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Molecules

Molecules is a leading international, peer-reviewed, open access journal of chemistry published semimonthly online by MDPI. The International Society of Nucleosides, Nucleotides & Nucleic Acids (IS3NA), Spanish Society of Medicinal Chemistry (SEQT) and International Society of Heterocyclic Chemistry (ISHC) are affiliated with Molecules and their members receive discounts on the article processing charges.

Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Reaxys, CaPlus / SciFinder, MarinLit, AGRIS, and other databases.
Journal Rank: JCR - Q2 (Biochemistry and Molecular Biology) / CiteScore - Q1 (Organic Chemistry)
Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 15.1 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the second half of 2025).
Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Sections: published in 25 topical sections.
Testimonials: See what our editors and authors say about Molecules.
Companion journal: Foundations.
Journal Cluster of Chemical Reactions and Catalysis: Catalysts, Chemistry, Electrochem, Inorganics, Molecules, Organics, Oxygen, Photochem, Reactions, Sustainable Chemistry.

Impact Factor: 4.6 (2024); 5-Year Impact Factor: 5.0 (2024)

Imprint Information Journal Flyer Open Access ISSN: 1420-3049

Latest Articles

20 pages, 1586 KB

Open AccessArticle

Preferential Solvation of Zwitterionic Benzo-[f]-Quinolinium Ylids in Binary Solvent Mixtures: Spectral Study and Quantum Chemical Calculations

by Mihaela Iuliana Avadanei, Ovidiu Gabriel Avadanei and Dana Ortansa Dorohoi

Molecules 2026, 31(2), 290; https://doi.org/10.3390/molecules31020290 - 13 Jan 2026

Three derivatives of benzo-[f]-quinolinium ylids, which all underwent an intermolecular charge transfer process, were used as solvatochromic indicators to study the specific solvent–solute interactions in binary mixtures of protic–aprotic solvents with different molar ratios. The microenvironment around the solute molecules was observed via [...] Read more.

Three derivatives of benzo-[f]-quinolinium ylids, which all underwent an intermolecular charge transfer process, were used as solvatochromic indicators to study the specific solvent–solute interactions in binary mixtures of protic–aprotic solvents with different molar ratios. The microenvironment around the solute molecules was observed via electronic absorption spectroscopy and was analyzed by employing solvation models and quantum chemical calculations. The spectral analysis suggested that the solute was preferentially solvated by the polar protic solvent, indicating a lack of synergy between the two solvents. The solvation microsphere was progressively occupied by the protic solvent, on the basis of specific solute–solvent interactions. By modeling the 1:2 (solute-coordinating solvent) complexes with explicit solvents, the binding energy for complex formation was estimated. Full article

(This article belongs to the Section Analytical Chemistry)

11 pages, 1001 KB

Open AccessArticle

Stereoselective Synthesis and Structural Confirmation of All Four 8-Hydroxyhexahydrocannabinol Stereoisomers

by Kei Ieuji, Kayo Nakamura and Hideyo Takahashi

Molecules 2026, 31(2), 289; https://doi.org/10.3390/molecules31020289 - 13 Jan 2026

Hexahydrocannabinol (HHC), a hydrogenated derivative of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), is a semi-synthetic cannabinoid marketed as an alternative to Δ⁹-THC. Its hydroxylated metabolite, 8-hydroxyhexahydrocannabinol (8-OH-HHC), exists as four stereoisomers: (6aR,8R,9R,10aR), (6a [...] Read more.

Hexahydrocannabinol (HHC), a hydrogenated derivative of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), is a semi-synthetic cannabinoid marketed as an alternative to Δ⁹-THC. Its hydroxylated metabolite, 8-hydroxyhexahydrocannabinol (8-OH-HHC), exists as four stereoisomers: (6aR,8R,9R,10aR), (6aR,8S,9S,10aR), (6aR,8S,9R,10aR), and (6aR,8R,9S,10aR). However, the lack of reference standards has hindered pharmacokinetic and forensic studies. This work reports the first stereoselective synthesis and structural confirmation of all four 8-OH-HHC stereoisomers. Two strategies were employed: hydroboration–oxidation and epoxidation–reduction. Hydroboration of Δ⁸-THC with BH₃·THF followed by oxidation predominantly produced anti-isomers (6aR,8R,9R,10aR) and (6aR,8S,9S,10aR) in moderate yields, along with small amounts of syn-isomer (6aR,8S,9R,10aR), suggesting an atypical mechanistic pathway. In contrast, syn-isomers (6aR,8S,9R,10aR) and (6aR,8R,9S,10aR) were accessed via epoxidation of Δ⁸-THC acetate using mCPBA and subsequent reduction with NaBH₃CN/BF₃·OEt₂, affording the desired products with moderate selectivity. Absolute configurations were confirmed by nuclear Overhauser effect spectroscopy (NOESY). These methods will facilitate future pharmacokinetic and forensic research and support the development of improved detection strategies. Full article

(This article belongs to the Special Issue Application of Organic Synthesis to Bioactive Compounds, 3rd Edition)

