Molecules, Volume 29, Issue 9 (May-1 2024) – 258 articles

In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at −60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products. Full article

Bovine milk is an essential supplement due to its rich energy- and nutrient-rich qualities. Caseins constitute the vast majority of the proteins in milk. Among these, β-casein comprises around 37% of all caseins, and it is an important type of casein with several different variants. The A1 and A2 variants of β-casein are the most researched genotypes due to the changes in their composition. It is accepted that the A2 variant is ancestral, while a point mutation in the 67th amino acid created the A1 variant. The digestion derived of both A1 and A2 milk is BCM-7. Digestion of A2 milk in the human intestine also forms BCM-9 peptide molecule. The opioid-like characteristics of BCM-7 are highlighted for their potential triggering effect on several diseases. Most research has been focused on gastrointestinal-related diseases; however other metabolic and nervous system-based diseases are also potentially triggered. By manipulating the mechanisms of these diseases, BCM-7 can induce certain situations, such as conformational changes, reduction in protein activity, and the creation of undesired activity in the biological system. Furthermore, the genotype of casein can also play a role in bone health, such as altering fracture rates, and calcium contents can change the characteristics of dietary products. The context between opioid molecules and BCM-7 points to a potential triggering mechanism for the central nervous system and other metabolic diseases discussed. Full article

The main objective of this study was to investigate the metabolism of miconazole, an azole antifungal drug. Miconazole was subjected to incubation with human liver microsomes (HLM) to mimic phase I metabolism reactions for the first time. Employing a combination of an HLM assay and UHPLC-HRMS analysis enabled the identification of seven metabolites of miconazole, undescribed so far. Throughout the incubation with HLM, miconazole underwent biotransformation reactions including hydroxylation of the benzene ring and oxidation of the imidazole moiety, along with its subsequent degradation. Additionally, based on the obtained results, screen-printed electrodes (SPEs) were optimized to simulate the same biotransformation reactions, by the use of a simple, fast, and cheap electrochemical method. The potential toxicity of the identified metabolites was assessed using various in silico models. Full article

Ullazines and their π-expanded derivatives have gained much attention as active components in various applications, such as in organic photovoltaic cells or as photosensitizers for CO₂ photoreduction. Here, we report the divergent synthesis of functionalized diazaullazines by means of two different domino-reactions consisting of either a Povarov/cycloisomerization or alkyne–carbonyl metathesis/cycloisomerization protocol. The corresponding quinolino-diazaullazine and benzoyl-diazaullazine derivatives were obtained in moderate to good yields. Their optical and electronic properties were studied and compared to related, literature-known compounds to obtain insights into the impact of nitrogen doping and π-expansion. Full article

A series of novel binuclear PNP ligands based on the cyclohexyldiamine scaffold were synthesized for this study. The experimental results showed that positioning the two PNP sites at the para-positions of the cyclohexyl framework led to a significant enhancement in the catalytic activity for selective tri/tetramerization of ethylene. The PNP/Cr(acac)₃/MAO(methylaluminoxane) catalytic system exhibited relatively high catalytic activity (up to 3887.7 kg·g⁻¹·h⁻¹) in selective ethylene oligomerization with a total selectivity of 84.5% for 1-hexene and 1-octene at 40 °C and 50 bar. The relationship between the ligand structure and ethylene oligomerization performance was further explored using density functional theory calculations. Full article

Crystalline cerium(III) phosphate (CePO₄), cerium(IV) phosphates, and nanocrystalline ceria are considered to be promising components of sunscreen cosmetics. This paper reports on a study in which, for the first time, a quantitative comparative analysis was performed of the UV-shielding properties of CePO₄, Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5, and CePO₄/CeO₂ composites. Both the sun protection factor and protection factor against UV-A radiation of the materials were determined. Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5 was shown to have a sun protection factor of 2.9, which is comparable with that of nanocrystalline ceria and three times higher than the sun protection factor of CePO₄. Composites containing both cerium dioxide and CePO₄ demonstrated higher sun protection factors (up to 1.8) than individual CePO₄. When compared with the TiO₂ Aeroxide P25 reference sample, cerium(III) and cerium(IV) phosphates demonstrated negligible photocatalytic activity. A cytotoxicity analysis performed using two mammalian cell lines, hMSc and NCTC L929, showed that CePO₄, Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5, and nanocrystalline ceria were all non-toxic. The results of this comparative study indicate that cerium(IV) phosphate Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5 is more advantageous for use in sunscreens than either cerium(III) phosphate or CePO₄/CeO₂ composites, due to its improved UV-shielding properties and low photocatalytic activity. Full article

