Molecules

17 pages, 2825 KiB

Open AccessArticle

Characterization of Key Aroma Compounds in Aged Chinese Nongxiangxing Baijiu Based on Sensory and Quantitative Analysis: Emphasis on the Contribution of Trace Compounds

by Peiqi Li, Yuting Ling, Xiaomei Shen, Chengcheng Liang, Youhong Tang, Shan Chen, Lisa Zhou Wang, Shuang Chen, Anjun Li and Yan Xu

Molecules 2025, 30(14), 2963; https://doi.org/10.3390/molecules30142963 (registering DOI) - 14 Jul 2025

Abstract

The characteristics and complexity of Baijiu are inseparable from the promotion of aging. While the impact of compounds such as alcohols, esters, and acids on the aroma of aged Baijiu has been extensively studied, the role of other trace compounds in the aging [...] Read more.

The characteristics and complexity of Baijiu are inseparable from the promotion of aging. While the impact of compounds such as alcohols, esters, and acids on the aroma of aged Baijiu has been extensively studied, the role of other trace compounds in the aging process should not be overlooked. To further investigate the relationship between volatile compounds and the aging of Nongxiangxing Baijiu, sensomics research methods were employed to analyze profiles of young and aged Nongxiangxing Baijiu. In this study, a total of 94 aroma compounds were analyzed in both young and aged Nongxiangxing Baijiu by GC-O/MS. Among these, 12 aroma compounds significantly associated with the aging process were identified by quantification and odor activity values (OAVs). Furthermore, the omission tests result showed that 4-methyl-2-methoxyphenol (2066.79 μg/L), benzaldehyde (3860.30 μg/L), β-phenylethanol (5638.85 μg/L), 3-(methylsulfanyl)propan-1-ol (8.82 μg/L), 3-(methylsulfanyl)propanal (15.91 μg/L), and linalool (17.36 μg/L) were key aroma compounds of aged Nongxiangxing Baijiu. This study reveals that trace compounds contribute to the distinct aroma complexity of aged Nongxiangxing Baijiu, providing a foundation to support aging process analysis. Full article

(This article belongs to the Special Issue Characterization and Instrumental Analysis of Aroma-Active Compounds in Fermented Food and Beverage, the Second Edition)

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20 pages, 4413 KiB

Open AccessArticle

Insights into Binding Mechanisms of Potential Inhibitors Targeting PCSK9 Protein via Molecular Dynamics Simulation and Free Energy Calculation

by Xingyu Wu, Xi Zhu, Min Fang, Fenghua Qi, Zhixiang Yin, John Z.H. Zhang, Shihua Luo, Tong Zhu and Ya Gao

Molecules 2025, 30(14), 2962; https://doi.org/10.3390/molecules30142962 (registering DOI) - 14 Jul 2025

Abstract

: The design of small-molecule inhibitors targeting proprotein convertase subtilisin/Kein type 9 (PCSK9) remains a forefront challenge in combating atherosclerosis. While various monoclonal antibodies have achieved clinical success, small-molecule inhibitors are hindered by the unique structural features of the PCSK9 binding interface. In [...] Read more.

: The design of small-molecule inhibitors targeting proprotein convertase subtilisin/Kein type 9 (PCSK9) remains a forefront challenge in combating atherosclerosis. While various monoclonal antibodies have achieved clinical success, small-molecule inhibitors are hindered by the unique structural features of the PCSK9 binding interface. In this study, a potential small-molecule inhibitor was identified through virtual screening, followed by molecular dynamics (MD) simulations to explore the binding mechanisms between the inhibitor and the PCSK9 protein. Binding free energies were calculated using molecular mechanics/Generalized Born surface area (MM/GBSA) with the interaction entropy (IE) method, and critical hot-spot residues were identified via alanine scanning analysis. Key residues, including ARG237, ILE369, ARG194 and PHE379, were revealed to form critical interactions with inhibitor and play dominant roles during the inhibitor’s binding. In addition, the polarization effect was shown to significantly influence PCSK9–ligand binding. The identified inhibitor exhibited highly similar binding patterns with two known active compounds, providing valuable insights for the rational design and optimization of small-molecule inhibitors targeting PCSK9. This work contributes to the development of more effective treatments for hyperlipidemia and associated cardiovascular diseases. Full article

17 pages, 2952 KiB

Open AccessArticle

Comparative Metabolomic Analysis of Three Medicinal Paphiopedilum Species Reveals Divergence in Antioxidant Capacity and Functional Compound Profiles

by Jinhan Sang, Yishan Yang, Kanghua Xian, Jiang Su, Jianmin Tang, Chuanming Fu, Fengluan Tang and Xiao Wei

Molecules 2025, 30(14), 2961; https://doi.org/10.3390/molecules30142961 - 14 Jul 2025

Abstract

This study explores the metabolite diversity and potential medicinal value of three Paphiopedilum species—P. dianthum, P. micranthum, and P. barbigerum—using widely targeted metabolomics via HPLC-MS/MS in conjunction with in vitro antioxidant assays. A total of 2201 metabolites were detected [...] Read more.

