Journal Description
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)
Latest Articles
Development of a Peptide-Based Photoimmunotherapy Drug Targeting PD-L1
Molecules 2026, 31(2), 302; https://doi.org/10.3390/molecules31020302 - 14 Jan 2026
Abstract
Near-infrared photoimmunotherapy (NIR-PIT) has recently attracted attention as a highly selective cancer treatment, with good treatment outcomes observed from the only antibody-based drug currently available for clinical use. However, since only a single agent is currently used clinically and the development of new
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Near-infrared photoimmunotherapy (NIR-PIT) has recently attracted attention as a highly selective cancer treatment, with good treatment outcomes observed from the only antibody-based drug currently available for clinical use. However, since only a single agent is currently used clinically and the development of new antibodies is costly, exploring other therapeutic modalities is important. In this study, we investigated a novel peptide-based PIT drug targeting programmed death-ligand 1 (PD-L1), which is overexpressed in many types of cancer. The WL12 peptide, which is known to bind to PD-L1, was conjugated with the photoabsorber IRDye700DX (IR700), and its usefulness was evaluated in vitro and in vivo. In therapeutic experiments on PD-L1-positive cells, NIR-PIT with WL12-IR700 induced PIT-like morphological changes in cells and reduced cancer cell viability in an NIR light dose- and drug concentration-dependent manner. In vivo experiments showed significant suppression of tumor growth and an extended overall survival rate. These results indicate that the developed peptide-based drug can be used for PD-L1-targeted NIR-PIT.
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(This article belongs to the Special Issue Exploring the Therapeutic Potential of Peptides in Anti-Cancer Treatments)
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Open AccessArticle
Discovery of a New Rosamicin Derivative from Endophytic Micromonospora rosaria FoRo54 Using Genome Mining Technology
by
Zhi-Bin Zhang, Qi Liu, Guo-Dong Song, Yi-Wen Xiao, Ri-Ming Yan and Du Zhu
Molecules 2026, 31(2), 301; https://doi.org/10.3390/molecules31020301 - 14 Jan 2026
Abstract
Endophytic FoRo54 was isolated from the roots of Oryza rufipogon (Dongxiang wild rice) collected in China. Based on morphological characteristics and phylogenetic analysis of the 16S rRNA gene sequence, strain FoRo54 was identified as closely related to Micromonospora rosaria. The complete genome
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Endophytic FoRo54 was isolated from the roots of Oryza rufipogon (Dongxiang wild rice) collected in China. Based on morphological characteristics and phylogenetic analysis of the 16S rRNA gene sequence, strain FoRo54 was identified as closely related to Micromonospora rosaria. The complete genome of FoRo54 consists of a linear chromosome of 7,057,852 bp with a GC content of 73.8 mol%. Genome mining using antiSMASH revealed 27 biosynthetic gene clusters (BGCs) potentially involved in secondary metabolite biosynthesis, including those associated with kanamycin, rosamicin, and asukamycin, consistent with the antibacterial activities of the strain. Application of a combined genome mining strategy enabled further exploration of the strain’s metabolic potential. One new rosamicin derivative, N-demethyl rosamicin (1), together with three known compounds, rosamicin (2), SCH 23831 (3), and tylactone (4), were isolated from fermentation broth. Antibacterial evaluation revealed that compounds 1-4 exhibited potent inhibitory activity against Staphylococcus aureus. Furthermore, based on genomic analysis, the biosynthetic pathway and putative gene functions responsible for these metabolites were proposed. Collectively, these findings highlight the metabolic versatility of the endophytic Micromonospora rosaria FoRo54, underscoring its potential as a valuable source of novel bioactive metabolites and providing a genomic framework for future heterologous expression and functional genetic characterization.