The photoredox-catalyzed decarboxylative cross-coupling reaction of aryl acetic acids and aryl nitriles has been achieved under an argon atmosphere in high yields. This method provides a fast way to obtain prevalent aryl acetic acids from an abundant natural source. A tentative radical mechanism has been proposed. Full article

The present study investigates the chemical composition variances among Pinelliae Rhizoma, a widely used Chinese herbal medicine, and its common adulterants including Typhonium flagelliforme, Arisaema erubescens, and Pinellia pedatisecta. Utilizing the non-targeted metabolomics technique of employing UHPLC-Q-Orbitrap HRMS, this research aims to comprehensively delineate the metabolic profiles of Pinelliae Rhizoma and its adulterants. Multivariate statistical methods including PCA and OPLS-DA are employed for the identification of differential metabolites. Volcano plot analysis is utilized to discern upregulated and downregulated compounds. KEGG pathway analysis is conducted to elucidate the differences in metabolic pathways associated with these compounds, and significant pathway enrichment analysis is performed. A total of 769 compounds are identified through metabolomics analysis, with alkaloids being predominant, followed by lipids and lipid molecules. Significant differential metabolites were screened out based on VIP > 1 and p-value < 0.05 criteria, followed by KEGG enrichment analysis of these differential metabolites. Differential metabolites between Pinelliae Rhizoma and Typhonium flagelliforme, as well as between Pinelliae Rhizoma and Pinellia pedatisecta, are significantly enriched in the biosynthesis of amino acids and protein digestion and absorption pathways. Differential metabolites between Pinelliae Rhizoma and Arisaema erubescens are mainly enriched in tyrosine metabolism and phenylalanine metabolism pathways. These findings aim to provide valuable data support and theoretical references for further research on the pharmacological substances, resource development and utilization, and quality control of Pinelliae Rhizoma. Full article

Ulcerative colitis (UC), as a chronic inflammatory disease, presents a global public health threat. However, the mechanism of Poria cocos (PC) in treating UC remains unclear. Here, LC-MS/MS was carried out to identify the components of PC. The protective effect of PC against UC was evaluated by disease activity index (DAI), colon length and histological analysis in dextran sulfate sodium (DSS)-induced UC mice. ELISA, qPCR, and Western blot tests were conducted to assess the inflammatory state. Western blotting and immunohistochemistry techniques were employed to evaluate the expression of tight junction proteins. The sequencing of 16S rRNA was utilized for the analysis of gut microbiota regulation. The results showed that a total of fifty-two nutrients and active components were identified in PC. After treatment, PC significantly alleviated UC-associated symptoms including body weight loss, shortened colon, an increase in DAI score, histopathologic lesions. PC also reduced the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β, as evidenced by the suppressed NF-κB pathway, restored the tight junction proteins ZO-1 and Claudin-1 in the colon, and promoted the diversity and abundance of beneficial gut microbiota. Collectively, these findings suggest that PC ameliorates colitis symptoms through the reduction in NF-κB signaling activation to mitigate inflammatory damage, thus repairing the intestinal barrier, and regulating the gut microbiota. Full article

