Molecules

24 pages, 1931 KB

Open AccessArticle

Comparison of Protein Binding and Fluorescence Quenching by Gold and Iron Oxide Nanoparticles: pH and Temperature Dependence

by Elena A. Molkova, Ruslan M. Sarimov, Tatyana A. Matveeva, Alexander V. Simakin, Arthur G. Akopdzhanov, Philipp Sharafullin, Polina Pichkur, Aleksey S. Dorokhov, Andrey Yu. Izmaylov and Sergey V. Gudkov

Molecules 2026, 31(12), 2008; https://doi.org/10.3390/molecules31122008 (registering DOI) - 8 Jun 2026

Abstract

Analysis of protein binding affinity to nanoparticles is essential for understanding how nanoparticles behave in biological systems and for optimizing their applications in medicine and biotechnology. This study demonstrates the dependence of protein binding and fluorescence quenching constants (HEWL and BSA) in the [...] Read more.

Analysis of protein binding affinity to nanoparticles is essential for understanding how nanoparticles behave in biological systems and for optimizing their applications in medicine and biotechnology. This study demonstrates the dependence of protein binding and fluorescence quenching constants (HEWL and BSA) in the presence of gold (AuNP) or iron oxide (IONP) nanoparticles on pH and temperature. The highest binding and quenching constants were observed for proteins with gold nanoparticles (~10⁹ M⁻¹). No clear effect of pH or temperature on either the binding or quenching constants of proteins with gold nanoparticles was detected. Conversely, different temperature trends were observed for the binding and quenching constants at different pH levels and for different proteins with iron oxide nanoparticles. It was shown that the nature of the nanoparticles has the strongest influence on their interactions with proteins, while the influence of environmental conditions can be considered secondary. Full article

(This article belongs to the Special Issue Macromolecules, Particles, and Colloids in Ionic Liquids: Structure, Stability, and Function)

16 pages, 3675 KB

Open AccessArticle

Tuning Electronic Structure and Piezoresistivity of Graphene by Monovacancy Defect Concentration: A First-Principles Investigation

by Shengsheng Wei, Shuaituan Wang, Ningning Su, Junqiang Wang and Mengwei Li

Molecules 2026, 31(12), 2007; https://doi.org/10.3390/molecules31122007 (registering DOI) - 8 Jun 2026

Abstract

Graphene, with its excellent mechanical and electrical properties, is an ideal candidate material for constructing high-performance piezoresistive sensors. However, lattice defects inevitably introduced during its preparation and transfer processes can significantly alter its electronic structure, thereby affecting the sensing performance of the devices. [...] Read more.

Graphene, with its excellent mechanical and electrical properties, is an ideal candidate material for constructing high-performance piezoresistive sensors. However, lattice defects inevitably introduced during its preparation and transfer processes can significantly alter its electronic structure, thereby affecting the sensing performance of the devices. Based on first-principles calculations, this work systematically investigates the effects of monovacancy defect concentrations ranging from 2% to 8% on the geometric structure, electronic structure, and piezoresistive performance of graphene. The results show that monovacancy defects induce local lattice distortions and bond reconstructions, forming 5–9 non-hexagonal ring structures at defect concentrations of 4% and 8%. In terms of electronic structure, the defects break the lattice symmetry and open a band gap. High concentrations of defects lead to severe overlapping of electronic states, causing the band gap to first increase and then decrease with increasing defect concentration, reaching a maximum value of 0.697 eV at a concentration of 6%. Meanwhile, the defects introduce localized electronic states, enhance the electron localization effect, and render the system p-type doped. Regarding piezoresistive performance, monovacancy defects significantly improve the gauge factor of graphene. At a defect concentration of 6%, the gauge factor reaches 118.23, which is approximately 36 times that of pristine graphene. These findings reveal the microscopic mechanism of strain-dependent electronic modulation in defective graphene and provide theoretical support for defect engineering design in high-performance graphene-based piezoresistive sensors. Full article

(This article belongs to the Special Issue New Trends in Graphene Nanomaterials)

24 pages, 5121 KB

Open AccessArticle

Senecio polyanthemoides Sch. Bip. (Asteraceae) Essential Oils: Chemical Composition, Interpopulation Variability Study and In Vitro Biological Activities of Eight Wild Populations

by Kehinde O. Amisu, Oladipupo A. Lawal, Olufemi A. Giwa-ajeniya, Victoria A. Dada, Kanyinsola O. Akinkunmi, Omobolanle E. Oladapo, Oyinlade C. Ogundare, Isyaku Bello, Emmanuel E. Aduak, Foluso O. Osunsanmi, Rebamang A. Mosa, Mona M. E. Eleiwa, Andy R. Opoku and Adebola O. Oyedeji

Molecules 2026, 31(12), 2006; https://doi.org/10.3390/molecules31122006 (registering DOI) - 8 Jun 2026

Abstract

The in vitro antibacterial, antioxidant, cytotoxic and larvicidal activities of essential oils isolated by hydrodistillation from the aerial parts (above the ground organs consisting of the leaves, stems and flowers) of Senecio polyanthemoides growing in three district municipalities of KwaZulu-Natal Province, South Africa [...] Read more.

