Molecules

28 pages, 4045 KiB

Open AccessArticle

The Absence of a Very Long Chain Fatty Acid (VLCFA) in Lipid A Impairs Agrobacterium fabrum Plant Infection and Biofilm Formation and Increases Susceptibility to Environmental Stressors

by Iwona Komaniecka, Kamil Żebracki, Andrzej Mazur, Katarzyna Suśniak, Anna Sroka-Bartnicka, Anita Swatek and Adam Choma

Molecules 2025, 30(5), 1080; https://doi.org/10.3390/molecules30051080 (registering DOI) - 26 Feb 2025

Abstract

The Agrobacterium fabrum C58 is a phytopathogen able to infect numerous species of cultivated and ornamental plants. During infection, bacteria genetically transform plant cells and induce the formation of tumours at the site of invasion. Bacterial cell wall components play a crucial role [...] Read more.

The Agrobacterium fabrum C58 is a phytopathogen able to infect numerous species of cultivated and ornamental plants. During infection, bacteria genetically transform plant cells and induce the formation of tumours at the site of invasion. Bacterial cell wall components play a crucial role in the infection process. Lipopolysaccharide is the main component of Gram-negative bacteria's outer leaflet of outer membrane. Its lipophilic part, called lipid A, is built of di-glucosamine backbone substituted with a specific set of 3-hydroxyl fatty acids. A. fabrum incorporates a very long chain hydroxylated fatty acid (VLCFA), namely 27-hydroxyoctacosanoic acid (28:0-(27OH)), into its lipid A. A. fabrum C58 mutants deprived of this component due to mutation in the VLCFA’s genomic region, have been characterised. High-resolution mass spectrometry was used to establish acylation patterns in the mutant’s lipid A preparations. The physiological properties of mutants, as well as their motility, ability to biofilm formation and plant infectivity, were tested. The results obtained showed that the investigated mutants were more sensitive to environmental stress conditions, formed a weakened biofilm, exhibited impaired swimming motility and were less effective in infecting tomato seedlings compared to the wild strain. Full article

(This article belongs to the Special Issue The 30th Anniversary of Molecules—Recent Advances in Chemical Biology)

16 pages, 868 KiB

Open AccessArticle

Synthesis, Characterization, and Evaluation of the Antifungal Properties of 3-Indolyl-3-Hydroxy Oxindole Derivatives Against Plant Pathogenic Fungi

by Zhiqiang Bai, Kunrong Dang, Jinrui Tang, Rongjing Yang, Liming Fan, Qiu Li, Yue Yang, Min Ye and Fawu Su

Molecules 2025, 30(5), 1079; https://doi.org/10.3390/molecules30051079 - 26 Feb 2025

Abstract

To discover novel fungicides with good inhibitory effects on plant fungal diseases, twenty-five 3-indolyl-3-hydroxy oxindole derivatives (3a–3y) were synthesized. These newly derivatives were characterized by NMR and HRMS. Their antifungal activities against five plant pathogenic fungi were assessed in vitro. Most of the [...] Read more.

To discover novel fungicides with good inhibitory effects on plant fungal diseases, twenty-five 3-indolyl-3-hydroxy oxindole derivatives (3a–3y) were synthesized. These newly derivatives were characterized by NMR and HRMS. Their antifungal activities against five plant pathogenic fungi were assessed in vitro. Most of the compounds exhibited moderate to excellent antifungal activities against the five pathogenic fungi. Notably, compounds 3t, 3u, 3v, and 3w displayed remarkable and broad-spectrum antifungal activities comparable to or superior to those of the fungicides carvacrol (CA) and phenazine-1-carboxylic acid (PCA). Among them, compound 3u displayed the most excellent antifungal activity against Rhizoctonia solani Kühn (R. solani), with an EC₅₀ of 3.44 mg/L, which was superior to CA (7.38 mg/L) and PCA (11.62 mg/L). Preliminary structure–activity relationship (SAR) results indicated that the introduction of I, Cl, or Br substituents at position 5 of the 3-hydroxy-2-oxindole and indole rings is crucial for compounds to exhibit good antifungal activity. The in vivo antifungal activity assay showed that compound 3u has good curative effects against R. solani. The current results suggest that these compounds are capable of serving as promising lead compounds. Full article

15 pages, 5041 KiB

Open AccessArticle

MOF-Derived N-Doped Carbon Nanotube-Confined Ni Nanoparticles for the Simultaneous Electrochemical Detection of Cu²⁺ and Hg²⁺ with High Sensitivity and Stability

by Jiapeng Li, Lili Chen, Yiming Qiao, Li Li, Xin Li, Linbo Deng, Xuemin Duan, Hui Chen and Yansha Gao

Molecules 2025, 30(5), 1078; https://doi.org/10.3390/molecules30051078 - 26 Feb 2025

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Abstract

Heavy metal pollution has posed a serious threat to the ecological environment and human health. Thus, the development of accurate and effective methods for their detection is crucial. In this study, a novel electrochemical sensor was fabricated to detect Cu²⁺ and Hg [...] Read more.

Heavy metal pollution has posed a serious threat to the ecological environment and human health. Thus, the development of accurate and effective methods for their detection is crucial. In this study, a novel electrochemical sensor was fabricated to detect Cu²⁺ and Hg²⁺, based on N-doped carbon nanotube-wrapped Ni nanoparticle (Ni@N-CNT) sensing material, which was derived from the pyrolysis of Ni²⁺ doped ZIF-8. For electrode material design, the packaging structure not only protected the encapsulated Ni nanoparticles from electrochemical corrosion in the acid electrolyte but also provided excellent electro-catalytic activity and electrical conductivity by controlling their size. Thanks to the overall performance of the Ni@N-CNT composite, the proposed sensor exhibited excellent analytical performance for Cu²⁺ and Hg²⁺ detection, with ultra-low detection limits of 33.3 ng⋅L⁻¹ and 33.3 ng⋅L⁻¹, respectively. The sensor also demonstrated good repeatability, reproducibility and selectivity. In addition, the method was successfully applied to the electrochemical analysis of Cu²⁺ and Hg²⁺ in actual Chinese cabbage samples with satisfactory recovery, confirming its practical applicability. Full article

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15 pages, 790 KiB

Open AccessArticle

Formation and Chemical Structure of Carbon-13 Tracer Lignin-Carbohydrate Complexes (LCCs) During Kraft Pulping

by Zhi Wang, Yimin Xie and Boxuan Zhao

Molecules 2025, 30(5), 1077; https://doi.org/10.3390/molecules30051077 - 26 Feb 2025

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Abstract

In this study, a modified synthetic method for labeling a lignin dimer (guaiacylglycerol-β-guaiacyl ether-[α-¹³C]) was developed. The chemical structure of the target compound was analyzed using ¹H-NMR, ¹³C-NMR, and other analytical techniques. Then, the ¹³C-labeled phenolic lignin model [...] Read more.

In this study, a modified synthetic method for labeling a lignin dimer (guaiacylglycerol-β-guaiacyl ether-[α-¹³C]) was developed. The chemical structure of the target compound was analyzed using ¹H-NMR, ¹³C-NMR, and other analytical techniques. Then, the ¹³C-labeled phenolic lignin model compound was subjected to kraft pulping in the presence of xylose. Finally, the resulting reaction products were fractionated using acid precipitation and ethyl acetate extraction, and each fraction was analyzed by carbon-13 nuclear magnetic resonance (¹³C-NMR) and two-dimensional heteronuclear multiple quantum coherence (HMQC) spectroscopy. This aimed to investigate the occurrence of lignin–carbohydrate complexes (LCCs) during the conventional kraft pulping process. Employing ethanol as the reaction medium facilitated the bromination of 4-acetylguaiacol-[α-¹³C], resulting in a homogeneous reaction and significantly improving the yield of the brominated product to over 90%. Additionally, kraft pulping of the phenolic lignin model compound in the presence of xylose led to the occurrence of minor quantities of benzyl ether-type lignin–carbohydrate complex (LCC) structures, which were predominantly detected in the ethyl acetate extractive. Full article

25 pages, 6133 KiB

Open AccessArticle

Chemical Looping CH₄ Reforming Through Isothermal Two-Step Redox Cycling of SrFeO₃ Oxygen Carrier in a Tubular Solar Reactor

by Stéphane Abanades, Xinhe Wang and Srirat Chuayboon

Molecules 2025, 30(5), 1076; https://doi.org/10.3390/molecules30051076 - 26 Feb 2025

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Abstract

The chemical looping reforming of methane using an SrFeO₃ oxygen carrier to produce synthesis gas from solar energy was experimentally investigated and validated. High-temperature solar heat was used to provide the reaction enthalpy, and therefore the methane feedstock was entirely dedicated to [...] Read more.

The chemical looping reforming of methane using an SrFeO₃ oxygen carrier to produce synthesis gas from solar energy was experimentally investigated and validated. High-temperature solar heat was used to provide the reaction enthalpy, and therefore the methane feedstock was entirely dedicated to producing syngas. The two-step isothermal process encompassed partial perovskite reduction with methane (partial oxidation of CH₄) and exothermic oxidation of SrFeO_3-δ with CO₂ or H₂O splitting under the same operating temperature. The oxygen carrier material was shaped in the form of a reticulated porous foam structure for enhancing heat and mass transfer, and it was cycled in a solar-heated tubular reactor under different operating parameters (temperature: 950–1050 °C, methane mole fraction: 5–30%, and type of oxidant gas: H₂O vs. CO₂). This study aimed to assess the fuel production capacity of the two-step process and to demonstrate the potential of using strontium ferrite perovskite during solar cycling for the first time. The maximum H₂ and CO production rates during CH₄-induced reduction were 70 and 25 mL/min at 1000 °C and 15% CH₄ mole fraction. The increase in both the cycle temperature and the methane mole fraction promoted the reduction step, thereby enhancing syngas yields up to 569 mL/g during reduction at 1000 °C under 30% CH₄ (778 mL/g including both cycle steps), and thus outperforming the performance of the benchmark ceria material. In contrast, the oxidation step was not significantly affected by the experimental conditions and the material’s redox performance was weakly dependent on the nature of the oxidizing gas. The syngas yield remained above 200 mL/g during the oxidation step either with H₂O or CO₂. Twelve successive redox cycles with stable patterns in the syngas production yields validated material stability. Combining concentrated solar energy and chemical looping reforming was shown to be a promising and sustainable pathway toward carbon-neutral solar fuels. Full article

(This article belongs to the Special Issue 10th Anniversary of Green Chemistry Section)

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19 pages, 3386 KiB

Open AccessArticle

Potential of Nb₂O₅ as a Catalyst in Biodiesel Production: A Study with Different Feedstock

by Helder de Lucena Pereira, Adriano Lima da Silva, Carlos Bruno Barreto Luna, Joyce Salviano Barros de Figueiredo, Simoni Margareti Plentz Meneghetti and Ana Cristina Figueiredo de Melo Costa

Molecules 2025, 30(5), 1075; https://doi.org/10.3390/molecules30051075 - 26 Feb 2025

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Abstract

The objective of this study was to evaluate the catalytic performance of commercial Nb₂O₅, supplied by CBMM, in the production of biodiesel by transesterification and esterification, using different feedstocks (soybean, corn, sunflower, and waste oils) and both methyl and [...] Read more.