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18 pages, 1166 KB

Open AccessArticle

Quercetin-Loaded Zein/Carboxymethyl Chitosan Nanoparticles: Preparation, Characterization and Evaluation for Enhanced Stability and Antioxidant Activity

by Haiqi Yu, Wanjun Chen, Yuhong Su, Mengdie Mo, Fei Yu and Xiaodong Chen

Molecules 2026, 31(2), 288; https://doi.org/10.3390/molecules31020288 - 13 Jan 2026

As a natural flavonoid compound, quercetin possesses excellent antioxidant, anti-inflammatory and anti-atherosclerotic activities. However, the poor water solubility and sensitivity to the environment severely limit the application of quercetin. Initially, quercetin-loaded zein/carboxymethyl chitosan nanoparticles (ZCQ NPs) were prepared using an anti-solvent precipitation method. [...] Read more.

As a natural flavonoid compound, quercetin possesses excellent antioxidant, anti-inflammatory and anti-atherosclerotic activities. However, the poor water solubility and sensitivity to the environment severely limit the application of quercetin. Initially, quercetin-loaded zein/carboxymethyl chitosan nanoparticles (ZCQ NPs) were prepared using an anti-solvent precipitation method. The fabricated ZCQ NPs exhibited a small particle size and polydispersity index (PDI). The ZCQ NPs had a negative zeta potential with an absolute value of 41.50 ± 1.76 mV. ZCQ NPs could remain highly stable against light, heat and ion strength. In addition, ZCQ NPs maintained good monodispersity and displayed minimal changes in particle size under long-term storage conditions. Additionally, a superior antioxidant capacity of ZCQ NPs was also observed in the free radical and reactive oxygen species (ROS) scavenging study compared to that of free quercetin. All these results of this study suggest that ZCQ NPs could serve as an effective drug delivery system for encapsulating and delivering quercetin. Full article

(This article belongs to the Section Food Chemistry)

42 pages, 1675 KB

Open AccessReview

Recent Insights into Protein-Polyphenol Complexes: Molecular Mechanisms, Processing Technologies, Synergistic Bioactivities, and Food Applications

by Hoang Duy Huynh, Thanh Huong Tran Thi, Thanh Xuan Tran Thi, Parushi Nargotra, Hui-Min David Wang, Yung-Chuan Liu and Chia-Hung Kuo

Molecules 2026, 31(2), 287; https://doi.org/10.3390/molecules31020287 - 13 Jan 2026

Modifying proteins through grafting with polyphenols has received much attention recently due to its immense application potential. This stems from the formation of protein-polyphenol complexes, altering the structural and functional properties of the constituent molecules. In food systems, the interaction between proteins and [...] Read more.

Modifying proteins through grafting with polyphenols has received much attention recently due to its immense application potential. This stems from the formation of protein-polyphenol complexes, altering the structural and functional properties of the constituent molecules. In food systems, the interaction between proteins and polyphenols, including covalent and non-covalent binding, represents a green, simple, and effective strategy to transform difficult-to-process protein sources into high-value functional ingredients. In addition, the complexes formed can increase stability, biological activity, and bioavailability of polyphenols, thereby expanding their applications. Gaining insight into protein-polyphenol complexes is essential for developing novel complexes, formulations, and other applications utilizing protein and natural polyphenols. Thus, this review outlines the binding affinities and interaction mechanisms, explains factors affecting complex formation, revisits structural modulation of protein, modern processing technologies, and systematically discusses the synergistic bioactivities of the resulting complexes. We also discuss strategies to address the applications of protein–polyphenol complexes for developing functional food products with prolonged shelf life. These applications can be expanded to other industrial areas, such as pharmaceuticals and material engineering, contributing towards better nutritional quality, beneficial healthy aspects, and sustainability. Full article

(This article belongs to the Special Issue Recent Advances in the Valorization of Food, Agricultural By-Products and Waste, 2nd Edition)

13 pages, 750 KB

Open AccessArticle

Thorough Characterization of Two Sessein Derivatives with Potential Biological Activity

by Abraham Gómez-Rivera, Cristian Octavio Barredo-Hernández, Santiago Santos-Vázquez, Carlos Ernesto Lobato-García, Ammy Joana Gallegos-García, Ricardo López-Rodríguez, Laura Alvarez, Ma Dolores Pérez-García, Manasés González-Cortazar, Jorge Luis Torres-López and Eric Jaziel Medrano-Sánchez

Molecules 2026, 31(2), 286; https://doi.org/10.3390/molecules31020286 - 13 Jan 2026

The diterpene sessein, isolated from Salvia sessei, is a metabolite of interest due to its conjugated p-quinone system, δ-lactone ring, and phenolic hydroxyl in C-12. These functionalities make it an ideal starting point for reactivity studies and semi-synthetic derivatization. In [...] Read more.