The in vitro antibacterial, antioxidant, cytotoxic and larvicidal activities of essential oils isolated by hydrodistillation from the aerial parts (above the ground organs consisting of the leaves, stems and flowers) of Senecio polyanthemoides growing in three district municipalities of KwaZulu-Natal Province, South Africa were investigated. The water-distilled oils were analyzed by GC and GC/MS. Sixty-three constituents were characterized in all the samples analyzed representing 86.0–99.2% of the total oil compositions. The major components of the oils were monoterpenoid compounds with β-pinene, myrcene, α-phellandrene, cis-β-ocimene, trans-β-ocimene, β-caryophyllene, α-humulene and germacrene D found in all samples. Numerical cluster and principal component analyses of the major constituents revealed four well-defined chemotypes and a high variability within the oil samples. The essential oils show significant multi-methods activities on antioxidant, cytotoxic, and larvicidal, alongside effective antibacterial action against some key pathogens (Staphylococcus aureus, Escherichia coli, Bacillus pumilus and Enterococcus faecalis), with inhibition zone ranging from (8.3 ± 0.6–27.3 ± 0.9) mm and MIC values of ≤5.0 mg/mL. Documenting the inaugural, in-depth analysis of S. polyanthemoides growing in South Africa, this study provides novel findings on its antioxidant, larvicidal, brine shrimp lethality, and antibacterial activities. Full article

(This article belongs to the Special Issue Essential Oils: Chemical Composition, Bioactive, and Application)

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48 pages, 4282 KB

Open AccessReview

Transforming the Buckyball: Regioselective Synthesis of Water-Soluble [60]Fullerene Derivatives for Biomedical Applications

by Olga A. Kraevaya and Pavel A. Troshin

Molecules 2026, 31(12), 2005; https://doi.org/10.3390/molecules31122005 (registering DOI) - 8 Jun 2026

Abstract

Water-soluble fullerene derivatives exhibit a wide range of fascinating biological properties, including antioxidant, antiviral, antitumor, antibacterial, and myogenic effects. During the initial stage of research, most of the reported data on the biological activity of fullerenes were obtained using complex, inseparable mixtures of [...] Read more.

Water-soluble fullerene derivatives exhibit a wide range of fascinating biological properties, including antioxidant, antiviral, antitumor, antibacterial, and myogenic effects. During the initial stage of research, most of the reported data on the biological activity of fullerenes were obtained using complex, inseparable mixtures of regiomers with a big focus on fullerenols as the most accessible form of water-soluble fullerene-based compounds. However, during the past decade, significant progress has been made in the synthesis of various isomerically pure water-soluble fullerene derivatives, which opens up possibilities for more directed investigations of their biological activity. In this review, we will highlight current methods for the straightforward synthesis of different types of water-soluble fullerene derivatives with well-defined molecular structures. Special attention will be paid to the possibilities of the precise control of the number, types, and positions of functional groups on the fullerene cage. We will also discuss the opportunities for and challenges within the biomedical applications of water-soluble fullerene derivatives. Full article

(This article belongs to the Section Organic Chemistry)

39 pages, 1983 KB

Open AccessReview

The 1,5-Benzodiazepin-2-Ones: A Review on Synthetic Strategies, Reactivity and Functional Applications

by Hasan Mtiraou, Ameni Ghabi, Hanan Al-Ghulikah and Mezna Saleh Altowyan

Molecules 2026, 31(12), 2004; https://doi.org/10.3390/molecules31122004 (registering DOI) - 8 Jun 2026

Abstract

1,5-Benzodiazepin-2-one is a significant class of heterocyclic compounds that have attracted considerable attention due to these versatile scaffolds and their multifunctional properties. Owing to the presence of a fused benzene–diazepine core, these compounds display rich chemical reactivity and various physicochemical characteristics, making them [...] Read more.

1,5-Benzodiazepin-2-one is a significant class of heterocyclic compounds that have attracted considerable attention due to these versatile scaffolds and their multifunctional properties. Owing to the presence of a fused benzene–diazepine core, these compounds display rich chemical reactivity and various physicochemical characteristics, making them valuable structures in both fundamental and applied research. This review provides a comprehensive and critical overview of the advances reported to date on 1,5-benzodiazepin-2-ones, with particular emphasis on their diverse synthetic methodologies, reaction mechanisms, and structure–property relationships. Classical and modern synthetic approaches are discussed, including condensation reactions, multicomponent processes, catalytic and green chemistry approaches, as well as recent developments toward more sustainable and efficient protocols. The intrinsic reactivity of the 1,5-benzodiazepin-2-one framework enables access to structurally diverse derivatives. Furthermore, the review summarizes the broad range of applications of these heterocycles, especially in medicinal chemistry, where they have demonstrated significant biological activities, as well as in corrosion inhibition and photoluminescent materials. Finally, current challenges, limitations, and future perspectives are outlined to provide guidance for further research and development of 1,5-benzodiazepin-2-one-based systems. Full article

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

21 pages, 3806 KB

Open AccessArticle

Dual-Functional CeO₂ Nanozyme-Based Fluorescent Sensing Platform for Chiral Recognition of Arginine and “On-Off-On” Detection of p-Nitrophenol and Alkaline Phosphatase

by Hui-Ling Chen, Jing-Jing Dai, Hua Chen, Guo-Ying Chen and Feng-Qing Yang

Molecules 2026, 31(12), 2003; https://doi.org/10.3390/molecules31122003 (registering DOI) - 8 Jun 2026

Abstract

Nanomaterials with multiple enzyme-like activities offer significant opportunity for constructing multifunctional sensing methods. In this work, a hydrangea flower-like cerium dioxide nanomaterial (CeO₂ NF) with both peroxidase (POD)- and hydrolase-like activities, which was surface-modified by polyvinylpyrrolidone (PVP) in situ, was prepared through [...] Read more.