The objective of this study was to evaluate the catalytic performance of commercial Nb₂O₅, supplied by CBMM, in the production of biodiesel by transesterification and esterification, using different feedstocks (soybean, corn, sunflower, and waste oils) and both methyl and ethyl routes. For this, the catalyst was characterized in terms of its crystal structure by X-ray diffraction (XRD), specific surface area using the Brunauer–Emmett–Teller (BET) technique, thermal stability by thermogravimetric analysis (TGA), morphology by scanning electron microscopy (SEM), acidity by ammonia desorption at programmed temperature (TPD-NH₃), and catalytic activity by gas chromatography. The results from the structural analyses indicated that Nb₂O₅ has a single monoclinic phase and a morphology consisting of irregular agglomerates. The specific surface area was 1.3 m²/g, and its density was 4.639 g/cm³. The thermogravimetric analysis showed that the material has thermal stability, maintaining its structural integrity up to temperatures as high as 1000 °C. The total acidity reached 301 μmol NH₃/g, indicating the presence of Brønsted and Lewis acidic sites. In catalytic tests, Nb₂O₅ showed higher efficiency in the methyl route, achieving an initial conversion of 96.43% in esters with soybean oil, outperforming other feedstocks. However, catalyst reuse over five cycles revealed a progressive decrease in catalytic activity, possibly due to blocking active sites by adsorbed products, as confirmed by FTIR and XRD analyses conducted on the catalyst. Despite decreased activity after the cycles, the catalyst maintained its crystal structure, indicating structural stability. These results demonstrate the potential of Nb₂O₅ as a heterogeneous catalyst for biodiesel production, particularly with the methyl route and high-quality oils. This study highlights the relevance of Nb₂O₅ in biodiesel synthesis, contributing to sustainable practices and technological advancement in the renewable energy sector. Full article

(This article belongs to the Special Issue Functional Nanomaterials in Green Chemistry, 2nd Edition)

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14 pages, 1877 KiB

Open AccessArticle

Spherical Amides with C₃ Symmetry: Improved Synthetic Approach and Structural/Optical Analysis

by Daiki Koike, Hyuma Masu, Haruka Uno, Shoko Kikkawa, Hidemasa Hikawa and Isao Azumaya

Molecules 2025, 30(5), 1074; https://doi.org/10.3390/molecules30051074 - 26 Feb 2025

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Abstract

A spherical amide with C₃ symmetry was synthesized by a one-step cyclization reaction using triphenylphosphine and hexachloroethane as coupling reagents. This method enabled synthesis of N-benzyl and N-allyl derivatives, which could not be obtained by the previously reported method. The [...] Read more.

A spherical amide with C₃ symmetry was synthesized by a one-step cyclization reaction using triphenylphosphine and hexachloroethane as coupling reagents. This method enabled synthesis of N-benzyl and N-allyl derivatives, which could not be obtained by the previously reported method. The optical resolution of each compound was measured, and their electronic circular dichroism spectra revealed that they were mirror images. The high structural symmetry resulted in a higher Δε (molar absorption difference against right or left circular polarization: ε_L − ε_R value compared to that of another structural isomer synthesized previously. The absolute structure of the enantiopure crystal of the N-benzyl derivative was determined using the Flack parameter obtained by X-ray crystallographic analysis. Full article

(This article belongs to the Section Organic Chemistry)

16 pages, 2139 KiB

Open AccessArticle

Influence of Aluminum Incorporation on the Adsorptive Performance of Silica-Based Supported Sulfonic Acid for the Chemical Recovery of Gaseous O-Xylene

by Yaxu Wang, Jiaxuan Chai, Yining Li and Zichuan Ma

Molecules 2025, 30(5), 1073; https://doi.org/10.3390/molecules30051073 - 26 Feb 2025

Abstract

A group of silica-based supports with varying Al/Si ratios (S−x) was synthesized using the sol–gel method, followed by a chlorosulfonic acid modification to produce supported sulfonic acids (SA−x). The S−x and SA−x materials, along with their adsorption products, were characterized via techniques such [...] Read more.

A group of silica-based supports with varying Al/Si ratios (S−x) was synthesized using the sol–gel method, followed by a chlorosulfonic acid modification to produce supported sulfonic acids (SA−x). The S−x and SA−x materials, along with their adsorption products, were characterized via techniques such as FTIR, BET, and HPLC-MS. The analysis revealed that the sulfonic acid groups in the SA−x materials existed in two anchoring states: the covalently bonded (CB) state [SiOx–O]^ɗ⁻–SO₃H^ɗ+ and the ion-paired (IP) state AlO_y⁺:OSO₃H⁻. The sulfonation reactivity of the CB-state sulfonic acid was enhanced, whereas that of the IP-state counterpart was diminished. The incorporation of a minor quantity of aluminum ions (x = 0.1) markedly enhanced the adsorption efficiency of SAs for o-xylene, extending the reaction temperature range to 110–190 °C and increasing the breakthrough adsorption capacity (Q_B) to 946.1 mg g⁻¹. However, excessive aluminum ion incorporation was detrimental to the adsorption performance of SAs for o-xylene. SA−0.1 showed superior adsorptive capabilities and excellent recyclability, maintaining its performance over four consecutive adsorption/regeneration cycles with only a minor decrease of 4.5%. These findings suggest that SAs prepared with a minor amount of aluminum ions have significant potential for application as adsorbents for the removal of benzene series pollutants. Full article

(This article belongs to the Section Green Chemistry)

19 pages, 5010 KiB

Open AccessArticle

Carbonation and Phase Evolution in MgO-SiO₂ Cements: Impact on Strength

by Gonzalo Mármol, Ana Fernández-Jiménez, María-Teresa Blanco-Varela and Inés García-Lodeiro

Molecules 2025, 30(5), 1072; https://doi.org/10.3390/molecules30051072 - 26 Feb 2025

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Abstract

Magnesium silicate hydrate (M-S-H) binders, synthesized from magnesia and silica, exhibit promising mechanical and thermal properties but face challenges in early strength development due to delayed kinetics and limited MgO solubility. This study investigates the impact of early exposure to CO₂-saturated [...] Read more.

Magnesium silicate hydrate (M-S-H) binders, synthesized from magnesia and silica, exhibit promising mechanical and thermal properties but face challenges in early strength development due to delayed kinetics and limited MgO solubility. This study investigates the impact of early exposure to CO₂-saturated atmospheres on MgO-SiO₂ cementitious systems, emphasizing the role of carbonation in phase evolution and mechanical performance. Early carbonation promotes the formation of hydrated magnesium hydroxycarbonates (HMHC), altering hydration pathways and reducing M-S-H gel content. Key analyses, including XRD, TGA, SEM-EDS, and FTIR, reveal that higher carbonation levels correlate with reduced Mg(OH)₂ stability at early ages, an enhanced precipitation of HMHC phases, and significant effects on mineralogy and strength. Results underscore the influence of formulation, water-to-cement ratio, and early carbonation in optimizing strength and phase development, providing a pathway to more efficient MgO-SiO₂ cement systems with reduced reliance on reactive SiO₂. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules—Recent Advances in Materials Chemistry)

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16 pages, 1261 KiB

Open AccessArticle

Development of a Scalable Extraction Process for Anthocyanins of Haskap Berry (Lonicera caerulea)

by Damith Costa and H.P. Vasantha Rupasinghe

Molecules 2025, 30(5), 1071; https://doi.org/10.3390/molecules30051071 - 26 Feb 2025

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Abstract

Haskap (Lonicera caerulea) berry is rich in anthocyanins, particularly cyanidin-3-O-glucoside (C3G). In this investigation, a response surface methodology was applied to optimize the anhydrous ethanol-based extraction parameters to obtain the maximum yield of anthocyanins from haskap berry and to [...] Read more.

Haskap (Lonicera caerulea) berry is rich in anthocyanins, particularly cyanidin-3-O-glucoside (C3G). In this investigation, a response surface methodology was applied to optimize the anhydrous ethanol-based extraction parameters to obtain the maximum yield of anthocyanins from haskap berry and to compare the recovery of anthocyanins from different extraction methods. The central composite design was employed to study the effect of three independent variables (X_A = ultrasonic bath power, X_B = extraction temperature, and X_C = extraction time) which were found to significantly affect the response variable total anthocyanin content (TAC) and fit to the second-order polynomial model. The optimum process parameters of X_A = 536 W, X_B = 62.3 °C, and X_C = 63.5 min provided a predicted TAC of 16.5 mg C3G equivalence (C3GE)/g dry weight (DW), which was experimentally validated with 16.1 mg of C3GE/g DW. The optimized ultrasonication-assisted extraction process using anhydrous ethanol was also effective in recovering quercetin glycosides, catechin, procyanidin B2, and iridoids, as determined by ultra-pressure liquid chromatography–mass spectrometry. Though the anthocyanin recovery was the highest (17.6 mg of C3GE/g DW) when a deep eutectic solvent consisting of citric acid and D-(+)-maltose was used, this solvent system has limitations when preparing dehydrated extracts for industrial applications. This study concludes that the effective extraction of anthocyanins and other phytochemicals from haskap berries can be performed using food-grade anhydrous ethanol. Full article

(This article belongs to the Special Issue Exploring Bioactive Polyphenolic Compounds in Food and Natural Real-World Samples II)

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Graphical abstract

Graphical abstract
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Response surface plots of the TAC (mg C3GE/g DW) extraction from haskap berry powder as a function of ultrasonic power (W), extraction temperature (°C), and extraction time (min). The following values were kept constant: (a) extraction time of 60 min, (b) ultrasonic power of 500 W, and (c) extraction temperature of 48 °C. Full article ">Figure 2
The TPC (A), FRAP (B), TAC (C), DPPH (D), ORAC (E), and C3G (F) content variations of different extraction processes. Abbreviations: C3GEs, C3G equivalents, OEE, optimum extraction condition using anhydrous ethanol and UAE; AA, anhydrous ethanol with 2% acetic acid/UAE); CA, anhydrous ethanol with 2% citric acid/UAE; DES, deep eutectic solvent system with UAE; W, deionized water with UAE. The different letters of means (A–D) indicate the significant differences (p > 0.05) among them. Full article ">Figure 3
Correlation coefficients among the TAC, TPC, C3G, ORAC, DPPH, and FRAP of haskap berry extracts prepared from various methods (n = 15). Full article ">Figure 4
TAC of haskap berry extracts in response to different ethanol concentrations (A) and different ultrasonic power levels (B). The different letters of means (A–D) indicate the significant differences (p > 0.05) among them. Full article ">

14 pages, 3994 KiB

Open AccessArticle

Impregnation of Se₂S₆ into a Nitrogen- and Sulfur-Co-Doped Functional Metal Carbides and Nitrides for High-Performance Li-S Batteries

by Lu Chen, Zhongyuan Zheng, Shuo Meng, Wenwei Wu, Weicheng Zhou, Shanshan Yang, Kexuan Liao, Yuanhui Zuo and Ting He

Molecules 2025, 30(5), 1070; https://doi.org/10.3390/molecules30051070 - 26 Feb 2025

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Abstract

In this study, nitrogen- and sulfur-co-doped MXene (NS-MXene) was developed as a high-performance cathode material for lithium–sulfur (Li-S) batteries. Heterocyclic Se₂S₆ molecules were successfully confined within the NS-MXene structure using a simple melt impregnation method. The resulting NS-MXene exhibited a [...] Read more.

