Molecules

29 pages, 2912 KB

Open AccessReview

Advances in Scalp Microbiome Research: Molecular Insights into the Metabolism-Inflammation-Barrier Axis and Dandruff Pathogenesis

by Le Deng, Xiao Ling, Li Li, Youjie He and Miaomiao Guo

Molecules 2026, 31(12), 2093; https://doi.org/10.3390/molecules31122093 (registering DOI) - 14 Jun 2026

Abstract

Dandruff (DF) is a prevalent, recurrent inflammatory scalp disorder increasingly recognized as a complex state of functional dysbiosis rather than a simple Malassezia overcolonization. The scalp microbiome is predominantly shaped by Malassezia species (M. restricta and M. globosa), Cutibacterium, and [...] Read more.

Dandruff (DF) is a prevalent, recurrent inflammatory scalp disorder increasingly recognized as a complex state of functional dysbiosis rather than a simple Malassezia overcolonization. The scalp microbiome is predominantly shaped by Malassezia species (M. restricta and M. globosa), Cutibacterium, and Staphylococcus species. Recent multi-omics evidence indicates that DF pathogenesis is driven by the destabilization of microbial interaction networks and strain-level functional heterogeneity, characterized by the disruption of the C. acnes/S. epidermidis balance and the opportunistic expansion of Staphylococcus aureus. Mechanistically, Malassezia utilizes its lipolytic repertoire to hydrolyze host sebum into irritant free fatty acids and peroxides. Concurrently, oxidative metabolites like squalene peroxide (SQOOH) penetrate the stratum corneum to activate the NF-κB and aryl hydrocarbon receptor (AhR) pathways, triggering a pro-inflammatory cascade that overexpresses keratins (K6/16/17) and downregulates filaggrin. This molecular cascade drives abnormal keratinocyte turnover and lipidomic remodeling, establishing a self-perpetuating “metabolism–inflammation–barrier disruption” pathological cycle. This review systematically elucidates the molecular etiology of DF as an ecological disorder driven by a tripartite imbalance among the microbiome, host physiology, and the environmental niche. We propose that next-generation therapeutic paradigms must transcend traditional antifungal eradication, focusing instead on targeted molecular intervention and microecological restoration to recalibrate overall scalp homeostasis. Full article

(This article belongs to the Special Issue Molecules Targeting the Human Microbiome: Natural Products, Metabolites and Mechanisms)

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14 pages, 6860 KB

Open AccessArticle

Mitochondria-Targeted Colorimetric and Ratiometric Fluorescent Probe for Hg²⁺ with Large Stokes Shift

by Dongjian Zhu, Yufei Zhang, Yuyan Pan, Sheng Li and Aishan Ren

Molecules 2026, 31(12), 2092; https://doi.org/10.3390/molecules31122092 (registering DOI) - 14 Jun 2026

Abstract

In this study, probe 1, a novel mitochondria-targeted fluorescent probe for the colorimetric and ratiometric detection of Hg²⁺, was developed. Upon addition of Hg²⁺ to the solution of 1, distinct spectral changes were observed. The absorption spectra underwent [...] Read more.

In this study, probe 1, a novel mitochondria-targeted fluorescent probe for the colorimetric and ratiometric detection of Hg²⁺, was developed. Upon addition of Hg²⁺ to the solution of 1, distinct spectral changes were observed. The absorption spectra underwent a blue shift from 510 nm to 450 nm (Δλ = 60 nm), and the solution color changed from red to pale yellow under daylight. Concurrently, a significant blue shift occurred from 645 nm to 540 nm (Δλ = 105 nm) in the fluorescence spectra. There were remarkable variations in the fluorescence intensity ratio of F_540nm/F_645nm with the R/R₀ value reaching up to 824-fold, and the fluorescence color changed from red to green under a 365 nm UV lamp. Probe 1 featured a large Stokes shift of 135 nm, high sensitivity with an LOD of 25.5 nM, and excellent selectivity for Hg²⁺ even in the presence of other analytes. Furthermore, 1 was successfully applied for the ratiometric imaging of intracellular Hg²⁺ and was confirmed to localize specifically within mitochondria. Full article