Nanomaterials with multiple enzyme-like activities offer significant opportunity for constructing multifunctional sensing methods. In this work, a hydrangea flower-like cerium dioxide nanomaterial (CeO₂ NF) with both peroxidase (POD)- and hydrolase-like activities, which was surface-modified by polyvinylpyrrolidone (PVP) in situ, was prepared through an oil bath method. Based on the POD-like activity of CeO₂ NFs, an “on-off” fluorescence method was established for chiral recognition of arginine (Arg) enantiomers. Meanwhile, utilizing the hydrolase-like activity of CeO₂ NFs and their synergistic interaction with alkaline phosphatase (ALP), an “on-off-on” fluorescence method was developed for the detection of p-nitrophenol (p-NP) and ALP. The sensor demonstrated excellent chiral selectivity for Arg enantiomers, with a high enantiomeric factor (ef) of up to 2.48, allowing for the quantitative detection of L-Arg in the range of 770–940 μM, with a limit of detection (LOD) of 26.00 μM. Furthermore, it exhibited high sensitivity for p-NP and ALP detection, with linear ranges of 10.0–84.3 μM and 300–2000 mU/mL, and LODs of 7.07 μM and 200 mU/mL, respectively. Through an enzyme kinetic analysis, fluorescence lifetime measurement, zeta potential analysis, and density functional theory (DFT) calculations, the underlying catalytic and chiral recognition mechanisms were proposed. Finally, the method was validated through the accurate detection of L-Arg, p-NP, and ALP in real samples (rabbit plasma, food-grade amino acid, and water samples). Full article

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

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18 pages, 2044 KB

Open AccessArticle

Pharmacokinetics, Excretion, and Metabolite Profiling of Leonurine in Rats: Evidence for Extensive Phase II Conjugations

by Xu Liu, Jing Hu, Yang Chen, Bin Shi, Zhanpeng Shang and Yan Liang

Molecules 2026, 31(12), 2002; https://doi.org/10.3390/molecules31122002 (registering DOI) - 8 Jun 2026

Abstract

Leonurine, a bioactive alkaloid from Leonurus japonicus, has attracted considerable pharmacological interest, yet its in vivo disposition remains insufficiently defined. In the present study, the pharmacokinetics, excretion, and metabolic profile of leonurine were systematically investigated in rats after intravenous (IV), oral (PO), [...] Read more.

Leonurine, a bioactive alkaloid from Leonurus japonicus, has attracted considerable pharmacological interest, yet its in vivo disposition remains insufficiently defined. In the present study, the pharmacokinetics, excretion, and metabolic profile of leonurine were systematically investigated in rats after intravenous (IV), oral (PO), and intraperitoneal (IP) administration. A validated LC–MS/MS method was used to quantify leonurine in plasma, urine, and feces, and high-resolution MS was applied for metabolite profiling. Following IV administration, leonurine exhibited rapid systemic disposition, with a half-life of 2.48 h and a clearance of 152 mL/min/kg. Oral exposure was negligible, with an absolute bioavailability of 0.14%, whereas IP administration produced markedly higher systemic exposure (66.6%). Recovery of unchanged leonurine in urine and feces remained low across all dosing routes, with total excretory recovery below 6% of doses. The results indicated that metabolic conversion, rather than parent drug excretion, was the dominant elimination pathway. A total of 30 leonurine-related components were characterized in vivo, including 24 previously unreported metabolites. The metabolic profile was dominated by phase II conjugation, comprising 12 glucuronidated and 12 sulfated metabolites, together with hydrolysis, methylation/demethylation, and other transformation products. Notably, ester bond cleavage was identified as one of the major primary biotransformation routes, and several glucuronide and sulfate conjugates were also formed on hydrolysis-derived fragments. These findings provide a more comprehensive view of leonurine disposition in rats and offer a mechanistic basis for its rapid clearance and limited systemic availability after oral administration. Full article

(This article belongs to the Special Issue The Application of LC-MS in Pharmaceutical Analysis—2nd Edition)

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6 pages, 172 KB

Open AccessEditorial

Bridging Discovery, Mechanism, and Application: An Integrated Strategy for Bioactive Natural Products

by Tao Liu, Clementina Manera and Francesca Gado

Molecules 2026, 31(12), 2001; https://doi.org/10.3390/molecules31122001 (registering DOI) - 8 Jun 2026

Abstract

Natural products remain one of the most reliable starting points for new medicines, agrochemicals, and functional ingredients [...] Full article

