Molecules

24 pages, 1117 KB

Open AccessReview

Environmental Behavior, Toxicological Pathways, and Risk Assessment of Polycyclic Aromatic Hydrocarbons (PAHs): From Molecular Structure to Human Health

by Joanna Harasym and Edyta Nizio

Molecules 2026, 31(13), 2211; https://doi.org/10.3390/molecules31132211 (registering DOI) - 23 Jun 2026

Abstract

Polycyclic aromatic hydrocarbons (PAHs) represent a major class of ubiquitous environmental pollutants, posing significant risks to ecosystems and human health due to their persistence, toxicity, and potential for bioaccumulation. This review provides a comprehensive synthesis of current scientific knowledge on PAHs, integrating insights [...] Read more.

Polycyclic aromatic hydrocarbons (PAHs) represent a major class of ubiquitous environmental pollutants, posing significant risks to ecosystems and human health due to their persistence, toxicity, and potential for bioaccumulation. This review provides a comprehensive synthesis of current scientific knowledge on PAHs, integrating insights from chemical kinetics, environmental fate, and toxicological mechanisms. The fundamental structural chemistry of PAHs and its direct influence on their physicochemical properties and environmental properties are discussed. The major anthropogenic and natural sources of PAHs are detailed, alongside the chemical kinetics behind their formation during incomplete combustion and their transformation in environmental media. Unlike previous reviews that address PAH sources, remediation, or health effects as separate topics, this review uniquely traces the mechanistic continuum from molecular formation kinetics through physicochemical partitioning and environmental transport to toxicological endpoints, providing a causally linked framework for understanding how structural properties ultimately determine biological outcomes. A central focus is placed on the environmental fate and transport of PAHs across atmospheric, aquatic, and terrestrial compartments, highlighting processes such as gas–particle partitioning, sediment accumulation, and long-range transport. The review further elucidates the complex toxicological pathways of PAHs, including metabolic activation to reactive intermediates, DNA adduct formation, oxidative stress, and their roles in carcinogenesis and other systemic health effects. The analysis reveals strong scientific consensus on the carcinogenic mechanism of parent PAHs via CYP450-mediated metabolic activation to diol-epoxide intermediates while identifying critical areas of uncertainty: the current regulatory framework based on 16 priority PAHs underestimates total carcinogenic risk by a factor of 2–5, mixture toxicology remains poorly characterized, and dose–response relationships for non-cancer endpoints (cardiovascular, neurodevelopmental, immunotoxic) lack the quantitative data needed for robust risk assessment. Finally, human exposure pathways and health risk characterization approaches are discussed, highlighting the need for cumulative, mixture-based assessment frameworks. Full article

(This article belongs to the Special Issue Featured Reviews in Organic Chemistry 2025–2026)

19 pages, 901 KB

Open AccessArticle

Experimental Development of an Enriched Tomato Juice with Bioactive Extracts from Unripe Green Tomatoes

by Gerardina Galdi, Emanuel Mauro, Mariateresa Rapacciuolo, Maria Ilenia Sessa, Giusi Varasano and Luca Sandei

Molecules 2026, 31(13), 2210; https://doi.org/10.3390/molecules31132210 (registering DOI) - 23 Jun 2026

Abstract

The growing prevalence of chronic degenerative diseases has increased interest in nutritional strategies based on natural bioactive compounds such as polyphenols. This study aimed to develop a polyphenol-fortified tomato juice using extracts from unripe green tomatoes and to evaluate its physicochemical, antioxidant, sensory, [...] Read more.

The growing prevalence of chronic degenerative diseases has increased interest in nutritional strategies based on natural bioactive compounds such as polyphenols. This study aimed to develop a polyphenol-fortified tomato juice using extracts from unripe green tomatoes and to evaluate its physicochemical, antioxidant, sensory, and storage properties. Polyphenolic extracts obtained from tomato by-products were characterized using spectrophotometric and HPLC analyses and incorporated into tomato juice, which was then pasteurized and stored for six months. Total polyphenol content increased from 40.97 to 82.45 mg GAE/100 g, decreasing to 71.44 mg after storage; HPLC confirmed higher levels of key phenolic compounds in fortified juice. DPPH antioxidant activity increased in fortified juice compared to control, since pasteurization had limited effects but decreased after storage, with a moderate reduction in bioactivity. Colorimetric and sensory analyses showed changes in color, aroma, and sweetness after storage, potentially affecting consumer acceptance, although overall composition remained largely stable. Overall, results demonstrate the feasibility of producing a polyphenol-enriched tomato juice from agro-industrial by-products with improved antioxidant properties and acceptable technological stability. These findings support the valorization of tomato processing waste and suggest potential applications in functional food development, human health promotion, and the sustainability of agri-food systems’ overall approach. Full article

(This article belongs to the Special Issue Bioactive Compounds in Food and Cosmetics Processing)

18 pages, 497 KB

Open AccessPerspective

Capillary Electrophoresis and Atomic Absorption Spectrometry—A Rare yet Valuable Liaison, also from a Pharmaceutical Perspective

by Daniel Baecker

Molecules 2026, 31(13), 2209; https://doi.org/10.3390/molecules31132209 (registering DOI) - 23 Jun 2026

Abstract

Both capillary electrophoresis (CE) and atomic absorption spectrometry (AAS) are analytical techniques of high performance given their efficient separation and their sensitive detection, respectively. They are predominantly adduced as standalone techniques, also widely used in pharmaceutical sciences. However, with CE, only indirect detection [...] Read more.