The diterpene sessein, isolated from Salvia sessei, is a metabolite of interest due to its conjugated p-quinone system, δ-lactone ring, and phenolic hydroxyl in C-12. These functionalities make it an ideal starting point for reactivity studies and semi-synthetic derivatization. In this work, we report the obtainment of two derivatives by selective esterification of phenolic hydroxyl in C-12, through acetylation and benzoylation reactions under mild conditions and with high yields. The structures were characterized by UPLC-MS, FTIR, and NMR spectroscopy ¹H, ¹³C, and 2D, which allowed to precisely confirm the modifications made in the derivatives. These results confirm that hydroxyl in C-12 constitutes a privileged site of reactivity within the royleanone family, consolidating sessein as a versatile nucleus for the generation of derivatives. Finally, the preliminary evaluation of the antimicrobial activity showed that sessein shows a broad spectrum of action against Gram-positive, Gram-negative, and Candida albicans strains. The acetylated derivative showed an increase in activity against gram-negative bacteria, while the benzoyl derivative had a loss of effect at the concentrations evaluated. These findings demonstrate that structural modifications influence the properties of the derivatives with respect to the compound sessein. Full article

(This article belongs to the Special Issue Advances in Natural Products and Their Biological Activities—2nd Edition)

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16 pages, 764 KB

Open AccessArticle

Establishment of CRISPR-Cas9-Mediated Gene Editing in the Swimming Crab Portunus trituberculatus

by Xiaopeng Wang, Xuhao Chen, Yueyue Zhou, Yun Zhao, Ce Shi, Ronghua Li, Lei Liu, Changkao Mu, Weiwei Song and Chunlin Wang

Molecules 2026, 31(2), 285; https://doi.org/10.3390/molecules31020285 - 13 Jan 2026

Portunus trituberculatus is an economically important marine crustacean in East Asia’s aquaculture industry. Nevertheless, precise genome modification has not yet been established. In this study, we evaluated the applicability of the CRISPR-Cas9 gene editing system in P. trituberculatus using electroporation for efficient delivery [...] Read more.

Portunus trituberculatus is an economically important marine crustacean in East Asia’s aquaculture industry. Nevertheless, precise genome modification has not yet been established. In this study, we evaluated the applicability of the CRISPR-Cas9 gene editing system in P. trituberculatus using electroporation for efficient delivery of the Cas9-sgRNA complex into zygotes. We systematically investigated electroporation parameters, including buffer composition, voltage, capacitance, and pulse times. Our results showed that artificial seawater was a superior buffer to phosphate-buffered saline (PBS) and identified an effective electroporation condition of 600 V, 1 μF capacitance, and two pulses, resulting in approximately 72.7% fluorescent zygotes. Under these electroporated conditions, we detected gene indels and putative insertion events at the targeted locus of myostatin (mstn) gene. These results demonstrate the feasibility of Cas9-based genome editing in P. trituberculatus and provide a proof-of-concept for functional genomics studies and future genetic improvement of this species. Full article

(This article belongs to the Special Issue Biotechnology and Biomass Valorization)

13 pages, 4553 KB

Open AccessArticle

Improving Mechanical Properties of Carboxyl-Terminated Polybutadiene (CTPB) Binder System Using a Cure Accelerator

by Xiao Qu, Peixuan Hu, Xinyi Ma, Yunfei Liu, Hongtao Yang, Wei Zhang and Yu Chen

Molecules 2026, 31(2), 284; https://doi.org/10.3390/molecules31020284 - 13 Jan 2026

To address the issues of slow curing rate, post-curing reactions, and suboptimal mechanical properties in the carboxyl-terminated polybutadiene (CTPB)/epoxy resin (EP) binder system used for solid propellants, this study optimized the curing system by introducing 593 aliphatic amine compounds containing primary and secondary [...] Read more.

To address the issues of slow curing rate, post-curing reactions, and suboptimal mechanical properties in the carboxyl-terminated polybutadiene (CTPB)/epoxy resin (EP) binder system used for solid propellants, this study optimized the curing system by introducing 593 aliphatic amine compounds containing primary and secondary amine groups as a cure accelerator. It is found that the incorporation of the cure accelerator improved the fracture strength and elongation at break of the CTPB/EP binder system. With the addition of 0.3 wt.% cure accelerator, the tensile fracture strength increased to 0.37 MPa, while the elongation at break reached 655%. Moreover, augmenting the quantity of cure accelerator can substantially elevate the crosslink density and gel fraction of the binder system. When the addition reaches 0.3 wt.%, the crosslink density is 4.3 × 10⁻⁴ mol/cm³. Further studies showed that 593 cure accelerator reduced the activation energy of the curing reaction of the CTPB/EP binder system, with higher levels of cure accelerator resulting in lower activation energy. This study established a preparation methodology for a CTPB/EP binder system with high elongation and tensile strength. These findings provide a solid scientific foundation for the application of CTPB-based binder systems in solid propellants. Full article

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12 pages, 1783 KB

Open AccessArticle

Development of a Fluorophore-Bound l-Tryptophan Derivative for Evaluating Indoleamine 2,3-Dioxygenase Activity by HPLC with Fluorescence Detection: An In Vivo Microdialysis Study Using Rat Kidney

by Mayu Onozato, Reika Aoki, Mai Yamaguchi, Honoka Fujimoto, Tatsuya Sakamoto and Takeshi Fukushima

Molecules 2026, 31(2), 283; https://doi.org/10.3390/molecules31020283 - 13 Jan 2026

Evaluating the activity of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan (Trp) metabolism, is important because IDO is involved in immune tolerance and drives the production of Trp metabolites implicated in psychiatric disorders and cancer. This study aimed to design and develop [...] Read more.