Full article
(This article belongs to the Section Bioorganic Chemistry)
Open AccessArticle
Production and Characterization of Novel Photocatalytic Materials Derived from the Sustainable Management of Agro-Food By-Products
by
Christina Megetho Gkaliouri, Eleftheria Tsampika Laoudikou, Zacharias Ioannou, Sofia Papadopoulou, Vasiliki Anastasia Giota and Dimitris Sarris
Molecules 2026, 31(2), 300; https://doi.org/10.3390/molecules31020300 - 14 Jan 2026
Abstract
Porous photocatalysts from agricultural waste, i.e., apricot and peach shell, with titanium dioxide were prepared by a carbonaceous method, the adsorption and photocatalytic degradation and its kinetics about methylene blue (MB) were studied systematically. The properties of the prepared composite sorbents were characterized
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Porous photocatalysts from agricultural waste, i.e., apricot and peach shell, with titanium dioxide were prepared by a carbonaceous method, the adsorption and photocatalytic degradation and its kinetics about methylene blue (MB) were studied systematically. The properties of the prepared composite sorbents were characterized using Brunauer–Emmett–Teller, surface area, scanning electron microscopy, and energy dispersive spectroscopy analyses. Several key factors, including radiation, pH, temperature, initial MB concentration, contact time, and sorbent dosage, as well as photocatalytic activity were investigated. All the waste-TiO2 adsorbents showed improved adsorption and photodegradation performance compared to commercial charchoal-TiO2. The produced materials presented high specific surface areas especially those derived from apricot shell-TiO2 with a combination of type I and IV adsorption isotherms with a hysteresis loop indicating micro and mesopore structures. In addition, under UV radiation, the composite sorbents exhibited greater MB removal efficiency than non-radiated composite sorbents. The examined conditions have shown the best MB adsorption results at pH greater than 7.5, temperature 30 °C, contact time 120 min, initial concentration 0.5 mg/L MB, and sorbent dosage equal to 2.0 g/L C/MB. The total removal rate of MB is 98.5%, while the respective amount of commercial charcoal-TiO2 is equal to 75.0%. The kinetic model that best describes the experimental data of MB degradation from the photocatalytic materials is the pseudo-second order model. In summary, this work highlights the effectiveness and feasibility of transforming agricultural waste into carbonaceous composite sorbent for the removal of cationic dyes from wastewater. Future work will involve scaling up the synthesis of the catalyst and evaluating its performance using bed reactors for industrial processes.
Full article
(This article belongs to the Special Issue Agricultural and Food Residues: Treatment and Valorization of By-Products and Wastes)
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Open AccessReview
Design and Application of Hetero-Multicomponent Metal Oxide Photocatalysts for Wastewater Treatment: Ti–Cu–Zn Catalysts and Future Research Directions
by
Maria-Anthoniette Oghenetejiro Onoriode-Afunezie, Justinas Krutkevičius and Agnė Šulčiūtė
Molecules 2026, 31(2), 299; https://doi.org/10.3390/molecules31020299 - 14 Jan 2026
Abstract
Hetero-multicomponent metal oxide catalysts are attracting increasing attention for wastewater remediation due to their tunable band structures, synergistic redox activity, and enhanced stability. This review thoroughly evaluates recent progress in the synthesis and application of such catalysts, highlighting Ti–Cu–Zn nanostructures as a representative
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Hetero-multicomponent metal oxide catalysts are attracting increasing attention for wastewater remediation due to their tunable band structures, synergistic redox activity, and enhanced stability. This review thoroughly evaluates recent progress in the synthesis and application of such catalysts, highlighting Ti–Cu–Zn nanostructures as a representative case study. We examine synthesis approaches—including hydrothermal, biosynthesis, precipitation, and spray-based methods, with additional insight into sol–gel and other less commonly applied techniques—with emphasis on their suitability for constructing layered and multicomponent heterostructures. Mechanistic aspects of photocatalysis, Fenton and Fenton-like processes, adsorption, and electrochemical routes are discussed, with particular focus on charge separation, reactive oxygen species (ROS) generation, and pollutant-specific degradation pathways. Comparative performance metrics against antibiotics, pesticides, dyes, and fertilizers are analyzed, alongside considerations of leaching, reusability, and scale-up potential. Importantly, while significant progress has been made for organic micropollutants, applications in heavy metal remediation remain scarce, highlighting an urgent research gap. By situating Ti–Cu–Zn systems within the broader class of multicomponent catalysts, this review not only synthesizes current advances but also identifies opportunities to expand their role in sustainable wastewater management, including field deployment, regulatory compliance, and integration into decentralized treatment systems.