(This article belongs to the Special Issue Bioactive Compounds from Natural Sources: Discovery, Evaluation and Applications, 2nd Edition)

15 pages, 3153 KB

Open AccessArticle

Pushing the Boundaries of Biomarker Discovery in Phenylketonuria: Metabolomic Profiling Reveals Novel Biomarkers and Their Associations with Phenylalanine

by Reem AlMalki, Shereen M. Aleidi, Maha Al Mogren, Shaima Almohsen, Khalid M. Sumaily, Ahmed Alfares and Anas M. Abdel Rahman

Molecules 2026, 31(12), 2000; https://doi.org/10.3390/molecules31122000 - 8 Jun 2026

Abstract

Background: Phenylketonuria (PKU) is a rare genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in a deficiency of the enzyme responsible for metabolizing phenylalanine (Phe) and its accumulation. PKU can be identified through newborn screening (NBS) or genetic sequencing; [...] Read more.

Background: Phenylketonuria (PKU) is a rare genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, resulting in a deficiency of the enzyme responsible for metabolizing phenylalanine (Phe) and its accumulation. PKU can be identified through newborn screening (NBS) or genetic sequencing; however, both approaches have limitations, including high false-discovery rates and variants of uncertain significance (VUS). This study aims to identify a PKU metabolomic profile using unique biomarkers to enhance early diagnosis and improve treatment outcomes. Methods: Dried blood spot (DBS) samples from 65 patients diagnosed with PKU and matched healthy controls were collected through the NBS program. An untargeted metabolomics analysis was conducted using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to profile metabolites and investigate altered metabolic pathways in patients with PKU. Results: A total of 418 significantly dysregulated metabolites were identified in PKU patients. Among them, 90 metabolites were identified as endogenous human metabolites. The most significantly affected pathways were those related to the metabolism of aromatic amino acids and polysaccharides. Moreover, lipid metabolic pathways were dysregulated, including those involved in fatty acid and phospholipid biosynthesis. In addition to phenylalanine (AUC = 0.994), 1,11-Undecanedicarboxylic acid (UDCA) (AUC = 0.969) was significantly elevated in patients with PKU, suggesting it is a promising potential biomarker for PKU. Conclusions: Untargeted metabolomics revealed distinct metabolic alterations in patients with PKU, providing insights into disease pathophysiology. The identification of UDCA as a consistently elevated metabolite supports its potential utility as a supplementary biomarker for PKU diagnosis and monitoring. Further validation in larger cohorts, using a targeted metabolomics approach, is warranted. Full article

(This article belongs to the Special Issue The Application of LC-MS in Pharmaceutical Analysis—2nd Edition)

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13 pages, 1540 KB

Open AccessArticle

Mitochondrial Targeting of MVA Pathway Triggers Severe Inhibition of Post-Squalene Cholesterol Biosynthesis: Transcriptomic and Proteomic Insights in Yeast

by Nan Tang, Yuliang Xu, Changfu Li and Yansheng Zhang

Molecules 2026, 31(12), 1999; https://doi.org/10.3390/molecules31121999 - 7 Jun 2026

Abstract

Expression of the mevalonate (MVA) pathway in yeast mitochondria is deployed at commercial scale for production of squalene, because mitochondria contain abundant acetyl-CoA, the starting molecule of the MVA pathway. However, it is still unknown whether this strategy is effective in boosting the [...] Read more.

Expression of the mevalonate (MVA) pathway in yeast mitochondria is deployed at commercial scale for production of squalene, because mitochondria contain abundant acetyl-CoA, the starting molecule of the MVA pathway. However, it is still unknown whether this strategy is effective in boosting the post-squalene pathway. Here the potential of this strategy is explored for production of the post-squalene chemical cholesterol, a precursor of many valuable steroidal drugs. A cholesterol-producing yeast strain, named CEN-Cho, was constructed by expressing the biosynthetic genes leading to cholesterol, accompanied by the augmentation of the cytosolic MVA pathway. The CEN-Cho strain produced 60.17 ng/mg fresh weight (FW) of squalene and 121.75 ng/mg FW of cholesterol in shake flask cultivation. When the complete MVA pathway was introduced into the mitochondria of CEN-Cho, yielding CEN-Cho-mMVA, the squalene level was increased to 325.24 ng/mg FW. Unexpectedly, the yield of cholesterol produced by CEN-Cho-mMVA was decreased to 1.5 ng/mg FW, demonstrating significant suppression on the post-squalene pathway due to the mitochondrial engineering. Comparative transcriptomic and proteomic analyses of the engineered cells provide insights into the metabolic and regulatory bottlenecks underlying this inhibition. This work reveals that the introduction of the MVA pathway into mitochondria generally inhibits the post-squalene pathway in yeast. Full article

(This article belongs to the Special Issue Advances in the Synthesis of Natural Bioactive Compounds)

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11 pages, 4897 KB

Open AccessArticle

Choline Fatty Acid Ionic Liquids Enhance Growth, Nitrogen Metabolism, and Grain Guality in Maize (Zea mays L.)

by Qiuchen Guo, Wenquan Chen, Mengfei Niu, Shixu Yang, Yanan Huang, Pei Zhang, Yulong Ma, Qingru Cai, Yajun Li and Xiaohong Chen

Molecules 2026, 31(12), 1998; https://doi.org/10.3390/molecules31121998 - 7 Jun 2026

Abstract

Choline-based ionic liquids (ILs) have emerged as promising candidates for application in multifaceted avenues, including electrochemistry, biomaterials, and environmental remediation technologies. However, their regulatory effects on the growth of agricultural plants have rarely been discussed. In this study, 14 choline–fatty acid ILs ([Chl][FA] [...] Read more.