This study explores the metabolite diversity and potential medicinal value of three Paphiopedilum species—P. dianthum, P. micranthum, and P. barbigerum—using widely targeted metabolomics via HPLC-MS/MS in conjunction with in vitro antioxidant assays. A total of 2201 metabolites were detected across the three species, with flavonoids emerging as the dominant class (480 compounds, accounting for 21.8% of total metabolites). Comparative metabolomic analysis showed that flavonoid levels varied most prominently among the species. Notably, the metabolic profile of P. barbigerum (PB) diverged substantially from those of P. dianthum (PD) and P. micranthum (PM), which shared a higher degree of similarity with each other. Quantitative evaluation of antioxidant-associated metabolites revealed that PB exhibited the greatest enrichment in compounds with antioxidant potential, particularly flavonoids and phenolic acids, followed by PM and PD. These results were corroborated by antioxidant assays, in which PB demonstrated the highest free radical scavenging activity, with PM and PD displaying progressively lower effects. Differences in flavonoid content likely underpin these variations in antioxidant capacity. KEGG pathway enrichment analysis indicated that differentially expressed metabolites were primarily involved in flavonoid-associated biosynthetic routes, notably flavonoid biosynthesis (ko00941) and isoflavonoid biosynthesis (ko00943), with ko00941 being the most enriched. Within this pathway, PB showed eight significantly upregulated flavonoid metabolites, while PM and PD had seven and five, respectively. The observed differences may stem from species-specific expression of key biosynthetic enzymes such as flavonoid 3′-hydroxylase (F3′H) in PM and flavonoid 3′,5′-hydroxylase (F3′5′H) in PB, which influence both flavonoid composition and antioxidant potential. Full article

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14 pages, 3047 KiB

Open AccessArticle

Investigation on the Underlying Mechanisms of the Mechanical and Electrical Enhancement of Nano-SiO₂-Doped Epoxy Resins: A Molecular Simulation Study

by Kunqi Cui, Yang Wang, Wenchao Yan, Teng Cao, Yan Du, Kai Wu and Li Guo

Molecules 2025, 30(14), 2960; https://doi.org/10.3390/molecules30142960 (registering DOI) - 14 Jul 2025

Abstract

As a key insulating material in power equipment, epoxy resins (EP) are often limited in practical applications due to space charge accumulation and mechanical degradation. This study systematically investigates the effects of SiO₂ nanoparticle doping on the electrical and mechanical properties of [...] Read more.

As a key insulating material in power equipment, epoxy resins (EP) are often limited in practical applications due to space charge accumulation and mechanical degradation. This study systematically investigates the effects of SiO₂ nanoparticle doping on the electrical and mechanical properties of SiO₂/EP composites through molecular dynamics simulations and first-principles calculations. The results demonstrate that SiO₂ doping enhances the mechanical properties of EP, with notable improvements in Young’s modulus, bulk modulus, and shear modulus, while maintaining excellent thermal stability across different temperatures. Further investigations reveal that SiO₂ doping effectively modulates the interfacial charge behavior between EP and metals (Cu/Fe) by introducing shallow defect states and reconstructing interfacial dipoles. Density of states analysis indicates the formation of localized defect states at the interface in doped systems, which dominate the defect-assisted hopping mechanism for charge transport and suppress space charge accumulation. Potential distribution calculations show that doping reduces the average potential of EP (1 eV for Cu layer and 1.09 eV for Fe layer) while simultaneously influencing the potential distribution near the polymer–metal interface, thereby optimizing the interfacial charge injection barrier. Specifically, the hole barrier at the maximum valence band (VBM) after doping significantly increased, rising from the initial values of 0.448 eV (Cu interface) and 0.349 eV (Fe interface) to 104.02% and 209.46%, respectively. These findings provide a theoretical foundation for designing high-performance epoxy-based composites with both enhanced mechanical properties and controllable interfacial charge behavior. Full article

(This article belongs to the Special Issue Epoxy Resin Synthesis, Performance and Application Research: Second Edition)

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45 pages, 7099 KiB

Open AccessReview

A Comprehensive Review of Radical-Mediated Intramolecular Cyano-Group Migration

by Jia-Liang Zhu and Mei-Lin Chen

Molecules 2025, 30(14), 2959; https://doi.org/10.3390/molecules30142959 - 14 Jul 2025

Abstract

The radical-mediated intramolecular translocation of cyano groups has been recognized as a useful tool for the site-selective functionalization of organic molecules. The process is believed to proceed through the addition of an in situ-generated carbon-centered radical to the nitrile triple bond, followed by [...] Read more.

The radical-mediated intramolecular translocation of cyano groups has been recognized as a useful tool for the site-selective functionalization of organic molecules. The process is believed to proceed through the addition of an in situ-generated carbon-centered radical to the nitrile triple bond, followed by the β-scission of the resulting cyclic iminyl radical intermediate to relocate the cyano group and produce a more stable carbon radical for further elaboration. Beginning in the early 1960s and continuing for the next forty years, the research in this particular area has seen a surge of growth during the past two decades with advancements in radical chemistry and photocatalysis. The present article attempts to conduct a comprehensive review of existing studies on this topic by covering the literature from 1961 to 2025. The procedures developed for the purpose are grouped and discussed in four sections according to the strategies used to generate the initial carbon radicals, which include (i) hydrogen-atom transfer (HAT), (ii) radical addition to the π system, (iii) halogen-atom transfer (XAT), and (iv) the homolytic fission of a C-C single bond. In each section, a specific emphasis will be placed on reaction conditions, substrate scopes, and mechanisms. Full article