31 pages, 41536 KB

Open AccessArticle

Metabolomic Profiles and Anti-Herpes Simplex Virus (Wild-Type and Drug-Resistant) Properties of Water-Based Extracts of Lentinula edodes, Hypsizygus marmoreus and Pleurotus eryngii

by Chaleampol Loymunkong, Chamsai Pientong, Tipaya Ekalaksananan, Yaovapa Aramsirirujiwet and Jureeporn Chuerduangphui

Molecules 2026, 31(12), 2091; https://doi.org/10.3390/molecules31122091 (registering DOI) - 14 Jun 2026

Abstract

Herpes simplex virus type 1 (HSV-1) remains a significant pathogen, particularly in immunocompromised patients. The emergence of drug-resistant strains necessitates alternative therapeutic agents. Lentinula edodes (LE), Hypsizygus marmoreus, and Pleurotus eryngii are edible mushrooms with recognized medicinal properties. However, their effects on [...] Read more.

Herpes simplex virus type 1 (HSV-1) remains a significant pathogen, particularly in immunocompromised patients. The emergence of drug-resistant strains necessitates alternative therapeutic agents. Lentinula edodes (LE), Hypsizygus marmoreus, and Pleurotus eryngii are edible mushrooms with recognized medicinal properties. However, their effects on drug-resistant HSV-1 remain unclear. This study characterized metabolites from high-temperature/high-pressure (121 °C) water extracts of fresh and dried fruiting bodies and evaluated anti-HSV-1 activities using in vitro and in silico approaches. Metabolic profiles were analyzed by electrospray ionization–quadrupole time-of-flight mass spectrometry. Antiviral activity against HSV-1 KOS (wild-type) and HSV-1 dxpiii (drug-resistant) strains was assessed by plaque assays and qPCR. Molecular docking and network pharmacology were performed on candidate compounds. LE extract from dried mushroom tended to show the highest levels of selected major bioactive constituents, along with greater antioxidant activities. All extracts significantly inhibited viral infection and gene expression in both strains. LE extract from dried mushroom modulated the expression of NFKB1 and IL6. Molecular docking analysis revealed that eritanidine showed a predicted binding affinity to HSV-1 DNA polymerase (−7.95 kcal/mol). Additionally, eritanidine, 5′-methylthioadenosine, and 3-indoleacrylic acid were predicted to interact with TNF and MAPK1. Several compounds also demonstrated favorable drug-likeness properties. Overall, these mushroom extracts are promising natural sources of antiviral agents against HSV-1, including drug-resistant variants. Full article

(This article belongs to the Section Natural Products Chemistry)

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16 pages, 325 KB

Open AccessArticle

How to Turn a Poisonous Plant into Medicine: Non-Polar Extracts of Rhododendron adamsii (Sagan Dalya) Are Free of Grayanotoxins and Inhibit the SARS-CoV-2 Main Protease

by Tatiana P. Kukina, Ivan A. Elshin, Ol’ga I. Sal’nikova, Svetlana V. Belenkaya, Evgeniia A. Kolosova, Ekaterina A. Volosnikova, Victoria O. Shchegolkova and Dmitry N. Shcherbakov

Molecules 2026, 31(12), 2090; https://doi.org/10.3390/molecules31122090 (registering DOI) - 14 Jun 2026

Abstract

The composition of low-polarity extracts obtained by sequential extraction of the aerial parts of Rhododendron adamsii Rehd. with hexane and methyl tert-butyl ether (MTBE) was investigated using GC-MS. The hexane extract was dominated by non-polar components: squalene, n-alkanes (nonacosane, hentriacontane), sesquiterpenes (trans [...] Read more.

