Molecules

26 pages, 6195 KB

Open AccessArticle

From Chains to Chromophores: Tailored Thermal and Linear/Nonlinear Optical Features of Asymmetric Pyrimidine—Coumarin Systems

by Prescillia Nicolas, Stephania Abdallah, Dong Chen, Giorgia Rizzi, Olivier Jeannin, Koen Clays, Nathalie Bellec, Belkis Bilgin-Eran, Huriye Akdas-Kiliç, Jean-Pierre Malval, Stijn Van Cleuvenbergen and Franck Camerel

Molecules 2025, 30(21), 4322; https://doi.org/10.3390/molecules30214322 - 6 Nov 2025

Viewed by 453

Abstract

Eleven novel asymmetric pyrimidine derivatives were synthesized. The pyrimidine core was functionalized with a coumarin chromophore and a pro-mesogenic fragment bearing either chiral or linear alkyl chains of variable length and substitution patterns. The thermal properties were investigated using polarized optical microscopy, differential [...] Read more.

Eleven novel asymmetric pyrimidine derivatives were synthesized. The pyrimidine core was functionalized with a coumarin chromophore and a pro-mesogenic fragment bearing either chiral or linear alkyl chains of variable length and substitution patterns. The thermal properties were investigated using polarized optical microscopy, differential scanning calorimetry, and small-angle X-ray scattering, revealing that only selected derivatives exhibited liquid crystalline phases with ordered columnar or smectic organizations. Linear and nonlinear optical properties were characterized by UV–Vis absorption, fluorescence spectroscopy, two-photon absorption, and second-harmonic generation. Optical responses were found to be highly sensitive to the substitution pattern: derivatives functionalized at the 4 and 3,4,5 positions exhibited enhanced 2PA cross-sections and pronounced SHG signals, whereas variations in alkyl chain length exerted only a minor influence. Notably, compounds forming highly ordered non-centrosymmetric mesophases produced robust SHG-active thin films. Importantly, strong SHG responses were obtained without the need for a chiral center, as the inherent asymmetry of the linear alkyl chain derivatives was sufficient to drive self-organization into non-centrosymmetric materials. These results demonstrate that asymmetric pyrimidine-based architectures combining π-conjugation and controlled supramolecular organization are promising candidates for nonlinear optical applications such as photonic devices, multiphoton imaging, and optical data storage. Full article

(This article belongs to the Section Materials Chemistry)

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19 pages, 2212 KB

Open AccessArticle

Advances in Lycopene Production: From Natural Sources to Microbial Synthesis Using Yarrowia lipolytica

by Paweł Moroz, Aleksandra Bartusiak, Julia Niewiadomska, Kacper Szymański, Tomasz Janek, Anna Kancelista, Anna Gliszczyńska and Zbigniew Lazar

Molecules 2025, 30(21), 4321; https://doi.org/10.3390/molecules30214321 - 6 Nov 2025

Viewed by 682

Abstract

Lycopene, a natural carotenoid with antioxidant and health-promoting properties, has attracted attention as a valuable compound for the food, pharmaceutical, and cosmetic industries. Conventional production methods based on plant extraction or chemical synthesis are limited by low yields, high costs, and environmental concerns. [...] Read more.

Lycopene, a natural carotenoid with antioxidant and health-promoting properties, has attracted attention as a valuable compound for the food, pharmaceutical, and cosmetic industries. Conventional production methods based on plant extraction or chemical synthesis are limited by low yields, high costs, and environmental concerns. In this study, the oleaginous yeast Yarrowia lipolytica was engineered as an alternative microbial cell factory for sustainable lycopene biosynthesis using short-chain fatty acids (SCFAs)—such as acetate, butyrate, and propionate—as inexpensive, renewable carbon sources. Four heterologous genes from Pantoea agglomerans (crtI, crtB, crtE, and idi) were codon-optimized and integrated into the Y. lipolytica genome using different expression systems, including the Golden Gate Assembly strategy. Among the tested strains, PS05/4lyc/GGA, characterized by enhanced phospholipid biosynthesis, demonstrated the highest lycopene yield of 462.9 mg/g dry cell weight and a titer of 3.41 g/L on butyrate medium—values comparable to or exceeding those reported for bioreactor-scale fermentations. The results indicate that co-activation of phospholipid and carotenoid biosynthesis pathways creates favorable intracellular conditions for hydrophobic pigment accumulation. Moreover, the use of SCFAs improved acetyl-CoA availability and redirected carbon flux through the mevalonate pathway, enhancing productivity. Strains with elevated membrane lipid biosynthesis also exhibited higher metabolic stability and stress tolerance. Full article

(This article belongs to the Section Chemical Biology)

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19 pages, 2384 KB

Open AccessArticle

Non-Invasive Regional Neurochemical Profiling of Zebrafish Brain Using Localized Magnetic Resonance Spectroscopy at 28.2 T

by Rico Singer, Wanbin Hu, Li Liu, Huub J. M. de Groot, Herman P. Spaink and A. Alia

Molecules 2025, 30(21), 4320; https://doi.org/10.3390/molecules30214320 - 6 Nov 2025

Viewed by 515

Abstract

Localized ¹H magnetic resonance spectroscopy (MRS) is a powerful tool in pre-clinical and clinical neurological research, offering non-invasive insight into neurochemical composition in localized brain regions. Zebrafish (Danio rerio) are increasingly being utilized as models in neurological disorder research, providing [...] Read more.

Localized ¹H magnetic resonance spectroscopy (MRS) is a powerful tool in pre-clinical and clinical neurological research, offering non-invasive insight into neurochemical composition in localized brain regions. Zebrafish (Danio rerio) are increasingly being utilized as models in neurological disorder research, providing valuable insights into disease mechanisms. However, the small size of the zebrafish brain and limited MRS sensitivity at low magnetic fields hinder comprehensive neurochemical analysis of localized brain regions. Here, we investigate the potential of ultra-high-field (UHF) MR systems, particularly 28.2 T, for this purpose. This present study pioneers the application of localized ¹H spectroscopy in zebrafish brain at 28.2 T. Point resolved spectroscopy (PRESS) sequence parameters were optimized to reduce the impact of chemical shift displacement error and to enable molecular level information from distinct brain regions. Optimized parameters included gradient strength, excitation frequency, echo time, and voxel volume specifically targeting the 0–4.5 ppm chemical shift regions. Exceptionally high-resolution cerebral metabolite spectra were successfully acquired from localized regions of the zebrafish brain in voxels as small as 125 nL, allowing for the identification and quantification of major brain metabolites with remarkable spectral clarity, including lactate, myo-inositol, creatine, alanine, glutamate, glutamine, choline (phosphocholine + glycerol-phospho-choline), taurine, aspartate, N-acetylaspartyl-glutamate (NAAG), N-acetylaspartate (NAA), and γ-aminobutyric acid (GABA). The unprecedented spatial resolution achieved in a small model organism enabled detailed comparisons of the neurochemical composition across distinct zebrafish brain regions, including the forebrain, midbrain, and hindbrain. This level of precision opens exciting new opportunities to investigate how specific diseases in zebrafish models influence the neurochemical composition of specific brain areas. Full article

(This article belongs to the Section Analytical Chemistry)

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20 pages, 5662 KB

Open AccessArticle

The Action of Cannabidiol on Doxycycline Cytotoxicity in Human Cells—In Vitro Study

by Lidia Radko, Tatiana Wojciechowicz, Oliwia Kończak, Paula Żakowicz, Oskar Łętowski, Julia Salmanowicz and Zuzanna Skrzypczak

Molecules 2025, 30(21), 4319; https://doi.org/10.3390/molecules30214319 - 6 Nov 2025

Viewed by 653

Abstract

Improper use of drugs in both animal and human therapy, such as doxycycline (DOX), lead to the accumulation of residues in edible animal tissues as well as in the environment. Plant-derived compounds reduce the adverse effects of drugs. This study aimed to evaluate [...] Read more.