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

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27 pages, 6079 KiB

Open AccessArticle

Bioactive Cyclopeptide Alkaloids and Ceanothane Triterpenoids from Ziziphus mauritiana Roots: Antiplasmodial Activity, UHPLC-MS/MS Molecular Networking, ADMET Profiling, and Target Prediction

by Sylvestre Saidou Tsila, Mc Jesus Kinyok, Joseph Eric Mbasso Tameko, Bel Youssouf G. Mountessou, Kevine Johanne Jumeta Dongmo, Jean Koffi Garba, Noella Molisa Efange, Lawrence Ayong, Yannick Stéphane Fotsing Fongang, Jean Jules Kezetas Bankeu, Norbert Sewald and Bruno Ndjakou Lenta

Molecules 2025, 30(14), 2958; https://doi.org/10.3390/molecules30142958 - 14 Jul 2025

Abstract

Malaria continues to pose a significant global health burden, driving the search for novel antimalarial agents to address emerging drug resistance. This study evaluated the antiplasmodial potential of Ziziphus mauritiana Lam. (Rhamnaceae) roots through an integrated phytochemical and pharmacological approach. The ethanol extract, [...] Read more.

Malaria continues to pose a significant global health burden, driving the search for novel antimalarial agents to address emerging drug resistance. This study evaluated the antiplasmodial potential of Ziziphus mauritiana Lam. (Rhamnaceae) roots through an integrated phytochemical and pharmacological approach. The ethanol extract, along with its derived fractions, demonstrated potent in vitro activity against the chloroquine-sensitive Plasmodium falciparum strain 3D7 (Pf3D7), with the ethyl acetate-soluble (IC₅₀ = 11.35 µg/mL) and alkaloid-rich (IC₅₀ = 4.75 µg/mL) fractions showing particularly strong inhibition. UHPLC-DAD-ESI-QTOF-MS/MS-based molecular networking enabled the identification of thirty-two secondary metabolites (1–32), comprising twenty-five cyclopeptide alkaloids (CPAs), five of which had not yet been described (11, 20, 22, 23, 25), and seven known triterpenoids. Bioactivity-guided isolation yielded thirteen purified compounds (5, 6, 14, 26–30, 32–36), with betulinic acid (30; IC₅₀ = 19.0 µM) and zizyberenalic acid (32; IC₅₀ = 20.45 µM) exhibiting the most potent antiplasmodial effects. Computational ADMET analysis identified mauritine F (4), hemisine A (10), and nummularine R (21) as particularly promising lead compounds, demonstrating favourable pharmacokinetic properties, low toxicity profiles, and predicted activity against both family A G protein-coupled receptors and evolutionarily distinct Plasmodium protein kinases. Quantitative analysis revealed exceptionally high concentrations of key bioactive constituents, notably zizyberenalic acid (24.3 mg/g) in the root extracts. These findings provide robust scientific validation for the traditional use of Z. mauritiana in malaria treatment while identifying specific cyclopeptide alkaloids and triterpenoids as valuable scaffolds for antimalarial drug development. The study highlights the effectiveness of combining advanced metabolomics, bioassay-guided fractionation, and computational pharmacology in natural product-based drug discovery against resistant malaria strains. Full article

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30 pages, 2664 KiB

Open AccessArticle

Comparative Phytochemical Analysis and Antimicrobial Properties of Ethanol and Macerated Extracts from Aerial and Root Parts of Achillea nobilis

by Aiman Berdgaleeva, Zere Zhalimova, Akzharkyn Saginbazarova, Gulbanu Tulegenova, Dana Zharylkassynova, Aliya Bazargaliyeva, Zhaidargul Kuanbay, Svetlana Sakhanova, Akmaral Ramazanova, Akzhamal Bilkenova and Aigul Sartayeva

Molecules 2025, 30(14), 2957; https://doi.org/10.3390/molecules30142957 - 14 Jul 2025

Abstract

Achillea nobilis represents a species of considerable medicinal importance within the Asteraceae family, historically employed in Central Asia and various Eurasian territories for the management of inflammatory, microbial, and gastrointestinal ailments. Notwithstanding its extensive ethnopharmacological significance, the phytochemical profile and pharmacological attributes of [...] Read more.

Achillea nobilis represents a species of considerable medicinal importance within the Asteraceae family, historically employed in Central Asia and various Eurasian territories for the management of inflammatory, microbial, and gastrointestinal ailments. Notwithstanding its extensive ethnopharmacological significance, the phytochemical profile and pharmacological attributes of its various anatomical components have not been comprehensively investigated. This research endeavor sought to delineate the phytochemical constituents and evaluate the antimicrobial efficacy of ethanol extracts derived from both the aerial and root segments of A. nobilis. Qualitative phytochemical analysis and GC–MS characterization unveiled a diverse array of bioactive compounds, encompassing flavonoids, phenolic compounds, organic acids, lactones, alcohols, and heterocyclic derivatives. In particular, the aerial oil extract exhibited the presence of terpenoids, fatty acids and their esters, sterols, hydrocarbons, and minor organosilicon and cyclobutanone derivatives, with notable compounds such as linoleic acid (8.08%), 6-tetradecyne (14.99%), isopropyl linoleate (14.64%), and E,Z-1,3,12-nonadecatriene (22.25%). In vitro antimicrobial activity was assessed against eight clinically relevant microbial strains employing the broth microdilution technique. The aerial ethanol extract exhibited pronounced antimicrobial properties, particularly against MRSA and C. albicans, with MICs ranging from 0.5 to 2 mg/mL, whereas the root ethanol extract displayed MICs of 1 to 3 mg/mL. Additionally, the aerial oil extract showed moderate inhibitory activity, with MIC values ranging from 1.5 to 3 mg/mL, demonstrating effectiveness particularly against C. albicans, C. neoformans, and MRSA. These findings underscore the therapeutic potential of A. nobilis, particularly its aerial component, as a viable natural source of antimicrobial agents. Full article