The composition of low-polarity extracts obtained by sequential extraction of the aerial parts of Rhododendron adamsii Rehd. with hexane and methyl tert-butyl ether (MTBE) was investigated using GC-MS. The hexane extract was dominated by non-polar components: squalene, n-alkanes (nonacosane, hentriacontane), sesquiterpenes (trans-nerolidol, spathulenol, β-farnesene), and β-sitosterol. The subsequent MTBE extract was enriched in more polar lipids, primarily free triterpenic acids (ursolic and oleanolic acids). A critical finding was the complete absence of diterpene grayanotoxins in all tested extracts, confirming the safety of the non-polar extraction approach. In bioactivity assays, the total hexane extract demonstrated potent inhibitory activity against the SARS-CoV-2 main protease (3CLpro) with IC₅₀ values of 0.0125–0.025 mg/mL, only one order of magnitude higher than the reference inhibitor disulfiram. Fractionation revealed that the activity was distributed among free acids, bound acids, and the unsaponifiable residue, indicating a multicomponent mechanism. Importantly, none of the samples inhibited HIV-1 protease (IC₅₀ > 0.1 mg/mL), demonstrating selectivity for the cysteine protease 3CLpro over the aspartyl protease of HIV-1. These results highlight that sequential non-polar extraction of R. adamsii provides a grayanotoxin-free lipophilic complex with selective anti-SARS-CoV-2 protease activity, paving the way for bioactivity-guided identification of individual inhibitors. Full article

(This article belongs to the Special Issue Advancement in Phytochemistry and Pharmacology of Medicinal Plants)

16 pages, 15712 KB

Open AccessArticle

Synthesis and In Silico Study of Pectolinarigenin–Metronidazole Hybrid Molecule as Anti-Helicobacter pylori

by Zeyneb Benramdane, Matteo Michelotti, Thamere Cheriet, Andrea Defant and Ines Mancini

Molecules 2026, 31(12), 2089; https://doi.org/10.3390/molecules31122089 (registering DOI) - 14 Jun 2026

Abstract

Metronidazole is an antibiotic used to treat Helicobacter pylori, a bacterium responsible for chronic infections in humans that cause gastric inflammation, ulcers, and cancer. However, its long-term administration is limited by toxicity and increased resistance. In the search for more effective agents [...] Read more.

Metronidazole is an antibiotic used to treat Helicobacter pylori, a bacterium responsible for chronic infections in humans that cause gastric inflammation, ulcers, and cancer. However, its long-term administration is limited by toxicity and increased resistance. In the search for more effective agents against H. pylori infection, molecular hybridization has now been applied to the synthesis of the new compound 3. Its structure connects the metronidazole moiety to pectolinarigenin, the latter obtained by acid hydrolysis of glycosylated flavonoids isolated from the plant Linaria reflexa Desf. The NOE effect supported the C-7 functionalization of 3, as evidenced by the energy-minimized DFT-calculated structure. The new molecule enriches the chemical space of known metronidazole–flavonoid analogs, among which the genistein derivative 2 was reported as the most active in inhibiting bacterial strains. The computational analysis of 2 and 3 compared with metronidazole as the reference has provided favorable data for both Absorption, Distribution, Metabolism, and Excretion (ADME) predictions and the probability of anti-H. pylori activity, besides rising docking evaluation on three specific targets and dynamics simulation as inhibitors of the flavodoxin enzyme. The results are promising for further in-depth biological investigation. Full article

(This article belongs to the Special Issue Molecular Modeling: Advancements and Applications, 4th Edition)

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19 pages, 4440 KB

Open AccessReview

BNC2 in Development and Disease: Regulatory Mechanisms and Translational Implications

by Xianji Wei, Yuxiang Du, Xiaohua Liu and Lingli Zhang

Molecules 2026, 31(12), 2088; https://doi.org/10.3390/molecules31122088 (registering DOI) - 14 Jun 2026

Abstract

Basonuclin 2 (BNC2) is a highly conserved cysteine–histidine (C2H2)-type zinc-finger nuclear regulatory protein characterized by three pairs of zinc-finger domains, a putative nuclear localization signal, a serine-rich region, broad tissue distribution, and remarkable transcript diversity generated through alternative promoter usage, alternative splicing, and [...] Read more.