A novel pretreatment strategy utilizing a combination of NaOH and 1-Butyl-3-methylimidazolium chloride ([Bmim]Cl) was proposed to enhance the enzymatic hydrolysis of abandoned Medium-density fiberboard (MDF). The synergistic effect of NaOH and [Bmim]Cl pretreatment significantly improved the glucose yield, reaching 445.8 mg/g within 72 h, which was 5.04 times higher than that of the untreated samples. The working mechanism was elucidated according to chemical composition, as well as FTIR, ¹³C NMR, XRD, and SEM analyses. The combined effects of NaOH and [Bmim]Cl led to lignin degradation, hemicellulose removal, the destruction and erosion of crystalline regions, pores, and an irregular microscopic morphology. In addition, by comparing the enzymatic hydrolysis sugar yield and elemental nitrogen content of untreated MDF samples, eucalyptus, and hot mill fibers (HMF), it was demonstrated that the presence of adhesives and additives in waste MDF significantly influences its hydrolysis process. The sugar yield of untreated MDF samples (88.5 mg/g) was compared with those subjected to hydrothermal pretreatment (183.2 mg/g), Ionic liquid (IL) pretreatment (406.1 mg/g), and microwave-assisted ionic liquid pretreatment (MWI) (281.3 mg/g). A long water bath pretreatment can reduce the effect of adhesives and additives on the enzymatic hydrolysis of waste MDF. The sugar yield produced by the combined pretreatment proposed in this study and the removal ability of adhesives and additives highlight the great potential of our pretreatment technology in the recycling of waste fiberboard. Full article

Photosynthetic water splitting, when synergized with hydrogen production catalyzed by hydrogenases, emerges as a promising avenue for clean and renewable energy. However, theoretical calculations have faced challenges in elucidating the low-lying spin states of iron–sulfur clusters, which are integral components of hydrogenases. To address this challenge, we employ the Extended Broken-Symmetry method for the computation of the cubane–[Fe₃S₄] cluster within the [FeNi] hydrogenase enzyme. This approach rectifies the error caused by spin contamination, allowing us to obtain the magnetic exchange coupling constant and the energy level of the low-lying state. We find that the Extended Broken-Symmetry method provides more accurate results for differences in bond length and the magnetic coupling constant. This accuracy assists in reconstructing the low-spin ground state force and determining the geometric structure of the ground state. By utilizing the Extended Broken-Symmetry method, we further highlight the significance of the geometric arrangement of metal centers in the cluster’s properties and gain deeper insights into the magnetic properties of transition metal iron–sulfur clusters at the reaction centers of hydrogenases. This research illuminates the untapped potential of hydrogenases and their promising role in the future of photosynthesis and sustainable energy production. Full article

An efficient access to the novel 5-(aryl)amino-1,2,3-triazole-containing 2,1,3-benzothiadiazole derivatives has been developed. The method is based on 1,3-dipolar azide–nitrile cycloaddition followed by Buchwald–Hartwig cross-coupling to afford the corresponding N-aryl and N,N-diaryl substituted 5-amino-1,2,3-triazolyl 2,1,3-benzothiadiazoles under NHC-Pd catalysis. The one-pot diarylative Pd-catalyzed heterocyclization opens the straightforward route to triazole-linked carbazole-benzothiadiazole D-A systems. The optical and electrochemical properties of the compound obtained were investigated to estimate their potential application as emissive layers in OLED devises. The quantum yield of photoluminescence (PLQY) of the synthesized D-A derivatives depends to a large extent on electron-donating strengths of donor (D) component, reaching in some cases the values closed to 100%. Based on the most photoactive derivative and wide bandgap host material mCP, a light-emitting layer of OLED was made. The device showed a maximum brightness of 8000 cd/m² at an applied voltage of 18 V. The maximum current efficiency of the device reaches a value of 3.29 cd/A. Full article

With accelerated advancements in various industries, water pollution has emerged as a significant issue characterized by two features: (1) the rapid increase in population and corresponding demands, leading to a sharp rise in wastewater discharge, and (2) the development of new technologies, contributing to a significant increase in the variety of emerging contaminants, resulting in a more complex wastewater composition [...] Full article