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

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19 pages, 1415 KiB

Open AccessArticle

Essential Oil from the Aerial Parts of Artemisia serotina Bunge (Winter Wormwood) Growing in Kazakhstan—Phytochemical Profile and Bioactivity

by Arshyn Kadyrbay, Liliya N. Ibragimova, Magdalena Iwan, Agnieszka Ludwiczuk, Anna Biernasiuk, Zuriyadda B. Sakipova, Łukasz Świątek, Kinga Salwa, Agnieszka Korga-Plewko, Karlygash A. Zhaparkulova, Tolkyn S. Bekezhanova, Aleksandra Józefczyk, Jolanta Szymańska and Anna Malm

Molecules 2025, 30(14), 2956; https://doi.org/10.3390/molecules30142956 - 14 Jul 2025

Abstract

Artemisia serotina Bunge represents one of the endemic Artemisia L. species in flora of Central Asia. There is scant information on the phytochemistry and biological activity of this species. The aim of the present study was to analyze the chemical composition of essential [...] Read more.

Artemisia serotina Bunge represents one of the endemic Artemisia L. species in flora of Central Asia. There is scant information on the phytochemistry and biological activity of this species. The aim of the present study was to analyze the chemical composition of essential oil from A. serotina (ASEO) growing in south Kazakhstan, together with the determination of its biological activity. ASEO isolation was carried out by hydrodistillation according to the State Pharmacopoeia of the Republic of Kazakhstan. Analysis of GC/MS data revealed that the most characteristic components of ASEO were irregular monoterpenes from three families: santolinane, artemisane, and lavandulane. The major compound was santolina alcohol (34.6%). Antimicrobial activity was studied against the reference bacterial and fungal strains using the recommended methods, allowing for an estimation of MIC (minimum inhibitory concentration). ASEO was most effective against Candida albicans (MIC = 2 mg/mL), exerting fungicidal activity. Thw MIC for bacterial species was higher, i.e., 4–16 mg/mL. Antiviral activity was tested against Coxsackievirus B3 (CVB3) and Human Herpesvirus type 1 (HHV-1) propagated in VERO cells. No antiviral effect against either virus was found at an ASEO concentration of 0.25 mg/mL, but a noticeable decrease in the intensity of HHV-1-related cytopathic effects was observed. Anticancer activity studies included several cancer cell lines. Cytotoxicity, cell cycle, thiol levels, and cell vitality were analyzed. Among the cancer cell lines tested, the breast cancer T47-D cell line exhibited the highest sensitivity to ASEO (IC₅₀ = 40.81 ± 4.21 µg/mL at 24 h; IC₅₀ = 33.17 ± 2.11 µg/mL at 48 h). The anticancer effect was suggested to be mainly due to the induction of cytostatic effects, accompanied by a disturbance of the intracellular redox balance. The obtained data provide novel information on the unique chemical composition of ASEO from south Kazakhstan, representing a new chemotype. Its bioactivity, including promising antifungal and anticancer properties, was demonstrated for the first time. Full article

(This article belongs to the Special Issue Chemical Analyses and Applications of Essential Oils)

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20 pages, 2020 KiB

Open AccessArticle

Diastereoselective Synthesis and Biological Evaluation of Spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones as Novel Antimicrobial and Antioxidant Agents

by Alena S. Karandeeva, Natalia A. Bogdanova, Mariya V. Kabanova, Sergey I. Filimonov, Zhanna V. Chirkova, Anna A. Romanycheva, Valeria A. Panova, Anton A. Shetnev, Nurila A. Togyzbayeva, Saken A. Kanzhar, Nurbol O. Appazov and Kyrill Yu. Suponitsky

Molecules 2025, 30(14), 2954; https://doi.org/10.3390/molecules30142954 - 14 Jul 2025

Abstract

This study reports an improved diastereoselective synthesis of substituted spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones via the acid-catalyzed condensation of 6-styryl-4-aryldihydropyrimidin-2-ones with resorcinol, 2-methylresorcinol, and pyrogallol. The optimized method allows for the isolation of diastereomerically pure products, with stereoselectivity controlled by varying acid catalysts (e.g., methanesulfonic [...] Read more.

This study reports an improved diastereoselective synthesis of substituted spiro[chromane-2,4′-pyrimidin]-2′(3′H)-ones via the acid-catalyzed condensation of 6-styryl-4-aryldihydropyrimidin-2-ones with resorcinol, 2-methylresorcinol, and pyrogallol. The optimized method allows for the isolation of diastereomerically pure products, with stereoselectivity controlled by varying acid catalysts (e.g., methanesulfonic acid vs. toluenesulfonic acid) and solvent conditions. The synthesized compounds were evaluated for antimicrobial and antioxidant activities. Notably, the (2S*,4R*,6′R*)-diastereomers exhibited significant antibacterial activity against both Gram-positive and Gram-negative bacterial strains with minimal inhibition concentration down to 2 µg/mL, while derivatives containing vicinal bisphenol moieties demonstrated potent antioxidant activity, with IC₅₀ values (12.5 µg/mL) comparable to ascorbic acid. Pharmacokinetic analysis of selected hit compounds revealed favorable drug-like properties, including high gastrointestinal absorption and blood-brain barrier permeability. These findings highlight the potential of spirochromane-pyrimidine hybrids as promising candidates for further development in the treatment of infectious diseases and oxidative stress-related pathologies. Full article