Basonuclin 2 (BNC2) is a highly conserved cysteine–histidine (C2H2)-type zinc-finger nuclear regulatory protein characterized by three pairs of zinc-finger domains, a putative nuclear localization signal, a serine-rich region, broad tissue distribution, and remarkable transcript diversity generated through alternative promoter usage, alternative splicing, and polyadenylation. Increasing evidence from human genetics, animal models, functional genomics, and transcriptomic studies indicates that BNC2 links nuclear regulatory mechanisms to tissue-specific developmental and disease phenotypes. In the nervous system, BNC2-positive neuronal populations and BNC2-derived circular RNAs have been implicated in energy-balance circuits and neuroinflammatory regulation. In the skeletal system, BNC2 contributes to osteochondral development, periosteal stem-cell activation, chromatin remodeling, fracture repair, and genetic susceptibility to adolescent idiopathic scoliosis. BNC2 variants have also been associated with congenital lower urinary tract obstruction, whereas its expression and regulatory landscape are closely related to germ-cell development, epithelial ovarian cancer susceptibility, pigmentation traits, fibrosis, and several tumor contexts. Mechanistically, BNC2-associated phenotypes appear to involve cysteine–histidine zinc-finger-mediated transcriptional regulation, non-coding enhancer activity, epigenetic alterations, RNA-processing-associated nuclear functions, and chromatin-remodeling-dependent control of cell proliferation, differentiation, and stromal activation. This review integrates current evidence on the molecular architecture and regulatory functions of BNC2, critically discusses its context-dependent roles across development and disease, and highlights unresolved questions regarding isoform-specific activity, cell-type-specific regulation, downstream target networks, and clinical translation. A clearer understanding of these mechanisms may support the future evaluation of BNC2 as a biomarker, genetic susceptibility locus, molecular stratification factor, and potential therapeutic regulatory node. Full article

(This article belongs to the Special Issue Featured Reviews in Chemical Biology 2026)

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20 pages, 531 KB

Open AccessArticle

Decarboxylative-Allylation of Pyroglutamic Acid Derivatives: Stereocontrolled Access to Acyclic and Conformationally Restricted α,γ-Disubstituted γ-Amino Acids

by Hugo Casas-Morales, Dácil Hernández, Mario Ordoñez, Alicia Boto and Ivan Romero-Estudillo

Molecules 2026, 31(12), 2087; https://doi.org/10.3390/molecules31122087 (registering DOI) - 14 Jun 2026

Abstract

The synthetic strategy relies on the highly diastereoselective alkylation at the C4 position of L-pyroglutamic acid derivatives, followed by a decarboxylation-allylation process that enables the incorporation of diverse substituents, including aromatic substituents, affording trans-3,5-disubstituted γ-lactams with excellent diastereiosmeric ratio (dr > [...] Read more.

The synthetic strategy relies on the highly diastereoselective alkylation at the C4 position of L-pyroglutamic acid derivatives, followed by a decarboxylation-allylation process that enables the incorporation of diverse substituents, including aromatic substituents, affording trans-3,5-disubstituted γ-lactams with excellent diastereiosmeric ratio (dr > 98:2). The resulting γ-lactams were efficiently transformed into a series of α,γ-disubstituted γ-amino acids through hydrogenation and acidic hydrolysis. Furthermore, cross-metathesis reactions with styrene and 1-decene enabled the introduction of structurally diverse lipophilic side chains, furnishing the corresponding γ-amino acids in good overall yields (71–77%) and high diastereoisomeric ratio from >98:2 to 92:8. In addition, N-allylation followed by ring-closing metathesis and hydrogenation provided access to a previously unexplored conformationally constrained γ-amino acid. Overall, seven α,γ-disubstituted γ-amino acids, including fluorinated and conformationally restricted derivatives, were synthesized from common intermediates with high stereocontrol. The developed methodology offers a versatile platform for the preparation of structurally diverse and underexplored γ-amino acid building blocks of potential interest in peptide synthesis, medicinal chemistry, and antimicrobial agent development. Full article