Improper use of drugs in both animal and human therapy, such as doxycycline (DOX), lead to the accumulation of residues in edible animal tissues as well as in the environment. Plant-derived compounds reduce the adverse effects of drugs. This study aimed to evaluate the effect of cannabidiol (CBD) in two concentrations: lower (1.56 µg/mL) (DOX + C1) and higher (3.125 µg/mL) (DOX + C2) on the cytotoxicity of doxycycline in human cells. The toxicity of DOX and its CBD-containing mixtures was assessed after 72 h of exposure in three human cell lines: neural (SH-SY5Y), hepatic (HepG2), and kidney (HEK-293). The exposure to DOX resulted in inhibition of mitochondrial activity (SH-SY5Y) and inhibition of DNA synthesis (HepG2 and HEK-293). IC₅₀ values for DOX ranged from 9.8 to >200 µg/mL in SH-SY5Y cells, 13.4 to 200 µg/mL in HepG2 cells, and 8.9 to 30.4 µg/mL in HEK-293 cells. The nature of the interaction depended on both the cell lines and the concentration of CBD in the mixture. Both CBD mixtures demonstrated a synergistic interaction in neuronal cells. In HepG2 cells, both mixtures showed additive and antagonistic interactions. In HEK-293 cells, the DOX + C1 mixture exhibited an antagonistic (protective) effect, while the DOX + C2 mixture showed an additive effect. There were no changes in oxidative stress levels; however, alterations in apoptosis levels and cell morphology were observed following exposure to the mixtures. The presence of doxycycline in the diet and the environment poses a health risk to consumers. The increasing consumption of CBD-containing products may reduce the risk associated with the presence of this drug in food. It is worth emphasizing the need for research aimed at minimizing the adverse effects of pharmaceuticals on the health of humans and animals. Full article

(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)

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26 pages, 1621 KB

Open AccessReview

Green Valorization Strategies of Pleurotus ostreatus and Its By-Products: A Critical Review of Emerging Technologies and Sustainable Applications

by Pablo Ayuso, Jhazmin Quizhpe, Rocío Peñalver, Pascual García-Pérez and Gema Nieto

Molecules 2025, 30(21), 4318; https://doi.org/10.3390/molecules30214318 - 6 Nov 2025

Viewed by 681

Abstract

Pleurotus ostreatus, commonly known as the oyster mushroom, is a widely cultivated edible mushroom characterized by its nutritional value and health benefits. However, its large-scale production generates significant amounts of agro-industrial by-products, such as stipes, residual mycelium, and spent mushroom substrate (SMS). [...] Read more.

Pleurotus ostreatus, commonly known as the oyster mushroom, is a widely cultivated edible mushroom characterized by its nutritional value and health benefits. However, its large-scale production generates significant amounts of agro-industrial by-products, such as stipes, residual mycelium, and spent mushroom substrate (SMS). These by-products are often discarded despite their high content of bioactive compounds such as dietary fiber, β-glucans, polyphenols, ergosterol, and essential minerals. This review provides a critical overview of emerging green extraction technologies (i.e., ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), supercritical fluid extraction (SFE), subcritical water extraction (SWE), enzyme-assisted extraction (EAE), and pulsed electric fields (PEF)) as a strategy for the sustainable valorization of bioactive compounds from P. ostreatus by-products. Despite promising results in the extraction of β-glucans and phenolic compounds, industrial scalability remains a challenge due to cost, energy demand, and regulatory issues. In addition, the potential incorporation of these compound by-products into functional food formulations is explored, highlighting their possible applications in meat, bakery, and dairy products. Although notable outcomes have been obtained in the use of the fruiting body as a functional ingredient, further research is needed into the potential use of by-products in order to optimize processing parameters, ensure safety, and validate consumer acceptance. Overall, the sustainable valorization of P. ostreatus by-products represents a dual opportunity to reduce food waste and develop innovative functional ingredients that contribute to health and sustainability. Full article

(This article belongs to the Special Issue Functional Foods Enriched with Natural Bioactive Compounds)

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31 pages, 616 KB

Open AccessReview

Phytochemicals as Epigenetic Modulators in Chronic Diseases: Molecular Mechanisms

by Daniel Cord, Mirela Claudia Rîmbu, Marius P. Iordache, Radu Albulescu, Sevinci Pop, Cristiana Tanase and Maria-Linda Popa

Molecules 2025, 30(21), 4317; https://doi.org/10.3390/molecules30214317 - 6 Nov 2025

Viewed by 818

Abstract

Phytochemicals are plant-derived bioactive compounds with antioxidant, anti-inflammatory, and epigenetic modulatory effects that may contribute to the prevention and management of chronic diseases. This review synthesizes recent evidence on the molecular mechanisms through which phytochemicals influence oxidative stress, inflammatory signaling, and epigenetic regulation. [...] Read more.

Phytochemicals are plant-derived bioactive compounds with antioxidant, anti-inflammatory, and epigenetic modulatory effects that may contribute to the prevention and management of chronic diseases. This review synthesizes recent evidence on the molecular mechanisms through which phytochemicals influence oxidative stress, inflammatory signaling, and epigenetic regulation. A targeted literature search of the PubMed and Web of Science databases (2015–2025) identified over 400 experimental and review studies investigating phytochemicals with documented antioxidant and epigenetic activities. Eligible articles were selected based on relevance to oxidative stress, inflammation, and DNA or histone modification pathways in chronic diseases. Data were qualitatively analyzed to highlight mechanistic links between redox balance, transcriptional regulation, and disease modulation. The results indicate that several phytochemicals, including hesperidin, phloretin, lycopene, and silybin, modulate signaling cascades—NF-κB, Nrf2, and PI3K/Akt—while also influencing DNA methylation and histone acetylation to restore gene expression homeostasis. Despite strong in vitro and in vivo evidence, translation to clinical practice remains limited by low bioavailability, lack of standardized formulations, and insufficient human trials. Future research should prioritize integrative study designs linking molecular mechanisms to clinical endpoints. Understanding the epigenetic actions of phytochemicals may guide the development of nutraceutical strategies for chronic disease prevention. Full article

(This article belongs to the Special Issue Phytochemistry, Human Health and Molecular Mechanisms)

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22 pages, 1471 KB

Open AccessArticle

Interacting Quantum Atoms Analysis of Covalent and Collective Interactions in Single Elongated Carbon–Carbon Bonds

by Antonio Bonesana-Espinoza, José Manuel Guevara-Vela, Evelio Francisco, Tomás Rocha-Rinza and Ángel Martín Pendás

Molecules 2025, 30(21), 4316; https://doi.org/10.3390/molecules30214316 - 6 Nov 2025

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Abstract

Chemical bonds among carbon atoms are central to chemistry. A general working principle regarding these interactions is that these contacts become stronger as the carbon atoms become closer to each other. Nevertheless, there are long, yet strong single C–C bonds that challenge this [...] Read more.

Chemical bonds among carbon atoms are central to chemistry. A general working principle regarding these interactions is that these contacts become stronger as the carbon atoms become closer to each other. Nevertheless, there are long, yet strong single C–C bonds that challenge this interpretation. Herein, we perform a quantitative thorough decomposition of the electronic energy of hexaphenylethane and several derivatives of this molecule with increasingly bulkier substituents. For this purpose, we exploit state-of-the-art methods of wave function analysis for the examination of the chemical bonding scenario in the examined systems, namely, the quantum theory of atoms in molecules (QTAIM) and the interacting quantum atoms (IQA) electronic energy partition. Our results reveal the predominance of collective non-covalent interactions over the central, covalent one in the chemical bonding of the examined molecules, in particular for those that have been synthesized in the laboratory. The QTAIM and IQA methods also showed that, besides London dispersion, electron sharing comprises an important contribution to the abovementioned collective interactions. Overall, our results give valuable insights about the importance of collective interactions in the investigated systems and they aid in the understanding of the nature of long, yet stable single C–C bonds. Full article

(This article belongs to the Special Issue Fundamental Aspects of Chemical Bonding—2nd Edition)

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22 pages, 4446 KB

Open AccessReview

Flavonoid-Based Cocrystals: A Comprehensive Study on Their Synthesis, Characterization, Physicochemical Properties and Applications

by Urszula Izabela Maciołek, Małgorzata Kosińska-Pezda, Tamara Martínez-Senra, Sonia Losada-Barreiro and Carlos Bravo-Díaz

Molecules 2025, 30(21), 4315; https://doi.org/10.3390/molecules30214315 - 6 Nov 2025

Viewed by 534

Abstract

Flavonoids are naturally occurring compounds with reported anticancer, antimicrobial, anti-inflammatory, cardio-protective and antioxidant effects. They are increasingly incorporated in functional foods designed to promote health, enhance well-being, and support physical performance. However, their practical use is limited because of their low water solubility [...] Read more.