Evaluating the activity of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan (Trp) metabolism, is important because IDO is involved in immune tolerance and drives the production of Trp metabolites implicated in psychiatric disorders and cancer. This study aimed to design and develop a novel fluorescent l-Trp derivative to fluorometrically monitor Trp-catabolizing enzyme activity via IDO. To evaluate IDO activity in vivo, 7-N,N-dimethylamino-2,1,3-benzoxadiazole (DBD), a fluorophore, was covalently bound at the 5-position of the indole ring in Trp to produce 5-DBD-l-Trp. An in vivo microdialysis (MD) study was conducted using the kidneys of Sprague–Dawley rats. Specifically, 5.0 μM 5-DBD-l-Trp in phosphate-buffered Ringer’s solution was infused into the rats, and the MD sample was analyzed via high-performance liquid chromatography with fluorescence detection. In the MD sample, two fluorescence peaks other than 5-DBD-l-Trp were observed during the 5-DBD-l-Trp infusion, and the main metabolite peak was proposed to be 5-DBD-kynurenine, verified by liquid chromatography-tandem mass spectrometry. The intensity of the fluorescent peak was significantly attenuated by co-infusion with an IDO inhibitor, 1-methyl-d-Trp. These results suggest that 5-DBD-l-Trp may be metabolized by renal IDO and can be used to evaluate IDO activity in vivo. Full article

(This article belongs to the Special Issue Analytical Chemistry in Asia, 2nd Edition)

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17 pages, 1432 KB

Open AccessArticle

Screening for Peptides to Bind and Functionally Inhibit SARS-CoV-2 Fusion Peptide Using Mirrored Combinatorial Phage Display and Human Proteomic Phage Display

by Ajay Pal, Neeladri Sekhar Roy, Matthew Angeliadis, Priyanka Madhu, Sophie O’Reilly, Indrani Bera, Nathan Francois, Aisling Lynch, Virginie Gautier, Marc Devocelle, David J. O’Connell and Denis C. Shields

Molecules 2026, 31(2), 282; https://doi.org/10.3390/molecules31020282 - 13 Jan 2026

To identify pancoronaviral inhibitors, we sought to identify peptides that bound the evolutionarily conserved SARS-CoV-2 spike fusion peptide (FP). We screened the NEB PhD-7-mer random combinatorial phage display library against FP, synthesised as a D-peptide, to identify peptides from the L-library to be [...] Read more.

To identify pancoronaviral inhibitors, we sought to identify peptides that bound the evolutionarily conserved SARS-CoV-2 spike fusion peptide (FP). We screened the NEB PhD-7-mer random combinatorial phage display library against FP, synthesised as a D-peptide, to identify peptides from the L-library to be synthesised as proteolytically resistant D peptides. We selected the top ten peptides that were not seen in another published screen with this library, as these were more likely to be specific. All ten D-peptides had no impact on the infection of Vero-E6/TMPRSS2 cells by SARS-CoV-2. Screening of a proteomic-derived phage display library from the disordered regions of human proteins identified two overlapping 14mer peptides from a region of OTUD1. While a synthetic peptide based on their sequences failed to markedly inhibit viral entry, molecular dynamics structural modelling highlighted a stable binding mode where positive residues on one side of the OTUD1 helix interacted with hydrophobic residues of the FP triple-helical wedge. Thus, while the two phage display strategies failed to yield peptide sequences that are themselves strong inhibitors of viral infection, they led to the development of a computational model that can underpin future designs of potential pancoronaviral FP disruptors. Full article

(This article belongs to the Special Issue Bioengineered Peptides and Proteins as Potential Therapeutic Agents)

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19 pages, 1528 KB

Open AccessArticle

Comparative Expression of Diacylglycerol Acyltransferases for Enhanced Accumulation of Punicic Acid-Enriched Triacylglycerols in Yarrowia lipolytica

by Veronika Hambalko, Simona Vevericová, Jaroslav Hambalko, Vladimír Štefuca, Peter Gajdoš and Milan Čertík

Molecules 2026, 31(2), 281; https://doi.org/10.3390/molecules31020281 - 13 Jan 2026

Punicic acid is an uncommon ω-5 conjugated fatty acid with significant biological activity, mainly found in pomegranate seed oil. Due to limited natural availability, heterologous production of punicic acid in oleaginous yeasts offers a sustainable alternative. In this study, Yarrowia lipolytica was engineered [...] Read more.