We modified C₃-symmetric benzene-1,3,5-tris-amide (BTA) by introducing flexible linkers in order to generate an N-centered BTA (N-BTA) molecule. The N-BTA compound formed gels in alcohols and aqueous mixtures of high-polar solvents. Rheological studies showed that the DMSO/water (1:1, v/v) gels were mechanically stronger compared to other gels, and a similar trend was observed for thermal stability. Powder X-ray analysis of the xerogel obtained from various aqueous gels revealed that the packing modes of the gelators in these systems were similar. The stimuli-responsive properties of the N-BTA towards sodium/potassium salts indicated that the gel network collapsed in the presence of more nucleophilic anions such as cyanide, fluoride, and chloride salts at the MGC, but the gel network was intact when in contact with nitrate, sulphate, acetate, bromide, and iodide salts, indicating the anion-responsive properties of N-BTA gels. Anion-induced gel formation was observed for less nucleophilic anions below the MGC of N-BTA. The ability of N-BTA gels to act as an adsorbent for hazardous anionic and cationic dyes in water was evaluated. The results indicated that the ethanolic gels of N-BTA successfully absorbed methylene blue and methyl orange dyes from water. This work demonstrates the potential of the N-BTA gelator to act as a stimuli-responsive material and a promising candidate for water purification. Full article

Copper-catalyzed azide–alkyne cycloaddition click (CuAAC) reaction is widely used to synthesize drug candidates and other biomolecule classes. Homogeneous catalysts, which consist of copper coordinated to a ligand framework, have been optimized for high yield and specificity of the CuAAC reaction, but CuAAC reaction with these catalysts requires the addition of a reducing agent and basic conditions, which can complicate some of the desired syntheses. Additionally, removing copper from the synthesized CuAAC-containing biomolecule is necessary for biological applications but inconvenient and requires additional purification steps. We describe here the design and synthesis of a PNN-type pincer ligand complex with copper (I) that stabilizes the copper (I) and, therefore, can act as a CuAAC catalyst without a reducing agent and base under physiologically relevant conditions. This complex was immobilized on two types of resin, and one of the immobilized catalyst forms worked well under aqueous physiological conditions. Minimal copper leaching was observed from the immobilized catalyst, which allowed its use in multiple reaction cycles without the addition of any reducing agent or base and without recharging with copper ion. The mechanism of the catalytic cycle was rationalized by density functional theory (DFT). This catalyst’s utility was demonstrated by synthesizing coumarin derivatives of small molecules such as ferrocene and sugar. Full article

Inkjet printing technology offers a unique approach to producing direct-patterned pixels without fine metal masks for active matrix displays. Organic light-emitting diodes (OLEDs) consisting of thermally activated delayed fluorescence (TADF) emitters facilitate efficient light emission without heavy metals, such as platinum and iridium. Multi-resonance TADF molecules, characterized by their small full width at half maxima (FWHM), are highly suitable for the requirements of wide color-gamut displays. Herein, host-free TADF inks with a low concentration of 1 mg/mL were developed and inkjet-printed onto a seeding layer, concurrently serving as the hole-transporting layer. Attributed to the proof-of-concept of host-free inks printed on a mixed seeding layer, a maximum external quantum efficiency of 13.1% (improved by a factor of 21.8) was achieved in the inkjet-printed OLED, with a remarkably narrow FWHM of only 32 nm. Highly efficient energy transfer was facilitated by the effective dispersion of the sensitizer around the terminal emitters. Full article