Flavonoids are naturally occurring compounds with reported anticancer, antimicrobial, anti-inflammatory, cardio-protective and antioxidant effects. They are increasingly incorporated in functional foods designed to promote health, enhance well-being, and support physical performance. However, their practical use is limited because of their low water solubility and poor absorption within the body. An effective strategy for developing new flavonoid-based formulations involves their transformation into molecular complexes (cocrystals) through cocrystallization, a method that has emerged a powerful tool to modulate the physicochemical and biological properties of polyphenols and other relevant drugs. Cocrystals are stabilized through non-covalent interactions, which can introduce new physicochemical properties to the original molecules (coformers) while retaining the chemical properties of the coformers, as no bonds are broken or formed. Flavonoid-based cocrystals can be obtained through a variety of methods using different coformers, and we aim here to review cocrystals containing flavonoids and coformers, with a focus on their methods of synthesis, physicochemical and biological characteristics, as well as their potential applications in both the food and pharmaceutical sectors. Full article

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21 pages, 899 KB

Open AccessArticle

Phytochemical Constituent of Devil Weed (Chromolaena odorata), Concurrent with Its Antioxidant, α-Glucosidase Inhibitory, and Antibacterial Activity

by Anastasia Wheni Indrianingsih, Muhammad F. F. Ahla, Anjar Windarsih, Suratno, Tri Wiyono, Eka Noviana, Nurrulhidayah Ahmad Fadzhillah and Ririn Nur Alfiani

Molecules 2025, 30(21), 4314; https://doi.org/10.3390/molecules30214314 - 6 Nov 2025

Viewed by 767

Abstract

This study aimed to investigate the phytochemical constituents of C. odorata leaves and stems and to evaluate their antioxidant, total phenol, α-glucosidase, and antibacterial activities. Furthermore, liquid chromatography-high-resolution mass spectrometry (LC–HRMS)-based metabolite profiling combined with principal component analysis (PCA) was applied to correlate [...] Read more.

This study aimed to investigate the phytochemical constituents of C. odorata leaves and stems and to evaluate their antioxidant, total phenol, α-glucosidase, and antibacterial activities. Furthermore, liquid chromatography-high-resolution mass spectrometry (LC–HRMS)-based metabolite profiling combined with principal component analysis (PCA) was applied to correlate metabolite composition with functional activities, providing comprehensive insights into the metabolomic diversity and bioactive differentiation between plant parts. The plant materials were extracted using 70% and 100% ethanol for 24 h. The leaf extract of ethanol 70% (EtOH 70) exhibited the highest antioxidant activity (IC₅₀ of 223.33 ± 9.20 µg/mL) and total phenolic content (113.15 mg GAE/g), while the stem EtOH 70% extract showed the strongest antidiabetic activity through α-glucosidase inhibitory activity (78.57%). Although appearing less potent, all extracts showed dose-dependent inhibitory activity, such as Staphylococcus aureus (highest value at 9.31 mm), Escherichia coli (highest value at 9.92 mm), and Salmonella typhimurium (highest value at 9.00 mm). Comparing the plant parts, leaf extracts generally showed more potent activity than stem extracts, particularly evident against E. coli (e.g., Leaf EtOH 70% at 5 mg/mL: 9.92 mm vs. Stem EtOH 70%: 7.97 mm). LC-HRMS analysis revealed the presence of phenolics, flavonoids, amino acids, organic acids, and alkaloids. Furthermore, the result indicates that C. odorata is a rich source of bioactive compounds with significant antioxidant, α-glucosidase inhibitory, and antibacterial potency. The findings advance existing knowledge beyond earlier phytochemical or single-activity studies, offering a more holistic understanding of C. odorata’s therapeutic potential and its relevance for natural product development. Full article

(This article belongs to the Special Issue Health Benefits and Applications of Bioactive Phenolic Compounds)

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22 pages, 1906 KB

Open AccessArticle

Effect of Torrefaction Condensate on the Growth and Exopolysaccharide Production of Chlamydomonas reinhardtii

by Salini Chandrasekharan Nair, Amal D. Premarathna, Anjana Hari, Christine Gardarin, Céline Laroche, Rando Tuvikene, Renu Geetha Bai and Timo Kikas

Molecules 2025, 30(21), 4313; https://doi.org/10.3390/molecules30214313 - 6 Nov 2025

Viewed by 463

Abstract

Torrefaction, a mild thermochemical pretreatment process, generates the fuel-torrefied biomass along with non-condensable and condensable gases. The latter can be condensed to yield a dark, viscous liquid called torrefaction condensate (TC). In this study, we investigated the effect of TC on growth and [...] Read more.

Torrefaction, a mild thermochemical pretreatment process, generates the fuel-torrefied biomass along with non-condensable and condensable gases. The latter can be condensed to yield a dark, viscous liquid called torrefaction condensate (TC). In this study, we investigated the effect of TC on growth and exopolysaccharide (EPS) production by the green microalgae Chlamydomonas reinhardtii, a well-known model organism. Aspen wood pellets were torrefied at different temperatures, and the condensate formed at each temperature was analyzed. Based on the GC-MS analysis, 225 °C TC was selected and used for the cultivation of C. reinhardtii. Results show that at 2 mL/L and 2.5 mL/L concentrations, TC negatively impacts growth, EPS production, as well as the composition of amino acids, lipids, and fatty acids n of C. reinhardtii. However, C. reinhardtii gradually adapted to TC and attained the growth patterns comparable to the control, showing the resilience of the culture. The biochemical and antioxidant properties of the EPS showed significant differences to that of the control. Therefore, cultivating these microalgae in TC suggests a new microalgal biorefinery approach through the utilization of low-value TC for the production of value-added products, such as EPS. Full article

(This article belongs to the Special Issue Bio-Based Polymers for Sustainable Future)

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20 pages, 6811 KB

Open AccessArticle

Plasma-Activated CO₂ Dissociation to CO in Presence of CeO₂ Mesoporous Catalysts

by Oleg V. Golubev, Alexey A. Sadovnikov and Anton L. Maximov

Molecules 2025, 30(21), 4312; https://doi.org/10.3390/molecules30214312 - 6 Nov 2025

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Abstract

The increasing atmospheric CO₂ concentration is one of the major environmental challenges, necessitating not only emission reduction but also effective carbon utilization. Non-thermal plasma-catalytic CO₂ conversion offers an efficient pathway under mild conditions by synergistically combining plasma activation with catalytic surface [...] Read more.

The increasing atmospheric CO₂ concentration is one of the major environmental challenges, necessitating not only emission reduction but also effective carbon utilization. Non-thermal plasma-catalytic CO₂ conversion offers an efficient pathway under mild conditions by synergistically combining plasma activation with catalytic surface reactions. In this study, mesoporous ceria catalysts were synthesized by different methods and characterized using N₂ adsorption–desorption, SEM, XRD, XPS, CO₂-TPD, and XRF techniques. The materials exhibited distinct textural and electronic properties, including variations in surface area, pore structure, and basicity. Plasma-catalytic CO₂ dissociation experiments were conducted in a dielectric barrier discharge reactor at near-room temperature. Among the synthesized catalysts, Ce(mp)-4 demonstrated the highest CO₂ conversion of 32.3% at a 5 kV input voltage and superior energy efficiency, which can be attributed to its meso-macroporous structure that promotes microdischarge formation and enhances CO₂ adsorption–desorption dynamics. CO was the only product obtained, with near-100% selectivity. Catalyst stability testing showed no deactivation while spent catalyst characterization indicated carbon-containing species. The findings in this study highlight the critical role of tailored pore structure and basic-site distribution in optimizing plasma-catalytic CO₂ dissociation performance, offering a promising strategy for energy-efficient CO₂ utilization. Full article

(This article belongs to the Special Issue Innovative Chemical Pathways for CO₂ Conversion)

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13 pages, 1615 KB

Open AccessArticle

A Comparative Study of C₂-Symmetric and C₁-Symmetric Hydroxamic Acids in Vanadium-Catalyzed Asymmetric Epoxidation of Allylic Alcohols

by Marco Valtierra-Galván, Alfredo Rodríguez-Hernández, Israel Bonilla-Landa, Felipe Barrera-Méndez, Francisco Javier Enríquez-Medrano, Ramón Enrique Díaz de León-Gómez and José Luis Olivares-Romero

Molecules 2025, 30(21), 4311; https://doi.org/10.3390/molecules30214311 - 6 Nov 2025

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Abstract

Hydroxamic acids are emerging as versatile chiral ligands for metal-catalyzed asymmetric oxidations due to their tunable electronic and steric environments. In this study, we systematically compared the catalytic behavior of C₂- and C₁-symmetric hydroxamic acid ligands in the vanadium-catalyzed [...] Read more.