Punicic acid is an uncommon ω-5 conjugated fatty acid with significant biological activity, mainly found in pomegranate seed oil. Due to limited natural availability, heterologous production of punicic acid in oleaginous yeasts offers a sustainable alternative. In this study, Yarrowia lipolytica was engineered for punicic acid biosynthesis by expressing the PgFADX gene from Punica granatum and subsequently modified to evaluate the influence of distinct diacylglycerol acyltransferases on punicic acid accumulation. The effects of seven acyltransferases, originating from P. granatum or Y. lipolytica, were compared under various cultivation conditions. The PgDGAT1 enzyme demonstrated the most favorable balance between total lipid content and punicic acid accumulation. Medium containing crude glycerol as a low-cost carbon source was initially tested in flask experiments with punicic acid accumulation in yeast cells of 129 mg/L. Further optimization of crude glycerol medium and subsequent scale-up experiments confirmed the potential of crude glycerol as an effective substrate, yielding up to 147.8 mg/L of punicic acid. Overall, this work identifies key enzymatic determinants for efficient punicic acid biosynthesis and supports Y. lipolytica as a robust host for the sustainable production of conjugated fatty acids from waste substrates. Full article

(This article belongs to the Special Issue Research Progress on Functional Lipids and Their Applications in Health Food Systems)

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21 pages, 1207 KB

Open AccessArticle

Yeast as a By-Product from Wine and Beer Production: Comparative Evaluation of Physico-Chemical Composition

by Ionuț Avrămia, Adriana Dabija, Mircea Oroian, Larisa Caisin, Vitalii Agapii, Aurelian Rotaru and Ancuta Chetrariu

Molecules 2026, 31(2), 280; https://doi.org/10.3390/molecules31020280 - 13 Jan 2026

The trend toward sustainable protein substitutes is driven by growing concerns about food security, sustainability, and human health. Spent brewer’s yeast and wine lees are two by-products of the beer and wine industry with high potential, owing to their complex composition, which remains [...] Read more.

The trend toward sustainable protein substitutes is driven by growing concerns about food security, sustainability, and human health. Spent brewer’s yeast and wine lees are two by-products of the beer and wine industry with high potential, owing to their complex composition, which remains insufficiently exploited. The purpose of this study was to perform a comparative analysis of the two by-products under two different drying techniques to observe if there are significant changes in composition: oven-drying and freeze-drying. Two samples of wine lees from producers in the Republic of Moldova were used—Asconi Winery and Cricova Winery (Republic of Moldova)—as well as a sample of spent brewer’s yeast offered by Efes Vitanta Moldova Brewery. The samples were characterized in terms of physicochemical properties, antioxidant activity (total polyphenol content (TPC), individual polyphenol content, and DPPH assay scavenging activity), color, mineral content, structural composition (FT-IR analysis), and microstructure, as well as organic acid and B vitamin content. The highest protein content was recorded in the samples from Cricova (45.35–46.81%). Regarding the polyphenols, the oven-dried Efes sample exhibited a TPC value of 3.98 mg GAE/g, while the highest DPPH value of 88.92% was observed in the Asconi sample. All analyzed samples showed a diverse composition of individual phenolic compounds, including 4-hydroxybenzoic acid, vanillic acid, caffeic acid, and rosmarinic acid. Wine lees samples have the highest content of B vitamins, with vitamin B3 being the most abundant across all samples, followed by vitamin B6. The microstructural examination revealed autolyzed yeast cells, with more permeable cell walls, favorable to subsequent valorization treatments, and in some cases, cells form clusters in a mother-daughter junction due to serial re-pitching. Full article

(This article belongs to the Special Issue Re-Valorization of Waste and Food Co-Products)

34 pages, 4418 KB

Open AccessReview

Recent Advances in Simultaneous Desulfurization and Denitrogenation of Fuel Oil

by Jianrui Wang and Rui Wang

Molecules 2026, 31(2), 279; https://doi.org/10.3390/molecules31020279 - 13 Jan 2026

The elimination of nitrogen and sulfur compounds from liquid fuel is a critical aspect of reducing environmental pollution. However, the widely utilized hydrodesulfurization and hydrodenitrogenation technologies require harsh operating conditions. Moreover, when operated simultaneously, these processes induce mutual competition and inhibition between the [...] Read more.

The elimination of nitrogen and sulfur compounds from liquid fuel is a critical aspect of reducing environmental pollution. However, the widely utilized hydrodesulfurization and hydrodenitrogenation technologies require harsh operating conditions. Moreover, when operated simultaneously, these processes induce mutual competition and inhibition between the two reactions, thereby limiting the actual removal efficiency. Conversely, non-hydrogenation technologies offer substantial advantages in terms of operating conditions and provide high levels of desulfurization and denitrogenation. Nevertheless, the presence of nitrogen-containing compounds has also been demonstrated to engender competition and inhibition. It is imperative to develop environmentally friendly technologies that can simultaneously desulfurize and denitrogenate. This paper reviews research progress in this field over the past decade, providing a detailed assessment and comparison of hydrogenation and non-hydrogenation technologies, including adsorption, extraction, oxidation and biological methods. Furthermore, it considers future research directions. The article’s aim is to furnish a novel perspective on the development of clean fuel sources and to investigate more economical, sustainable, and commercially viable desulfurization and denitrogenation methods. Full article

(This article belongs to the Topic Environmental Pollutant Management and Control)

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13 pages, 1671 KB

Open AccessArticle

Structural Elucidation and Moisturizing Potential of a Polysaccharide Derived from Tremella mesenterica

by Geu-Rim Song, Hye-Ryung Park, Hye-Won Lee, Seo-Young Choi, You-Ah Kim, Byoung-Jun Park and Kwang-Soon Shin

Molecules 2026, 31(2), 278; https://doi.org/10.3390/molecules31020278 - 13 Jan 2026

Tremella mesenterica, commonly known as the yellow brain or golden jelly fungus, has been traditionally used for its medicinal properties. In this study, we elucidated the structural characteristics of T. mesenterica polysaccharide (TMP) and evaluated its potential moisturizing mechanism in vitro, comparing [...] Read more.