(This article belongs to the Special Issue A Themed Issue in Honor of the 20th Anniversary of the Mexican Academy of Organic Chemistry (AMQO))

34 pages, 2059 KB

Open AccessReview

A Comparative Evaluation of Current and Emerging Strategies for Almond Protein Extraction

by Muhammad Adil Farooq and Jianmei Yu

Molecules 2026, 31(12), 2086; https://doi.org/10.3390/molecules31122086 (registering DOI) - 14 Jun 2026

Abstract

Almonds (Prunus dulcis; family Rosaceae) contain 18–25% protein (dry weight). They are an important plant-based protein source in dairy alternatives and other functional foods. The hard and dense nature of almond kernels and the localization of proteins with lipid bodies in [...] Read more.

Almonds (Prunus dulcis; family Rosaceae) contain 18–25% protein (dry weight). They are an important plant-based protein source in dairy alternatives and other functional foods. The hard and dense nature of almond kernels and the localization of proteins with lipid bodies in the cotyledons of almond seeds make it challenging to recover protein from the seed efficiently and preserve its function. Therefore, this review evaluates the influence of pretreatments, including blanching, grinding, and defatting, on almond protein recovery and functionality, and compares conventional and emerging technologies for almond protein. Traditional protein extraction techniques such as alkaline extraction–isoelectric precipitation (AE–IEP), aqueous extraction, and salt extraction provide moderate-to-high protein yields, but harsh processing conditions denature the proteins, decrease solubility, and cause functional properties to be lost. On the other hand, emerging protein extraction technologies (including enzyme-assisted aqueous extraction (EAE) ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), high-pressure processing (HPP), and pulsed electric field (PEF) treatment) improve protein recovery, resulting in protein extract with superior functional properties and reduced allergenicity. However, their application in industry remain challenging. This review reveals that pretreatment approaches and conditions/parameters significantly influence protein extraction efficiency and the functional and structural properties of almonds, and that no single method is universally optimal. This review concludes that controlled enzymatic hydrolysis combined with physical pretreatment may be the best approach for producing high-value-added almond protein ingredients with specific techno-functional properties for use in plant-based beverages, hypoallergenic products, or nutraceuticals. More research is needed to develop an efficient, applicable, sustainable and eco-friendly almond protein extraction process, optimizing processing conditions to achieve high protein recovery while retaining desirable functional properties, and reduce operating costs. Full article

(This article belongs to the Special Issue Current Emerging Trends of Extraction and Encapsulation in Food, 2nd Edition)

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19 pages, 2751 KB

Open AccessReview

Phytochemical Composition and Bioactivity of Circaea lutetiana

by Gaukhar Tazhkenova, Togzhan Mashan, Zhanar Iskakova, Aizhan Zeinuldina, Bakhyt Igenbayeva, Raushan Baikanova, Akmaral Kozhantayeva and Yerbolat Tashenov

Molecules 2026, 31(12), 2085; https://doi.org/10.3390/molecules31122085 (registering DOI) - 13 Jun 2026

Abstract

Circaea lutetiana (Onagraceae) is a perennial medicinal species widely distributed across temperate forest ecosystems of Europe, Asia, and North America. This mini-review integrates current knowledge on the botanical characteristics, ecological distribution, phytochemical composition, and biological properties of Circaea lutetiana, with [...] Read more.

