylethynyl)uracil scaffold can be effectively modulated by substituents in positions 1 and 3. The high antiviral activity of these new compounds, coupled with low toxicity advocate their potential role in antiviral therapy., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

A series of analogues of potent antiviral perylene nucleoside dUY11 with methylthiomethyl (MTM), azidomethyl (AZM) and HO-C 1-4 -alkyl-1,2,3-triazol-1,4-diyl groups at 3'-O-position as well as the two products of copper-free alkyne-azide cycloaddition of the AZM derivative were prepared and evaluated against tick-borne encephalitis virus (TBEV). Four compounds (4, 6, 8a, 8b) showed EC 50  ≤ 10 nM, thus appearing the most potent TBEV inhibitors to date. Moreover, these nucleosides have higher lipophilicity (clogP) and increased solubility in aq. DMSO vs. parent compound dUY11., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)