Hydroxamic acids are emerging as versatile chiral ligands for metal-catalyzed asymmetric oxidations due to their tunable electronic and steric environments. In this study, we systematically compared the catalytic behavior of C₂- and C₁-symmetric hydroxamic acid ligands in the vanadium-catalyzed asymmetric epoxidation of allylic alcohols. A series of chiral hydroxamic acids (HA1–HA7) was synthesized and evaluated under varied conditions to elucidate the influence of ligand symmetry on enantioinduction and reactivity. The results demonstrate that C₂-symmetric bishydroxamic acids generate a highly organized chiral environment, leading to high enantioselectivity but often limited conversion, consistent with the Sabatier principle. Conversely, certain C₁-symmetric ligands—particularly HA3—produced notable enantioselectivity (up to 71% e.e.) and full conversion under optimized conditions with VO(OiPr)₃ in CH₂Cl₂. A quadrant-based stereochemical model is proposed to rationalize the differential performance of these ligands. These findings highlight the critical role of ligand desymmetrization in modulating the chiral environment around vanadium centers, providing valuable design principles for next-generation hydroxamic acid-based catalysts in asymmetric synthesis. The optimized system (VO(OiPr)₃/HA3 in CH₂Cl₂) afforded >99% conversion and 71% e.e., providing a basis for extending hydroxamic acid scaffolds to diverse allylic alcohols. Full article

(This article belongs to the Special Issue Synthesis, Properties, and Applications of Chiral Molecules)

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30 pages, 1043 KB

Open AccessReview

In Vitro Anti-Inflammatory and Anticancer Potential of Pecan Nut (Carya illinoinensis) Kernel Extracts: Modulation of Cell Signaling Pathways—A Scoping Review

by Ifeoma Roseline Ezeanolue, Chiugo Francisca Ezeanolue, Pierluigi Plastina, Francieli Moro Stefanello, Rejane Giacomelli Tavares and Roselia Maria Spanevello

Molecules 2025, 30(21), 4310; https://doi.org/10.3390/molecules30214310 - 5 Nov 2025

Viewed by 571

Abstract

This scoping review synthesized evidence from 2015 to 2025 on the anti-inflammatory and anticancer potential of pecan (Carya illinoinensis) kernel extracts, focusing on bioactive composition and cell signaling pathway modulation. Pecan kernels contain diverse phenolic compounds including gallic acid, catechin, epicatechin, [...] Read more.

This scoping review synthesized evidence from 2015 to 2025 on the anti-inflammatory and anticancer potential of pecan (Carya illinoinensis) kernel extracts, focusing on bioactive composition and cell signaling pathway modulation. Pecan kernels contain diverse phenolic compounds including gallic acid, catechin, epicatechin, and ellagic acid, along with tocopherols and unsaturated fatty acids, exhibiting significant cultivar-dependent variation influenced by ripening stage, processing conditions, and orchard management practices. In vitro studies demonstrate that kernel extracts possess substantial antioxidant capacity and exert antiproliferative and cytotoxic effects against various human cancer cell lines, including colon cancer cells, with evidence of apoptosis induction. Extraction methodologies significantly influence bioactive compound recovery and biological activity, with both lipid and phenolic fractions contributing to therapeutic potential. While current evidence highlights promising anti-inflammatory and anticancer properties mediated through modulation of apoptotic pathways, research remains predominantly limited to compositional analyses and in vitro models. Future investigations should elucidate specific molecular mechanisms, identify precise signaling pathway targets, conduct in vivo validation studies, and optimize processing conditions to maximize bioactive retention for potential therapeutic applications in cancer prevention and treatment. Full article

(This article belongs to the Special Issue Featured Review Papers in Food Chemistry—2nd Edition)

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21 pages, 8900 KB

Open AccessArticle

Photocatalytic Evaluation of Fe₂O₃–TiO₂ Nanocomposites: Influence of TiO₂ Content on Their Structure and Activity

by Israel Águila-Martínez, Pablo Eduardo Cardoso-Avila, Isaac Zarazúa, Héctor Pérez Ladrón de Guevara, José Antonio Pérez-Tavares, Efrén González-Aguiñaga and Rita Patakfalvi

Molecules 2025, 30(21), 4309; https://doi.org/10.3390/molecules30214309 - 5 Nov 2025

Viewed by 491

Abstract

In this study, Fe₂O₃–TiO₂ nanocomposites with different TiO₂ contents (1–50%) were synthesized via a solvothermal method using pre-formed α-Fe₂O₃ nanoparticles as cores. We systematically evaluated the influence of TiO₂ loading on the nanocomposites’ [...] Read more.

In this study, Fe₂O₃–TiO₂ nanocomposites with different TiO₂ contents (1–50%) were synthesized via a solvothermal method using pre-formed α-Fe₂O₃ nanoparticles as cores. We systematically evaluated the influence of TiO₂ loading on the nanocomposites’ structural, morphological, optical, and photocatalytic properties. X-ray diffraction revealed the coexistence of hematite and anatase phases, with an increase in TiO₂ content inducing reduced crystallite size, enhanced dislocation density, and microstrain, indicating interfacial lattice distortion. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) showed a uniform elemental distribution at low TiO₂ contents, evolving into irregular agglomerates at higher loadings. Fourier-transform infrared (FTIR) spectra indicated the suppression of Fe–O vibrations and the appearance of hydroxyl-related bands with TiO₂ enrichment. Diffuse reflectance spectroscopy (DRS) analysis confirmed the simultaneous presence of hematite (~2.0 eV) and anatase (3.2–3.35 eV) absorption edges, with a slight blue shift in the TiO₂ band gap at higher concentrations. Photocatalytic activity, assessed using methylene blue degradation under xenon lamp irradiation, demonstrated a strong dependence on the TiO₂ fraction. The composite containing 33% TiO₂ achieved the best performance, with 98% dye removal and a pseudo-first-order rate constant of 0.045 min⁻¹, outperforming both pure hematite and commercial P25 TiO₂. These results highlight that intermediate TiO₂ content (~33%) provides an optimal balance between structural integrity and photocatalytic efficiency, making Fe₂O₃–TiO₂ heterostructures promising candidates for water purification under simulated solar irradiation. Full article

(This article belongs to the Special Issue Nanomaterials and Nanocomposites: Synthesis, Characterization and Applications in Environmental and Biomedical Sciences)

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12 pages, 1184 KB

Open AccessArticle

Racemosol Derivatives and Other Metabolites from Bauhinia malabarica Bark with Antibacterial Activity

by Wanchat Sirisarn, Apisara Somteds, Supachai Jadsadajerm, Sutin Kaennakam, Nuttapon Yodsin and Awat Wisetsai

Molecules 2025, 30(21), 4308; https://doi.org/10.3390/molecules30214308 - 5 Nov 2025

Viewed by 397

Abstract

Racemosol, a natural phenolic compound, is known for its antimicrobial potential, yet experimental studies remain limited. In this study, two new racemosol derivatives (4 and 5) and four known compounds (1–3, 6) were isolated from the [...] Read more.

Racemosol, a natural phenolic compound, is known for its antimicrobial potential, yet experimental studies remain limited. In this study, two new racemosol derivatives (4 and 5) and four known compounds (1–3, 6) were isolated from the bark of Bauhinia malabarica and structurally elucidated using spectroscopic analyses. Most of isolated compounds exhibited notable activity against Gram-positive bacteria, including Staphylococcus aureus, Bacillus subtilis, and Listeria monocytogenes, while showing limited effects on Gram-negative strains. Racemosol (1) and its derivatives (2, 4, and 6) displayed potent antibacterial activity with MIC values of 0.156–0.625 µg/µL and bactericidal properties confirmed by comparable MBCs. Compound 6 exhibited the highest potency, indicating that specific structural modifications enhance activity. These findings provide new insights into the structure activity relationships of racemosol derivatives and highlight B. malabarica as a promising natural source of phenolic antibacterial agents. Full article

(This article belongs to the Special Issue Phytochemicals and Bioactivity: Advances in Natural Product Chemistry and Applications)

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22 pages, 5222 KB

Open AccessArticle

Liquid Phase Catalytic Transfer Hydrogenation of Crotonaldehyde over ReO_x-Supported Catalysts Using Formic Acid as In Situ Hydrogen Donor

by Carlos Esteban Aristizábal-Alzate, Verónica Naharro-Ovejero, Manuel Romero-Sáez and Ana Belén Dongil

Molecules 2025, 30(21), 4307; https://doi.org/10.3390/molecules30214307 - 5 Nov 2025

Viewed by 418

Abstract

The selective hydrogenation of the C=O bond over the C=C bond in α,β-unsaturated aldehydes remains a well-known challenge. This work investigates the liquid-phase catalytic transfer hydrogenation of crotonaldehyde to crotyl alcohol over ReOx-based catalysts, using formic acid (FA) as an in situ hydrogen [...] Read more.