Choline-based ionic liquids (ILs) have emerged as promising candidates for application in multifaceted avenues, including electrochemistry, biomaterials, and environmental remediation technologies. However, their regulatory effects on the growth of agricultural plants have rarely been discussed. In this study, 14 choline–fatty acid ILs ([Chl][FA] ILs) containing different FA anions were synthesized, and their effects on the maize growth were investigated. Hydroponic experiments revealed that low concentrations (20 mg/L) of dicarboxylic acid-based [Chl][FA] ILs (e.g., choline pentane diacid [Chl][Pent]) significantly promoted maize root and shoot biomass, whereas higher concentrations inhibited it. Specifically, [Chl][Pent] enhanced chlorophyll content without altering Fv/F₀, upregulated nitrate reductase (NR) and glutamine synthetase (GS) activities, and stimulated the expression of key nitrogen metabolism (NR and GS) and photosynthetic (Rubisco) genes. Pathway analyses of differentially expressed genes indicated that [Chl][Pent] was associated with the upregulation of nitrogen and glycerophospholipid metabolism. [Chl][Pent] increased the average grain yield by 6.88% over two years compared to CK. Field application of [Chl][Pent] increased grain yield and protein accumulation relative to both control and choline chloride treatments. Overall, these findings demonstrate the potential of dicarboxylic acid-based [Chl][FA] ionic liquids as eco-friendly biostimulants for enhancing crop growth, yield, and quality. Full article

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18 pages, 4322 KB

Open AccessArticle

Mobility Control Mechanism of In Situ Viscosity-Enhancing Graphene Quantum Dots in Assisted CO₂ Flooding

by Fang Shi, Weibin Jin, Jingchun Wu, Bo Zhao, Chunlong Zhang and Lifeng Mao

Molecules 2026, 31(12), 1997; https://doi.org/10.3390/molecules31121997 - 7 Jun 2026

Abstract

To address gas channeling, low sweep efficiency, and water sensitivity in CO₂ flooding of shale reservoirs, amidine-functionalized graphene quantum dots (FN-GQDs) were synthesized via amidation of citric acid-derived GQDs. FTIR and UV-Vis confirmed successful grafting. Conductometric titration showed an optimal reaction time [...] Read more.

To address gas channeling, low sweep efficiency, and water sensitivity in CO₂ flooding of shale reservoirs, amidine-functionalized graphene quantum dots (FN-GQDs) were synthesized via amidation of citric acid-derived GQDs. FTIR and UV-Vis confirmed successful grafting. Conductometric titration showed an optimal reaction time of 24 h with a grafting ratio of 58%, in good agreement with the 60% saturation predicted by molecular dynamics simulation. Upon CO₂ introduction, protonation of amidine groups induced a nonlinear viscosity increase from 0.298 to 2.0 mPa·s at 0.02 wt% via electrostatic attraction and hydrogen bonding, forming a dynamic crosslinking network. FN-GQDs maintained low oil-water interfacial tension of 0.12–0.25 mN/m at 80–120 °C and rapidly reversed rock wettability from strongly oil-wet to water-wet, reducing the contact angle from 141.7° to 38.9° within 80 min. The positively charged surface inhibited clay swelling, achieving 92% at 0.20 wt%. Core flooding and NMR T₂ spectra revealed that alternating CO₂ and FN-GQDs injection at a 2:1 gas–water ratio achieved a final oil recovery of 52.5%, significantly higher than pure CO₂ flooding. Through synergistic effects of interfacial tension reduction, wettability alteration, viscosity enhancement, and anti-swelling, FN-GQDs improve microscopic displacement efficiency and macroscopic sweep volume, showing great potential for CO₂-enhanced oil recovery in shale reservoirs. Full article

(This article belongs to the Section Nanochemistry)

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19 pages, 1658 KB

Open AccessReview

FAAH as a Molecular Regulator of Endocannabinoid Signaling: Mechanistic Insights into Reproductive, Metabolic, and Inflammatory Dysfunctions in Polycystic Ovary Syndrome

by Qinghe Lin, Defan Wang, Pingting Guo, Zhenghong Zhang and Zhengchao Wang

Molecules 2026, 31(12), 1996; https://doi.org/10.3390/molecules31121996 - 7 Jun 2026

Abstract

Fatty acid amide hydrolase (FAAH) is a critical metabolic enzyme in the endocannabinoid system. Through regulating the metabolism of lipid signaling molecules, FAAH is involved in a variety of physiological and pathological processes, including cell proliferation, inflammatory responses, and metabolic homeostasis. Polycystic ovary [...] Read more.