The cyclometalated terpyridine complexes [Ru(η²-OAc)(NC-tpy)(PP)] (PP = dppb 1, (R,R)-Skewphos 4, (S,S)-Skewphos 5) are easily obtained from the acetate derivatives [Ru(η²-OAc)₂(PP)] (PP = dppb, (R,R)-Skewphos 2, (S,S)-Skewphos 3) and tpy in methanol by elimination of AcOH. The precursors 2, 3 are prepared from [Ru(η²-OAc)₂(PPh₃)₂] and Skewphos in cyclohexane. Conversely, the NNN complexes [Ru(η¹-OAc)(NNN-tpy)(PP)]OAc (PP = (R,R)-Skewphos 6, (S,S)-Skewphos 7) are synthesized in a one pot reaction from [Ru(η²-OAc)₂(PPh₃)₂], PP and tpy in methanol. The neutral NC-tpy 1, 4, 5 and cationic NNN-tpy 6, 7 complexes catalyze the transfer hydrogenation of acetophenone (S/C = 1000) in 2-propanol with NaOiPr under light irradiation at 30 °C. Formation of (S)-1-phenylethanol has been observed with 4, 6 in a MeOH/iPrOH mixture, whereas the R-enantiomer is obtained with 5, 7 (50–52% ee). The tpy complexes show cytotoxic activity against the anaplastic thyroid cancer 8505C and SW1736 cell lines (ED₅₀ = 0.31–8.53 µM), with the cationic 7 displaying an ED₅₀ of 0.31 µM, four times lower compared to the enantiomer 6. Full article

Plant in vitro cultures can be an effective tool in obtaining desired specialized metabolites. The purpose of this study was to evaluate the effect of light-emitting diodes (LEDs) on phenolic compounds in Rhaponticum carthamoides shoots cultured in vitro. R. carthamoides is an endemic and medicinal plant at risk of extinction due to the massive harvesting of its roots and rhizomes from the natural environment. The shoots were cultured on an agar-solidified and liquid-agitated Murashige and Skoog’s medium supplemented with 0.1 mg/L of indole-3-acetic acid (IAA) and 0.5 mg/L of 6-benzyladenine (BA). The effect of the medium and different treatments of LED lights (blue (BL), red (RL), white (WL), and a combination of red and blue (R:BL; 7:3)) on R. carthamoides shoot growth and its biosynthetic potential was observed. Medium type and the duration of LED light exposure did not affect the proliferation rate of shoots, but they altered the shoot morphology and specialized metabolite accumulation. The liquid medium and BL light were the most beneficial for the caffeoylquinic acid derivatives (CQAs) production, shoot growth, and biomass increment. The liquid medium and BL light enhanced the content of the sum of all identified CQAs (6 mg/g DW) about three-fold compared to WL light and control, fluorescent lamps. HPLC-UV analysis confirmed that chlorogenic acid (5-CQA) was the primary compound in shoot extracts regardless of the type of culture and the light conditions (1.19–3.25 mg/g DW), with the highest level under R:BL light. BL and RL lights were equally effective. The abundant component was also 3,5-di-O-caffeoylquinic acid, accompanied by 4,5-di-O-caffeoylquinic acid, a tentatively identified dicaffeoylquinic acid derivative, and a tricaffeoylquinic acid derivative 2, the contents of which depended on the LED light conditions. Full article

meso-Tetrahexylporphyrin was converted to its corresponding 7,8-dihydroxychlorin using an osmium tetroxide-mediated dihydroxylation strategy. Its diol moiety was shown to be able to undergo a number of subsequent oxidation reactions to form a chlorin dione and porpholactone, the first meso-alkylporphyrin-based porphyrinoid containing a non-pyrrolic building block. Further, the diol chlorin was shown to be susceptible to dehydration, forming the porphyrin enol that is in equilibrium with its keto-chlorin form. The meso-hexylchlorin dione could be reduced and it underwent mono- and bis-methylation reactions using methyl-Grignard reagents, and trifluoromethylation using the Ruppert-Prakash reagent. The optical and spectroscopic properties of the products are discussed and contrasted to their corresponding meso-aryl derivatives (where known). This contribution establishes meso-tetrahexyl-7,8-dihydroxychlorins as a new and versatile class of chlorins that is susceptible to a broad range of conversions to generate functionalized chlorins and a pyrrole-modified chlorin analogue. Full article