The selective hydrogenation of the C=O bond over the C=C bond in α,β-unsaturated aldehydes remains a well-known challenge. This work investigates the liquid-phase catalytic transfer hydrogenation of crotonaldehyde to crotyl alcohol over ReOx-based catalysts, using formic acid (FA) as an in situ hydrogen donor. A series of 10 wt% Re catalysts supported on G200, g-C₃N₄, TiO₂, and ZrO₂ were synthesized and tested in a batch reactor at 20 bar and temperatures of 140–180 °C. Catalysts were characterized by XRD, BET, NH₃-TPD, and XPS to correlate their physicochemical properties with catalytic behavior. Among the studied materials, ReO_x/ZrO₂ and ReO_x/g-C₃N₄ exhibited the highest crotyl alcohol selectivity above 57% for all reaction temperatures, evaluated at crotonaldehyde conversion of 25%. The nature of the support strongly influenced the dispersion and oxidation state of Re species, as well as the surface acidity, which governed the activation of both the carbonyl group and the FA decomposition. Compared with molecular hydrogen, FA improved both conversion and selectivity due to its superior hydrogen-donating ability in the aqueous phase. These findings demonstrate that tailoring the acid–base characteristics of ReO_x catalysts and employing biomass-derived hydrogen donors represent an effective strategy for selective hydrogenation of α,β-unsaturated aldehydes. Full article

(This article belongs to the Special Issue Recent Advances on Biomass Conversion and CO₂ Valorization: Steeping Towards a Circular Economy, 2nd Edition)

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20 pages, 2363 KB

Open AccessArticle

On the Question of the Application Potential and the Molecular Mechanism of the Formation of 1,3-Diaryl-5-Nitropyrazoles from Trichloromethylated Diarylnitropyrazolines

by Karolina Kula and Radomir Jasiński

Molecules 2025, 30(21), 4306; https://doi.org/10.3390/molecules30214306 - 5 Nov 2025

Viewed by 598

Abstract

The molecular mechanism of the formation of 1,3-diaryl-5-nitropyrazoles via a CHCl₃-elimination reaction was investigated using ωB97xD/6-31+G(d,p) (PCM) calculations. It was found that, regardless of the polarity of the reaction environment or the nature of the substituents on the phenyl rings of [...] Read more.

The molecular mechanism of the formation of 1,3-diaryl-5-nitropyrazoles via a CHCl₃-elimination reaction was investigated using ωB97xD/6-31+G(d,p) (PCM) calculations. It was found that, regardless of the polarity of the reaction environment or the nature of the substituents on the phenyl rings of the starting molecules, the elimination process proceeds through a single-step mechanism characterized by an extremely asynchronous transition state. The ELF (Electron Localization Function) analysis of selected critical structures confirms the proposed mechanism and reveals a pronounced reorganization of electrons within the heterocyclic ring. The in silico analysis based on ADME (Activity, Distribution, Metabolism, and Excretion) and PASS (Prediction of Activity Spectra for Substances) predictions indicates that the title 1,3-diaryl-5-nitropyrazoles exhibit promising biological potential, showing inhibitory activity against both oxidoreductases and proteases. The most consistent targets include hyponitrite reductase, (R)-6-hydroxynicotine oxidase, acrocylindropepsin, saccharopepsin, and chymosin. Thus, the presented CHCl₃-elimination provides an efficient and versatile route to functionalized pyrazoles, and, together with their promising bioactivity, confirms the utility of this approach for their synthesis. Full article

(This article belongs to the Special Issue Selectivity and Theoretical Studies of Cycloaddition Reactions)

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21 pages, 7819 KB

Open AccessArticle

Multiway Analysis of the Electrochemical Oxidation Pathway of a Lignin Using Chemometrics

by Gobind Sah, John A. Staser and Peter B. Harrington

Molecules 2025, 30(21), 4305; https://doi.org/10.3390/molecules30214305 - 5 Nov 2025

Viewed by 457

Abstract

The electrochemical oxidation mechanism of biopolymer lignin is challenging to characterize due to its complex structure. Controlling the oxidation process is crucial for ensuring the economic feasibility of electrochemical depolymerization of lignin, as it often generates numerous undesirable compounds. Regulating the depolymerization process [...] Read more.

The electrochemical oxidation mechanism of biopolymer lignin is challenging to characterize due to its complex structure. Controlling the oxidation process is crucial for ensuring the economic feasibility of electrochemical depolymerization of lignin, as it often generates numerous undesirable compounds. Regulating the depolymerization process can lead to the production of high-yield aromatic compounds, such as phenols and carboxylic acids. In addition to the depolymerization of lignin by the electrocatalyst, hydroxyl radicals (^•OH) during the electrochemical oxidation could also depolymerize lignin. Previous studies have reported that ^•OH forms during electrochemical oxidation; however, it is still uncertain whether these radicals or electrocatalysts are responsible for depolymerizing lignin. This study investigates the pivotal issue of whether the depolymerization process is driven by ^•OH or by a direct electrochemical route. In this study, lignin compounds were electrochemically oxidized using a nickel-cobalt (Ni-Co) electrocatalyst at several electrode potentials, and the oxidized products were analyzed using headspace solid-phase micro-extraction gas chromatography–mass spectrometry (SPME-GC-MS) and factor analysis (FA). Electrochemical depolymerization of lignin yielded mainly phenolic compounds (e.g., tert-butyl phenols), phthalate esters (e.g., dibutyl phthalate, bis(2-methylpropyl) phthalate), furan derivatives (e.g., 2-butyltetrahydrofuran), and short-chain carboxylic acid esters. This work has successfully predicted that both electrocatalyst and ^•OH radicals contribute to the electrochemical depolymerization of lignin. Radical-mediated depolymerization yielded a broader range of products. Full article

(This article belongs to the Topic Advanced Bioenergy and Biofuel Technologies)

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35 pages, 1832 KB

Open AccessReview

Recent Approaches for Bioactive Peptides Production from Pulses and Pseudocereals

by Manuel Martoccia, Vincenzo Disca, Yassine Jaouhari, Matteo Bordiga and Jean Daniel Coïsson

Molecules 2025, 30(21), 4304; https://doi.org/10.3390/molecules30214304 - 5 Nov 2025

Viewed by 895

Abstract

Pulses and pseudocereals are sustainable protein sources of bioactive peptides (BAPs) with potential antioxidant, antihypertensive, antidiabetic, antimicrobial, and immunomodulatory activities. BAPs are typically liberated during gastrointestinal digestion or through bio-based processes, among which enzymatic hydrolysis and microbial fermentation represent the most widely applied [...] Read more.

Pulses and pseudocereals are sustainable protein sources of bioactive peptides (BAPs) with potential antioxidant, antihypertensive, antidiabetic, antimicrobial, and immunomodulatory activities. BAPs are typically liberated during gastrointestinal digestion or through bio-based processes, among which enzymatic hydrolysis and microbial fermentation represent the most widely applied strategies. Enzymatic hydrolysis provides controlled and reproducible release of short peptide motifs; recent advances such as ultrasound- or high-pressure–assisted hydrolysis enhance yield and bioactivity. Fermentation exploits microbial proteolytic activity to generate complex peptide mixtures, while improving sensory quality, reducing antinutritional compounds, and responding to consumer demand for natural and “clean-label” products. In silico tools increasingly complement these approaches by accelerating peptide discovery, predicting interactions with molecular targets, and guiding process design. This review provides an updated overview of bio-based methods to produce BAPs from pulses and pseudocereals, emphasizing the comparative advantages of enzymatic and fermentation technologies and their integration with computational tools. Moreover, it examines regulatory frameworks in the European Union, the United States, Japan, and China, while discussing current challenges for industrial scale-up and application in functional foods and nutraceuticals. These combined strategies offer a promising pathway to unlock the health and sustainability potential of plant proteins. Full article

(This article belongs to the Special Issue Bioproducts for Health, 4th Edition)

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35 pages, 3381 KB

Open AccessReview

From Triads to Tools: A Comprehensive Review of the Expanding Roles of G-Triplex Structures

by Mitchell W. Myhre, Malay Kumar Das, Elizabeth P. Williams, Wendi M. David and Sean M. Kerwin

Molecules 2025, 30(21), 4303; https://doi.org/10.3390/molecules30214303 - 5 Nov 2025

Viewed by 708

Abstract

Interest in non-canonical DNA structures continues to grow, in part fueled by the recent discovery of a new structure, G-triplex DNA. Originally proposed as folding intermediates for G-quadruplex DNA, G-triplex DNA has more recently been shown to form from truncated G-quadruplex sequence oligonucleotides [...] Read more.