Both capillary electrophoresis (CE) and atomic absorption spectrometry (AAS) are analytical techniques of high performance given their efficient separation and their sensitive detection, respectively. They are predominantly adduced as standalone techniques, also widely used in pharmaceutical sciences. However, with CE, only indirect detection or direct detection of metal complexes using additives to the background electrolyte is feasible, while AAS is not capable of separating different compounds of the same metal. Combining these two techniques would compensate for these limitations by complementing each other. Surprisingly, the hyphenation of CE and AAS represents rather a rare liaison. Therefore, the aim of the current perspective was to shed light on examples where the hybrid technique of CE-AAS was successfully applied thus far. In this context, particular attention was paid to the extent to which the studies and the analytes under investigation might also be relevant from a pharmaceutical point of view. It revealed that the combination of CE and AAS has great potential for research in pharmaceutical sciences. With respect to online hyphenation, this would be even better if interfaces were more widely available. Nevertheless, this overview demonstrates that CE-AAS is a valuable combination. Its potential just needs to be exploited. Full article

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

24 pages, 1332 KB

Open AccessReview

Natural Source, Chemical Classification and Medicinal Application of the Stilbene-Type Compounds: A Review of Structural Modification Around Stilbene Scaffold

by Shengying Lin, Roy Wai-Lun Tang, Ran Duan, Ka Wing Leung, Tina Ting-Xia Dong and Karl Wah-Keung Tsim

Molecules 2026, 31(13), 2208; https://doi.org/10.3390/molecules31132208 (registering DOI) - 23 Jun 2026

Abstract

Stilbene-type compounds are vital plant secondary metabolites that are classified under polyphenols and generally exhibit significant biological activities, as well as potential health benefits. These compounds, prevalent in food sources and medicinal plants, are recognized for their complex structures and their roles in [...] Read more.

Stilbene-type compounds are vital plant secondary metabolites that are classified under polyphenols and generally exhibit significant biological activities, as well as potential health benefits. These compounds, prevalent in food sources and medicinal plants, are recognized for their complex structures and their roles in plant defense mechanisms against environmental stressors. Despite their beneficial properties, the natural stilbenes face limitations related to their bioavailability and solubility, highlighting the need for chemical modifications to enhance their therapeutic efficacy. Studies have focused on structural modifications of the stilbene scaffold, including the introduction of carbon-based fragments, aiming to improve the compounds’ stability, selectivity, and overall biological activities. The development of stilbene analogues through chemical modifications not only expands the library of valuable stilbene-type compounds but also holds promise for new therapeutic applications in combating chronic diseases. This review summarizes current knowledge on the sources, biological activities, and chemical modifications of stilbene compounds, emphasizing their potential in healthcare and nutrition. Full article

(This article belongs to the Special Issue Natural and Synthetic Bioactive Compounds in Food—Risks and Benefits)

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25 pages, 2579 KB

Open AccessArticle

Characterizing the Antihyperglycemic Activity and Underlying Mechanisms of the Aqueous Extract of the Leaves from Ficus carica L.

by Fernando Calzada, Jesica Ramírez-Santos, Hannia Pérez-Álvarez, Miguel Valdes, Elizabeth Barbosa and Claudia Velázquez

Molecules 2026, 31(13), 2207; https://doi.org/10.3390/molecules31132207 (registering DOI) - 23 Jun 2026

Abstract

Ficus carica L. is traditionally used for diabetes management. This study evaluated the antihyperglycemic activity, safety, possible mechanisms, and phytochemical composition of its aqueous leaf extract (EAcFc). EAcFC activity was evaluated in streptozotocin–nicotinamide-induced type 2 diabetic (ST2D) mice under acute and subchronic conditions. [...] Read more.

Ficus carica L. is traditionally used for diabetes management. This study evaluated the antihyperglycemic activity, safety, possible mechanisms, and phytochemical composition of its aqueous leaf extract (EAcFc). EAcFC activity was evaluated in streptozotocin–nicotinamide-induced type 2 diabetic (ST2D) mice under acute and subchronic conditions. EAcFc showed low acute toxicity (LD₅₀ > 3000 mg/kg). Acute and subchronic oral administration of EAcFc (300 mg/kg) significantly reduced blood glucose levels in ST2D mice. Although sustained HbA1c reduction was not observed, EAcFc improved lipid profiles, notably reducing triglyceride concentrations in ST2D males (from 156 ± 19.4 to 89.7 ± 3.3 mg/dL at week 4) and females (from 138 ± 2.0 to 77 ± 16.0 mg/dL at week 4). In oral sucrose and lactose tolerance tests (3 g/kg load), EAcFc (300 mg/kg) significantly attenuated postprandial hyperglycemia at 30, 60, and 120 min, an effect comparable to acarbose (50 mg/kg). No significant activity was observed during the oral glucose tolerance test (1.5 mg/kg load), suggesting the effect is not mediated by SGLT-1 inhibition. Preparative TLC and NMR analysis identified narcissin, nicotiflorin, and β-sitosterol. Thus, EAcFc possesses antihyperglycemic and lipid-modulating properties partially associated with α-glucosidase inhibition and bioactive flavonoids and phytosterol. Full article