Fatty acid amide hydrolase (FAAH) is a critical metabolic enzyme in the endocannabinoid system. Through regulating the metabolism of lipid signaling molecules, FAAH is involved in a variety of physiological and pathological processes, including cell proliferation, inflammatory responses, and metabolic homeostasis. Polycystic ovary syndrome (PCOS), one of the most common endocrine and metabolic disorders affecting women of reproductive age, is closely associated with abnormal follicular development, dysregulated hormone secretion, insulin resistance, dyslipidemia, and inflammatory imbalance. Emerging evidence suggests that FAAH-mediated dysregulation of endocannabinoid metabolism is associated with the pathogenesis of PCOS through the modulation of inflammatory pathways, insulin sensitivity, and hormone secretion. This review systematically summarizes the structure, biological functions, and regulatory mechanisms of FAAH, with particular emphasis on its roles in PCOS-associated pathological processes, including reproductive dysfunction, hormonal dysregulation, metabolic imbalance, and inflammatory responses. This review aims to provide a theoretical foundation for elucidating the molecular mechanisms underlying PCOS and for the development of novel therapeutic strategies. Full article

(This article belongs to the Special Issue Small Molecules for Gonadal Diseases)

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19 pages, 5510 KB

Open AccessArticle

Comparative Structural Modeling Suggests Distinct Signatures of Conformational Plasticity and Surface Physicochemistry in Phytoene Synthase and Dehydrosqualene Synthase

by Ade Rizqi Ridwan Firdaus, Muhammad Yusuf, Shun Tamaki, Keiichi Mochida and Toto Subroto

Molecules 2026, 31(12), 1995; https://doi.org/10.3390/molecules31121995 - 7 Jun 2026

Abstract

Carotenoids are essential metabolites involved in photosynthesis, cellular protection, pigmentation, and antioxidant activities. Phytoene synthase (PSY/CrtB) utilizes C20 substrates in carotenoid biosynthesis, whereas its structural homolog, dehydrosqualene synthase (CrtM), preferentially accepts C15 substrates. Although previous studies have identified CrtM mutations that expand substrate [...] Read more.

Carotenoids are essential metabolites involved in photosynthesis, cellular protection, pigmentation, and antioxidant activities. Phytoene synthase (PSY/CrtB) utilizes C20 substrates in carotenoid biosynthesis, whereas its structural homolog, dehydrosqualene synthase (CrtM), preferentially accepts C15 substrates. Although previous studies have identified CrtM mutations that expand substrate scope, the molecular basis of substrate discrimination in PSY/CrtB remains poorly understood, largely because of the absence of experimentally determined three-dimensional structures. Here, we integrated comparative sequence analysis, homology modeling, and molecular dynamics (MD) simulations to investigate the structural basis of substrate discrimination in PSY/CrtB. Comparative sequence analysis suggested distinct overall conservation landscapes in PSY/CrtB and CrtM, with 20 highly conserved positions shared between them and clustered around the catalytic core. MD simulations suggest that PSY models exhibit minimal differentiation under cross-ligand conditions, consistent with its greater conformational plasticity. Surface property analysis suggested hydrophobic patches and an amphipathic helix (Helix-13) in PSY that were preferentially conserved in PSY homologs relative to CrtM homologs. Taken together, our analyses suggest that greater conformational plasticity may facilitate the accommodation of C20 substrates in PSY and that its conserved hydrophobic surface architecture may shape its surface physicochemistry. These findings suggest that differences in substrate accommodation between PSY/CrtB and CrtM may reflect coordinated variation in conformational dynamics, pocket hydrophobicity, and surface architecture, rather than substantial alterations to the conserved catalytic core. Full article

(This article belongs to the Special Issue Application of Bioenzyme Engineering and Enzyme Catalysis in the Food Industry)

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19 pages, 4856 KB

Open AccessArticle

Unveiling Superior Fracture Toughness in MnCoSb Half-Heusler Alloy: A First-Principles Guide for Designing Damage-Tolerant Functional Materials

by Ai Qin, Shao-Bo Chen, Lin-Zi Tu, Jia-Hao Wang, Wan-Jun Yan, Tinghong Gao, Kuang-Min Gao and Jing Zhao

Molecules 2026, 31(12), 1994; https://doi.org/10.3390/molecules31121994 - 7 Jun 2026

Abstract

In this study, the stability, electronic, structural, and fracture toughness, and mechanical properties of the Half-Heusler(HH) alloys MnCoSb, MnCoAs, MnCoP, and MnNiSb were comprehensively investigated using first-principles calculations based on density functional theory (DFT). The calculated results reveal that all four alloys exhibit [...] Read more.