Circaea lutetiana (Onagraceae) is a perennial medicinal species widely distributed across temperate forest ecosystems of Europe, Asia, and North America. This mini-review integrates current knowledge on the botanical characteristics, ecological distribution, phytochemical composition, and biological properties of Circaea lutetiana, with particular emphasis on its dominant polyphenolic constituents. Available studies demonstrate that the species is rich in flavonoids, phenolic acids, ellagic acid derivatives, and ellagitannins, among which oenothein B represents a characteristic and major constituent. Beyond polyphenols, structurally characterized glycosides, lipophilic metabolites, phytosterols, triterpenoids, fatty acids, tocopherols, and mineral elements contribute to the chemical complexity of the species. The reported biological activities of Circaea lutetiana, including antioxidant, anti-inflammatory, antihypertensive, and antimicrobial effects, are discussed in relation to the phytochemical profile of the plant and the biological significance of its major constituents. Recent research in green nanotechnology has additionally highlighted the potential of Circaea lutetiana extracts, particularly in the biosynthesis of silver nanoparticles, where plant metabolites act as reducing and stabilizing agents and may contribute to improved antimicrobial performance. Full article

(This article belongs to the Special Issue Functional Evaluation of Bioactive Compounds from Natural Sources, 2nd Edition)

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19 pages, 9536 KB

Open AccessArticle

Membrane Access and Orbital Localization Govern ABC Transporter Substrate Recognition

by Saad Harrizi, Imane Nait Irahal, Kaouthar El Birgui and Mostafa Kabine

Molecules 2026, 31(12), 2084; https://doi.org/10.3390/molecules31122084 (registering DOI) - 13 Jun 2026

Abstract

The ATP-binding cassette transport protein Pdr5p is known to play a role in multidrug resistance in Saccharomyces cerevisiae by effluxing structurally diverse xenobiotics; yet the physicochemical determinants of substrate recognition remain poorly defined. To address this, density functional theory (DFT) calculations at the [...] Read more.

The ATP-binding cassette transport protein Pdr5p is known to play a role in multidrug resistance in Saccharomyces cerevisiae by effluxing structurally diverse xenobiotics; yet the physicochemical determinants of substrate recognition remain poorly defined. To address this, density functional theory (DFT) calculations at the B3LYP-D3BJ/def2-SVP level were combined with machine learning to derive a predictive model of substrate recognition using a curated dataset of 66 compounds spanning 9 functional categories. A hybrid support vector machine (SVM) classifier achieved 96.3% accuracy (95% CI: 81.0–99.9%, Clopper–Pearson exact) in discriminating substrates from non-substrates under leave-one-out cross-validation. Feature importance analysis identified lipophilicity (LogP, F-score = 37.5) as the dominant descriptor, suggesting that membrane partitioning constitutes the initial recognition step. The HOMO–LUMO gap contributed secondarily (F-score = 12.4). Substrates were further distinguished by high frontier orbital focalization, with frontier orbital spread of 1.8–2.6%, compared to 4.18–7.22% for non-substrates. Notably, a model trained exclusively on Pdr5p data achieved 87% prediction accuracy when applied without retraining to the human P-glycoprotein (ABCB1) dataset, suggesting conserved physicochemical principles of substrate recognition across evolutionarily distant ABC transporters. These findings provide a quantum chemical framework for understanding and potentially predicting MDR transporter substrate specificity. Full article

(This article belongs to the Section Computational and Theoretical Chemistry)

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36 pages, 6029 KB

Open AccessArticle

Dissolving Microneedles with Smart Design—A Tool for Enhancing Skin Permeation of Naltrexone Hydrochloride

by Teodora Popova, Ivaylo Ganchev and Christina Voycheva

Molecules 2026, 31(12), 2083; https://doi.org/10.3390/molecules31122083 (registering DOI) - 13 Jun 2026

Abstract

Dissolving microneedles (DMN) could be considered as a minimally invasive alternative for transdermal delivery of naltrexone hydrochloride (NTX). In the present study, DMN patches with smart design were developed via a two-step micromoulding technique. The systems were composed of drug-free polyvinylpyrrolidone (PVP) and [...] Read more.