(This article belongs to the Special Issue Biological Evaluation of Plant Extracts, 2nd Edition)

27 pages, 2808 KB

Open AccessReview

3D Printing of Biopolymer-Based Scaffolds for Bone Tissue Engineering: Materials, Fabrication, and Translational Strategies

by Yeajin Song, Hongyoon Kim and Seunghun S. Lee

Molecules 2026, 31(13), 2206; https://doi.org/10.3390/molecules31132206 (registering DOI) - 23 Jun 2026

Abstract

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, [...] Read more.

Bone defects from trauma, tumour resection, infection, and degenerative disease remain a major clinical burden, and autografts face limitations of supply and donor-site morbidity. Three-dimensional (3D) printing offers a route to patient-specific, architecturally defined bone scaffolds, while biopolymers from natural sources provide biodegradability, biocompatibility, and extracellular matrix-mimicking cues consistent with sustainable, green biomaterials science. This review synthesises recent progress in 3D printing of biopolymer-based scaffolds for bone tissue engineering. We first examine the principal feedstocks—alginate, gelatin and gelatin methacryloyl, collagen, chitosan, silk fibroin, cellulose, and microbial polyesters—and their preparation, crosslinking chemistry, and printability. We then compare extrusion, light-based, and indirect printing technologies and the process–property relationships governing resolution, mechanical competence, and cell viability. Composite and functionalisation strategies, including biopolymer–bioceramic hybrids and controlled delivery of growth factors and antimicrobial agents, are analysed as routes to osteoinduction, vascularisation, and infection control. Finally, we evaluate translational performance in preclinical models and outline central challenges of vascularisation, mechanical–degradation matching, scalability, and regulatory standardisation. Biopolymer 3D printing is positioned as a ve rsatile, sustainable platform whose clinical maturation depends on integrated material, structural, and biological design. Full article

(This article belongs to the Special Issue Biopolymer-Based Materials: Preparation, Properties and Applications)

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15 pages, 1389 KB

Open AccessFeature PaperArticle

Electrocatalytic Mn₂Mo₃O₈/MnO-Carbon Nanocomposite Electrodes for Hydrogen Peroxide and Glucose Sensing

by Foroozan Samimi, Jorge Urraca, Anabel Villalonga, Esther García-Díez, Alfredo Sánchez, Irene Ojeda, Masoud Salavati-Niasari and Reynaldo Villalonga

Molecules 2026, 31(13), 2205; https://doi.org/10.3390/molecules31132205 (registering DOI) - 23 Jun 2026

Abstract

Metal oxide nanomaterials tailored at the nanoscale are opening new avenues for advanced electroanalytical sensing devices with enhanced properties, including improved electrocatalytic activity. In this work, a novel Mn₂Mo₃O₈/MnO-MWCNT nanocomposite was employed to modify a screen-printed carbon [...] Read more.

Metal oxide nanomaterials tailored at the nanoscale are opening new avenues for advanced electroanalytical sensing devices with enhanced properties, including improved electrocatalytic activity. In this work, a novel Mn₂Mo₃O₈/MnO-MWCNT nanocomposite was employed to modify a screen-printed carbon electrode, enabling the fabrication of an amperometric sensor for H₂O₂ operating at relatively low applied potential due to the catalytic activity of the nanocomposite. Further functionalization of this nanostructured surface with glucose oxidase allowed the construction of an electrochemical glucose biosensor, where the Mn₂Mo₃O₈/MnO-MWCNT material acted as an efficient electrocatalyst for hydrogen peroxide detection. The H₂O₂ sensor exhibited a linear response from 0.06 mM to 3.00 mM, with a sensitivity of (2.22 ± 0.02) µA mM⁻¹ and a detection limit of 22 µM. The glucose biosensor showed a linear response in the range from 0.10 mM to 18.9 mM glucose, with a sensitivity of (0.345 ± 0.005) µA mM⁻¹, and a detection limit of 29 µM. The biosensor displayed excellent selectivity and high stability and was successfully applied to the determination of glucose in lactose-free skimmed milk. Full article

(This article belongs to the Special Issue Nanomaterial-Based Biosensors: From Design to Analytical Applications)

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20 pages, 9967 KB

Open AccessArticle

Antidiabetic Potential of Aronia melanocarpa–β-Glucan System: From Extraction Optimization Through In Silico Understanding of Activity to Stabilization of Anthocyanins

by Anna Gościniak, Emmanuelle Lainé, Sandrine Chalancon, Filip Stojceski, Natalia Rosiak, Gabriele Maroni and Judyta Cielecka-Piontek

Molecules 2026, 31(13), 2204; https://doi.org/10.3390/molecules31132204 (registering DOI) - 23 Jun 2026

Abstract

Aronia melanocarpa is a rich source of anthocyanins with well-documented antioxidant and antidiabetic potential; however, their application is limited by low stability. In this study, extraction conditions were optimized using response surface methodology, with the highest total polyphenol content obtained at an ethanol [...] Read more.