Interest in non-canonical DNA structures continues to grow, in part fueled by the recent discovery of a new structure, G-triplex DNA. Originally proposed as folding intermediates for G-quadruplex DNA, G-triplex DNA has more recently been shown to form from truncated G-quadruplex sequence oligonucleotides and other, specifically designed sequences. In this review, we provide the first, comprehensive survey of G-triplex DNA and RNA, covering the literature up to 2024. We include reports of G-triplex DNA from bulk solution and single-molecule approaches, the structural characterization of G-triplex DNA, and the breadth of oligonucleotide sequences that have been reported to form these structures. The formation of G-triplex RNA structures is also reviewed. The evolving understanding of sequence and environmental effects on G-triplex formation are presented together with challenges due to structural polymorphism and competing formation of multimeric G-quadruplex structures. Hints of the biological relevance of G-triplexes are provided by reports of protein recognition of these structures and their effects on DNA replication in vitro. Interaction of G-triplex DNA with a variety of ligands has been reported, although the search for selective ligands that can distinguish G-triplex from G-quadruplex is on-going. The vast majority of publications in the area have focused on the utilization of G-triplex in biosensing applications, which has shown some advantages compared to G-quadruplex-based systems. These results highlight the potential utility of G-triplex structures in a variety of domains and show its promise in applications in biotechnology, medicine, and research. Full article

(This article belongs to the Section Molecular Structure)

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41 pages, 4051 KB

Open AccessReview

Advances in Naturally and Synthetically Derived Bioactive Sesquiterpenes and Their Derivatives: Applications in Targeting Cancer and Neurodegenerative Diseases

by Liana R. Cutter, Alexandra R. Ren and Ipsita A. Banerjee

Molecules 2025, 30(21), 4302; https://doi.org/10.3390/molecules30214302 - 5 Nov 2025

Viewed by 1220

Abstract

Sesquiterpenes are a diverse class of natural products that have garnered considerable interest for their potent bioactivity and structural variability. This review highlights advances in the derivatization of various sesquiterpene lactones, quinones, and alcohols, particularly in targeting cancer and neurodegenerative diseases. The structural [...] Read more.

Sesquiterpenes are a diverse class of natural products that have garnered considerable interest for their potent bioactivity and structural variability. This review highlights advances in the derivatization of various sesquiterpene lactones, quinones, and alcohols, particularly in targeting cancer and neurodegenerative diseases. The structural modifications discussed include the incorporation of triazole, arylidene, or thiol moieties with eudesmane, guaiane, and germacranolide-type sesquiterpenes, among others. In addition, the conjugation with chemotherapeutics, as well as the development of nanoscale therapeutics, is also discussed. Such modifications have expanded the pharmacological potential, enabling improved specificity, cytotoxicity profiles, and sensitization toward tumor cells. Additionally, sesquiterpenes such as parthenolide (20), pterosinsade A (176), and cedrol (186) have demonstrated potential in mitigating neurodegeneration via anti-inflammatory and antioxidant signaling pathway-modulation mechanisms, with potential applications in Alzheimer’s, Parkinson’s, and ALS diseases. Mechanistic insights into redox signaling modulation, NF-κB inhibition, ROS regulation, and disruption of aggregation underscore their multifaceted modes of action. This review highlights the translational promise of sesquiterpene derivatives as dual-action agents for potential drug development in a plethora of diseases that are caused by inflammation and free-radical damage. It provides a framework for future rational design of multifunctional drug candidates and therapeutics. Full article

(This article belongs to the Section Medicinal Chemistry)

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34 pages, 2774 KB

Open AccessReview

Degradable Alternatives to Single-Use Plastics: Mechanisms, Materials, and Strategies for Sustainable Polyolefin Replacement

by Hamza Fakhrizada and Yaser Dahman

Molecules 2025, 30(21), 4301; https://doi.org/10.3390/molecules30214301 - 5 Nov 2025

Viewed by 562

Abstract

The widespread use of single-use plastics, particularly polyethylene (PE) and polypropylene (PP), has resulted in severe environmental pollution due to their durability and resistance to degradation. This report reviews current degradable alternatives to conventional polyolefins and strategies for enhancing their breakdown in natural [...] Read more.

The widespread use of single-use plastics, particularly polyethylene (PE) and polypropylene (PP), has resulted in severe environmental pollution due to their durability and resistance to degradation. This report reviews current degradable alternatives to conventional polyolefins and strategies for enhancing their breakdown in natural and managed environments. Mechanisms of abiotic and biotic degradation are examined alongside the influence of environmental factors and standardized testing protocols. Commercially available biodegradable polymers—such as polylactic acid (PLA), polyhydroxyalkanoates (PHAs), poly(butylene succinate) (PBS), poly(butylene adipate-co-terephthalate) (PBAT), starch-based plastics, cellulose derivatives, chitosan, and protein-based materials—are evaluated for their sources, degradation behavior, applications, scalability, and limitations. In addition, modification techniques for PE and PP, including copolymerization, pro-degradant additives, blending with biodegradable fillers, surface functionalization, enzyme-assisted degradation, and photocatalytic additives, are critically assessed for their potential to reduce environmental persistence. Key challenges such as performance trade-offs, incomplete degradation, ecotoxicity, cost, scalability, and end-of-life management are discussed within the context of circular economic integration. This report concludes with future research directions aimed at developing cost-effective, high-performance materials that degrade completely under real-world conditions while minimizing ecological impacts. Full article

(This article belongs to the Special Issue Bio-Based Polymers for Sustainable Future)

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17 pages, 2153 KB

Open AccessArticle

Analytical Determination of the Lipid Fraction of Nigella sativa Fatty Oil by GC and NMR Analysis and Evaluation of Its Cytotoxic and Antioxidant Activity

by Martina Dentato, Antonella Porrello, Elena De Marino, Stefania Ponticelli, Alessia Postiglione, Alessandra Pollice, Maurizio Bruno, Natale Badalamenti, Giuseppe Bazan and Viviana Maresca

Molecules 2025, 30(21), 4300; https://doi.org/10.3390/molecules30214300 - 5 Nov 2025

Viewed by 533

Abstract

Nigella sativa, or black cumin, is used as a spice in cooking and as a food supplement like seeds or oil for its biological properties, including antioxidant capacity, anti-inflammatory action, and support for the immune system. In the present study, the chemical [...] Read more.