(This article belongs to the Special Issue Design, Synthesis and Applications of Bioactive Compounds)

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11 pages, 581 KiB

Open AccessCommunication

Rapid and One-Pot Synthesis of Aryl Ynamides from Aryl Alkynyl Acids by Metal-Free C-N Cleavage of Tertiary Amines

by Yong Liu, Xiaoyong Liu, Hongwei Li and Shengmei Guo

Molecules 2025, 30(14), 2955; https://doi.org/10.3390/molecules30142955 - 13 Jul 2025

Abstract

Herein a rapid, metal-free, and highly efficient synthesis of aryl ynamides from aryl alkynyl acids has been described. This approach, utilizing tertiary amines as an amino source via metal-free C-N cleavage, enabled the construction of a diverse range of aryl ynamides with medium [...] Read more.

Herein a rapid, metal-free, and highly efficient synthesis of aryl ynamides from aryl alkynyl acids has been described. This approach, utilizing tertiary amines as an amino source via metal-free C-N cleavage, enabled the construction of a diverse range of aryl ynamides with medium to excellent yields (33 examples, up to 95% yield). This reaction exhibits significantly enhanced efficiency compared to the conventional stepwise approach involving aryl alkynyl acids and secondary amines. It can be successfully scaled up, providing a practical and environmentally benign strategy for alkynamide synthesis. Full article

(This article belongs to the Special Issue Advances in Alkyne Chemistry)

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14 pages, 2472 KiB

Open AccessArticle

Role of Substitution Patterns in Four Regioisomeric Tetraphenylethylene–Thiophene Derivatives

by Shuai Hou, Hanxiao Tian, Ruiyao Li, Zishuai Huang, Dongyuan Zhu, Fan Xiao, Yunmeng Zhao and Jingjing Xu

Molecules 2025, 30(14), 2953; https://doi.org/10.3390/molecules30142953 - 13 Jul 2025

Abstract

Tetraphenylethylene (TPE)–thiophene compounds are promising candidates for stimuli-responsive luminescent materials, yet systematic investigations into the influence of substitution patterns on their photophysical properties remain limited. Herein, four regioisomeric TPE–thiophene derivatives have been synthesized by systematically varying the number and positions of TPE substituents [...] Read more.

Tetraphenylethylene (TPE)–thiophene compounds are promising candidates for stimuli-responsive luminescent materials, yet systematic investigations into the influence of substitution patterns on their photophysical properties remain limited. Herein, four regioisomeric TPE–thiophene derivatives have been synthesized by systematically varying the number and positions of TPE substituents on the thiophene core. A comprehensive spectroscopic characterization reveals that substitution patterns critically modulate the photoluminescence quantum yields (PLQYs). The ortho-monosubstituted isomer exhibits the highest PLQY (52.86% in solid state) compared with the meta-monosubstituted isomer (13.87% in solid state). Interestingly, thiophenes with two or three TPEs substituted at positions 2,5 or 2,3,5 have lower PLQYs, which is rare due to the common understanding that increasing the number of AIE parts should increase the PLQY. Further single-crystal structure analyses show that the key factor impacting the PLQY is the dihedral angles of the TPE subunit, which determines the degree of intramolecular twisting. This work establishes regiochemistry as a powerful design lever for tuning TPE–thiophene photophysics, offering underlying principles for the design of TPE-based thiophene molecules with high photoluminescent performance in the future. Full article

(This article belongs to the Special Issue Photochemistry in Asia)

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16 pages, 2096 KiB

Open AccessArticle

Environmental Antidepressants Disrupt Metabolic Pathways in Spirostomum ambiguum and Daphnia magna: Insights from LC-MS-Based Metabolomics

by Artur Jędreas, Sylwia Michorowska, Agata Drobniewska and Joanna Giebułtowicz

Molecules 2025, 30(14), 2952; https://doi.org/10.3390/molecules30142952 - 13 Jul 2025

Abstract

Pharmaceuticals such as fluoxetine, paroxetine, sertraline, and mianserin occur in aquatic environments at low yet persistent concentrations due to their incomplete removal in wastewater treatment plants. Although frequently detected, these neuroactive compounds remain underrepresented in ecotoxicological assessments. Given their pharmacodynamic potency, environmentally relevant [...] Read more.

Pharmaceuticals such as fluoxetine, paroxetine, sertraline, and mianserin occur in aquatic environments at low yet persistent concentrations due to their incomplete removal in wastewater treatment plants. Although frequently detected, these neuroactive compounds remain underrepresented in ecotoxicological assessments. Given their pharmacodynamic potency, environmentally relevant concentrations may induce sublethal effects in non-target organisms. In this study, we applied untargeted LC-MS-based metabolomics to investigate the sublethal effects of four widely used antidepressants—paroxetine, sertraline, fluoxetine (SSRIs), and mianserin (TeCA)—on two ecologically relevant freshwater invertebrates: S. ambiguum and D. magna. Organisms were individually exposed to each compound for 48 h at a concentration of 100 µg/L and 25 µg/L, respectively. Untargeted metabolomics captured the sublethal biochemical effects of these antidepressants, revealing both shared disruptions—e.g., in glycerophospholipid metabolism and cysteine and methionine metabolism—and species-specific responses. More pronounced pathway changes observed in D. magna suggest interspecies differences in metabolic capacity or xenobiotic processing mechanisms between taxa. Among the four antidepressants tested, sertraline in D. magna and fluoxetine in S. ambiguum exerted the most extensive metabolomic perturbations, as evidenced by the highest number and pathway impact scores. In D. magna, fluoxetine and mianserin produced similar metabolic profiles, largely overlapping with those of sertraline, whereas paroxetine affected only a single pathway, indicating minimal impact. In S. ambiguum, paroxetine and mianserin elicited comparable responses, also overlapping with those of fluoxetine, while sertraline triggered the fewest changes. These results suggest both compound-specific effects and a conserved metabolic response pattern among the antidepressants used. They also underscore the considerable potential of metabolomics as a powerful and sensitive tool for ecotoxicological risk assessments, particularly when applied across multiple model organisms to capture interspecies variations. However, further research is essential to identify which specific pathway disruptions are most predictive of adverse effects on organismal health. Full article