Aronia melanocarpa is a rich source of anthocyanins with well-documented antioxidant and antidiabetic potential; however, their application is limited by low stability. In this study, extraction conditions were optimized using response surface methodology, with the highest total polyphenol content obtained at an ethanol concentration of 36.9% (v/v), an extraction temperature of 34.1 °C, and a solvent-to-solid ratio of 54.5 mL/g. The extract exhibited antioxidant activity and inhibited α-amylase in vitro, with an IC₅₀ value of 3.18 ± 0.27 mg/mL, compared with 6.76 ± 0.21 mg/mL for acarbose under the same assay conditions. Molecular modeling suggested that cyanidin derivatives may play a major role in the observed α-amylase inhibitory activity. The optimized extract was subsequently incorporated into yeast-derived β-glucan systems at different ratios to improve anthocyanin stability and formulation performance. Incorporation of β-glucan significantly modified dissolution behavior and reduced anthocyanin degradation in a ratio-dependent manner. The highest stabilization effect was observed for the aronia: β-glucan 1:2 system, in which the degradation rate decreased approximately 4.7-fold. Full article

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17 pages, 1140 KB

Open AccessArticle

Toxicokinetic-Informed Evidential Learning for Applicability-Domain-Aware QSAR/QSPR Prediction of Environmental Contaminant Toxicity

by Xiankun Huang, Junkai Zheng, Zhihong Zheng and Wenhao Xu

Molecules 2026, 31(13), 2203; https://doi.org/10.3390/molecules31132203 (registering DOI) - 23 Jun 2026

Abstract

Quantitative structure–activity relationship and quantitative structure–property relationship (QSAR/QSPR)-based molecular toxicity prediction provides an in silico strategy for prioritizing environmental contaminants when longer-duration bioassay data are sparse. However, many Simplified Molecular-Input Line-Entry System (SMILES)-based machine learning models treat exposure duration as an unconstrained numerical [...] Read more.

Quantitative structure–activity relationship and quantitative structure–property relationship (QSAR/QSPR)-based molecular toxicity prediction provides an in silico strategy for prioritizing environmental contaminants when longer-duration bioassay data are sparse. However, many Simplified Molecular-Input Line-Entry System (SMILES)-based machine learning models treat exposure duration as an unconstrained numerical covariate and provide limited information on whether predictions are supported by the observed temporal domain. Here, we evaluated an applicability-domain-aware chemoinformatics framework that combines transformer-derived molecular representations with toxicokinetic-informed temporal encoding and evidential uncertainty estimation. The approach replaces conventional

{log}_{10}

-transformed time encoding with a bounded first-order toxicokinetic saturation feature and combines this representation with Deep Evidential Regression to support a joint chemical–temporal view of the QSAR/QSPR applicability domain. Using experimentally derived U.S. EPA Ecotoxicology Knowledgebase (ECOTOX) fish EC50 mortality records, models were trained on 48,728 acute-duration observations and evaluated retrospectively on 2090 temporally separated longer-duration observations. The combined toxicokinetic and evidential model reduced temporal extrapolation error relative to conventional time encoding while maintaining comparable within-domain validation performance. The learned population-level timescale converged to 221 ± 3 h, consistent with accumulation timescales extending beyond standard acute fish test durations. Epistemic uncertainty was positively associated with absolute prediction error across all 10 folds, suggesting that the uncertainty estimates retained sample-level information relevant to applicability-domain-aware molecular toxicity screening. Cross-species analyses further showed that model behavior depended on training time coverage, with greater convergence when available assays covered a larger fraction of the learned timescale. These results suggest that toxicokinetic-informed temporal encoding can improve uncertainty-aware QSAR/QSPR modeling of environmental contaminant toxicity and support prioritization of compounds for further testing, while complementing rather than replacing chronic bioassays. Full article

(This article belongs to the Special Issue QSAR and QSPR: Recent Developments and Applications, 5th Edition)

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16 pages, 16212 KB

Open AccessArticle

Phosphogypsum Processing into Blue Fluorescent Pigments Under Ultraviolet Excitation

by Marina A. Egorova, Darya V. Yakhonova, Vera A. Baranova, Oleg A. Medennikov, Valentina V. Utochnikova, Anastasia V. Orlova, Nina P. Shabelskaya, Asatullo M. Radzhabov, Alexandr V. Vyaltsev and Sergey I. Sulima

Molecules 2026, 31(13), 2202; https://doi.org/10.3390/molecules31132202 (registering DOI) - 23 Jun 2026

Abstract

In this work, we introduce the novel possibility of producing blue fluorescent ultraviolet pigments from phosphogypsum. The obtained materials are characterized by X-ray diffraction (XRD), transmission electron microscopy, and X-ray photoelectron spectroscopy (XPS). The formation of the CaS phase in the sample during [...] Read more.