In this study, the stability, electronic, structural, and fracture toughness, and mechanical properties of the Half-Heusler(HH) alloys MnCoSb, MnCoAs, MnCoP, and MnNiSb were comprehensively investigated using first-principles calculations based on density functional theory (DFT). The calculated results reveal that all four alloys exhibit half-metallic characteristics, characterized by the presence of a substantial band gap in the spin-down channel. The phonon spectra and negative formation energies confirm that these alloys possess both dynamic and thermodynamic stability. The Born criteria further validate the structural stability in terms of mechanical properties. Three-dimensional representations of the Young’s modulus, bulk modulus, and shear modulus for the four alloys indicate that MnCoP exhibits the most pronounced anisotropy. The overall fracture toughness of the alloys ranges from 1.58 MPa·m^1/2 to 2.63 MPa·m^1/2, which falls within the typical range for half-metallic materials, albeit at the lower end, attributable to the relatively ductile nature of the four alloys. Although the two methods yield different absolute values, the explicit crack model (Method I) is considered more reliable for anisotropic systems because it directly simulates crack propagation and accounts for local relaxations, while the empirical formula (Method II) provides a useful reference for high-throughput screening. Among the alloys, MnCoSb demonstrates a superior mechanical performance, with K_IC values of 2.63 MPa·m^1/2 and 1.58 MPa·m^1/2 and brittleness indices M of 8.97 and 14.94, indicating excellent damage tolerance compared to the other three alloys. In contrast, MnCoP exhibits higher brittleness and lower mechanical reliability, with K_IC values of 2.00 MPa·m^1/2 and 1.63 MPa·m^1/2 and higher M values of 13.83 and 16.99. This study provides quantitative predictions of fracture toughness and establishes a relationship between microscopic and mechanical properties. These findings offer a theoretical foundation for the application of damage-tolerant HH alloys in fields such as spintronics and magnetism. Full article

(This article belongs to the Special Issue Novel Two-Dimensional Energy-Environmental Materials; 2nd Edition)

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13 pages, 816 KB

Open AccessArticle

Biological Evaluation of Esters of 4-Carboxylate-1,2,3-triazine and Analogs as New Potential Anti-Mycobacterium tuberculosis Agents

by Gildardo Rivera, Diana V. Navarrete-Carriola, Luca De Angelis, Alma D. Paz-González, Ana Verónica Martínez-Vázquez, Eyra Ortiz-Pérez, Baojie Wan, Scott Franzblau, Marlet Martínez-Archundia, Adriana Moreno-Rodríguez, Isidro Palos and Michael P. Doyle

Molecules 2026, 31(12), 1993; https://doi.org/10.3390/molecules31121993 - 7 Jun 2026

Abstract

In searching for novel molecules to act as antibacterial agents, particularly against Mycobacterium tuberculosis bacteria, three series of C5- and C6-substituted 1,2,3-triazine compounds were investigated: 1,2,3-triazine-4-carboxylate 1-oxide (series 1), 1,2,3-triazine-4-carboxylate (series 2), and 3,6-dihydro-1,2,3-triazine-4-carboxylate 1-oxide derivatives (series 3). Their structural [...] Read more.

In searching for novel molecules to act as antibacterial agents, particularly against Mycobacterium tuberculosis bacteria, three series of C5- and C6-substituted 1,2,3-triazine compounds were investigated: 1,2,3-triazine-4-carboxylate 1-oxide (series 1), 1,2,3-triazine-4-carboxylate (series 2), and 3,6-dihydro-1,2,3-triazine-4-carboxylate 1-oxide derivatives (series 3). Their structural elucidation was confirmed by ¹H-NMR, ¹³C-NMR, and HRMS. We determined their antibacterial activity (MIC value) using the MABA against the M. tuberculosis H37Rv strain, as well as their physicochemical and pharmacokinetic properties. Finally, to determine their potential mode of action, an inhibition assay against M. tuberculosis DNA gyrase was performed. Compounds 4-ethoxycarbonyl-5-(3-methoxyphenyl)-1,2,3-triazine (2l) and 4-ethoxycarbonyl-5 -(n-propyl)-1,2,3-triazine (3s) exhibited high activity against M. tuberculosis with MIC values < 5.90 µg/mL and selectivity index of 18.56 and 8.36, respectively. Additionally, compound 2m also exhibited anti-mycobacterial activity with MIC values < 10.0 µg/mL. However, none of the selected compounds inhibited the activity of M. tuberculosis DNA gyrase, suggesting that another drug target may be involved as a mode of action. These results encourage exploring the use of 1,2,3-triazine as a scaffold for the development of new anti-mycobacterium agents. Full article

(This article belongs to the Special Issue Heterocycles in Medicinal Chemistry, 4th Edition)

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13 pages, 5044 KB

Open AccessArticle

Ultra-High-Density Tripotassium 4,5-Bis(gem-dinitromethyl)-1,2,3-triazolate Hydrate (3K₃BNOT·4H₂O): A Lead-Free Triazole-Based Energetic Salt

by Ruokai Pei, Yang Wu and Yinglei Wang

Molecules 2026, 31(12), 1992; https://doi.org/10.3390/molecules31121992 - 7 Jun 2026

Abstract

Energetic materials face dual challenges of enhancing detonation performance and replacing toxic lead-based formulations. Triazole-based energetic potassium salts typically struggle to achieve simultaneous high-density and excellent detonation properties. Herein, a novel gem-dinitro-functionalized 1,2,3-triazole energetic salt, tripotassium 4,5-bis(gem-dinitromethyl)-2H-1,2,3-triazolate (3K₃BNOT·4H₂O), was [...] Read more.