(This article belongs to the Special Issue Advances in the Mass Spectrometry of Chemical and Biological Samples)

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25 pages, 1491 KiB

Open AccessReview

Toxicological Risk Assessment of Coffee Oil (Coffee Seed Oil and Spent Coffee Grounds Oil) as a Novel Food with Focus on Cafestol

by Bernadette Maier, Heike Franke, Steffen Schwarz and Dirk W. Lachenmeier

Molecules 2025, 30(14), 2951; https://doi.org/10.3390/molecules30142951 - 12 Jul 2025

Abstract

Coffee oil derived from spent coffee grounds of Coffea arabica is considered a novel food in the European Union (EU), requiring pre-market approval supported by comprehensive toxicological data. The effects of coffee oil on human health, particularly on blood parameters and liver enzymes, [...] Read more.

Coffee oil derived from spent coffee grounds of Coffea arabica is considered a novel food in the European Union (EU), requiring pre-market approval supported by comprehensive toxicological data. The effects of coffee oil on human health, particularly on blood parameters and liver enzymes, have been investigated in several studies. This review article summarizes the available toxicological literature on coffee oil, including its bioactive diterpenes cafestol and kahweol, which are known for their potential health effects. Considering the different modes of action of these two diterpenes, moderate consumption of coffee oil may be considered safe for healthy adults. Based on the changes in serum values in humans, this review provides initial estimations of LOAEL, NOAEL, and ADI for these diterpenes. The findings suggest that an intake of 225 mg of coffee oil per day might be considered safe assuming that coffee oil contains about 0.4% diterpenes. In summary, the assessment based on the published data indicates that (i) the consumption of coffee oil contained in any type of prepared coffee appears to be safe because the homeostasis of lipid levels in the blood is not significantly affected, and (ii) a low consumption of coffee oil as such might be acceptable but would require a refined risk assessment considering the exposure levels of the intended food product, which must be provided for novel food approval procedures. Full article

(This article belongs to the Special Issue Food Sustainability: Promising By-Products for Valorization—2nd Edition)

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21 pages, 1407 KiB

Open AccessArticle

Trends in Colistin Resistance and Multidrug-Resistant Phenotypes Among Gram-Negative Bacilli: A Retrospective Analysis

by Madalina Alexandra Vlad, Maria Dan, Andreea Nicoleta Catana, Sebastian Dumitriu and Cristina Gabriela Tuchilus

Molecules 2025, 30(14), 2950; https://doi.org/10.3390/molecules30142950 - 12 Jul 2025

Abstract

Colistin has re-emerged as a last-resort antibiotic for treating infections caused by multidrug-resistant (MDR) Gram-negative bacilli (GNB). However, increasing resistance threatens its efficacy. This study aimed to evaluate colistin resistance trends among clinical isolates of Gram-negative bacilli isolated over a five-year period at [...] Read more.

Colistin has re-emerged as a last-resort antibiotic for treating infections caused by multidrug-resistant (MDR) Gram-negative bacilli (GNB). However, increasing resistance threatens its efficacy. This study aimed to evaluate colistin resistance trends among clinical isolates of Gram-negative bacilli isolated over a five-year period at a large Emergency Hospital in North-Eastern Romania. A total of 23,143 GNB strains were isolated during the study period, including 14,531 Enterobacterales and 8294 non-fermenting Gram-negative bacilli. The percentage of colistin-resistant strains among those analyzed was 3.98%. Species-specific analysis focused on Klebsiella spp., Escherichia coli, Enterobacter spp., Citrobacter spp., Pseudomonas spp., and Acinetobacter spp. Klebsiella spp. exhibited the highest prevalence of colistin resistance, accounting for over 80% of all colistin-resistant strains, with annual resistance rates fluctuating between 12.97% and 21.64%. Colistin resistance among E. coli was low (0.18–1.25%). Citrobacter spp. showed no resistance in the last three years of the study, and Enterobacter spp. maintained relatively stable resistance (3–5%). Resistance in Pseudomonas spp. remained below 1%, while Acinetobacter spp. showed a resistance rate of 5.43%. Several distinct resistance phenotypes were identified among Klebsiella spp., Pseudomonas spp., and Acinetobacter spp. strains, reflecting both endemic and sporadic circulation patterns. The study highlights a persistent presence of colistin resistance, especially in Klebsiella spp., underlining the importance of ongoing surveillance. Despite low resistance in other species, the emergence of resistant strains underscores the need for robust antimicrobial stewardship and infection control policies. Full article

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23 pages, 1744 KiB

Open AccessArticle

Rhododendron Microshoot Culture as a Source of Phenolic Antioxidants for Biomedicine

by Vera M. Katanskaya, Olga G. Vasilyeva, Elena P. Khramova, Natalia N. Sazhina, Evgenia A. Goncharuk, Tatiana L. Nechaeva, Maria Y. Zubova, Maria A. Aksenova, Petr V. Lapshin and Natalia V. Zagoskina

Molecules 2025, 30(14), 2949; https://doi.org/10.3390/molecules30142949 - 12 Jul 2025

Abstract

The search for alternative sources of biologically active compounds of plant origin, including phenolic compounds (PCs), is of great importance in medicine and pharmacology. Morphophysiological characteristics, photosynthetic pigments, PCs content, phenolic profile, as well as antioxidant (AOA) and antiradical activity (ARA), were studied [...] Read more.