In this work, we introduce the novel possibility of producing blue fluorescent ultraviolet pigments from phosphogypsum. The obtained materials are characterized by X-ray diffraction (XRD), transmission electron microscopy, and X-ray photoelectron spectroscopy (XPS). The formation of the CaS phase in the sample during the reduction of calcium sulfate was established. Thermal treatment of phosphogypsum in the presence of a reducing agent (potato starch) under environmental isolation conditions is found to yield high-quality products with high added value. The highest luminosity is established in samples containing 0.6 mol. %, which were heat-treated under a temperature of 1100 °C for 60 min. The synthesized CaS:Cu materials are shown to emit light in the blue region of the spectrum, with an emission maximum at a wavelength of 480–490 nm. The developed technological methods open the possibility to recycle chemical industry waste, which contributes to the achievement of sustainable development goals, in particular, the goal of ensuring rational consumption and production patterns. Full article

(This article belongs to the Special Issue Metal Recovery from Waste Polymetallic Materials)

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26 pages, 7176 KB

Open AccessArticle

Sensory Perception of Six Essential Oils in Humans and Tenebrio molitor: Relationship with Volatile Compound Physicochemical Properties

by Antonella Rosa, Alessandra Piras, Silvia Porcedda, Carla Masala and Paolo Solari

Molecules 2026, 31(13), 2201; https://doi.org/10.3390/molecules31132201 (registering DOI) - 23 Jun 2026

Abstract

Olfactory detection of essential oils (EOs), natural plant-derived mixtures of odorous volatile compounds, stimulates neural pathways involved in emotion, cognitive function, and memory in humans and significantly influences insect behavior (inducing attractiveness or repellency). In this study, the olfactory perception of rose (EO [...] Read more.

Olfactory detection of essential oils (EOs), natural plant-derived mixtures of odorous volatile compounds, stimulates neural pathways involved in emotion, cognitive function, and memory in humans and significantly influences insect behavior (inducing attractiveness or repellency). In this study, the olfactory perception of rose (EO 1, a synthetic mixture with rose aroma), eucalyptus (EO 2), lemon (EO 3), clove (EO 4), rosemary (EO 5), and caraway (EO 6) EOs in untrained human participants was compared to the behavioral responses induced in Tenebrio molitor (adult insects) by EO exposure. Significant differences emerged in the perception of EO odor dimensions (pleasantness, intensity, and familiarity) using a Likert-type scale in untrained participants. The tested EOs elicited different behavioral responses in T. molitor insects, as assessed by repellency, escape, and choice tests. A positive correlation (r = 0.7861, p < 0.05) emerged between EO odor intensity perceived by participants and escape induction in T. molitor adults. GC–MS analysis revealed citronellol, 1,8-cineole, limonene, eugenol, α-pinene, and carvone as the most abundant volatile compounds in EO 1, EO 2, EO 3, EO 4, EO 5, and EO 6, respectively. The EO odor dimensions in participants and insect behavioral responses were also related to the in silico physicochemical/pharmacokinetic properties of the main EO components. Our results provide new insights into the chemical basis of olfactory preferences both in T. molitor adults and humans. Full article

(This article belongs to the Special Issue Impact of Aromatic Plants and Their Extracts on Insect Models for Nutritional, Medicinal, and Crop Protection Research)

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18 pages, 8498 KB

Open AccessArticle

Optimization of Ultrasound-Assisted Deep Eutectic Solvent Extraction and Mechanism Evaluation of Saponins from Panax japonicus

by Jing Wang, Zhengwen Li, Xia Zeng, Miao Zheng, Minqian Wang, Qianlong Duan, Yong Jiang, Jia Li and Zhengyou He

Molecules 2026, 31(13), 2200; https://doi.org/10.3390/molecules31132200 (registering DOI) - 23 Jun 2026

Abstract

This study investigated an efficient approach for extracting saponins from Panax japonicus using deep eutectic solvents (DES) coupled with ultrasound-assisted (UA) extraction, and compared its performance with the methanol extraction method. Twenty-six DES were screened, and choline chloride–urea was selected as the optimal [...] Read more.

This study investigated an efficient approach for extracting saponins from Panax japonicus using deep eutectic solvents (DES) coupled with ultrasound-assisted (UA) extraction, and compared its performance with the methanol extraction method. Twenty-six DES were screened, and choline chloride–urea was selected as the optimal solvent. The total extraction yield was evaluated based on the sum of the yields of chikusetsusaponin IVa (CS-IVa) and ginsenoside Ro (G-Ro). The extraction process was optimized using single-factor experiments combined with an orthogonal array design. Molecular dynamics (MD) simulation was applied to reveal the extraction mechanism at the molecular level. The results showed that the optimal conditions were as follows: a choline chloride-to-urea molar ratio of 1:3, a solid-to-liquid ratio of 1:50, a water content of 60%, an ultrasonic temperature of 40 °C, and an ultrasonic time of 60 min. Under these conditions, the total extraction yield of Panax japonicus saponins reached 7.4%, which was 13% higher than that obtained with the pharmacopeia methanol extraction method. MD simulation demonstrated that DES weakens intermolecular interactions among saponins through hydrogen bonds and van der Waals forces, promoting the dispersion of saponin aggregates and enabling efficient dissolution. Compared with CS-IVa, G-Ro displayed a more pronounced solvation effect, which was likely attributed to the difference in the number of polar sites in their molecular structures. The UA-DES extraction method established herein is green and efficient. It provides a practical reference for the industrial extraction of Panax japonicus saponins and a theoretical foundation for mechanistic studies on natural product extraction using DES. Full article