In this study, nitrogen- and sulfur-co-doped MXene (NS-MXene) was developed as a high-performance cathode material for lithium–sulfur (Li-S) batteries. Heterocyclic Se₂S₆ molecules were successfully confined within the NS-MXene structure using a simple melt impregnation method. The resulting NS-MXene exhibited a unique wrinkled morphology with a stable structure which facilitated rapid ion transport and provided a physical barrier to mitigate the shuttle effect of polysulfide. The introduction of nitrogen and sulfur heteroatoms into the MXene structure not only shifted the Ti d-band center towards the Fermi level but also significantly polarizes the MXene, enhancing the conversion kinetics and ion diffusion capability while preventing the accumulation of Li₂S₆. Additionally, the incorporation of Se and S in Se₂S₆ improved the conductivity compared to S alone, resulting in reduced polarization and enhanced electrical properties. Consequently, NS-MXene/Se₂S₆ exhibited excellent cycling stability, high reversible capacity, and reliable performance at high current densities and under extreme conditions, such as high sulfur loading and low electrolyte-to-sulfur ratios. This work presents a simple and effective strategy for designing heteroatom-doped MXene materials, offering promising potential for the development of high-performance, long-lasting Li-S batteries for practical applications. Full article

(This article belongs to the Special Issue Innovative Materials for Advanced Lithium, Sodium and Zinc Batteries: Design, Synthesis and Application)

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29 pages, 10041 KiB

Open AccessArticle

Unveiling the Role of Fractionated Graphene Oxide in Nitric Oxide Scavenging

by Grigoriy R. Chermashentsev, Ivan V. Mikheev, Daria-Mariia V. Ratova, Elena V. Proskurnina and Mikhail A. Proskurnin

Molecules 2025, 30(5), 1069; https://doi.org/10.3390/molecules30051069 - 26 Feb 2025

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Abstract

The feasibility of saturating aqueous anoxic solutions with in situ-generated high-purity nitric oxide (NO) is shown herein. A methemoglobin assay estimated the average nitric oxide concentration to be ca. 20 ± 3 µM. Graphene oxide aqueous dispersions were prepared by ultrasound-assisted extra exfoliation. [...] Read more.

The feasibility of saturating aqueous anoxic solutions with in situ-generated high-purity nitric oxide (NO) is shown herein. A methemoglobin assay estimated the average nitric oxide concentration to be ca. 20 ± 3 µM. Graphene oxide aqueous dispersions were prepared by ultrasound-assisted extra exfoliation. These dispersions, including unpurified (pristine) samples and samples purified from transition metal impurities (bulk) fractions (bulkGO) and (nano) separated fractions (nanoGO) in a range of 0.5 to 14 kDa were prepared with ppm level concentrations. A robust and reproducible chemiluminescence (CL) assay validated the interaction between graphene oxide and NO in a luminol-based system. The results showed a significant increase in NO scavenging activity within the bulkGO fractions to nanofractions ranging from 14 to 3.5 kDa. The different reaction pathways underlying the transformation of nitric oxide are being evaluated, focusing on understanding how its presence or absence affects these processes. Our kinetic model suggests a significant difference in nitric oxide regulation; nanoGO demonstrates an interception rate seventy-times higher than that achieved through CL quenching. Full article

(This article belongs to the Special Issue Molecular Spectroscopy in Applied Chemistry)

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40 pages, 1548 KiB

Open AccessReview

The Role of Genistein in Type 2 Diabetes and Beyond: Mechanisms and Therapeutic Potential

by Mateusz Kciuk, Weronika Kruczkowska, Katarzyna Wanke, Julia Gałęziewska, Damian Kołat, Somdutt Mujwar and Renata Kontek

Molecules 2025, 30(5), 1068; https://doi.org/10.3390/molecules30051068 - 26 Feb 2025

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Abstract

The global prevalence of type 2 diabetes mellitus (T2DM) necessitates the exploration of novel therapeutic approaches to mitigate its complex molecular pathogenesis. This review investigates the potential role of genistein, a prominent isoflavone derived from soybeans, in the management of T2DM. Recognized for [...] Read more.

The global prevalence of type 2 diabetes mellitus (T2DM) necessitates the exploration of novel therapeutic approaches to mitigate its complex molecular pathogenesis. This review investigates the potential role of genistein, a prominent isoflavone derived from soybeans, in the management of T2DM. Recognized for its selective estrogen receptor modulator (SERM) activity, genistein exerts a multifaceted influence on key intracellular signaling pathways, which are crucial in regulating cell proliferation, apoptosis, and insulin signaling. Genistein’s anti-inflammatory, anti-oxidant, and metabolic regulatory properties position it as a promising candidate for T2DM intervention. This review synthesizes current research spanning preclinical studies and clinical trials, emphasizing genistein’s impact on insulin sensitivity, glucose metabolism, and inflammatory markers. Additionally, this review addresses genistein’s bioavailability, safety, and potential influence on gut microbiota composition. By consolidating these findings, this review aims to provide a comprehensive understanding of genistein’s therapeutic potential in T2DM management, offering valuable insights for future research and clinical practice. Full article

(This article belongs to the Special Issue Phytochemicals as Valuable Tools for Fighting Metabolic Disorders)

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Chemical structures of genistin and genistein. Both of the compounds contain two aromatic benzene rings (A and B) and a non-aromatic heterocyclic pyran ring (C), forming a 3-phenylchromen-4-one backbone. Created in BioRender. Kciuk, M. (2025) <a href="https://BioRender.com/n34w609" target="_blank">https://BioRender.com/n34w609</a> (accessed on 17 February 2025). Full article ">Figure 2
Pathological alterations associated with type II diabetes mellitus (T2DM) and the influence of genistein on the systemic basis (A) and molecular level (B) for the treatment of the disease. (A) In T2DM, there is a complex interplay between the pancreas, liver, skeletal muscles, adipose tissue, and intestinal microbiota, all contributing to the disease’s pathophysiology. The pancreas initially compensates for insulin resistance in peripheral tissues by increasing insulin secretion, but over time, beta-cell dysfunction leads to impaired insulin secretion. The liver exacerbates hyperglycemia by increasing gluconeogenesis due to insulin resistance, contributing to elevated fasting glucose levels. In skeletal muscles, reduced glucose uptake further worsens hyperglycemia, as muscles are major sites of insulin-mediated glucose disposal. Adipose tissue dysfunction in T2DM leads to altered secretion of adipokines like reduced adiponectin and increased inflammatory cytokines, which promote systemic insulin resistance. Additionally, altered intestinal microbiota composition, or dysbiosis, can influence inflammation and metabolic pathways, further impairing glucose metabolism and contributing to insulin resistance. This interconnected dysfunction among these organs and systems drives the progression and complications of T2DM. (B) In T2DM, chronic hyperglycemia triggers a cascade of metabolic disturbances, including oxidative stress and the formation of advanced glycation end products (AGEs). Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and anti-oxidants, activates key signaling pathways such as protein kinase C (PKC) and nuclear factor kappa B (NF-κB). These pathways promote inflammation by upregulating pro-inflammatory cytokines like interleukins (ILs) and tumor necrosis factor-alpha (TNF-α). This inflammatory environment exacerbates insulin resistance by interfering with insulin signaling. Specifically, inflammation impairs the insulin receptor substrate (IRS) and its downstream signaling through phosphoinositide 3-kinase (PI3K) and AKT pathways, which are critical for glucose uptake. The disruption of this signaling cascade leads to reduced translocation of glucose transporter proteins (GLUTs), particularly GLUT4, to the cell membrane, diminishing glucose uptake in muscle and adipose tissues and perpetuating hyperglycemia and insulin resistance. Genistein was shown to impact particularly every aspect of these pathological changes, ameliorating hyperglycemia, hyperlipidemia, oxidative stress, inflammatory cascades, alleviating insulin resistance, or even contributing to the changes in microbiota composition. Created in BioRender. Kciuk, M. (2025) <a href="https://BioRender.com/v14w660" target="_blank">https://BioRender.com/v14w660</a> (accessed on 17 January 2025). Full article ">Figure 3
Genistin and genistein metabolism following oral consumption. Genistein metabolism in the human body involves several key processes, primarily occurring in the gastrointestinal tract and liver. After ingestion, genistein is typically absorbed in the small intestine, where it undergoes phase I metabolism, involving oxidation, reduction, or hydrolysis. Enzymes such as beta-glucosidases (β-GLU) play a crucial role in hydrolyzing genistin, the glycosylated form, into genistein, the aglycone form. Once absorbed, genistein undergoes phase II metabolism in the liver, where it is conjugated with glucuronic acid or sulfate through the actions of UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), forming glucuronides and sulfates. In addition to the liver, the intestinal mucosa contains UGTs and SULTs that contribute to the conjugation of genistein. These conjugated metabolites are then circulated in the bloodstream or excreted via bile and urine. The metabolic transformations significantly affect the bioavailability and biological activity of genistein, influencing its potential health benefits. For abbreviation details, see the Abbreviations Section. Created in BioRender. Kciuk, M. (2025) <a href="https://BioRender.com/h28m531" target="_blank">https://BioRender.com/h28m531</a> (accessed on 17 January 2025). Full article ">

14 pages, 1318 KiB

Open AccessArticle

Novel One-Step Total Synthesis of trans-Dehydroosthol and Citrubuntin

by Zhiwen Liu, Baoyue Ge, Xushun Gong, Fusheng Wang, Ting Lei and Shizhi Jiang

Molecules 2025, 30(5), 1067; https://doi.org/10.3390/molecules30051067 - 26 Feb 2025

Viewed by 30

Abstract

Efficient and simple syntheses of trans-dehydroosthol and citrubuntin were achieved in a single step by implementing a protecting-group-free, redox-neutral strategy that utilized readily available starting materials. In this approach, a practical one-pot (domino) Heck/dehydration reaction was carried out utilizing less reactive bromocoumarin, [...] Read more.