Full article
(This article belongs to the Special Issue Recent Advances in Chemical Treatments of Wastewater)
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Open AccessArticle
Fortification of Durum Wheat Pasta with Mealworm (Tenebrio molitor) Powder: Physicochemical, Nutraceutical, and Sensory Effects
by
Ewelina Zielińska, Paulina Sidor and Urszula Pankiewicz
Molecules 2026, 31(2), 298; https://doi.org/10.3390/molecules31020298 - 14 Jan 2026
Abstract
Edible insects are gaining popularity as an alternative food source, highlighting the urgent need for research on their incorporation into traditional food products. This study investigated the impact of incorporating mealworm (Tenebrio molitor) powder (MP) at 2%, 5%, and 10% levels
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Edible insects are gaining popularity as an alternative food source, highlighting the urgent need for research on their incorporation into traditional food products. This study investigated the impact of incorporating mealworm (Tenebrio molitor) powder (MP) at 2%, 5%, and 10% levels on the nutritional, functional, and sensory properties of pasta. Proximate composition, mineral content, color parameters, cooking quality, antioxidant activity and sensory properties were evaluated. Starch digestibility fractions and predicted glycemic index (pGI) were calculated based on in vitro enzymatic hydrolysis. Results showed that 10% MP addition significantly increased protein (1.45-fold) and fat content (12-fold), enriched minerals (Fe, Zn, Mg, K), and improved antioxidant capacity (ABTS+·: 1.3-fold; DPPH·: 2.6-fold) and phenolic content (14.4-fold) compared to control. Color analysis revealed a decrease in lightness and an increase in redness, indicating darker tones with higher MP levels. This supplementation reduced rapidly digestible starch and pGI while increasing slowly digestible starch, suggesting benefits for glycemic control. Sensory evaluation revealed no significant differences (p > 0.05) among samples for appearance, color, taste, and overall impression, confirming good acceptability. Overall, MP fortification improved nutritional and functional properties without compromising sensory quality, supporting its application in developing high-protein, health-oriented foods.
Full article
(This article belongs to the Special Issue Functional Foods Enriched with Natural Bioactive Compounds)
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Open AccessArticle
Luteolin Inhibits Invasion of Listeria monocytogenes by Interacting with SortaseA and InternalinB
by
Junlu Liu, Rui Liu, Hang Pan, Jiahui Lu, Qiong Liu and Guizhen Wang
Molecules 2026, 31(2), 297; https://doi.org/10.3390/molecules31020297 - 14 Jan 2026
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Listeria monocytogenes (LM) is a lethal foodborne intracellular pathogen. Internalins A and B (inlA and inlB) are critical virulence factors that promote LM’s adhesion and invasion into host cells. InlA is covalently anchored to the cell wall by LM SortaseA (SrtA), while inlB
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Listeria monocytogenes (LM) is a lethal foodborne intracellular pathogen. Internalins A and B (inlA and inlB) are critical virulence factors that promote LM’s adhesion and invasion into host cells. InlA is covalently anchored to the cell wall by LM SortaseA (SrtA), while inlB is anchored to the cell wall via non-covalent bonds. Therefore, inhibiting SrtA and inlB is expected to suppress LM’s adhesion and invasion of host cells, enabling the prevention and control of infections. This study demonstrated that Luteolin inhibited the activity of purified LM SrtA protein in vitro. Interactive mechanism analysis indicated that Luteolin generates interaction with the critical active sites of SrtA, which may affect its binding to its natural substrates, thereby reducing the anchoring of inlA on the cell wall and achieving the inhibition of bacterial adhesion and invasion. In addition, Luteolin binds to the groove at the binding interface between inlB and its host receptor. The key residues in inlB that interact with the host receptor form weak interactions (Hydrogen bonds and van der Waals interactions) with Luteolin, this binding may inhibit their binding, suppressing LM’s adhesion and invasion of host cells. At the tested concentrations, Luteolin did not affect the growth of LM, but remarkably reduced the mortality and alleviated the infection symptoms of LM-infected Galleria mellonella. These results provide additional theoretical evidence for the application of Luteolin in the prevention and control of LM infections, which is expected to accelerate its application progress.
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Open AccessArticle
Chemical Composition, Antimicrobial, Antioxidant, and Anticancer Activities of Jacquemontia pentantha Essential Oils
by
Noorah A. Alkubaisi, Mashail Fahad Alsayed, Hissah Abdulrahman Alodaini, Fuad Alanazi, Abdulhadi M. Abdulwahed and Ibrahim M. Aziz
Molecules 2026, 31(2), 296; https://doi.org/10.3390/molecules31020296 - 14 Jan 2026
Abstract
Jacquemontia pentantha (Jacq.) G. Don. (Convolvulaceae): This is a plant with rich ethnobotanical uses, but its essential oil (EO) composition and overall biological properties remain largely uninvestigated. In this research, the J. pentantha EO (JPEO) is characterized in a thorough manner,
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Jacquemontia pentantha (Jacq.) G. Don. (Convolvulaceae): This is a plant with rich ethnobotanical uses, but its essential oil (EO) composition and overall biological properties remain largely uninvestigated. In this research, the J. pentantha EO (JPEO) is characterized in a thorough manner, with an evaluation of its in vitro antioxidant, antimicrobial, and cytotoxic properties, aiming to provide scientific support for ethnobotanical uses, as well as the definition of new potentialities. The EOs were isolated from the aerial part of the plant via hydrodistillation, and a qualitative analysis of the components was carried out via GC–MS. The biological properties were investigated by means of standard in vitro assays: namely, DPPH and ABTS for the measurement of antioxidant activity, the disk diffusion technique, and the microbroth dilution assay for the evaluation of antimicrobial activity against six bacterial species, as well as for the assessment of the activity against five species of Candida fungi, whereas the cytotoxic activity against MCF-7 and HepG2 cells was assessed using the MTT assay. Preliminary characterization of the EOs via GC/MS revealed a particular “chemical profile” with a high concentration of himachalene-type sesquiterpenes, namely, β-himachalene (6.47%) and (+)-α-himachalene (6.46%), together with phenolic monoterpenoids. The EOs showed significant antioxidant activity (IC50 = 172.41 and 378.94 µg/mL, respectively), high phenolic content (97.34 mg GAE/g), and significant antibacterial activity (MIC = 4.68 µg/mL), especially against Pseudomonas aeruginosa, as well as against Candida albicans (MFC = 3.90 µg/mL), together with dose-dependent cytotoxic effects on the two cell lines, with IC50 = 161.62 and 151.87 µg/mL, respectively. This research indicates that the EO of this plant is a potential source of a certain “chemical profile” with noteworthy antibacterial and cytotoxic properties, thus providing scientific support for its ethnobotanical use and highlighting its particular potential for developing pharmaceutical agents against infections and cancer.