(This article belongs to the Section Green Chemistry)

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16 pages, 22336 KB

Open AccessArticle

Bacterial Nanocellulose-Based Active Packaging for Vapor-Phase Delivery of Cinnamaldehyde to Control Fungal Spoilage in Bread

by Érika Leão Ajala Caetano, Joana Garrossino Magalhães, Nicolli Carriel de Souza, Jair Vaz Nogueira Junior, Angela Faustino Jozala and Denise Grotto

Molecules 2026, 31(13), 2199; https://doi.org/10.3390/molecules31132199 (registering DOI) - 23 Jun 2026

Abstract

Active packaging systems have emerged as a promising strategy to control microbial spoilage without direct incorporation of preservatives into food matrices. In this context, this study evaluated bacterial nanocellulose (BNC) as a nanostructured carrier for vapor-phase delivery of natural antifungal compounds in bread [...] Read more.

Active packaging systems have emerged as a promising strategy to control microbial spoilage without direct incorporation of preservatives into food matrices. In this context, this study evaluated bacterial nanocellulose (BNC) as a nanostructured carrier for vapor-phase delivery of natural antifungal compounds in bread preservation. Cinnamaldehyde (CIN), cinnamon extract and clove extract were screened against Aspergillus niger, Penicillium chrysogenum, and Rhizopus microsporus using minimum inhibitory concentration (MIC) and inverted halo assays. CIN demonstrated complete fungal inhibition at 0.19% (v/v), corresponding to approximately 2.0 mg/mL, outperforming plant extracts, which exhibited limited and concentration-dependent activity. When incorporated into BNC at a 1:1 ratio (50% reduced loading), CIN maintained inhibition halos comparable to the free compound, indicating effective release and preserved bioavailability. The performance of the system was further evaluated in a bread model using a non-contact active packaging approach. Fungal growth in control samples was detected by day 6 (>10⁵ CFU/g), while incorporation of plant extracts into BNC delayed spoilage to day 9 (≈50% shelf-life extension). In contrast, breads treated with CIN, either free or BNC-incorporated, showed no detectable fungal growth throughout 21 days of storage, corresponding to a shelf-life extension of at least 15 days. These results demonstrate that antifungal efficacy in vapor-phase systems depends primarily on the intrinsic potency of the active compound, while BNC acts as an effective carrier matrix that promotes sustained retention and functional availability of CIN. The use of BNC-based active packaging for cinnamaldehyde delivery represents a promising clean-label strategy to control fungal spoilage and extend the shelf life of bread without direct incorporation into the food matrix. Full article

(This article belongs to the Special Issue Biodegradable Polymers in Biological Application)

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15 pages, 1690 KB

Open AccessArticle

Highly Stereoselective (3+2) Cycloadditions of Levoglucosenone (LGO) with the In Situ-Generated Thiocarbonyl S-Methanides (Thiocarbonyl Ylides) Derived from Aromatic and Cycloaliphatic Thioketones

by Grzegorz Mlostoń, Małgorzata Celeda, Marcin Palusiak, Heinz Heimgartner and Zbigniew J. Witczak

Molecules 2026, 31(13), 2198; https://doi.org/10.3390/molecules31132198 (registering DOI) - 23 Jun 2026

Abstract

The in situ-generated thiocarbonyl S-methanides derived from cycloaliphatic thioketones undergo (3+2) cycloaddition onto the C=C bond of levoglucosenone yielding anticipated, polycyclic tetrahydrothiophene derivatives in a regio- and stereoselective manner. The cycloaddition process occurred stereoselectively via the less hindered exo-face approach; exo-diastereoisomers were formed [...] Read more.

The in situ-generated thiocarbonyl S-methanides derived from cycloaliphatic thioketones undergo (3+2) cycloaddition onto the C=C bond of levoglucosenone yielding anticipated, polycyclic tetrahydrothiophene derivatives in a regio- and stereoselective manner. The cycloaddition process occurred stereoselectively via the less hindered exo-face approach; exo-diastereoisomers were formed in all studied reactions. Some of the obtained crystalline (3+2) cycloadducts were studied by the monocrystal X-ray diffraction analysis, which unambiguously confirmed the postulated structure. Stable (3+2) cycloadducts were isolated in good yields (50–80%). Full article

(This article belongs to the Special Issue Advances in Heterocyclic Synthesis, 2nd Edition)

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64 pages, 35278 KB

Open AccessReview

1,4-Diazatriphenylene and Its Hetero-Fused Analogs: Synthesis and Applications

by Egor V. Verbitskiy, Elizaveta M. Krynina, Yuriy A. Kvashnin and Valery N. Charushin

Molecules 2026, 31(12), 2197; https://doi.org/10.3390/molecules31122197 (registering DOI) - 22 Jun 2026

Abstract

This review highlights the recent advances in the synthesis of 1,4-diazatriphenylenes and their various structural analogs. It focuses on several methodologies, including condensation reactions and intramolecular cyclizations of 2,3-di(het)aryl-substituted pyrazine derivatives. These methods exploit either oxidative photocyclization (the Mallory reaction), intramolecular cyclodehydrogenation (the [...] Read more.