The search for alternative sources of biologically active compounds of plant origin, including phenolic compounds (PCs), is of great importance in medicine and pharmacology. Morphophysiological characteristics, photosynthetic pigments, PCs content, phenolic profile, as well as antioxidant (AOA) and antiradical activity (ARA), were studied for in vitro rhododendrons’ microshoots (R. smirnowii, R. PJM Elite, R. japonicum). The microshoots of R. PJM Elite had the highest photosynthetic pigments content (chlorophylls a and b), exceeding that of R. smirnowii and R. japonicum, it was 33% and 42%, respectively. The total phenolic content increased in the row R. PJM Elite < R. smirnowii < R. japonicum. Twelve to twenty phenolic compounds were identified in ethanol extracts of rhododendron microshoots, using high-performance liquid chromatography. Quercetin, kaempferol, and myricetin dominated in the phenolic complex of R. japonicum and R. smirnowii, whereas in R. PJM Elite, they were taxifolin and (−)-epicatechin. The AOA and ARA evaluation in DPPH-radical system and the model of initiated liposomes oxidation allowed to determine the highest activity in both systems for R. japonicum extracts, which was not typical for the other two species extracts. A high correlation was found between AOA extracts and the flavonoid content in them. The results obtained indicate the prospects of using R. japonicum and R. PJM Elite microshoots as an alternative source of flavonols and flavanols, accordingly. Full article

(This article belongs to the Special Issue Bioactive Natural Products and Derivatives)

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12 pages, 1972 KiB

Open AccessArticle

Design and Biological Evaluation of hBest1-Containing Bilayer Nanostructures

by Pavel Bakardzhiev, Teodora Koleva, Kirilka Mladenova, Pavel Videv, Veselina Moskova-Doumanova, Aleksander Forys, Sławomira Pusz, Tonya Andreeva, Svetla Petrova, Stanislav Rangelov and Jordan Doumanov

Molecules 2025, 30(14), 2948; https://doi.org/10.3390/molecules30142948 - 12 Jul 2025

Abstract

Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the BEST1 gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated [...] Read more.

Bestrophinopathies are a group of inherited retinal diseases caused by mutations in the BEST1 gene. The protein encoded by this gene, bestorphin-1 (hBest1), is a calcium-dependent transmembrane channel localized on the basolateral membrane of retinal pigment epithelial (RPE) cells. We have already demonstrated the surface behavior and organization of recombinant hBest1 and its interactions with membrane lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), sphingomyelin (SM) and cholesterol (Chol) in models of biological membranes, which affect the hBest1 structure–function relationship. The main aim of our current investigation is to integrate pure hBest1 protein into lipid bilayer nanostructures. We synthesized and characterized various hBest1-containing nanostructures based on 1,2-Dipalmitoylphosphatidylcholine (DPPC), SM, glycerol monooleate (GMO) and Chol in different ratios and determined their cytotoxicity and incorporation into cell membranes and/or cells by immunofluorescence staining. Our results show that these newly designed nanoparticles are not cytotoxic and that their incorporation into MDCK II cell membranes (used as a model system) may provide a mechanism that could be applied to RPE cells expressing mutated hBest1 in order to restore their ion transport functions, affected by mutated and malfunctioning hBest1 molecules. Full article

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

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14 pages, 3013 KiB

Open AccessArticle

Observation of a Relationship Between Orbital-Specific Molecular Similarity Index and Toxicity of Methylcarbamate Derivatives

by Sihan Long, Yuuki Onitsuka, Soichiro Nagao and Masahiko Takahashi

Molecules 2025, 30(14), 2947; https://doi.org/10.3390/molecules30142947 - 12 Jul 2025

Abstract

We report a computational investigation on the reachability of the molecular similarity index (MSI) approach for predicting the relative drug strength of methylcarbamate derivatives. Traditional MSI values have been obtained by calculating the overlap integral of total electron momentum densities between one molecule [...] Read more.