Dissolving microneedles (DMN) could be considered as a minimally invasive alternative for transdermal delivery of naltrexone hydrochloride (NTX). In the present study, DMN patches with smart design were developed via a two-step micromoulding technique. The systems were composed of drug-free polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) blend microneedle tips, combined with a drug-loaded backing layer based on PVP and Poloxamer 407. The influence of polymer concentration in DMN tips and backing-layer composition on morphology, mechanical properties, drug release and permeation was evaluated. Mechanical studies revealed that intermediate polymer concentration (formulation MN-20%/2:1) provided superior structural integrity (13.57 ± 1.43% height reduction after compression) and efficient penetration up to the fourth Parafilm^® layer. Incorporation of NTX into the backing layer allowed for high drug loading, while a 2:1 PVP:P407 ratio provided higher toughness (1806 g/mm) as well as thermoresponsive and controlled drug release. In vitro permeation studies demonstrated significantly enhanced NTX delivery from DMN systems compared to simple matrix patches—an almost 4-fold increase in flux with 56% permeation of NTX up to 8 h. These findings highlight the importance of polymer composition in DMN design and demonstrate the potential of the developed systems as an effective platform for transdermal delivery of NTX. Full article

(This article belongs to the Special Issue Alternative Routes for the Delivery of Drug Molecules)

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9 pages, 1570 KB

Open AccessCommunication

A Zero-Dimensional Zn(II)-Based Organic–Inorganic Hybrid Metal Halide with Blue-Green Emission for White Light-Emitting Diode Application

by Hua-Peng Liu, Yu-Chen Wang, Zhen-Chao Hu and Yuan-Chun He

Molecules 2026, 31(12), 2082; https://doi.org/10.3390/molecules31122082 (registering DOI) - 13 Jun 2026

Abstract

Organic–inorganic hybrid metal halides (OIMHs), especially zero-dimensional (0D) ones, have been recognized as an excellent class of luminescent materials due to their structural diversity and tunable emission properties. In this work, using the environmentally friendly Zn(II) ion as the central metal and 1,4,7,10-tetraazacyclododecane [...] Read more.

Organic–inorganic hybrid metal halides (OIMHs), especially zero-dimensional (0D) ones, have been recognized as an excellent class of luminescent materials due to their structural diversity and tunable emission properties. In this work, using the environmentally friendly Zn(II) ion as the central metal and 1,4,7,10-tetraazacyclododecane (Cyclen) as the organic component, we successfully synthesized a novel OIMH, (H₃Cyclen)(ZnBr₄)·Br·H₂O. Single-crystal X-ray diffraction analysis reveals that (H₃Cyclen)(ZnBr₄)·Br·H₂O possesses a 0D structure, in which the [ZnBr₄]²⁻ tetrahedra are uniformly separated by the organic amine cations. This structural feature is expected to enhance the material’s stability and optimize its optoelectronic properties. Under UV lamp irradiation, (H₃Cyclen)(ZnBr₄)·Br·H₂O emits bright blue-green light. Therefore, we systematically investigated its luminescence properties. The emission mechanism was further elucidated using UV–vis absorption spectroscopy and DFT calculations. Finally, (H₃Cyclen)(ZnBr₄)·Br·H₂O was employed as a luminescent material to fabricate a white light-emitting diode (WLED), demonstrating its potential as an excellent phosphor material. Full article

(This article belongs to the Section Inorganic Chemistry)

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76 pages, 9266 KB

Open AccessReview

Recent Advances in Quinoline Synthesis: Sustainable Catalytic Strategies and Emerging Methodologies

by Ignacio M. López-Coca, Shima Ghafouriraz, Silvia Izquierdo, Carlos J. Durán-Valle, Mohammad Qandalee and Alireza Soltani

Molecules 2026, 31(12), 2081; https://doi.org/10.3390/molecules31122081 (registering DOI) - 13 Jun 2026

Abstract

Quinoline derivatives constitute a privileged class of nitrogen-containing heterocycles with extensive applications in medicinal chemistry, agrochemicals, materials science, and functional organic materials. Owing to their broad biological and industrial relevance, the development of efficient, selective, and sustainable synthetic methodologies for quinoline construction remains [...] Read more.