This review highlights the recent advances in the synthesis of 1,4-diazatriphenylenes and their various structural analogs. It focuses on several methodologies, including condensation reactions and intramolecular cyclizations of 2,3-di(het)aryl-substituted pyrazine derivatives. These methods exploit either oxidative photocyclization (the Mallory reaction), intramolecular cyclodehydrogenation (the Scholl reaction), or intramolecular S_N^H reactions (nucleophilic aromatic substitution of hydrogen) involving 2-bis(het)aryl-substituted 1,4-diazine derivatives. Additionally, the review explores the potential applications of these compounds as fluorescent and/or semiconducting materials in organic electronics, as well as their role in coordination chemistry and biological issues. It summarizes the literature from 2018 to March 2026, complementing the data discussed in our previous review. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Heterocyclic Compounds and Their Applications, 2nd Edition)

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24 pages, 1033 KB

Open AccessArticle

Comparative Phytochemical Studies on the Aerial Parts of Teucrium davaeanum Coss. and Teucrium zanonii Pamp.

by Randa Aldaba, Azmi Hanoğlu, Duygu Yiğit Hanoğlu, Kemal Hüsnü Can Başer, Mehmet Öztürk, Ahmet Ceyhan Gören, Simon Jurt and İhsan Çalış

Molecules 2026, 31(12), 2196; https://doi.org/10.3390/molecules31122196 (registering DOI) - 22 Jun 2026

Abstract

Phytochemical studies performed on the aerial parts of Teucrium davaeanum Coss. resulted in the isolation of an iridoid diglycoside, teucardoside; two phenylethanoid triglycosides, poliumoside and 3-O-methyl-poliumoside; a flavon C-diglycoside, vicenin-2 (apigenin-6,8-di-C-glycoside); and a newly described bisdesmosidic oleanane-type triterpene saponin, davaeanoside. Structure [...] Read more.

Phytochemical studies performed on the aerial parts of Teucrium davaeanum Coss. resulted in the isolation of an iridoid diglycoside, teucardoside; two phenylethanoid triglycosides, poliumoside and 3-O-methyl-poliumoside; a flavon C-diglycoside, vicenin-2 (apigenin-6,8-di-C-glycoside); and a newly described bisdesmosidic oleanane-type triterpene saponin, davaeanoside. Structure elucidations of all isolated metabolites are based on extensive spectroscopic analysis and chemical derivatizations. The extract and isolated compounds (1–5) were tested for α-amylase and α-glucosidase inhibitory activity. IC50 values were measured for all extracts and compounds and compared against acarbose. Results revealed weak or moderate α-amylase and α-glucosidase inhibitory activity at the tested concentrations of the isolated compounds, especially compound 5. However, these findings do not exclude antidiabetic activity mediated by other mechanisms such as modulation of insulin signaling, enhancement of glucose uptake, or antioxidant effects. Further studies are warranted to explore these potential pathways. In addition, the essential oils of T. davaeanum and T. zanonii were obtained by hydrodistillation and simultaneously analyzed by GC-FID and GC/MS. The major compounds of T. davaeanum essential oil were germacrene D (31.4%) and bicyclogermacrene (15.9%); the main compounds of T. zanonii were β-pinene (19.5%), α-muurolene (13.4%), oxo-7,8-dihydro-β-ionol (9.2%), and α-pinene (6.9%). Full article

(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 3rd Edition)

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13 pages, 1072 KB

Open AccessArticle

π-Interrupted Chiral Emitters with Cooperative LE–TADF Emission for Single-Molecule White Circularly Polarized OLEDs

by Shuang Yang, Wei-Chen Guo, Pei Zhao, Hai-Yan Lu and Chuan-Feng Chen

Molecules 2026, 31(12), 2195; https://doi.org/10.3390/molecules31122195 (registering DOI) - 22 Jun 2026

Abstract

Single-molecular white circularly polarized luminescence emitters show promise for use in chiral displays and solid-state lighting, but their design remains challenging because broadband emission, exciton utilization, color balance, and chiroptical activity must be integrated within one molecule. Herein, we report a chiral single-molecular [...] Read more.

Single-molecular white circularly polarized luminescence emitters show promise for use in chiral displays and solid-state lighting, but their design remains challenging because broadband emission, exciton utilization, color balance, and chiroptical activity must be integrated within one molecule. Herein, we report a chiral single-molecular white emitter, DCz-PTZ, constructed through a π-interrupted strategy by combining a rigid spiro framework, an oxygen-bridged carbazole/cyanobenzene segment, and a phenothiazine donor. The interrupted conjugation suppresses excessive charge-transfer (CT) domination and enables dual emissive channels, including short-wavelength locally excited (LE) emission and long-wavelength CT emission. DCz-PTZ exhibits near-ideal white emission in dilute toluene solution with CIE coordinates of (0.33, 0.33), and maintains balanced dual emission in 5 wt% doped films with CIE coordinates of (0.32, 0.34). Photophysical studies support the assignment of the yellow emission to a thermally activated delayed fluorescence (TADF)-active CT state. The enantiomers show mirror-image circularly polarized signals with |g_lum| up to 2.9 × 10⁻³. Optimized white organic light-emitting diodes (WOLEDs) achieve color rendering index (CRI) up to 92 and a maximum external quantum efficiency (EQE_max) of 1.3%. This work demonstrates a π-interrupted molecular strategy for integrating dual emission, TADF exciton utilization, and circularly polarized electroluminescence (CPEL) in a single chiral emitter. Full article