Cellular slime molds are excellent model organisms in the field of cell and developmental biology because of their simple developmental patterns. During our studies on the identification of bioactive molecules from secondary metabolites of cellular slime molds toward the development of novel pharmaceuticals, we revealed the structural diversity of secondary metabolites. Cellular slime molds grow by feeding on bacteria, such as Klebsiella aerogenes and Escherichia coli, without using medium components. Although changing the feeding bacteria is expected to affect dramatically the secondary metabolite production, the effect of the feeding bacteria on the production of secondary metabolites is not known. Herein, we report the isolation and structure elucidation of clavapyrone (1) from Dictyostelium clavatum, intermedipyrone (2) from D. magnum, and magnumiol (3) from D. intermedium. These compounds are not obtained from usual cultural conditions with Klebsiella aerogenes but obtained from coincubated conditions with Pseudomonas spp. The results demonstrate the diversity of the secondary metabolites of cellular slime molds and suggest that widening the range of feeding bacteria for cellular slime molds would increase their application potential in drug discovery. Full article

In this study, we investigated the catalytic properties of mono- and bimetallic palladium (Pd) and platinum (Pt) nanoparticles deposited via supercritical fluid reactive deposition (SFRD) on titanium dioxide (TiO₂) powder. Transmission electron microscopy analyses verified that SFRD experiments performed at 353 K and 15.6 MPa enabled the deposition of uniform mono- and bimetallic nanoparticles smaller than 3 nm on TiO₂. Electron-dispersive X-ray spectroscopy demonstrated the formation of alloy-type structures for the bimetallic PdPt nanoparticles. H₂O₂ is an excellent oxidizing reagent for the production of fine and bulk chemicals. However, until today, the design and preparation of catalysts with high H₂O₂ selectivity and productivity remain a great challenge. The focus of this study was on answering the questions of (a) whether the catalysts produced are suitable for the direct synthesis of hydrogen peroxide (H₂O₂) in the liquid phase and (b) how the metal type affects the catalytic properties. It was found that the metal type (Pd or Pt) influenced the catalytic performance strongly; the mean productivity of the mono- and bimetallic catalysts decreased in the following order: Pd > PdPt > Pt. Furthermore, all catalysts prepared by SFRD showed a significantly higher mean productivity compared to the catalyst prepared by incipient wetness impregnation. Full article

This manuscript details a comprehensive investigation into the synthesis, structural characterization, thermal stability, and optical properties of nickel-containing hybrid perovskites, namely CH₃NH₃NiCl₃, CsNiCl₃, and CH₃NH₃NiBrCl₂. The focal point of this study is to unravel the intricate crystal structures, thermal behaviors, and optical characteristics of these materials, thereby elucidating their potential application in energy conversion and storage technologies. X-ray powder diffraction measurements confirm that CH₃NH₃NiCl₃ adopts a crystal structure within the Cmcm space group, while CsNiCl₃ is organized in the P6₃/mmc space group, as reported previously. Such structural diversity underscores the complex nature of these perovskites and their potential for tailored applications. Thermal analysis further reveals the stability of CH₃NH₃NiCl₃ and CH₃NH₃NiBrCl₂, which begin to decompose at 260 °C and 295 °C, respectively. The optical absorption properties of these perovskites studied by UV-VIS-NIR spectroscopy revealed the bands characteristic of Ni²⁺ ions in an octahedral environment. Notably, these absorption bands exhibit subtle shifts upon bromide substitution, suggesting that optical properties can be finely tuned through halide modification. Such tunability is paramount for the design and development of materials with specific optical requirements. By offering a detailed examination of these properties, the study lays the groundwork for future advancements in material science, particularly in the development of innovative materials for sustainable energy technologies. Full article

The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than K_m. Thus, the bimolecular rate constant was found to be k_cat/K_m = 7.7 × 10⁴ M⁻¹ min⁻¹. Rough estimates of catalytic parameters provided slow k_cat < 40 min⁻¹ and high K_m = 0.3–3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug. Full article