Tremella mesenterica, commonly known as the yellow brain or golden jelly fungus, has been traditionally used for its medicinal properties. In this study, we elucidated the structural characteristics of T. mesenterica polysaccharide (TMP) and evaluated its potential moisturizing mechanism in vitro, comparing it to Tremella fuciformis polysaccharide (TFP) and hyaluronic acid (HA). TMP was isolated through enzyme assisted extraction and it has a molecular weight (MW) of approximately 143 kDa. We investigated the composition of mannose, xylose, glucuronic acid, and glucose as a ratio of 59.8 ± 0.3, 24.0 ± 1.2, 11.0 ± 0.8, 5.2 ± 0.0, respectively. Through methylation and GC-MS analysis, we discovered TMP was composed of a main chain of β-(1→3)-linked mannopyranoside, substituted with various side chains such as xylopyranoside, glucuronopyranoside, glucopyranoside at the C-2 or C-4 positions of the backbone. TMP upregulated the expression of key moisturizing-related factors compared to TFP and HA, such as aquaporin-3 (AQP3) with 55% and 57% at 25 and 50 μg/mL and hyaluronic acid synthase-2 (HAS2) with 22% at 25 μg/mL, as confirmed through qRT-PCR analysis. Additionally, TMP significantly enhanced the expression of filaggrin (FLG), a critical protein involved in skin barrier function, with 22% at 25 μg/mL. Immunocytochemistry (ICC) analysis further revealed that TMP achieved the highest improvement in hyaluronic acid synthase-3 (HAS3) protein levels by 475% at 50 μg/mL. While further in vivo studies are required to substantiate its functional moisturizing efficacy, these findings suggest that TMP serves as a promising moisturizing agent. The structural and functional properties of TMP provide a potential foundation for its application in diverse industries, including cosmetics, food, biopolymers, and pharmaceuticals. Full article

(This article belongs to the Special Issue New Perspective on Polysaccharides: From Isolation to Biological Evaluation)

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15 pages, 1585 KB

Open AccessArticle

Comparative Analysis of Phytochemical Profile and Antioxidant and Antimicrobial Activity of Green Extracts from Quercus ilex and Quercus robur Acorns

by Diego Gonzalez-Iglesias, Francisco Martinez-Vazquez, Laura Rubio, Jesús María Vielba, Trinidad de Miguel and Marta Lores

Molecules 2026, 31(2), 277; https://doi.org/10.3390/molecules31020277 - 13 Jan 2026

An environmentally friendly extraction strategy based on an MSAT (Medium Scale Ambient Temperature) system was applied to Quercus ilex and Quercus robur acorns with the aim of maximizing polyphenolic yield and antioxidant activity while minimizing solvent consumption. Operational parameters were first optimized for [...] Read more.

An environmentally friendly extraction strategy based on an MSAT (Medium Scale Ambient Temperature) system was applied to Quercus ilex and Quercus robur acorns with the aim of maximizing polyphenolic yield and antioxidant activity while minimizing solvent consumption. Operational parameters were first optimized for Quercus ilex using a BBD-RSM (Box–Behnken response surface methodology), where the optimum working zone corresponds to the values of 200 g of acorn, 100 mL of extracting solvent, and 0.5 dispersant/acorn ratio. Subsequently, these conditions were applied to Quercus robur to enable an interspecific comparison. Extracts were evaluated in terms of total polyphenolic content, antioxidant activity, reducing sugars, proteins, targeted polyphenols quantified by UHPLC-QToF, and antimicrobial activity. Optimal extractions from Quercus ilex reached 25,072 mgGAE L⁻¹ and 162 mmolTE L⁻¹, while Quercus robur extracts showed markedly superior values of 35,822 mgGAE L⁻¹ and 234 mmolTE L⁻¹. Polyphenol quantification revealed higher concentrations of gallotannins in Quercus robur and procyanidins and catechin in Quercus ilex. The extracts showed strong antibacterial activity, especially Quercus ilex against S. aureus with a MIC ≤ 0.63%. Furthermore, it has been demonstrated for the first time that acorn extracts can inhibit the growth of Phytophthora cinnamomi in vitro, with Quercus robur extracts having a MIC ≤ 0.1% and Quercus ilex extracts ≤ 1%. Full article

(This article belongs to the Section Natural Products Chemistry)

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25 pages, 975 KB

Open AccessArticle

Formal Synthesis of Ortho-Cyanated N-Heterocycles via Direct, Metal-Free Cyanation of N-Oxides Under Benign Conditions

by Hua Xiao, Reziyamu Wufuer and Dong Wang

Molecules 2026, 31(2), 276; https://doi.org/10.3390/molecules31020276 - 13 Jan 2026

The introduction of cyano groups into aza-heterocyclic compounds plays a pivotal role in accessing diverse derivatives that are essential for the development of natural products, pharmaceuticals, and agrochemicals. Herein, we report a unified strategy for the direct ortho-C-H cyanation of a broad [...] Read more.