(This article belongs to the Special Issue Recent Advances in Circularly Polarized Luminescence Materials)

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12 pages, 1138 KB

Open AccessArticle

Metabolomic Changes in the Rat Eye Lens During the Cataract Onset

by Olga A. Snytnikova, Anton A. Smolentsev, Nataliya G. Kolosova, Anzhella Z. Fursova and Yuri P. Tsentalovich

Molecules 2026, 31(12), 2194; https://doi.org/10.3390/molecules31122194 (registering DOI) - 22 Jun 2026

Abstract

This study aimed to characterize metabolomic changes in the eye lens of senescence-accelerated OXYS rats in comparison with control Wistar rats, and to identify biochemical shifts associated with genotype, age, and cataract progression. Cataract severity was clinically graded. Rats’ lenses were analyzed using [...] Read more.

This study aimed to characterize metabolomic changes in the eye lens of senescence-accelerated OXYS rats in comparison with control Wistar rats, and to identify biochemical shifts associated with genotype, age, and cataract progression. Cataract severity was clinically graded. Rats’ lenses were analyzed using quantitative ¹H NMR spectroscopy at 3.6 and approximately 4.5 months of age. A total of 43 metabolites were quantified. We found that at 3.6 months of age, OXYS lenses exhibited a significant accumulation of 17 metabolites, primarily amino acids, compared to Wistar rats, suggesting an imbalance between amino acid uptake and crystallin biosynthesis. However, by 4.5 months, OXYS lenses exhibited rapid metabolic changes characterized by significant decreases in amino acid, glucose, and key energy/antioxidant markers, including NAD, adenylate energy charge, and hypotaurine. Clinical cataract grade (Grade 2 vs. 3) had a negligible impact on the overall metabolomic profile. Our results indicate that profound metabolic reorganization, including an initial amino acid excess followed by energy and antioxidant depletion, precedes the morphological manifestation of cataracts in OXYS rats. We suggest that a biochemical “point of no return” occurs early in cataractogenesis, while subsequent increase in lens opacification is a secondary consequence of preexisting metabolic disturbances. Full article

(This article belongs to the Special Issue Next-Generation Molecular Diagnostics: Mass Spectrometry-Based Omics Insights into Complex Disease Architectures)

19 pages, 2125 KB

Open AccessArticle

Discovery and Putative Perception Mechanisms of Novel Umami Peptides from Ruditapes philippinarum Cooking Liquid: In Silico Screening, Molecular Docking, Sensory Evaluation, and STC-1 Cell-Based Validation

by Ruiying Wang, Qi Sun, Siyu Zhang, Haibo Wang, Tanye Xu, Qiancheng Zhao and Zhibo Li

Molecules 2026, 31(12), 2193; https://doi.org/10.3390/molecules31122193 (registering DOI) - 22 Jun 2026

Abstract

Cooking liquid from Manila clam (Ruditapes philippinarum) is an underutilized byproduct rich in water-soluble taste compounds, representing a potential source of natural umami peptides. In this study, peptide fractions were separated from the cooking liquid. A total of 764 peptide sequences [...] Read more.

Cooking liquid from Manila clam (Ruditapes philippinarum) is an underutilized byproduct rich in water-soluble taste compounds, representing a potential source of natural umami peptides. In this study, peptide fractions were separated from the cooking liquid. A total of 764 peptide sequences were identified from the most potent fraction, F3 (<3 kDa), by UPLC-ESI-Q-TOF-MS/MS. Machine learning prediction and molecular docking were further used for screening. Five candidate peptides were selected: TQDTVVALDA, KEY, YKD, RND, and GEAF. Sensory evaluation (on a 0–5 scale) and electronic tongue measurements independently confirmed that peptide YKD possessed the strongest taste profile, with an electronic tongue relative umami score of 8.81 ± 0.22. Furthermore, cell-based assays demonstrated that YKD effectively up-regulated the transcriptional expression of taste-related receptors, including GPRC6A, in STC-1 cells, revealing a multi-receptor synergetic mechanism for umami perception. In STC-1 cells, all peptides induced intracellular Ca²⁺ responses and showed no obvious cytotoxicity at 0.5–8.0 mmol/L. YKD produced the highest fluorescence response (0.59) at 1.0 mmol/L. Quantitative RT-PCR analysis suggested that YKD was associated with T1R1/T1R3-related expression, whereas TQDTVVALDA induced stronger CaSR expression. These findings elucidate the specific peptide sequence that engages multiple receptors to create complex tastes, providing a theoretical basis for converting seafood processing byproducts into natural flavor enhancers. Full article

(This article belongs to the Section Food Chemistry)

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