Full article
(This article belongs to the Special Issue Chemical Composition and Biological Activity of Essential Oils and Other Extracts: From Extraction to Application Second Edition)
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Open AccessEditorial
Bioactivity of Natural Compounds: From Plants to Humans
by
Guglielmina Froldi
Molecules 2026, 31(2), 295; https://doi.org/10.3390/molecules31020295 - 14 Jan 2026
Abstract
Thanks to advancements in biochemistry, biology, and pathology, natural products (NPs) continue to be a subject of intense scientific investigation [...]
Full article
(This article belongs to the Special Issue Bioactivity of Natural Compounds: From Plants to Humans)
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Open AccessArticle
Two New Andrastin-Type Meroterpenoids from Marine Sponge-Derived Fungus Botryosporium sp. S5I2-1
by
Hui-Xian Liang, Wan-Ying Guo, Shi-Hai Xu and Bing-Xin Zhao
Molecules 2026, 31(2), 294; https://doi.org/10.3390/molecules31020294 - 14 Jan 2026
Abstract
Botryomeroterpenoids A (1) and B (2), two new andrastin-type meroterpenoids, along with two known analogues (3 and 4), were isolated from sponge-derived fungus Botryosporium sp. S5I2-1. Their structures were characterized by detailed spectroscopic analysis. Meanwhile, the absolute
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Botryomeroterpenoids A (1) and B (2), two new andrastin-type meroterpenoids, along with two known analogues (3 and 4), were isolated from sponge-derived fungus Botryosporium sp. S5I2-1. Their structures were characterized by detailed spectroscopic analysis. Meanwhile, the absolute configurations of 1 and 2 were elucidated by comparing experimental and calculated ECD spectra. Compounds 1 and 2 were the first examples of andrastin-type meroterpenoids isolated from this genus, especially Compound 1 which represented the initial instance of 18-norandrastin-type meroterpenoids. Furthermore, the antibacterial activities of all compounds were also evaluated. However, the results indicated that these compounds showed no significant inhibitory activity against the tested bacteria with minimum inhibitory concentration (MIC) values of 32–64 μg/mL.
Full article
(This article belongs to the Special Issue Exploring Microorganisms and Their Bioactive Secondary Metabolites: From Nature to Application)
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Open AccessArticle
Physicochemical Characteristics of Potato Starch Extrudates Enriched with Edible Oils
by
Marzena Włodarczyk-Stasiak, Małgorzata Jurak and Agnieszka Ewa Wiącek
Molecules 2026, 31(2), 293; https://doi.org/10.3390/molecules31020293 - 14 Jan 2026
Abstract
Starch systems and their extrudates can be used as edible films, carriers, and encapsulants for bioactive substances in various industries, primarily the food, medicine, and pharmacy industries. Using appropriate modification methods, it is possible to alter their physicochemical properties to improve specific functional
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Starch systems and their extrudates can be used as edible films, carriers, and encapsulants for bioactive substances in various industries, primarily the food, medicine, and pharmacy industries. Using appropriate modification methods, it is possible to alter their physicochemical properties to improve specific functional parameters, thereby enhancing their application potential. The aim of this study was to characterize potato starch extrudates enriched with two types of edible oils (rapeseed or sunflower) at concentrations of 3%, 6%, and 9%. Chemical modification was carried out using K2CO3 as a catalyst. The structure of native and modified starch extrudates was examined using optical/confocal microscopy, FTIR, and LTNA (low-temperature nitrogen adsorption). Analogous starch dispersions were studied using static and dynamic light scattering, SLS/DLS, nephelometric methods, and electrophoretic mobility measurements to determine surface charge levels and stability. Additionally, viscosity curves were determined as a function of time and temperature. It was found that starch extrudates with 6% sunflower oil content showed optimal functional properties, characterized by greater stability, higher structural order, and better oil complexation. These findings directly translate into significant potential applications, including the development of functional products in the food industry.