A series of novel amine triphenolate iron complexes were synthesized and characterized using UV, IR, elemental analysis, and high-resolution mass spectrometry. These complexes were applied to the ring-opening polymerization (ROP) of cyclohexene oxide (CHO), demonstrating excellent activity (TOF > 11050 h⁻¹) in the absence of a co-catalyst. In addition, complex C1 maintained the dimer in the presence of the reaction substrate CHO, catalyzing the ring-opening polymerization of CHO to PCHO through bimetallic synergy. Furthermore, a two-component system consisting of iron complexes and TBAB displayed the ability to catalyze the reaction of CHO with CO₂, resulting in the formation of cis-cyclic carbonate with high selectivity. Complex C4 exhibited the highest catalytic activity, achieving 80% conversion of CHO at a CHO/C4/TBAB molar ratio of 2000/1/8 and a CO₂ pressure of 3 MPa for 16 h at 100 °C, while maintaining >99% selectivity of cis-cyclic carbonates, which demonstrated good conversion and selectivity. Full article

This work presents the design, synthesis and biological activity of novel N-substituted benzimidazole carboxamides bearing either a variable number of methoxy and/or hydroxy groups. The targeted carboxamides were designed to investigate the influence of the number of methoxy and/or hydroxy groups, the type of substituent placed on the N atom of the benzimidazole core and the type of substituent placed on the benzimidazole core on biological activity. The most promising derivatives with pronounced antiproliferative activity proved to be N-methyl-substituted derivatives with hydroxyl and methoxy groups at the phenyl ring and cyano groups on the benzimidazole nuclei with selective activity against the MCF-7 cell line (IC₅₀ = 3.1 μM). In addition, the cyano-substituted derivatives 10 and 11 showed strong antiproliferative activity against the tested cells (IC₅₀ = 1.2–5.3 μM). Several tested compounds showed significantly improved antioxidative activity in all three methods compared to standard BHT. In addition, the antioxidative activity of 9, 10, 32 and 36 in the cells generally confirmed their antioxidant ability demonstrated in vitro. However, their antiproliferative activity was not related to their ability to inhibit oxidative stress nor to their ability to induce it. Compound 8 with two hydroxy and one methoxy group on the phenyl ring showed the strongest antibacterial activity against the Gram-positive strain E. faecalis (MIC = 8 μM). Full article

Fluorescence lifetime imaging microscopy (FLIM) has proven to be a useful method for analyzing various aspects of material science and biology, like the supramolecular organization of (slightly) fluorescent compounds or the metabolic activity in non-labeled cells; in particular, FLIM phasor analysis (phasor-FLIM) has the potential for an intuitive representation of complex fluorescence decays and therefore of the analyzed properties. Here we present and make available tools to fully exploit this potential, in particular by coding via hue, saturation, and intensity the phasor positions and their weights both in the phasor plot and in the microscope image. We apply these tools to analyze FLIM data acquired via two-photon microscopy to visualize: (i) different phases of the drug pioglitazone (PGZ) in solutions and/or crystals, (ii) the position in the phasor plot of non-labelled poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), and (iii) the effect of PGZ or PGZ-containing NPs on the metabolism of insulinoma (INS-1 E) model cells. PGZ is recognized for its efficacy in addressing insulin resistance and hyperglycemia in type 2 diabetes mellitus, and polymeric nanoparticles offer versatile platforms for drug delivery due to their biocompatibility and controlled release kinetics. This study lays the foundation for a better understanding via phasor-FLIM of the organization and effects of drugs, in particular, PGZ, within NPs, aiming at better control of encapsulation and pharmacokinetics, and potentially at novel anti-diabetics theragnostic nanotools. Full article

A concise synthesis of the sex pheromones of elm spanworm as well as painted apple moth has been achieved. The key steps were the alkylation of acetylide ion, Sharpless asymmetric epoxidation and Brown’s P2-Ni reduction. This approach provided the sex pheromone of the elm spanworm (1) in 31% total yield and those of the painted apple moth (2, 3) in 26% and 32% total yields. The ee values of three final products were up to 99%. The synthesized pheromones hold promising potential for use in the management and control of these pests. Full article