Efficient and simple syntheses of trans-dehydroosthol and citrubuntin were achieved in a single step by implementing a protecting-group-free, redox-neutral strategy that utilized readily available starting materials. In this approach, a practical one-pot (domino) Heck/dehydration reaction was carried out utilizing less reactive bromocoumarin, resulting in excellent stereoselectivity and atomic economy. Through the implementation of this new, efficient, and scalable synthesis method, the formal synthesis of a series of novel meroterpenoid natural products was successfully achieved. Full article

(This article belongs to the Special Issue Advances in Organic Synthesis in Pharmaceuticals, Agrochemicals and Materials)

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15 pages, 3281 KiB

Open AccessArticle

Nucleocapsid Protein of SARS-CoV-2 Upregulates RANTES Expression in A172 Glioblastoma Cells

by Bakhytgul Gadilgereyeva, Zhanar Kunushpayeva, Mira Abdrakhmanova, Aizere Khassenova, Nail Minigulov, Timo Burster and Olena Filchakova

Molecules 2025, 30(5), 1066; https://doi.org/10.3390/molecules30051066 - 26 Feb 2025

Viewed by 70

Abstract

SARS-CoV-2, the pathogenic virus that induces COVID-19 disease, contains four structural proteins in its virion. The nucleocapsid (N) protein is one of the four structural proteins that play a crucial role in the assembly of viral RNA into ribonucleoprotein. In addition, the N [...] Read more.

SARS-CoV-2, the pathogenic virus that induces COVID-19 disease, contains four structural proteins in its virion. The nucleocapsid (N) protein is one of the four structural proteins that play a crucial role in the assembly of viral RNA into ribonucleoprotein. In addition, the N protein contributes to viral pathogenesis. One of the functions attributed to the N protein is the triggering of cytokine release by lung epithelial cells, macrophages, and monocytes. This study addresses the cellular effects of the N protein of SARS-CoV-2 on cells of glial origin. We report the upregulation of the RANTES chemokine in A172 glioblastoma cells at both the mRNA and protein levels in response to exposure to SARS-CoV-2 nucleocapsid protein. The N protein did not have an effect on cell viability and cell migration. Full article

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Figure 1
Representative cytokine array results for A172 cell line. A172 cells were treated either with PBS (A,C) or with 1 μg/mL of recombinant N protein (B,D) for 48 h. The area under the curve (AUC) densitometry values for most expressed cytokines on both arrays were analyzed by image J (<a href="https://imagej.net/ij/" target="_blank">https://imagej.net/ij/</a>); normalized data are shown (E); error bars correspond to SEM; n = 4. There was a non-significant difference for MCP-1 and TIMP-2 pairs; for RANTES pair, p-value is 0.006 determined by Student’s t-test. ** corresponds to a p-value less than 0.01. Full article ">Figure 2
Representative cytokine array results for U87 cell line. U87 cells were treated either with PBS (A) or with 1 μg/mL of recombinant N protein (B) for 48 h. (C) The area under the curve (AUC) densitometry values were analyzed using image J, and normalized data are shown. Full article ">Figure 3
Relative change in expression for cytokines as measured by RT-qPCR. The fold change expression is shown, and the data were normalized to GAPD control. (A) Cytokines expressed by A172 cells are shown—RANTES, MCP-1, and TIMP-2. The number of biological replicates are 4, 5, and 5 for RANTES, MCP-1, and TIMP-2, respectively. A p-value of 0.02 was calculated for the RANTES pair. (B) The cytokines tested on U87 are IL-6, IL-8, and TIMP-2. The data from 4, 8, and 5 biological replicates for IL-6, IL-8, and TIMP-2, respectively, are shown. Three technical replicates were used for each biological replicate. The ΔΔCt method was used to analyze the data; error bars represent standard errors. * p-value less than 0.05. Full article ">Figure 4
Graphical representation of the cell viability measurements. The A172 cells (A) and U87 cells (B) were treated with 1 µg/mL of N protein for 48 h. PBS was used as a control. The data are from five independent experiments. Student’s t-test was used for statistical analysis, and a non-significant difference was found between the control and treatment groups. Error bars represent standard deviation. Full article ">Figure 5
Scratch wound healing assay to determine cell migration. Wound healing assays were performed at 10 min, 12 h, 24 h, and 36 h following the scratch in untreated (PBS) control cells and A172 cells treated with 1 µg/mL of N protein. The images were analyzed using the Image J software. The graph shows the average values of four independent experiments with n = 16 for the PBS group and n = 17 for the N protein group. Error bars represent standard errors. Student’s t-test was used for statistical analysis, and a non-significant difference was detected between the control and experimental groups. Full article ">Figure 6
Representative protease array on A172 and U87 cell lines. The cells were cultured with either 1 µg/mL or 4 µg/mL of N protein for 24 h. Afterwards a panel of 35 different proteases was analyzed by using the Protease Profiler Array to assess the changes in protease levels. The experiment was repeated three times. The images of the arrays (A) and the quantitative analysis of the array results (B) are shown. PBS was used as a negative control; PAC-1 [40 µM] and staurosporine [0.5 µM] were used as positive controls for A172 and U87 cells, respectively. One representative blot is shown (A172 (n = 3), and U87 (n = 2) for control vs. 1 or 4 µg/mL N protein). Red arrows point to a corresponding proteases shown on the right side of the array. Full article ">Figure 6 Cont.
Representative protease array on A172 and U87 cell lines. The cells were cultured with either 1 µg/mL or 4 µg/mL of N protein for 24 h. Afterwards a panel of 35 different proteases was analyzed by using the Protease Profiler Array to assess the changes in protease levels. The experiment was repeated three times. The images of the arrays (A) and the quantitative analysis of the array results (B) are shown. PBS was used as a negative control; PAC-1 [40 µM] and staurosporine [0.5 µM] were used as positive controls for A172 and U87 cells, respectively. One representative blot is shown (A172 (n = 3), and U87 (n = 2) for control vs. 1 or 4 µg/mL N protein). Red arrows point to a corresponding proteases shown on the right side of the array. Full article ">

18 pages, 8413 KiB

Open AccessArticle

Discovery of N-(2-Acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide Derivatives as Novel Potential BCR-ABL1 Inhibitors Through Structure-Based Virtual Screening

by Shuaixing Wang, Minyi Wang, Zi Li, Guofeng Xu and Dayan Wang

Molecules 2025, 30(5), 1065; https://doi.org/10.3390/molecules30051065 - 26 Feb 2025

Viewed by 95

Abstract

BCR-ABL1 kinase is a critical driver of chronic myeloid leukemia (CML) pathophysiology. The approval of allosteric inhibitor asciminib brings new hope for overcoming drug resistance caused by mutations in the ATP-binding site. To expand the chemical diversity of BCR-ABL1 kinase inhibitors with positive [...] Read more.

BCR-ABL1 kinase is a critical driver of chronic myeloid leukemia (CML) pathophysiology. The approval of allosteric inhibitor asciminib brings new hope for overcoming drug resistance caused by mutations in the ATP-binding site. To expand the chemical diversity of BCR-ABL1 kinase inhibitors with positive anti-tumor effect with asciminib, structure-based virtual screening and molecular dynamics simulations were employed to discover novel scaffolds. This approach led to the identification of a series of N-(2-acetamidobenzo[d]thiazol-6-yl)-2-phenoxyacetamide derivatives as new BCR-ABL1 inhibitors. The most potent compound, 10m, demonstrated inhibition of BCR-ABL-dependent signaling and showed an anti-tumor effect against K562 cells, with an IC₅₀ value of 0.98 μM. Compound 10m displayed powerful synergistic anti-proliferation and pro-apoptotic effects when combined with asciminib, highlighting its potential as a promising lead for the development of potential BCR-ABL inhibitors. Full article

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Representative small-molecular BCR-ABL1 inhibitors. Full article ">Figure 2
(A) Schematic flow of the virtual screening campaign. (B) Chemical structure of virtual hits A1–A11. (C) The anti-proliferative effect of hit compounds on Ba/F3 (BCR-ABL1) cells was evaluated by CCK8. Data are represented as mean ± SD (n = 3). (D) The dose-dependency curves against parental Ba/F3 cells and Ba/F3 (BCR-ABL1) cells of compound A8. Full article ">Figure 3
Molecular design of compound A8 as a novel BCR-ABL1 inhibitor. (A) The predicted binding modes of A8 and asciminib with the BCR-ABL crystal structure (PDB id: 8SSN). Hydrogen bonds were indicated by yellow dashed lines. (B) A 50-ns molecular dynamics simulation was conducted using Desmond. The stability of the ligand-receptor complex was evaluated through root mean-square deviation (RMSD) analysis of: (i) heavy atoms of compound A8 (magenta line), (ii) interacting side chains of the receptor (blue line), and (iii) heavy atoms of compound A8 relative to the kinase backbone atoms (red line). (C,D) Protein–ligand contact histogram of compound A8 and the corresponding 2D diagram predicted through MD simulations, including red ball: Charged (negative), blue ball: Charged (positive), gray ball: Glycine and green ball: Hydrophobic. The percentage value suggests that for X% of the simulation time, the specific interaction is maintained. Full article ">Figure 4
Synergy studies were performed using compound 10m in combination with asciminib. (A) K562 cells were incubated with the compound combinations across a dose range for 72 h, and the level of cell growth relative to DMSO-treated cells was determined. (B,C) Synergy studies were performed using asciminib in combination with imatinib (B) or 10m (C). K562 cells were incubated with the compound combinations across a dose range for 48 h. The level of cell growth relative to DMSO-treated cells was determined. (D) The apoptotic effects on K562 cells were assessed using flow cytometry following treatment with compound 10m (10 μM) or asciminib (5 μM) for 48 or 72 h. Experimental results are presented as mean ± SEM, with statistical significance determined by Student’s t-test (** p < 0.01, *** p < 0.001, **** p < 0.0001). Full article ">Figure 5
K562 cells were incubated with a range of compound concentrations for 1 h and immunoblots were run to detect total BCR–ABL1 and pBCR–ABL1 (Tyr245), total STAT5 and pSTAT5 (Tyr694), total CRKL and pCRKL (Tyr207), and GAPDH as a loading control. Full article ">Scheme 1
Synthesis of Compounds 10a–10w. Reagents and conditions: (a) acetic anhydride, pyridine, 120 °C, 84%; (b) sodium dithionite, NH4OH, r.t, 78%.; (c) acid, BOP, DIPEA, DMF, 40 °C, 36–86%. Full article ">

16 pages, 1324 KiB

Open AccessArticle

Evaluation of Model and Process Optimization for the Treatment of Drilling Wastewater Using Electrocoagulation

by Muhammed Kamil Öden

Molecules 2025, 30(5), 1064; https://doi.org/10.3390/molecules30051064 - 26 Feb 2025

Viewed by 77

Abstract

The extraction of underground resources has accelerated globally, in response to the demands of advancing technology and the rapidly growing population. The increase in drilling activities has caused an increase in environmental pollution problems caused by waste generated during drilling activities, namely drilling [...] Read more.