Full article
(This article belongs to the Special Issue Chitosan, Chitosan Derivatives, Polysaccharides and Their Applications—3rd Edition)
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Open AccessPerspective
Calculation of the pH Values of Aqueous Systems Containing Carbonic Acid and Significance for Natural Waters, Following (Near-)Exact and Approximated Solutions: The Importance of the Boundary Conditions
by
Arianna Rosso and Davide Vione
Molecules 2026, 31(2), 292; https://doi.org/10.3390/molecules31020292 - 14 Jan 2026
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Calculating the pH values of carbonic acid solutions is an important task in studies of chemical equilibria in freshwater systems, with applications to environmental chemistry, geology, and hydrology. These pH values are also highly relevant in the context of climate change, since increasing
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Calculating the pH values of carbonic acid solutions is an important task in studies of chemical equilibria in freshwater systems, with applications to environmental chemistry, geology, and hydrology. These pH values are also highly relevant in the context of climate change, since increasing atmospheric CO2 affects the concentration of dissolved carbon dioxide and carbonic acid, collectively denoted as [H2CO3*] = [H2CO3(aq)] + [CO2(aq)]. Solving equilibrium systems to obtain analytical functions is particularly useful when such functions are required, for example, in data fitting. We show here that, although exact or near-exact solutions typically result in third- to fourth-order equations that must be solved numerically, reasonable approximations can be derived that lead to analytical second-order equations. In this framework, the chosen approximations need to meet the boundary conditions of the systems, particularly for cT → 0 and for high cT values (where cT = [H2CO3*] + [HCO3−] + [CO32−]). Finally, we provide exact solutions for a closed system containing both H2CO3* and alkalinity, which enables the description of virtually any aquatic environment without assuming equilibrium with atmospheric CO2. Implications for pH calculations in natural waters are also briefly discussed.
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Open AccessArticle
Mutagenic Potentials of DNA Interstrand Cross-Links Induced by 7,8-Dihydro-8-Oxoadenine
by
Lillian F. Schmaltz, Nestor Rodriguez and Seongmin Lee
Molecules 2026, 31(2), 291; https://doi.org/10.3390/molecules31020291 - 14 Jan 2026
Abstract
DNA interstrand cross-links (ICLs) are among the most cytotoxic forms of DNA damage, arising when the two strands of the DNA helix are covalently linked by crosslink-inducing agents such as bifunctional alkylating agents and reactive aldehydes. Several studies have demonstrated that ICLs can
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DNA interstrand cross-links (ICLs) are among the most cytotoxic forms of DNA damage, arising when the two strands of the DNA helix are covalently linked by crosslink-inducing agents such as bifunctional alkylating agents and reactive aldehydes. Several studies have demonstrated that ICLs can also be induced by reactive oxygen and nitrogen species. We previously reported that under oxidative conditions, the major oxidative adenine lesion 7,8-dihydro-8-oxoadenine (oxoA) can efficiently generate a novel class of oxoA-G ICLs, structurally resembling guanine–guanine (G–G) cross-links that can be induced by reactive nitrogen species. To investigate the mutagenic potential of these oxidation-induced ICLs in cells, we employed a SupF-based mutagenesis assay using bacterial cells. A single site-specific oxoA–G ICL was synthesized and incorporated into a plasmid, which was then introduced into an E. coli reporter strain to assess mutation profiles induced by both oxoA and oxoA–G ICLs. Our results show that oxoA–G ICLs cause A-to-C/T and G-to-C transversion mutations at the oxoA-G cross-link site, demonstrating highly promutagenic nature of the lesion in bacterial cells. We propose that the oxoA–G ICL may promote transversion mutations, likely driven by a syn conformer of unhooked oxoA-G ICL repair intermediates during translesion synthesis.
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(This article belongs to the Section Bioorganic Chemistry)
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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
Abstract
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
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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)
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
Abstract
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
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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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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
Abstract
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.
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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)
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
Abstract
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
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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)
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
Abstract
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
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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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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
Abstract
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
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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)
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
Abstract
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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
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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.
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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
Abstract
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
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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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