The current study comprehensively investigates the adsorption behavior of chromium (Cr(III)) in wastewater using Algerian kaolinite clay. The structural and textural properties of the kaolinite clay are extensively characterized through a range of analytical methods, including XRD, FTIR, SEM-EDS, XPS, laser granulometry, N₂ adsorption isotherm, and TGA–DTA. The point of zero charge and zeta potential are also assessed. Chromium adsorption reached equilibrium within five minutes, achieving a maximum removal rate of 99% at pH 5. Adsorption equilibrium is modeled using the Langmuir, Freundlich, Temkin, Elovich, and Dubinin–Radushkevitch equations, with the Langmuir isotherm accurately describing the adsorption process and yielding a maximum adsorption capacity of 8.422 mg/g for Cr(III). Thermodynamic parameters suggest the spontaneous and endothermic nature of Cr(III) sorption, with an activation energy of 26.665 kJ/mol, indicating the importance of diffusion in the sorption process. Furthermore, advanced DFT computations, including COSMO-RS, molecular orbitals, IGM, RDG, and QTAIM analyses, are conducted to elucidate the nature of adsorption, revealing strong binding interactions between Cr(III) ions and the kaolinite surface. The integration of theoretical and experimental data not only enhances the understanding of Cr(III) removal using kaolinite but also demonstrates the effectiveness of this clay adsorbent for wastewater treatment. Furthermore, this study highlights the synergistic application of empirical research and computational modeling in elucidating complex adsorption processes. Full article

Upon a variety of environmental stresses, eukaryotic cells usually recruit translational stalled mRNAs and RNA-binding proteins to form cytoplasmic condensates known as stress granules (SGs), which minimize stress-induced damage and promote stress adaptation and cell survival. SGs are hijacked by cancer cells to promote cell survival and are consequently involved in the development of anticancer drug resistance. However, the design and application of chemical compounds targeting SGs to improve anticancer drug efficacy have rarely been studied. Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp, respectively. We obtained 11 SG-inducing anticancer compounds from cell-based screens and explored the potential application of SIPs in overcoming resistance to the SG-inducing anticancer drug sorafenib. We found that SIPs increased the sensitivity of HeLa cells to sorafenib via the disruption of SGs. Therefore, anticancer drugs which are competent to induce SGs could be combined with SIPs to sensitize cancer cells, which might provide a novel therapeutic strategy to alleviate anticancer drug resistance. Full article

Gerty T. and Carl F. Cori discovered, during research on the metabolism of sugars in organisms, the important role of the phosphate ester of a simple sugar. Glucose molecules are released from glycogen—the glucose stored in the liver—in the presence of phosphates and enter the blood as α-D-glucose-1-phosphate (Glc-1PH₂). Currently, the crystal structure of three phosphates, Glc-1PNa₂·3.5·H₂O, Glc-1PK₂·2H₂O, and Glc-1PHK, is known. Research has shown that reactions of Glc-1PH₂ with carbonates produce new complexes with ammonium ions [Glc-1P(NH₄)₂·3H₂O] and mixed complexes: potassium–sodium and ammonium–sodium [Glc-1P(X)_1.5Na_0.5·4H₂O; X = K or NH₄]. The crystallization of dicationic complexes has been carried out in aqueous systems containing equimolar amounts of cations (1:1; X–Na). It was found that the first fractions of crystalline complexes always had cations in the ratio 3/2:1/2. The second batch of crystals obtained from the remaining mother liquid consisted either of the previously studied Na+, K+ or NH₄+ complexes, or it was a new sodium hydrate—Glc-1PNa₂·5·H₂O. The isolated ammonium–potassium complex shows an isomorphic cation substitution and a completely unique composition: Glc-1PH(NH₄)_xK_1−x (x = 0.67). The Glc-1P²⁻ ligand has chelating fragments and/or bridging atoms, and complexes containing one type of cation show different modes of coordinating oxygen atoms with cations. However, in the case of the potassium–sodium and ammonium–sodium structures, high structural similarities are observed. The 1D and 2D NMR spectra showed that the conformation of Glc-1P²⁻ is rigid in solution as in the solid state, where only rotations of the phosphate group around the C-O-P bonds are observed. Full article