Nigella sativa, or black cumin, is used as a spice in cooking and as a food supplement like seeds or oil for its biological properties, including antioxidant capacity, anti-inflammatory action, and support for the immune system. In the present study, the chemical composition and biological activities of the Nigella sativa seeds’ fatty oil (NS) were investigated. The analytical composition was carried out by several techniques, such as GC-MS spectrometry and ¹H- and ¹³C-NMR spectroscopies using appropriate internal standards. The GC-MS analysis highlighted the presence of palmitic and linoleic acid as major compounds. The antioxidant potential was evaluated through the DPPH radical-scavenging assay, and, furthermore, the NS effect on intracellular reactive oxygen species (ROS) levels was assessed in HaCaT cells (non-tumorigenic human keratinocytes) under oxidative stress induced by hydrogen peroxide. The cytotoxic and genotoxic profiles were evaluated on Caco-2 cells (human colorectal adenocarcinoma cells) using the CCK-8 viability assay and the Comet assay, respectively. Overall, the results demonstrated that NS possessed antioxidant activity, as evidenced by concentration-dependent DPPH radical scavenging and reduced intracellular ROS levels in HaCaT cells under oxidative stress. In Caco-2 colorectal cancer cells, NS induced significant cytotoxicity and DNA damage at higher concentrations, suggesting potential genotoxic effects. These findings support the dual role of NS as a natural antioxidant and a promising candidate for nutraceutical and dermatological applications, including those targeting oxidative stress-related conditions and cancer. Full article

(This article belongs to the Special Issue Biological Evaluation of Plant Extracts)

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24 pages, 3795 KB

Open AccessArticle

A Controlled System for Parahydrogen Hyperpolarization Experiments

by Lorenzo Franco, Federico Floreani, Salvatore Mamone, Ahmed Mohammed Faramawy, Marco Ruzzi, Cristina Tubaro and Gabriele Stevanato

Molecules 2025, 30(21), 4299; https://doi.org/10.3390/molecules30214299 - 5 Nov 2025

Viewed by 431

Abstract

Parahydrogen-induced hyperpolarization (PHIP), introduced nearly four decades ago, provides an elegant solution to one of the fundamental limitations of nuclear magnetic resonance (NMR)—its notoriously low sensitivity. By converting the spin order of parahydrogen into nuclear spin polarization, NMR signals can be boosted by [...] Read more.

Parahydrogen-induced hyperpolarization (PHIP), introduced nearly four decades ago, provides an elegant solution to one of the fundamental limitations of nuclear magnetic resonance (NMR)—its notoriously low sensitivity. By converting the spin order of parahydrogen into nuclear spin polarization, NMR signals can be boosted by several orders of magnitude. Here we present a portable, compact, and cost-effective setup that brings PHIP and Signal Amplification by Reversible Exchange (SABRE) experiments within easy reach, operating seamlessly across ultra-low-field (0–10 μT) and high-field (>1 T) conditions at 50% parahydrogen enrichment. The system provides precise control over bubbling pressure, temperature, and gas flow, enabling systematic studies of how these parameters shape hyperpolarization performance. Using the benchmark Chloro(1,5-cyclooctadiene)[1,3-bis(2,4,6-trimethylphenyl)imidazole-2-ylidene]iridium(I) (Ir–IMes) catalyst, we explore the catalyst activation time and response to parahydrogen flow and pressure. Polarization transfer experiments from hydrides to [1-¹³C]pyruvate leading to the estimation of heteronuclear J-couplings are also presented. We further demonstrate the use of Chloro(1,5-cyclooctadiene)[1,3-bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene]iridium(I) (Ir–SIPr), a recently introduced catalyst that can also be used for pyruvate hyperpolarization. The proposed design is robust, reproducible, and easy to implement in any laboratory, widening the route to explore and expand the capabilities of parahydrogen-based hyperpolarization. Full article

(This article belongs to the Special Issue Emerging Horizons of Hyperpolarization in Chemistry and Biomedicine)

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15 pages, 1776 KB

Open AccessArticle

Selected Biochemical Properties of Medicinal Plant (Urtica dioica L.) Leaves in Relation to the Enzymatic Activity of Soils Exposed to the Impact of Road Traffic

by Joanna Lemanowicz and Iwona Jaskulska

Molecules 2025, 30(21), 4298; https://doi.org/10.3390/molecules30214298 - 5 Nov 2025

Viewed by 346

Abstract

This study examined the impact of distance from the road traffic on soil enzymatic activity, which we used as a tool to assess the relationship between soil and common nettle (Urtica dioica L.) used in herbalism and phytotherapy. A section of national [...] Read more.

This study examined the impact of distance from the road traffic on soil enzymatic activity, which we used as a tool to assess the relationship between soil and common nettle (Urtica dioica L.) used in herbalism and phytotherapy. A section of national road No. 10 (DK10) was selected for the study. Soil and common nettle leaf samples were collected from locations 5 m, 15 m, 25 m, and 100 m away from the road traffic and a control location (C). The activity of catalase (CAT), dehydrogenases (DEH), alkaline phosphatase (AlP), acid phosphatase (AcP), protease (PRO) and β-glucosidase (BG) was examined in the soil. Soil quality indices (RCh, RS, AlP/AcP, GMea, TEI) were calculated based on the enzyme activity results. The leaves of common nettles were tested for chlorophylls a and b (Chl a and b), carotenoids (Car), ascorbic acid (AAC), pH, relative water content (RWC), catalase (CATp) and superoxide dismutase (SOD) activity. Based on the values of Chl a+b, Car, pH, and RWC, the air pollution tolerance index (APTI) was calculated. The activity of the tested enzymes was statistically lowest in soil collected 5 m from traffic compared to the control (C), which was also confirmed by the results of the enzymatic soil quality indicators. In the case of CAT, AlP, AcP, and BG, based on the coefficient of determination (R2), it was found that over 70% of the variability of these enzymes was related to the distance from the road. It was found that the content of Ch a and b, Car, AAC, RWC, and pH was also lowest in soil 5 m away, whereas the activity of the antioxidant enzymes CATp and SOD was highest at this point. The ATPI values determined in common nettle leaf samples collected from locations 5 m, 15 m, 25 m, and 100 m from the road traffic were sensitive to pollution. The results indicate that the distance from the road strongly influenced the changes in the parameters studied. The enzymatic properties of the soil and selected biochemical parameters of common nettle leaves were similar at locations 15 m and 25 m, as well as 100 m and the control. The results of the enzymatic soil quality indicators show that soil 5 m from the road traffic is subject to degradation, and the nettles growing in this location are sensitive to road pollution. Therefore, it is not recommended to collect common nettle leaves from this location for medical or cosmetic purposes. Full article

(This article belongs to the Special Issue Biologically Active Molecules: Extraction Strategies, Therapeutic Potential and Biomedical Perspective)

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20 pages, 2408 KB

Open AccessArticle

Hydrothermal and Organosolv Treatments for Hydroxycinnamate Release from Corn Stover: Strong versus Mild Alkaline Catalysis

by Evangelia Brimo-Alevra, Marina Koutli, Elli Marielou, Theodoros Chatzimitakos and Dimitris P. Makris

Molecules 2025, 30(21), 4297; https://doi.org/10.3390/molecules30214297 - 5 Nov 2025

Viewed by 369

Abstract

Corn stover (CS) is an abundant biomaterial, which is regularly rejected during corn harvesting. This biowaste is a typical lignocellulosic source rich in hydroxycinnamates, which are mainly represented by p-coumaric acid and ferulic acid. These polyphenols are largely bound onto the lignocellulosic [...] Read more.

Corn stover (CS) is an abundant biomaterial, which is regularly rejected during corn harvesting. This biowaste is a typical lignocellulosic source rich in hydroxycinnamates, which are mainly represented by p-coumaric acid and ferulic acid. These polyphenols are largely bound onto the lignocellulosic complex and can be effectively liberated using alkaline catalysis. On this basis, the work described herein targeted at developing a high-performance process for producing hydroxycinnamate-enriched extracts, by deploying alkali-catalyzed hydrothermal and organosolv treatments. For this purpose, sodium carbonate was tested as a benign, natural alkali catalyst, along with the well-studied sodium hydroxide. The kinetic study demonstrated that both the alkali catalyst and the organic solvent (ethanol) may significantly affect polyphenol recovery, a fact further investigated by carrying out response surface optimization. The hydrothermal treatment was shown to be more efficacious than the organosolv one, with regard to total polyphenol recovery, while the sodium carbonate catalysis was less efficient compared to the sodium hydroxide one. Under optimized conditions, the hydrothermal treatment afforded 74.4 ± 3.6 mg gallic acid equivalents per g of dry CS mass. On the other hand, a more thorough investigation of the polyphenolic profile of the extracts obtained clearly demonstrated that the sodium hydroxide-catalyzed organosolv treatment provided almost 76 and 98% higher yields for p-coumaric and ferulic acid, respectively, compared to the hydrothermal treatment. Extract composition impacted the antioxidant activity, and it was revealed that the higher the p-coumaric acid/ferulic acid ratio, the stronger the antioxidant effect. It is proposed that the sodium hydroxide-catalyzed ethanol organosolv treatment of CS may be a particularly promising technique in a lignocellulose biorefinery frame, although improvements might be necessary to further increase treatment performance. Such a process might contribute to fully valorizing agricultural biowastes for the production of high value-added chemicals, in line with the “lignin first’ philosophy. Full article

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28 pages, 1127 KB

Open AccessReview

A Full-Spectrum Evaluation of Sigma-1 Receptor (S1R) Positron Emission Tomography (PET) Radioligands from Binding Affinity to Clinical Imaging

by Francesco Mastropasqua, Friedrich-Alexander Ludwig and Carmen Abate

Molecules 2025, 30(21), 4296; https://doi.org/10.3390/molecules30214296 - 5 Nov 2025

Viewed by 817

Abstract

Several pieces of evidence have demonstrated the sigma-1 receptor (S1R) as a druggable protein with important therapeutic potentials, including neurodegeneration, cancer, and neuropathic pain. The density of S1R is altered in pathological processes so that its imaging is under study for diagnostic purposes. [...] Read more.