We report a computational investigation on the reachability of the molecular similarity index (MSI) approach for predicting the relative drug strength of methylcarbamate derivatives. Traditional MSI values have been obtained by calculating the overlap integral of total electron momentum densities between one molecule and another. Furthermore, we have proposed and tested orbital-specific MSI (OS-MSI) values, obtained by doing the same but with electron momentum densities of a selected molecular orbital (MO) such as the highest occupied MO (HOMO) and the lowest unoccupied MO (LUMO). In the calculations, a Boltzmann-weighted electron momentum density estimated by a theoretical probability distribution of rotamers was used, while the solvation effect was considered using the polarizable continuum model. It is shown that the traditional MSI values as well as the OS-MSI values for the HOMO do not have any correlation with experimental relative toxicity of the methylcarbamate derivatives. In contrast, it has been observed and found that the OS-MSI values for the LUMO exhibit a noticeable correlation with the experimental data. The reason behind this observation is discussed in relation to the drug reaction mechanism of the methylcarbamate derivatives. Full article

(This article belongs to the Special Issue Advances in Chemical Research on Biomarkers, Drugs of Abuse, Medicines, and Computational Approaches)

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13 pages, 2546 KiB

Open AccessArticle

Interference Structures in the High-Order Above-Threshold Ionization Spectra of Polyatomic Molecules in a Bicircular Laser Field

by Elvedin Hasović, Azra Gazibegović-Busuladžić and Mustafa Busuladžić

Molecules 2025, 30(14), 2946; https://doi.org/10.3390/molecules30142946 - 11 Jul 2025

Abstract

We analyze the high-order above-threshold ionization (HATI) process of a small polyatomic molecule with C₃ symmetry, which is induced by a bicircular strong laser field. This field consists of two coplanar, counter-rotating, circularly polarized components with frequencies

r ω

and

s ω

[...] Read more.

We analyze the high-order above-threshold ionization (HATI) process of a small polyatomic molecule with C₃ symmetry, which is induced by a bicircular strong laser field. This field consists of two coplanar, counter-rotating, circularly polarized components with frequencies

r ω

and

s ω

where r and s are integers. In our study, we use an improved molecular strong-field approximation to obtain electron energy-angle-resolved and momentum spectra of the BF₃ molecule. We analyze the contributions of individual atoms as well as the impact of molecular symmetries on these spectra. We find that these spectra are significantly affected by the characteristics of the molecule and the laser-field parameters. Furthermore, we observe pronounced interference minima in the HATI spectra. We demonstrate that these minima result from the destructive interference of rescattered wave packets from different atomic centers, and we determine the conditions under which they occur, including two-, three-, and four-center interference. Full article

(This article belongs to the Special Issue Exclusive Feature Papers on Molecular Structure, 2nd Edition)

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26 pages, 5873 KiB

Open AccessArticle

Pyridine–Quinoline and Biquinoline-Based Ruthenium p-Cymene Complexes as Efficient Catalysts for Transfer Hydrogenation Studies: Synthesis and Structural Characterization

by Nikolaos Zacharopoulos, Gregor Schnakenburg, Eleni I. Panagopoulou, Nikolaos S. Thomaidis and Athanassios I. Philippopoulos

Molecules 2025, 30(14), 2945; https://doi.org/10.3390/molecules30142945 - 11 Jul 2025

Abstract

Searching for new and efficient transfer hydrogenation catalysts, a series of new organometallic ruthenium(II)-arene complexes of the formulae [Ru(η⁶-p-cymene)(L)Cl][PF₆] (1–8) and [Ru(η⁶-p-cymene)(L)Cl][Ru(η⁶-p-cymene)Cl₃] ( [...] Read more.

Searching for new and efficient transfer hydrogenation catalysts, a series of new organometallic ruthenium(II)-arene complexes of the formulae [Ru(η⁶-p-cymene)(L)Cl][PF₆] (1–8) and [Ru(η⁶-p-cymene)(L)Cl][Ru(η⁶-p-cymene)Cl₃] (9–11) were synthesized and fully characterized. These were prepared from the reaction of pyridine–quinoline and biquinoline-based ligands (L) with [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂, in 1:2 and 1:1, metal (M) to ligand (L) molar ratios. Characterization includes a combination of spectroscopic methods (FT-IR, UV-Vis, multi nuclear NMR), elemental analysis and single-crystal X-ray crystallography. The pyridine–quinoline organic entities encountered, were prepared in high yield either via the thermal decarboxylation of the carboxylic acid congeners, namely 2,2′-pyridyl-quinoline-4-carboxylic acid (pqca), 8-methyl-2,2′-pyridyl-quinoline-4-carboxylic acid (8-Mepqca), 6′-methyl-2,2′-pyridyl-quinoline-4-carboxylic acid (6′-Mepqca) and 8,6′-dimethyl-2,2′-pyridyl-quinoline-4-carboxylic acid (8,6′-Me₂pqca), affording the desired ligands pq, 8-Mepq, 6′-Mepq and 8,6′-Me₂pq, or by the classical Friedländer condensation, to yield 4,6′-dimethyl-2,2′-pyridyl-quinoline (4,6′-Me₂pq) and 4-methyl-2,2′-pyridyl-quinoline (4-Mepq), respectively. The solid-state structures of complexes 1–4, 6, 8 and 9 were determined showing a distorted octahedral coordination geometry. The unit cell of 3 contains two independent molecules (Ru-3), (Ru′-3) in a 1:1 ratio, due to a slight rotation of the arene ring. All complexes catalyze the transfer hydrogenation of acetophenone, using 2-propanol as a hydrogen donor in the presence of KOiPr. Among them, complexes 1 and 5 bearing methyl groups at the 8 and 4 position of the quinoline moiety, convert acetophenone to 1-phenylethanol quantitatively, within approximately 10 min with final TOFs of 1600 h⁻¹. The catalytic performance of complexes 1–11, towards the transfer hydrogenation of p-substituted acetophenone derivatives and benzophenone, ranges from moderate to excellent. An inner-sphere mechanism has been suggested based on the detection of ruthenium(II) hydride species. Full article

(This article belongs to the Special Issue Advances in Coordination Chemistry, 3rd Edition)

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