The introduction of cyano groups into aza-heterocyclic compounds plays a pivotal role in accessing diverse derivatives that are essential for the development of natural products, pharmaceuticals, and agrochemicals. Herein, we report a unified strategy for the direct ortho-C-H cyanation of a broad range of heterocyclic N-oxides, including pyridine, quinoline, isoquinoline, and pyrimidine derivatives. This transformation proceeds under mild conditions without the need for external activating agents or catalysts, and has been successfully applied to structurally complex, biologically relevant molecules. Compared to existing methodologies, our approach offers several distinct advantages: the use of non-prefunctionalized heteroarene substrates, environmentally benign reaction solvents, operational simplicity, broad substrate scope, and high efficiency in generating diverse ortho-cyanated heterocyclic compounds. Moreover, the method demonstrates considerable potential for scalable synthesis. Full article

(This article belongs to the Special Issue C-H Bond Functionalization of Heterocyclic Compounds)

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23 pages, 1905 KB

Open AccessArticle

Anticancer and Antimicrobial Activity of Chlorella vulgaris BA02 Algae Extract Containing Indole-3-Acetic Acid

by Agata Jabłońska-Trypuć, Urszula Wydro, Elżbieta Wołejko, Paweł Kondzior, Maja Leszczyńska, Carmen Estevan Martínez, Özge Karakaş Metin, Marzena Ewa Smolewska, Rafał Krętowski, Marzanna Cechowska-Pasko and Adam Cudowski

Molecules 2026, 31(2), 275; https://doi.org/10.3390/molecules31020275 - 13 Jan 2026

In recent years, the incidence of breast cancer has increased significantly; therefore, much attention is being paid to research on natural plant-based raw materials in the treatment and prevention of cancer as well as in the treatment of antibiotic-resistant infections. Therefore, Chlorella vulgaris [...] Read more.

In recent years, the incidence of breast cancer has increased significantly; therefore, much attention is being paid to research on natural plant-based raw materials in the treatment and prevention of cancer as well as in the treatment of antibiotic-resistant infections. Therefore, Chlorella vulgaris algae extract and indole-3-acetic acid (IAA)—a plant hormone with potential anticancer and antimicrobial properties—were selected for the study. The main objective was to evaluate the effect of algae extract and IAA on the proliferation of cells from three different breast cancer lines: MCF-7, ZR-75-1, and MDA-MB-231. In addition, an analysis of apoptosis and oxidative stress parameters in cancer cells was performed, as well as an assessment of IAA toxicity towards E. coli, S. aureus, and C. albicans. The results obtained allow us to conclude that the extract is effective against estrogen-dependent cells, while the effect of IAA alone varies depending on the microorganism studied, the cell line analyzed, and the concentration used. The extract in selected concentrations induces apoptosis and activates oxidative stress mechanisms, while IAA exhibits cytotoxicity at higher concentrations and stimulates proliferation at lower concentrations. This indicates the need to investigate the mechanisms of action of both Chlorella vulgaris algae extract and IAA in cancer and bacterial cells. Full article

(This article belongs to the Special Issue Potential of Natural Products as Drug Leads Possessing Antioxidant, Antiaging and Anticancer Properties)

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18 pages, 2914 KB

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Various Analytical Techniques Reveal the Presence of Damaged Organic Remains in a Neolithic Adhesive Collected During Archeological Excavations in Cantagrilli (Florence Area, Italy)

by Federica Valentini, Lucia Sarti, Fabio Martini, Pasquino Pallecchi, Ivo Allegrini, Irene Angela Colasanti, Camilla Zaratti, Andrea Macchia, Angelo Gismondi, Alessia D’Agostino, Antonella Canini and Anna Neri

Molecules 2026, 31(2), 274; https://doi.org/10.3390/molecules31020274 - 13 Jan 2026

In this work, an archeological adhesive collected at Cantagrilli (near Florence) was chemically analyzed by applying gas chromatography/mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectrometry combined with the archeobotanical investigations. Data identify triterpenes, aged anhydride, benzoyl resin, and gelatinized starch in the [...] Read more.