The extraction of underground resources has accelerated globally, in response to the demands of advancing technology and the rapidly growing population. The increase in drilling activities has caused an increase in environmental pollution problems caused by waste generated during drilling activities, namely drilling sludge and drilling wastewater. In this study, the treatability of wastewater generated during drilling operations in a basin, where an underground gas storage area was created, was investigated using an electrocoagulation (EC) process, using different electrode pairs. The removal efficiencies of the pollution parameters were determined using the response surface method. The wastewater parameters included different organic and inorganic pollutants, such as sodium, chloride, magnesium, and chemical oxygen demand (COD). The concentrations of sodium, chloride, and COD in drilling industry wastewater were found to be very high, at 128,567, 185,292, and 7500 mg/L, respectively. The data obtained in this study yielded a removal efficiency of approximately 65% and above. Sodium achieved the highest pollutant removal efficiency of 85% and above. The statistical values were interpreted for all the pollutants and the suitability of second-degree regression was observed. Full article

(This article belongs to the Special Issue Wastewater Treatment: Functional Materials and Advanced Technology, 2nd Edition)

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14 pages, 2038 KiB

Open AccessArticle

Type II ZnO-MoS₂ Heterostructure-Based Self-Powered UV-MIR Ultra-Broadband p-n Photodetectors

by Badi Zhou, Xiaoyan Peng, Jin Chu, Carlos Malca, Liz Diaz, Andrew F. Zhou and Peter X. Feng

Molecules 2025, 30(5), 1063; https://doi.org/10.3390/molecules30051063 - 26 Feb 2025

Viewed by 110

Abstract

This study presents the fabrication and characterization of ZnO-MoS₂ heterostructure-based ultra-broadband photodetectors capable of operating across the ultraviolet (UV) to mid-infrared (MIR) spectral range (365 nm–10 μm). The p-n heterojunction was synthesized via RF magnetron sputtering and spin coating, followed by annealing. [...] Read more.

This study presents the fabrication and characterization of ZnO-MoS₂ heterostructure-based ultra-broadband photodetectors capable of operating across the ultraviolet (UV) to mid-infrared (MIR) spectral range (365 nm–10 μm). The p-n heterojunction was synthesized via RF magnetron sputtering and spin coating, followed by annealing. Structural and optical analyses confirmed their enhanced light absorption, efficient charge separation, and strong built-in electric field. The photodetectors exhibited light-controlled hysteresis in their I-V characteristics, attributed to charge trapping and interfacial effects, which could enable applications in optical memory and neuromorphic computing. The devices operated self-powered, with a peak responsivity at 940 nm, which increased significantly under an applied bias. The response and recovery times were measured at approximately 100 ms, demonstrating their fast operation. Density functional theory (DFT) simulations confirmed the type II band alignment, with a tunable bandgap that was reduced to 0.20 eV with Mo vacancies, extending the detection range. The ZnO-MoS₂ heterostructure’s broad spectral response, fast operation, and defect-engineered bandgap tunability highlight its potential for imaging, environmental monitoring, and IoT sensing. This work provides a cost-effective strategy for developing high-performance, ultra-broadband, flexible photodetectors, paving the way for advancements in optoelectronics and sensing technologies. Full article

(This article belongs to the Special Issue Two-Dimensional Materials: From Synthesis to Applications, 2nd Edition)

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(a) SEM image of ZnO coated with MoS2, with a scale bar of 1 μm. Inset: ZnO nanoparticles; scale bar: 500 nm. (b) Raman spectrum of the ZnO-MoS2 sample. (c) EDX spectra of ZnO and ZnO-MoS2 after annealing. Full article ">Figure 2
(a) Schematic of the ZnO-MoS2 heterostructure-based broadband photodetector. (b) The room-temperature current–voltage (I-V) characteristics without and with light illumination, corresponding to a dark current and a photocurrent (illuminated by 450 nm light with an intensity of 50 mW/cm2). Each hysteresis loop represents 10 repeated measurements. Full article ">Figure 3
The measured photocurrent of the prototype when the device was operating at room temperature under 0 V bias, with on–off illumination light of different wavelengths at the same light intensity of 1.2 mW/cm2. (a) λUV = 365 nm, (b) λblue = 450 nm, (c) λred = 650 nm, (d) λNIR = 940 nm, and (e) λMIR = 10,000 nm. (f) The measured photocurrent under 0 V and 0.5 V bias as a function of the illumination wavelength. (g) The response time and (h) recovery time corresponding to 940 nm radiation. Full article ">Figure 4
Simulated energy bandgaps of (a) ZnO and MoS2 monolayers and (b) ZnO-MoS2 heterostructure. The valence band maximum (VBM) is set to zero. (c) Schematic presentation of type II heterostructure formed of ZnO and MoS2. CBM: conduction band minimum. Full article ">Figure 5
(a) Side view and (b) top view of the hexagonal-shaped wurtzite crystal structure of a ZnO monolayer with one Mo vacancy. (c) Band structure of MoS2 with one Mo vacancy. (d) Side view and (e) top view of a ZnO-MoS2 bilayer with one Mo vacancy. (f) Band structure of a ZnO-MoS2 bilayer with one Mo vacancy. The valence band maximum is set to zero. Full article ">

11 pages, 946 KiB

Open AccessCommunication

The Development and Validation of a Simple HPLC-UV Method for the Determination of Vancomycin Concentration in Human Plasma and Application in Critically Ill Patients

by Asma Aboelezz, Novel Solomon Tesfamariam, Maged Kharouba, Tamara Gligoric and Sherif Hanafy Mahmoud

Molecules 2025, 30(5), 1062; https://doi.org/10.3390/molecules30051062 - 26 Feb 2025

Viewed by 142

Abstract

Vancomycin is an antimicrobial agent that exhibits high efficacy against Gram-positive bacteria. The importance of therapeutic drug monitoring (TDM) for vancomycin has been substantiated in specific patient cohorts, underscoring the significance of determining vancomycin plasma levels. This study presents the development and validation [...] Read more.

Vancomycin is an antimicrobial agent that exhibits high efficacy against Gram-positive bacteria. The importance of therapeutic drug monitoring (TDM) for vancomycin has been substantiated in specific patient cohorts, underscoring the significance of determining vancomycin plasma levels. This study presents the development and validation of a simple, reproducible, and practical approach for quantifying vancomycin levels in human plasma samples through high-performance liquid chromatography (HPLC). Deproteinization of plasma samples (0.3 mL) was achieved using 10% perchloric acid. The chromatographic separation was achieved using a C18 column. The mobile phase, consisting of phosphate buffer and acetonitrile (90:10, v/v), was run at a flow rate of 1 mL/min. Ultraviolet detection was conducted at a wavelength of 192 nm and the method was linear in the range of 4.5–80 mg/L (r² > 0.99). Inter- and intra-day assay precision and accuracy were determined to be within the acceptable range. The run time was noted to be 10 min. This method was evaluated using different greenness tools, which indicated that the method is environmentally friendly. Our method was effectively applied to analyze vancomycin concentrations in critically ill patients. Thus, our approach has the potential for practical implementation in routine TDM procedures. Full article

(This article belongs to the Special Issue Exploring Analytical Techniques in Pharmaceutical and Biomedical Analysis)

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23 pages, 3202 KiB

Open AccessArticle

Flavonoids and Saponins from Two Chenopodium Species (C. foliosum Asch. and C. bonus-henricus L.)—Preliminary Evaluation for hMAO-A/B, Neuroprotective Activity, and Validated UHPLC-HRMS Quantification of Ethanolic Extract from C. foliosum

by Magdalena Kondeva-Burdina, Dona Panayotova, Paraskev T. Nedialkov and Zlatina Kokanova-Nedialkova

Molecules 2025, 30(5), 1061; https://doi.org/10.3390/molecules30051061 - 26 Feb 2025

Viewed by 123

Abstract

The development of more effective treatments for neurodegenerative disorders presents a significant challenge in modern medicine. Currently, scientists are focusing on discovering bioactive compounds from plant sources to prevent and treat neurodegenerative diseases. Fifteen flavonoids and saponins from C. foliosum Asch. and C. [...] Read more.

The development of more effective treatments for neurodegenerative disorders presents a significant challenge in modern medicine. Currently, scientists are focusing on discovering bioactive compounds from plant sources to prevent and treat neurodegenerative diseases. Fifteen flavonoids and saponins from C. foliosum Asch. and C. bonus-henricus L. were tested for their inhibitory activity on hMAO-A and hMAO-B. Five compounds (1 μM) exhibit a weak inhibitory effect on hMAO-A and show good inhibitory activity against the hMAO-B enzyme (30–35%), compared to the positive control selegiline (55%). These active compounds were examined on rat brain synaptosomes and mitochondria obtained by multiple differential centrifugations using a Percoll gradient. Their effects were also monitored on rat brain microsomes obtained by double differential centrifugation. The main parameters characterizing the functional–metabolic status of subcellular fractions are synaptosomal viability, GSH level, and MDA production. All tested compounds (50 μM) demonstrated significant neuroprotective and antioxidant activities across models of induced oxidative stress, including 6-OHDA, t-BuOOH, and Fe^2+/AA-induced lipid peroxidation. The plausible mechanisms of neuroprotection rely on MAO-B inhibition, the scavenging of ROS, stabilizing the cell membrane by reducing MDA production, and neutralizing free radicals by maintaining GSH levels. In addition, we developed and validated a UHPLC-HRMS method for identifying and simultaneously quantificatying flavonoids and saponins in the aerial parts of C. foliosum. Compounds 30-normedicagenic acid- HexA-Hex-TA 22f and medicagenic acid-HexA-Hex-TA 25f were considered new natural compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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13 pages, 1472 KiB

Open AccessArticle

Liquid-Assisted Grinding Enables Efficient Ni-Catalyzed, Mn-Mediated Denitrogenative Cross-Electrophile Coupling of Benzotriazinones with Benzyl Chlorides

by Xuanxuan Zhang, Yingying Hong and Gang Zou

Molecules 2025, 30(5), 1060; https://doi.org/10.3390/molecules30051060 - 26 Feb 2025

Viewed by 63

Abstract

An efficient and air-tolerant Ni-catalyzed denitrogenative cross-electrophile coupling of benzotriazinones with benzyl chlorides has been developed via liquid-assisted grinding by using Mn powders as reductant and DMF as assisting liquid in the presence of anhydrous calcium chloride. Scope and limitations of the protocol [...] Read more.