Energetic materials face dual challenges of enhancing detonation performance and replacing toxic lead-based formulations. Triazole-based energetic potassium salts typically struggle to achieve simultaneous high-density and excellent detonation properties. Herein, a novel gem-dinitro-functionalized 1,2,3-triazole energetic salt, tripotassium 4,5-bis(gem-dinitromethyl)-2H-1,2,3-triazolate (3K₃BNOT·4H₂O), was rationally designed and synthesized via a six-step mild route using diaminomaleonitrile as the starting material. The structure was fully characterized by IR, NMR, elemental analysis, and single-crystal X-ray diffraction (SC-XRD). 3K₃BNOT·4H₂O crystallizes in the triclinic system (space group P-1) and forms a three-dimensional K-O/K-N ionic coordination network, delivering an ultra-high anhydrous crystal density of 2.077 g·cm⁻³ at 193K. It exhibits a peak decomposition temperature of 183.8 °C (10 °C·min⁻¹), impact sensitivity of 5 J, and friction sensitivity of 60 N (standard BAM methods). The calculated detonation velocity and pressure reach 8836 m·s⁻¹ and 28.6 GPa, respectively, outperforming the classical explosive RDX. This work provides a structural analysis of triazole-based energetic potassium salt hydrates, and 3K₃BNOT·4H₂O shows structural potential as a high-energy energetic material; its initiating performance needs further experimental verification. Full article

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14 pages, 664 KB

Open AccessArticle

Quality Comparative Evaluation of Eungyosan Formulations by a Validated HPLC–PDA Method for 11 Marker Components

by Chang-Seob Seo

Molecules 2026, 31(12), 1991; https://doi.org/10.3390/molecules31121991 - 7 Jun 2026

Abstract

Eungyosan (EGS) is a traditional multi-herbal formulation widely used for the treatment of respiratory diseases; however, its quality control remains challenging due to its complex chemical composition. This study aimed to develop and validate a high-performance liquid chromatography coupled with photodiode array detection [...] Read more.

Eungyosan (EGS) is a traditional multi-herbal formulation widely used for the treatment of respiratory diseases; however, its quality control remains challenging due to its complex chemical composition. This study aimed to develop and validate a high-performance liquid chromatography coupled with photodiode array detection (HPLC–PDA) method for simultaneous determination of 11 representative marker compounds in EGS and to apply the method to the comparative quality evaluation of laboratory-prepared and commercial EGS formulations. Chromatographic conditions were optimized, and the marker compounds were selected based on their herbal origin, phytochemical relevance, and chromatographic detectability. The method was validated in terms of linearity, sensitivity (limits of detection and quantification), precision, accuracy, and stability. All analytes exhibited excellent linearity (coefficient of determination > 0.9999), along with satisfactory precision (relative standard deviation < 2%) and recovery (95.64–105.69%). The validated method was successfully applied to a laboratory-prepared extract and three commercial granule formulations. Considerable differences in the levels of marker compounds were observed among the samples; several marker compounds were either not detected or could not be quantified because of UV spectral mismatch in certain commercial products. These findings demonstrate variability in the chemical composition of the tested EGS formulations and highlight the usefulness of the validated HPLC–PDA method for comparative quality evaluation of multi-herbal formulations. Full article

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

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28 pages, 21873 KB

Open AccessStudy Protocol

Photoprotective Effects of Dendrobium officinale Protein Hydrolysate Fractions Against UVB-Induced Photoaging Associated with Modulation of MAPK/NF-κB and TGF-β/Smad Signaling

by Jinghan Zhang, Yue Sun, Jinhao Zheng, Can Yang, Mingshuo Yang and Liming Pan

Molecules 2026, 31(12), 1990; https://doi.org/10.3390/molecules31121990 - 7 Jun 2026

Abstract

Dendrobium officinale has attracted increasing attention as a functional food because of its diverse biological activities; however, the photoprotective potential of its protein-derived peptides remains poorly understood. In this study, D. officinale protein hydrolysates were fractionated by ultrafiltration according to molecular weight, and [...] Read more.

Dendrobium officinale has attracted increasing attention as a functional food because of its diverse biological activities; however, the photoprotective potential of its protein-derived peptides remains poorly understood. In this study, D. officinale protein hydrolysates were fractionated by ultrafiltration according to molecular weight, and their protective effects against ultraviolet B (UVB)-induced photoaging were systematically evaluated in HaCaT keratinocytes. Among the tested fractions, low-molecular-weight peptide fractions exhibited relatively stronger antioxidant activity and effectively reduced intracellular reactive oxygen species (ROS) accumulation in UVB-irradiated cells. In addition, the peptide fractions alleviated UVB-induced inflammatory responses and decreased matrix metalloproteinase (MMP) expression, which was associated with modulation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Higher-molecular-weight fractions showed relatively stronger effects on maintaining skin barrier-related functions and were associated with regulation of transforming growth factor-β/Smad (TGF-β/Smad) signaling and collagen-related protein expression. Overall, these findings demonstrate functional differences among Dendrobium officinale peptide fractions and suggest their potential application as natural photoprotective ingredients in functional foods and cosmeceutical products. Full article

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

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