In this work, an archeological adhesive collected at Cantagrilli (near Florence) was chemically analyzed by applying gas chromatography/mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance spectrometry combined with the archeobotanical investigations. Data identify triterpenes, aged anhydride, benzoyl resin, and gelatinized starch in the sample. The multi-analytical approach allowed us to identify some molecular compounds, as well as their state of chemical decomposition (especially by applying the mass spectrometry techniques). On the other hand, archeobotanical measurements have provided useful but not unequivocal information regarding the possible origin of triterpenes from some terrestrial plants, combined with the presence of microorganisms and transformed chemicals (such as starch modified into gelatin). All this information is very useful to Prehistoric Archeologists for understanding the cultural processes and technologies used by ancient populations. Full article

(This article belongs to the Special Issue Advances in the Chemical Analysis of Prehistoric Materials)

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15 pages, 531 KB

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Disrupted Vitamin D Metabolism in Hepatocellular Carcinoma: Free and Bioavailable 25(OH)D as Novel Biomarkers of Hepatic Reserve and Clinical Risk

by Joško Osredkar, Matej Rakusa, Aleš Jerin, Borut Štabuc, Martin Zaplotnik, Saša Štupar and Darko Siuka

Molecules 2026, 31(2), 273; https://doi.org/10.3390/molecules31020273 - 13 Jan 2026

Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. [...] Read more.

Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer. Full article

(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)

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23 pages, 6327 KB

Open AccessArticle

Influence of Cross-Linking Agents on the Structure and Stability of Chitosan and Carboxymethyl Chitosan Thin Films

by Katarzyna Lewandowska

Molecules 2026, 31(2), 272; https://doi.org/10.3390/molecules31020272 - 13 Jan 2026

Chitosan (CS) and carboxymethyl chitosan (CMCS) are polysaccharides valued for their biocompatibility, reactivity, and film-forming capabilities. This study compares the surface characteristics and stability of CS and CMCS thin films crosslinked with citric acid (CTA), polyethylene glycol diglycidyl ether (PEGDE), and glutaraldehyde (G). [...] Read more.

Chitosan (CS) and carboxymethyl chitosan (CMCS) are polysaccharides valued for their biocompatibility, reactivity, and film-forming capabilities. This study compares the surface characteristics and stability of CS and CMCS thin films crosslinked with citric acid (CTA), polyethylene glycol diglycidyl ether (PEGDE), and glutaraldehyde (G). Flow behavior was assessed using steady-shear measurements, while film structure, morphology, and physical properties were analyzed by infrared spectroscopy, SEM, AFM, mechanical testing, and swelling experiments. Crosslinking generated new chemical bonds in both CS and CMCS films; however, interactions in CMCS did not result in stable cross-links and were comparatively weaker. These structural modifications influenced swelling behavior and enhanced stability, particularly in CS-based systems. Before neutralization, CS/PEGDE films exhibited the lowest swelling (67% ± 19) relative to unmodified CS (118% ± 25) and crosslinked samples such as CS/G2 (185% ± 30), CS/G1 (475% ± 88), and CS/CTA (520% ± 90). After neutralization, CS/G1 and CS/CTA maintained the highest swelling capacity. In contrast, CMCS films crosslinked with CTA and G1 dissolved rapidly in aqueous media due to high water uptake, while PEGDE- and G2-modified CMCS films demonstrated stability comparable to CS. Overall, the results highlight the superior stability and tunable surface properties of CS-based films, underscoring their potential for biomedical and packaging applications. Full article

(This article belongs to the Special Issue Applications of Natural Polymers in Biomedicine)

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11 pages, 650 KB

Open AccessArticle

Four New Sesquiterpene Pyridine Alkaloids from the Roots of Tripterygium wilfordii Hook. f

by Ya-Dan Wang, Yu-Tong Li, Yong-Jian Wang, Zhong-Mou Zhang, Bo-Rui Zou, Ying-Lin Dai, Hui-Ying Yang and Xian-Fu Wu

Molecules 2026, 31(2), 271; https://doi.org/10.3390/molecules31020271 - 13 Jan 2026

Investigation of the roots of Tripterygium wilfordii Hook. f. resulted in the isolation of nine sesquiterpene pyridine alkaloids (SPAs), including four previously undescribed compounds 1–4. The structures of all compounds were elucidated by extensive spectroscopic analysis, including NMR and HRESIMS. [...] Read more.

Investigation of the roots of Tripterygium wilfordii Hook. f. resulted in the isolation of nine sesquiterpene pyridine alkaloids (SPAs), including four previously undescribed compounds 1–4. The structures of all compounds were elucidated by extensive spectroscopic analysis, including NMR and HRESIMS. In particular, compound 1 was found to possess an unprecedented cage-like ether moiety, representing the first report of such a structural feature within this class of alkaloids. All isolated compounds were evaluated for their anti-inflammatory activity using a lipopolysaccharide (LPS)-induced RAW264.7 macrophage model. Compounds 1, 2, and 4 exhibited significant inhibition of nitric oxide (NO) production, with IC₅₀ values of 7.14 ± 1.89, 8.55 ± 0.37, and 14.76 ± 0.39 μM. Furthermore, compounds 1 and 2 suppressed the secretion of key pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, in the same cellular model. These results not only enhanced the structural diversity of SPAs identified from T. wilfordii, but also highlight their potential as promising anti-inflammatory lead compounds. Full article

(This article belongs to the Section Natural Products Chemistry)

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