An efficient and air-tolerant Ni-catalyzed denitrogenative cross-electrophile coupling of benzotriazinones with benzyl chlorides has been developed via liquid-assisted grinding by using Mn powders as reductant and DMF as assisting liquid in the presence of anhydrous calcium chloride. Scope and limitations of the protocol to access diarylmethanes have been demonstrated with more than 20 examples, showing acceptable tolerance to functional group and steric hindrance. Although electron-withdrawing substituents on benzotriazinone or benzyl counterparts decrease the yields significantly, a series of N-alkyl-2-benzylbenzamides, diarylmethanes bearing an ortho-carbamoyl aryl group, could be obtained in modest to good yields. Full article

(This article belongs to the Section Organometallic Chemistry)

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15 pages, 1520 KiB

Open AccessArticle

Insights from Femtosecond Transient Absorption Spectroscopy into the Structure–Function Relationship of Glyceline Deep Eutectic Solvents

by Rathiesh Pandian and Clemens Burda

Molecules 2025, 30(5), 1059; https://doi.org/10.3390/molecules30051059 - 26 Feb 2025

Viewed by 36

Abstract

This study aimed to determine the structure–function relationship (SFR) for ChCl–glycerol mixtures, a deep eutectic solvent (DES), by investigating their microscopic solvation dynamics and how it relates to their macroscopic properties across varying concentrations of ChCl. Femtosecond transient absorption (fs-TA) spectroscopy revealed two [...] Read more.

This study aimed to determine the structure–function relationship (SFR) for ChCl–glycerol mixtures, a deep eutectic solvent (DES), by investigating their microscopic solvation dynamics and how it relates to their macroscopic properties across varying concentrations of ChCl. Femtosecond transient absorption (fs-TA) spectroscopy revealed two distinct solvation dynamics time constants: τ₁, governed by glycerol–glycerol interactions, and τ₂, dominated by the choline response. The τ₂ minimum at 25–30 mol % ChCl closely aligned with the eutectic composition (~33.33 mol % ChCl), where the glycerol network was the most organized and the choline ions exhibited the fastest relaxation. The viscosity decreased sharply up to ~25 mol % ChCl and then plateaued, while the conductivity increased monotonically with ChCl concentration, reflecting enhanced ionic mobility. The density decreased with both increasing ChCl concentration and temperature, indicating disrupted hydrogen bonding and reduced molecular packing. The polarity, measured using betaine-30 (B30) and the E_T(30) polarity scale, increased steeply up to approximately 25 mol % ChCl before reaching a plateau. These findings identified the eutectic composition as the optimal concentration range for balancing stability, fluidity, conductivity, and enhanced dynamics within the glycerol system. Full article

(This article belongs to the Special Issue New Horizons in Deep Eutectic Solvents (DESs): Synthesis, Characterization and Applications)

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Figure 1
Sample fs-TA spectra of B30 dissolved in (a) 15 mol % and (b) 22 mol % ChCl in glycerol. The negative signal primarily corresponds to ground-state bleaching. As the delay time increases, the signal becomes less negative, which shows the recovery of the ground state. The corresponding biexponential kinetic decay traces are shown in panels (c,d), respectively. Fitting was performed in the spectral range of λfitted = 500–600 nm. T = 298 K. Full article ">Figure 2
Fast (τ1; blue y-axis on left) and slow (τ2; red y-axis on right) solvent relaxation components for the ChCl–glycerol mixture as a function of mol % ChCl. There is a clear minimum in τ1 at ~5 mol % ChCl, followed by an increase and plateauing after ~20–25 mol % ChCl. For τ2, there are two distinct minima, with the slower one at ~10 mol % ChCl and the faster one at ~25–30 mol % ChCl. The kinetics data were acquired from fitting the transient absorption spectra at λfitted = 500–600 nm. See <a href="#app1-molecules-30-01059" class="html-app">Table S1</a> for numerical values. T = 298 K. Full article ">Figure 3
Viscosity (left y-axis) and ionic conductivity (right y-axis) as a function of mol % ChCl in glycerol. Viscosity decreases as ChCl is added, until it plateaus after ~25 mol ChCl. Conductivity increases monotonically throughout the entire composition range. See <a href="#app1-molecules-30-01059" class="html-app">Table S2</a> for numerical values and standard deviations. N = 3, T = 298 K. Full article ">Figure 4
Density of glyceline as a function of mol % ChCl in glycerol. The legend depicts the data points representing the various temperatures from 298.15 to 323.15 K in 5 K increments. See <a href="#app1-molecules-30-01059" class="html-app">Table S3</a> for numerical values and standard deviations. See <a href="#app1-molecules-30-01059" class="html-app">Figure S1</a> for density represented as a function of temperature. N = 3. Full article ">Figure 5
ET(30) polarity versus mol % ChCl in glycerol. The increase in polarity plateaus at >25 mol % ChCl. See <a href="#app1-molecules-30-01059" class="html-app">Table S1</a> for numerical values. T = 298 K. Full article ">Scheme 1
Representative molecular structures for the laser pulse-induced intramolecular charge transfer process that occurs in B30 upon its photoexcitation from its Zwitterionic ground state to its radicalized excited state, depicted from left to right. The structures of ChCl and glycerol are also shown. Full article ">

14 pages, 607 KiB

Open AccessReview

Anti-Epstein–Barr Virus Activities of Flavones and Flavonols with Effects on Virus-Related Cancers

by Sherif T. S. Hassan

Molecules 2025, 30(5), 1058; https://doi.org/10.3390/molecules30051058 - 26 Feb 2025

Viewed by 147

Abstract

The Epstein–Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, [...] Read more.

The Epstein–Barr virus (EBV), a member of the human gamma-herpesviruses, is intricately linked to various human malignancies. Current treatment options for EBV infection involve the use of acyclovir and its derivatives, which exhibit limited efficacy and are associated with drug resistance issues. Therefore, there is a critical need for new medications with more effective therapeutic actions and less susceptibility to resistance. This review explores the therapeutic promise of flavones and flavonols, naturally occurring molecules, against EBV and its correlated cancers. It thoroughly delves into the molecular mechanisms underlying the therapeutic efficacy of these compounds and scrutinizes their complex interplay in EBV-linked processes and cancer transformation by targeting key genes and proteins pivotal to both the viral life cycle and tumor development. Additionally, the review covers current research, highlights key findings, and discusses promising avenues for future investigations in the pursuit of targeted therapies against EBV and its related tumors. Full article

(This article belongs to the Special Issue Advances in Natural Products and Their Biological Activities)

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14 pages, 1706 KiB

Open AccessArticle

A Simplified Guide RNA Synthesis Protocol for SNAP- and Halo-Tag-Based RNA Editing Tools

by Daniel Tobias Hofacker, Sebastian Kalkuhl, Jana Franziska Schmid, Shubhangi Singh and Thorsten Stafforst

Molecules 2025, 30(5), 1049; https://doi.org/10.3390/molecules30051049 - 26 Feb 2025

Viewed by 30

Abstract

SNAP-tag and Halo-tag have been employed to achieve targeted RNA editing by directing the deaminase domain of human ADAR to specific sites in the transcriptome. This targeting is facilitated by short guide RNAs (gRNAs) complementary to the target transcript, which are chemically modified [...] Read more.

SNAP-tag and Halo-tag have been employed to achieve targeted RNA editing by directing the deaminase domain of human ADAR to specific sites in the transcriptome. This targeting is facilitated by short guide RNAs (gRNAs) complementary to the target transcript, which are chemically modified with benzylguanine or chloroalkane moieties to enable covalent binding to the respective self-labeling enzymes. However, broad application of this approach has been limited by challenges such as low scalability, the requirement for specialized chemical expertise and equipment, and labor-intensive protocols. In this study, we introduce streamlined, efficient protocols for the synthesis and purification of these linkers, suitable for SNAP-tag and Halo-tag applications, without the need for advanced chemical equipment. Our methods enable linker coupling in a kit-like manner and support the high-yield production of modified gRNAs. We demonstrate that the newly synthesized linkers and gRNA designs perform similarly to previously published constructs with regard to RNA editing efficiency. Moreover, large-scale production of modified gRNAs facilitates their use in studies involving cellular uptake and in vivo experiments. Full article

(This article belongs to the Section Chemical Biology)

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Self-labeling enzymes have various applications. (a) Various effectors are covalently conjugated to SNAP-tagged/Halo-tagged fusion proteins by using the self-labeling moieties benzylguanine (BG) or chloroalkane (CA), respectively. In protein-centric assays (left panel), an effector molecule is recruited to a protein of interest (POI). In drug-centric assays (right panel), an effector protein is recruited to a drug-of-interest (DOI). (b) Schematic representation of different applications of self-labeling enzyme tags in protein-centric (left panel) and drug-centric (right panel) approaches. (c) Detailed scheme representing SNAP-tag/Halo-tag-based RNA editing platforms. ADAR’s double-stranded RNA binding domains (dsRBD) were replaced by a SNAP-tag or Halo-tag to allow for in situ conjugation of guide RNA and deaminase. Hybridization of the guide RNA to the target RNA controls precise and efficient A-to-I RNA base editing. PROTAC = proteasomal targeting chimeras, ASO = antisense oligonucleotide. Full article ">Figure 2
Synthesis of NHS-activated self-labeling moieties for BG and CA. (a) BG-GLA-NHS (3) was synthesized from commercially available BG-NH2 (1) in two steps. (b) CA-GLA-NHS (6) was synthesized analogously from commercially available CA-NH2 (4). Both syntheses allow for fast and simple cleanup on the gram scale. Full article ">Figure 3
Benchmark of guide RNAs carrying two self-labeling moieties (BG or CA) generated with the new, simplified versus old protocol. (a) In the old protocol, a complex branched linker, derived from NHS ester 8 (BG) or 10 (CA), was coupled to mono-amino guide RNAs carrying one 5′-terminal amino linker, e.g., gRNA 11 and 13. In the new protocol, two linear linkers, derived from simple NHS esters 3 (BG) or 6 (CA), are coupled to bis-amino guide RNAs like gRNA 12 and 14, which carry an additional amino-modified dT nucleobase at their 5′-terminus, next to their 5′-amino linker. (b) Analytical urea PAGE shows increased turnover and purity of gRNAs prepared by the new protocol. (c) Editing performance of BG guide RNAs (generated via old or new protocol, respectively) targeting the endogenous STAT1 transcript (Tyr 701) in HeLa-PB-SNAP-ADAR1Q cells induced with 1 µg/mL doxycycline for 24 h. (d) Editing performance of CA guide RNAs (generated via old or new protocol, respectively) targeting the endogenous ACTB transcript (Ile 5) in 293 Flp-In Halo-ADAR1Q cells induced with 10 ng/mL doxycycline for 24 h. n = 3 independent experiments. Modifications: LNA = locked nucleic acid, PS = phosphorothioate, amino-dT = amino-C6-deoxythymidine, 2′OMe = 2′O-methyl. Full article ">

17 pages, 572 KiB

Open AccessArticle

Synthesis, Characterization, and Docking Studies of Some New Chalcone Derivatives to Alleviate Skin Damage Due to UV Light

by Arun Kumar Mishra, Kamal Y. Thajudeen, Chandra Shekhar, Mhaveer Singh, Harpreet Singh, Arvind Kumar, Sarvesh Kumar Paliwal, Emdad Hossain and Shahana Salam

Molecules 2025, 30(5), 1057; https://doi.org/10.3390/molecules30051057 - 25 Feb 2025

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Abstract

Increasing cases of sunburn is one of the serious problems across the globe. In this connection, there is an urgent requirement for some effective sun screening agents. In the search for the same, nanoemulsions of some new synthesized and characterized chalcone derivatives were [...] Read more.