Several pieces of evidence have demonstrated the sigma-1 receptor (S1R) as a druggable protein with important therapeutic potentials, including neurodegeneration, cancer, and neuropathic pain. The density of S1R is altered in pathological processes so that its imaging is under study for diagnostic purposes. Thus, research has been focused on the development of S1R positron emission tomography (PET) radioligands, not only as diagnostic tools but also as powerful means to assist in the drug-development process. Herein, we comprehensively review the most important S1R PET radiotracers belonging to different classes that have been developed in the last two decades. Starting from the structural modifications impacting on the S1R affinity and selectivity, we report (i) the differences in metabolism and pharmacokinetics, (ii) the in vivo behavior in different animal models, (iii) the in vitro autoradiography outcomes, and (iv) the dosimetric profiles. The successful use of the best-performing S1R PET radiotracers in the characterization of novel S1R drugs is also reported together with the approaches to assess the potential for clinical translation. What emerges from this review is that, although the development of reliable PET agents appears to be extremely challenging, these radiotracers hold incredible potential and play a fundamental role in the exploitation of S1R in health and disease. Full article

(This article belongs to the Section Medicinal Chemistry)

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23 pages, 4099 KB

Open AccessArticle

Hydrothermal Modification of Activated Carbon Enhances Acetaminophen Adsorption: Experimental and Computational Evidence of π–π Interaction Dominance

by Astrid G. Cortés-Cruz, Marta Adame-Pereira, Carlos J. Durán-Valle and Ignacio M. López-Coca

Molecules 2025, 30(21), 4295; https://doi.org/10.3390/molecules30214295 - 5 Nov 2025

Viewed by 619

Abstract

Acetaminophen (APAP) is a widely used pharmaceutical increasingly detected as a contaminant in aquatic environments due to its persistent nature and incomplete removal by conventional wastewater treatment. This study investigates the adsorption performance and mechanisms of commercial activated carbon (M) and its hydrothermally [...] Read more.

Acetaminophen (APAP) is a widely used pharmaceutical increasingly detected as a contaminant in aquatic environments due to its persistent nature and incomplete removal by conventional wastewater treatment. This study investigates the adsorption performance and mechanisms of commercial activated carbon (M) and its hydrothermally modified form (MH) for APAP removal. Characterization via elemental analysis, X-ray photoelectron spectroscopy (XPS), and N₂ adsorption isotherms revealed that hydrothermal treatment reduced oxygen content and enhanced micro- and mesopore volumes, resulting in a more homogeneous and carbon-rich surface. Batch adsorption experiments conducted under varying pH (5–7) and temperature (30–40 °C) conditions showed that MH achieved up to 94.3% APAP removal, outperforming the untreated carbon by more than 15%. Kinetic modeling indicated that adsorption followed a pseudo-second-order mechanism (R² > 0.99), and isotherm data fitted best to the Langmuir model for MH and the Freundlich model for M, reflecting their differing surface properties. Adsorption was enhanced at lower pH and higher temperatures, consistent with an endothermic and pH-dependent mechanism. Complementary density functional theory (DFT) simulations confirmed that π–π stacking is the dominant interaction between APAP and the carbon surface. The most favorable configuration involved coplanar stacking with non-oxidized graphene (ΔG = −33 kJ/mol), while oxidized graphene models exhibited weaker interactions. Natural Bond Orbital (NBO) analysis further supported the prevalence of π–π interactions over dipole interactions. These findings suggest that surface deoxygenation and improved pore architecture achieved via hydrothermal treatment significantly enhance APAP adsorption, offering a scalable strategy for pharmaceutical pollutant removal in water treatment applications. Full article

(This article belongs to the Special Issue New Insights into Porous Materials in Adsorption and Catalysis)

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26 pages, 2062 KB

Open AccessArticle

Screening of Cytotoxic and Genotoxic Activities of Subcritical Water Extracts from R. damascena and R. alba Flowers

by Tsvetelina Gerasimova, Svetla Gateva, Gabriele Jovtchev, Ana Dobreva, Milka Mileva, Zlatina Kokanova-Nedialkova, Milena Gospodinova, Tsveta Angelova and Paraskev Nedialkov

Molecules 2025, 30(21), 4294; https://doi.org/10.3390/molecules30214294 - 5 Nov 2025

Viewed by 425

Abstract

Regulatory changes in the EU for safety purposes require strict control and high safety standards for essential oils obtained by steam distillation, as they are classified as chemical mixtures with potential toxic effects. Subcritical water extracts (SWEs) are considered safer. This study evaluated [...] Read more.

Regulatory changes in the EU for safety purposes require strict control and high safety standards for essential oils obtained by steam distillation, as they are classified as chemical mixtures with potential toxic effects. Subcritical water extracts (SWEs) are considered safer. This study evaluated the cytotoxicity and genotoxicity of SWEs from Rosa damascena Mill. and Rosa alba L. in three test systems at different hierarchical levels: higher plants (root meristems of Hordeum vulgare), somatic cells of Mus musculus ICR strain, and human lymphocytes in vitro. The chromatographic fingerprint of the extracts revealed the presence of key components such as flavonoids, phenolic acids, and glycoside derivatives, with species-dependent variations and concentrations. No significant cytotoxicity was detected in the concentration range of 6–20%. SWE from R. alba showed a higher level of safety at high doses. Genotoxicity tests showed a weak, dose-dependent induction of chromosomal aberrations and micronuclei in barley and lymphocytes (greater in R. alba), a lack of genotoxicity in mouse bone marrow, and a slight increase in micronuclei in mouse erythrocytes after exposure to R. alba extract. The results highlight the suitability of SWEs from R. damascena and R. alba for safe application in the medical, food, and cosmetic industries. Full article

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15 pages, 2406 KB

Open AccessArticle

Chemical and Microscopic Characterization of the Yellow Passion Fruit Peel

by Daniel Arrieta-Baez, Denise Larissa Díaz de la Torre, Héctor Francisco Mendoza-León, María de Jesús Perea-Flores and Mayra Beatriz Gómez-Patiño

Molecules 2025, 30(21), 4293; https://doi.org/10.3390/molecules30214293 - 5 Nov 2025

Viewed by 449

Abstract

Passion fruit (Passiflora edulis f. flavicarpa), commonly known as yellow passion fruit, is widely grown across tropical and subtropical regions worldwide, with Brazil as one of the top producers. Mexico also produces a significant amount of this variety, mainly for juices, [...] Read more.

Passion fruit (Passiflora edulis f. flavicarpa), commonly known as yellow passion fruit, is widely grown across tropical and subtropical regions worldwide, with Brazil as one of the top producers. Mexico also produces a significant amount of this variety, mainly for juices, jams, or flavoring in desserts. Since this fruit is highly perishable with a short shelf life, it needs to be consumed or used quickly. Although different preservation methods have been suggested, no structural analyses of the peel have been performed to improve these processes. This study aimed to analyze the structural and chemical properties of the peel’s cuticular matrix to better understand water loss. CPMAS ¹³C NMR analysis revealed a matrix containing polysaccharides, a small amount of aliphatics, and a notable group of aromatic signals that may indicate lignin presence. This was supported by alkaline hydrolysis, which achieved only 30% hydrolysis. Soluble compounds identified included hexoses, palmitic acid, stearic acid, and derivatives of ferulic and caffeic acids, the latter being parts of lignin monomers. MCL and SEM analyses showed features similar to cutans, including pores along the structures. The BET surface area measurement indicated that the insoluble cuticular material (ICM) has a significant specific surface area. The lignin in the yellow passion fruit peel gives the shell toughness, which, along with its pores, may contribute to dehydration and a short shelf life. Full article

(This article belongs to the Section Natural Products Chemistry)

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Molecules, Volume 30, Issue 21 (November-1 2025) – 174 articles

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