Increasing cases of sunburn is one of the serious problems across the globe. In this connection, there is an urgent requirement for some effective sun screening agents. In the search for the same, nanoemulsions of some new synthesized and characterized chalcone derivatives were prepared and evaluated in vitro and in vivo. In order to meet the said objective, in the first step, vanillin was reacted with 4-aminoacetophenone in the presence of 15% sodium hydroxide and ethanol to synthesize the target compounds (C-1 to C-5). Progress of reaction was monitored using thin-layer chromatography (TLC). The crystals of purified compounds were characterized using spectroscopic techniques such as Infrared (IR) spectroscopy, ¹H-NMR spectroscopy, ¹³C-NMR, and mass spectrometry. We prepared the nanoemulsions of the final compounds (C-1 to C-5) and subsequently evaluated them for in vitro sun protection factor activity. The concentration of the nanoemulsions, consistently ranging from 0.88 to 0.91 mg/mL across all formulations, demonstrated a high degree of consistency. The range of particle size varied from approximately 172 to 183 nm, with low polydispersity index values (approximately 0.11 to 0.15). The negative zeta potentials recorded for all the formulations (ranging from −35.87 mV to −39.30 mV) showed that the nanoemulsions are electrostatically stable enough to keep them from sticking together. The pH values of the nanoemulsions ranged narrowly from approximately 5.00 to 5.16, which indicated the compatibility of emulsion with biological systems and the potential to reduce irritation or instability during administration. The viscosity of the nanoemulsions varied between 2.00 and 2.12 cP. In silico studies were performed using MMP-I and MMP-2 as target receptors. For in vitro SPF evaluation, the Mansur equation was employed. COLIPA guidelines were compiled for in vivo SPF evaluation. The nanoemulsions derived from compounds C-3 and C-4, designated as C-3 NE and C-4 NE, were more effective as anti-aging agents. Findings suggested the possible scope of further synthesis of newer synthetic derivatives of chalcones for furfur development nanoemulsions for better SPF activity. Full article

(This article belongs to the Section Medicinal Chemistry)

18 pages, 20316 KiB

Open AccessArticle

Efficient Removal of Sulfamethoxazole in Electro-Oxidation System with Boron-Doped Diamond Anode and Electrolyte NaCl: Degradation Mechanisms

by Xinghui Du, Wenxi Xie, Xianhu Long, Dazhen Li, Weixiong Huang, Igor Ying Zhang and Rongfu Huang

Molecules 2025, 30(5), 1056; https://doi.org/10.3390/molecules30051056 - 25 Feb 2025

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Abstract

In recent years, the pollutant sulfamethoxazole (SMX) that is widely used in medical therapy has been frequently detected in different water systems. Thereby, it is necessary to develop green and effective advanced oxidation strategies, especially the electro-oxidation process. In this study, an electro-oxidation [...] Read more.

In recent years, the pollutant sulfamethoxazole (SMX) that is widely used in medical therapy has been frequently detected in different water systems. Thereby, it is necessary to develop green and effective advanced oxidation strategies, especially the electro-oxidation process. In this study, an electro-oxidation system featuring a boron-doped diamond (BDD) anode and NaCl as the supporting electrolyte was implemented to effectively remove sulfamethoxazole (SMX) without the addition of external oxidants. The operational parameters were optimized using the response surface methodology with a pH 7.5, current density of 4.44 mA/cm², and NaCl concentration of 20 mmol/L. The optimization significantly enhanced the degradation efficiency of SMX to obtain 100% removal in 5 min. Results of scavenging and chemical probe experiments indicated the presence of hydroxyl radicals (^•OH) and chlorine radicals (Cl^•), with the latter primarily forming between the reaction of Cl⁻ and ^•OH. A competition experiment further revealed the relative oxidative contribution of Cl^• of 38.6%, highlighting its significant role in the degradation process. Additionally, ion chromatography analysis confirmed the presence of Cl^• without the formation of harmful by-products such as ClO₄⁻, affirming the environmentally friendly nature of the system. The toxicity of the degradation by-products was also assessed. The application of current was investigated to explore the influence of coexistence ions as well as repeatability. Overall, this work highlighted the effectiveness of the electro-oxidation system for the degradation of organic pollutants in saline wastewater, demonstrating the significance of optimization of operational parameters for efficient and sustainable environmental remediation. Full article

(This article belongs to the Special Issue Cutting-Edge Characterizations for Expanding Energy Material Chemistries)

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Effect of (a) electrolyte, (b) current density, (c) pH, and (d) electrolyte concentration on the SMX degradation in EC/BDD system. Reaction condition: current density = 4.44 mA/cm2, [SMX] = 8 μmol/L, pH = 7.5 ± 0.1, conductivity = 2.53 mS, [NaCl] = 20 mmol/L. Full article ">Figure 2
Response surface analysis of the SMX degradation efficiency between (a) pH and NaCl concentration, (b) current density and NaCl concentration, (c) current density and pH. Reaction condition: [SMX] = 8 μmol/L, current density = 1.11–5.56 mA/cm2, [NaCl] = 0–20 mmol/L, pH = 3.0–9.0. Full article ">Figure 3
The SMX degradation curves in the electro-oxidation system with the presence of (a) TBA, (b) methanol. (c) Generated 7-HC concentrations in the electro-oxidation system under the condition of different NaCl concentrations. (d) Contribution of reactive species to the SMX degradation in the electro-oxidation system. Reaction conditions: current density = 4.44 mA/cm2, [SMX] = [BA] = [NB] = 8 μmol/L, pH = 7.5 ± 0.1, [NaCl] = 20 mmol/L. Full article ">Figure 4
Ion chromatography experiments. Concentration of (a) Cl−, ClO3−, ClO4−, ClO2−, (b) Cl−, (c) ClO3−, (d) ClO4−. Reaction conditions: current density = 4.44 or 11.1 mA/cm2, [SMX] = 8 or 0 μmol/L, pH = 7.5 ± 0.1, [NaCl] = 20 or 10 mmol/L. NaClO4 was used as electrolyte supplement when NaCl concentration was adjusted. Condition A: 4.44 mA/cm2 (current density) + 20 mmol/L (NaCl concentration) + 8 μmol/L (SMX concentration); condition B: 4.44 mA/cm2 (current density) + 10 mmol/L (NaCl concentration) + 8 μmol/L (SMX concentration); condition C: 11.11 mA/cm2 (current density) + 20 mmol/L (NaCl concentration) + 8 μmol/L (SMX concentration); condition D: 4.44 mA/cm2 (current density) + 20 mmol/L (NaCl concentration). Full article ">Figure 5
(a) Chemical structure of SMX. (b) Fukui index of SMX. (c) Degradation pathways of SMX in the electro-oxidation systems. Reaction condition: current density = 4.44 mA/cm2, [SMX] = 8 μmol/L, [NaCl] = 20 mmol/L, pH = 7.5 ± 0.1. The SMX degradation byproducts were identified using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS, Agilent 6545, Santa Clara, CA, USA). Full article ">Figure 6
Effects of (a) HCO3−, (b) H2PO4−, (c) SO42−, and (d) NO3− on the degradation of SMX in the electro-oxidation system. (e) Degradation experiments of different pollutants. (f) Lifetime experiments. Reaction conditions: current density = 4.44 mA/cm2, [SMX] = [SIZ] = [BA] = [BPA] = [Phenol] = 8 μmol/L, [NaCl] = 20 mmol/L, pH = 7.5 ± 0.1. Full article ">

21 pages, 4153 KiB

Open AccessArticle

Identification of Acanthopanax trifoliatus (L.) Merr as a Novel Potential Therapeutic Agent Against COVID-19 and Pharyngitis

by Qi Chen, Hui He, Yanghong Zhu, Xiang Li, Junhao Fang, Zhexi Li, Panghui Liu, Lin Zhou, Yufang Pan and Guoyu Wu

Molecules 2025, 30(5), 1055; https://doi.org/10.3390/molecules30051055 - 25 Feb 2025

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Abstract

Individuals infected with COVID-19 often experience the distressing discomfort of pharyngitis. Thus, it is crucial to develop novel drugs to improve therapeutic options. In this study, we investigated the interaction between bioactive compounds isolated from Acanthopanax trifoliatus (L.) Merr and proteins associated with [...] Read more.

Individuals infected with COVID-19 often experience the distressing discomfort of pharyngitis. Thus, it is crucial to develop novel drugs to improve therapeutic options. In this study, we investigated the interaction between bioactive compounds isolated from Acanthopanax trifoliatus (L.) Merr and proteins associated with COVID-19 and pharyngitis through in silico analysis. Several molecules demonstrated high affinities to multiple targets, indicating significant potential for alleviating pharyngitis and other COVID-19-related symptoms. Among them, rutin and isochlorogenic acid C, two major components in Acanthopanax trifoliatus (L.) Merr ethanol extracts, were further experimentally demonstrated to exhibit strong inhibitory effects against SARS-CoV-2 and to possess significant anti-inflammatory activities. Inhibition of over 50% in several key genes was observed, demonstrating the efficacy of in silico methods in identifying high-affinity target binders. Our findings provide a theoretical foundation for the development of Acanthopanax trifoliatus (L.) Merr as a novel multi-target therapeutic agent for both COVID-19 and pharyngitis. Full article

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Workflow for ligand–protein interactions discovery. Full article ">Figure 2
Violin plots of the docking scores of molecules from virtual screens targeting proteins related to COVID-19/pharyngitis. (A,B) The COVID-19-related proteins were categorized into four groups: cytokines, enzymes, receptors, and viral proteins. The scores of ligand–protein dockings performed utilizing the Smina Vinardo program (A) or AutoDock Vina program (B). (C,D) Proteins associated with pharyngitis were categorized into five groups: cytokines, enzymes, receptors, inhibitors, and transcription factors. The scores of ligand–protein dockings performed utilizing the Smina Vinardo program (C) or AutoDock Vina program (D). The docking score serves as an estimate of the free energy of binding (in kcal/mol). Thus, the more negative the value, the stronger the binding affinity of the ligand to the target. Red dots: compounds with docking scores lower than −8.0. Full article ">Figure 3
Multi-target action mode of the compounds extracted from Acanthopanax trifoliatus (L.) Merr. The ligand–protein pairs with docking scores lower than −8.0 were summarized, and molecules were ranked by the number of predicted binding proteins. (A,B) The top eight candidates targeting COVID-19-related proteins are shown, using either the Smina Vinardo (A) or AutoDock Vina (A) as the docking program. (C,D) The top eight candidates targeting pharyngitis-associated proteins are displayed, with results from the Smina Vinardo (C) and AutoDock Vina (D) docking programs. Full article ">Figure 4
Docking poses and experimental validation of rutin. (A) The 2D chemical structure of rutin. (B) The 3D chemical structure of rutin. (C) The docking poses of rutin bound to FXR/RXR, DPP4, JAK2, and ACE. Green dash lines: hydrogen bond; blue dash lines: perpendicular π stacking; yellow dash lines: parallel π-stacking; red dash lines: π–cation interaction; orange dash lines: salt bridge. (D) Relative mRNA levels of FXR/RXR, DPP4, JAK2, and ACE, with GAPDH as a loading control, were assayed by RT-qPCR. The relative mRNA levels for proteins of interest were normalized to GAPDH. (E) The docking poses of rutin bound to CNGA1, BLT1, COX-2, and 5-LOX. Green dash lines: hydrogen bond; blue dash lines: perpendicular π-stacking; yellow dash lines: parallel π-stacking; red dash lines: π–cation interaction; orange dash lines: salt bridge. (F) Relative mRNA levels of CNGA1, BLT1, COX-2, and 5-LOX, with GAPDH as a loading control, were assayed by RT-qPCR. The relative mRNA levels for proteins of interest were normalized to GAPDH. NC: negative control; DC: disease control, cells stimulated with 1 μg/mL LPS; PC: positive control, stimulated cells treated with 10 μM dexamethasone; Rutin-L, Rutin-M, and Rutin-H: stimulated cells treated with 100, 150, or 200 μM rutin, respectively. Significant differences between the two groups were indicated by asterisks or pound symbols (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; ## p < 0.01; #### p < 0.0001). Full article ">Figure 5
Docking poses and experimental validation of isochlorogenic acid C. (A) The 2D chemical structure of isochlorogenic acid C. (B) The 3D chemical structure of isochlorogenic acid C. (C) The docking poses of isochlorogenic acid C bound to FXR/RXR, DPP4, JAK2, and ACE. Green dash lines: hydrogen bond; blue dash lines: perpendicular π-stacking; yellow dash lines: parallel π-stacking; red dash lines: π–cation interaction; orange dash lines: salt bridge. (D) Relative mRNA levels of FXR/RXR, DPP4, JAK2, and ACE, with GAPDH as a loading control, were assayed by RT-qPCR. The relative mRNA levels for proteins of interest were normalized to GAPDH. (E) The docking poses of isochlorogenic acid C bound to CNGA1, BLT1, COX-2, and 5-LOX. Green dash lines: hydrogen bond; blue dash lines: perpendicular π-stacking; yellow dash lines: parallel π-stacking; red dash lines: π–cation interaction; orange dash lines: salt bridge. (F) Relative mRNA levels of CNGA1, BLT1, COX-2, and 5-LOX, with GAPDH as a loading control, were assayed by RT-qPCR. The relative mRNA levels for proteins of interest were normalized to GAPDH. NC: negative control; DC: disease control, cells stimulated with 1 μg/mL LPS; PC: positive control, stimulated cells treated with 10 μM dexamethasone; ICAC-L, ICAC -M, and ICAC -H: stimulated cells treated with 25, 75, or 150 μM isochlorogenic acid C, respectively. Significant differences between the two groups were indicated by asterisks or pound symbols (* p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; ## p < 0.01; #### p < 0.0001). Full article ">

17 pages, 1784 KiB

Open AccessArticle

Research on Hydrogen Production from Ammonia Decomposition by Pulsed Plasma Catalysis

by Yuze He, Neng Zhu and Yunkai Cai

Molecules 2025, 30(5), 1054; https://doi.org/10.3390/molecules30051054 - 25 Feb 2025

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Abstract

Driven by dual-carbon targets, marine engines are accelerating their transition towards low-carbon and zero-carbon. Ammonium–hydrogen fusion fuel is considered to be one of the most promising fuels for ship decarbonization. Using non-thermal plasma (NTP) catalytic ammonia on-line hydrogen production technology to achieve hydrogen [...] Read more.

Driven by dual-carbon targets, marine engines are accelerating their transition towards low-carbon and zero-carbon. Ammonium–hydrogen fusion fuel is considered to be one of the most promising fuels for ship decarbonization. Using non-thermal plasma (NTP) catalytic ammonia on-line hydrogen production technology to achieve hydrogen supply is one of the most important means to guarantee the safety and effectiveness of hydrogen energy in the storage and transportation process. However, the efficiency of ammonia catalytic hydrogen production can be influenced to some extent by the presence of several factors, and the reaction mechanism is complex under the conditions of ship engine temperature emissions. This makes it difficult to realize the precise control of plasma catalytic hydrogen production from ammonia technology under temperature emission conditions, thus restricting an improvement in the ammonia conversion rate. In this study, a kinetic model of hydrogen production from ammonia catalyzed by NTP was established. The influencing factors (reaction temperature, pressure, N₂/NH₃ ratio in the feed gas) and mechanism path of hydrogen production from ammonia decomposition were explored. The results show that the increase in reaction temperature will lead to an increase in the ammonia conversion rate, while the ammonia conversion rate will decrease with the increase in reaction pressure and N₂/NH₃ ratio. When the reaction temperature is 300 K, the pressure is 1 bar, the feed gas is 98%N₂/2%NH₃, and the ammonia conversion rate is 16.7%. The reason why the addition of N₂ is conducive to the hydrogen production from NH₃ decomposition is that the reaction N₂(A3) + NH₃ => N₂ + NH₂ + H, triggered by the electron excited-state N₂(A3), is the main reaction for NH₃ decomposition. Full article

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15 pages, 2907 KiB

Open AccessArticle

Thermodynamic Cards of Classic NADH Models and Their Related Photoexcited States Releasing Hydrides in Nine Elementary Steps and Their Applications

by Bao-Chen Qian, Xiao-Qing Zhu and Guang-Bin Shen

Molecules 2025, 30(5), 1053; https://doi.org/10.3390/molecules30051053 - 25 Feb 2025

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Abstract

Thermodynamic cards of three classic NADH models (XH), namely 1-benzyl-1,4-dihydronicotinamide (BNAH), Hantzsch ester (HEH), and 10-methyl-9,10-dihydroacridine (AcrH), as well as their photoexcited states (XH*: BNAH*, HEH*, AcrH*) releasing hydrides in nine elementary steps in acetonitrile are established. According to these thermodynamic cards, the [...] Read more.

Thermodynamic cards of three classic NADH models (XH), namely 1-benzyl-1,4-dihydronicotinamide (BNAH), Hantzsch ester (HEH), and 10-methyl-9,10-dihydroacridine (AcrH), as well as their photoexcited states (XH*: BNAH*, HEH*, AcrH*) releasing hydrides in nine elementary steps in acetonitrile are established. According to these thermodynamic cards, the thermodynamic reducing abilities of XH* are remarkably enhanced upon photoexcitation, rendering them thermodynamically highly potent electron, hydrogen atom, and hydride donors. The application of these thermodynamic cards to imine reduction is demonstrated in detail, revealing that photoexcitation enables XH* to act as better hydride donors, transforming the hydride transfer process from thermodynamically unfeasible to feasible. Most intriguingly, AcrH* is identified as the most thermodynamically favorable electron, hydride, and hydrogen atom donor among the three classic NADH models and their photoexcited states. The exceptional thermodynamic properties of XH* in hydride release inspire further investigation into the excited wavelengths, excited potentials, and excited state stabilities of more organic hydrides, as well as the discovery of novel and highly effective photoexcited organic hydride reductants. Full article

(This article belongs to the Section Organic Chemistry)

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16 pages, 2990 KiB

Open AccessArticle

Ni-Mg-Al Hydrotalcite-Derived Catalysts for Ammonia Decomposition—From Precursor to Effective Catalyst

by Andrzej Kowalczyk, Martyna Zaryczny, Zofia Piwowarska and Lucjan Chmielarz

Molecules 2025, 30(5), 1052; https://doi.org/10.3390/molecules30051052 - 25 Feb 2025

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Abstract

A series of Ni-Mg-Al hydrotalcite-derived mixed metal oxides with different Ni/Mg ratios were prepared by the coprecipitation method followed by calcination at 600 °C. The hydrotalcite-like materials, as well as their calcined forms, were characterized with respect to structure (XRD, UV-Vis DRS), chemical [...] Read more.

A series of Ni-Mg-Al hydrotalcite-derived mixed metal oxides with different Ni/Mg ratios were prepared by the coprecipitation method followed by calcination at 600 °C. The hydrotalcite-like materials, as well as their calcined forms, were characterized with respect to structure (XRD, UV-Vis DRS), chemical composition (ICP-OES), textural parameters (low-temperature N₂ sorption), dispersion of nickel species (H₂-chemisorption) and nickel species reducibility (H₂-TPR). Moreover, the process of hydrotalcite-like materials’ thermal transformation to mixed metal oxide systems in air and argon flow was studied by the TG-DTA method. The activity of the studied catalysts in the reaction of ammonia decomposition increased with an increase in nickel content in the samples. It was shown that nickel species incorporated into the Mg-Al oxide matrix segregated under conditions of reduction in a flow of H₂/Ar mixture with the formation of metallic nickel crystallites of the average size of about 10 nm. The size of nickel crystallites was practically no change in the subsequent reduction cycles and resulted in increased catalytic activity in comparison to larger crystallites of metallic nickel (20.2–23.6 nm) deposited on Al₂O₃ and MgO. Full article

(This article belongs to the Special Issue Exclusive Papers of Editorial Board Members and Invited Scholars in “Materials Chemistry”)

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