Quinoline derivatives constitute a privileged class of nitrogen-containing heterocycles with extensive applications in medicinal chemistry, agrochemicals, materials science, and functional organic materials. Owing to their broad biological and industrial relevance, the development of efficient, selective, and sustainable synthetic methodologies for quinoline construction remains an active area of research. This review provides a comprehensive overview of recent advances in quinoline synthesis, with particular emphasis on catalytic strategies aligned with the principles of green and sustainable chemistry. Classical transformations, including the Friedländer, Skraup, and Povarov reactions, are revisited in the context of modern catalytic developments that improve reaction efficiency, substrate scope, selectivity, and environmental compatibility. Special attention is devoted to homogeneous and heterogeneous catalytic systems based on both platinum-group and earth-abundant transition metals, highlighting the growing importance of borrowing-hydrogen and acceptorless dehydrogenative coupling methodologies. Recent progress in nanocatalysis, photocatalysis, multicomponent reactions, ionic-liquid-mediated transformations, and metal-free protocols is also critically discussed. Furthermore, solvent-free processes, microwave-assisted synthesis, and recyclable catalytic systems are examined as practical approaches toward minimizing waste generation and energy consumption. Mechanistic aspects, catalytic design principles, substrate limitations, and sustainability metrics are evaluated throughout the review to provide a critical perspective on current methodologies. Collectively, the advances summarized herein demonstrate the rapid evolution of quinoline synthesis toward more atom-economical, environmentally benign, and operationally efficient processes, while also identifying future opportunities for the development of next-generation catalytic platforms for quinoline-based heterocycle construction. Full article

(This article belongs to the Special Issue Exploring Organic Synthesis in Green Chemistry: From Catalytic Reactions to Advanced Applications)

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28 pages, 4789 KB

Open AccessArticle

Comparative Evaluation of the Antidiabetic, Hypolipidemic and Antioxidant Effects of Polygonum persicaria L. Herb and Vaccinium myrtillus L. Leaves in Streptozotocin-Induced Diabetes

by Kostici Roxana, Pirscoveanu Denisa Floriana Vasilica, Diana-Maria Trasca, Adina Maria Kamal, Carmen Vladulescu, Renata Maria Varut, Pluta Ion Dorin, Daniela Cîrțînă, Maria Stoica, Romeo Popa and Gabriela Pura

Molecules 2026, 31(12), 2080; https://doi.org/10.3390/molecules31122080 (registering DOI) - 13 Jun 2026

Abstract

Background/Objectives: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, dyslipidemia, and oxidative stress, leading to severe systemic complications. Medicinal plants rich in polyphenolic compounds have gained increasing attention as complementary therapeutic agents. This study aimed to comparatively evaluate the chemical composition, [...] Read more.

Background/Objectives: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, dyslipidemia, and oxidative stress, leading to severe systemic complications. Medicinal plants rich in polyphenolic compounds have gained increasing attention as complementary therapeutic agents. This study aimed to comparatively evaluate the chemical composition, as well as the antidiabetic, hypolipidemic, and antioxidant effects of Polygonum persicaria and Vaccinium myrtillus in a streptozotocin-induced diabetic model. Although Vaccinium myrtillus has been more extensively investigated for its antidiabetic potential, the pharmacological relevance of Polygonum persicaria in diabetes remains insufficiently characterized, particularly in direct comparison with a recognized phytotherapeutic comparator. Methods: Hydroalcoholic tinctures prepared from Polygonum persicaria L. herb and Vaccinium myrtillus L. leaves were subjected to phytochemical analysis using High-Performance Thin-Layer Chromatography (HPTLC) for the identification of flavonoids and phenolcarboxylic acids, alongside spectrophotometric determination of total polyphenol and flavonoid content. Experimental diabetes was induced in CD1 mice by streptozotocin administration. Animals were treated orally for 35 days, and glycemic parameters, lipid profile, body weight, food and water intake, and oxidative stress markers (MDA, SOD, TAC, and GPx) were evaluated. Results: HPTLC/CSS screening indicated the presence of rutin, chlorogenic acid, and caffeic acid in Polygonum persicaria, while Vaccinium myrtillus showed stronger densitometric signals for phenolcarboxylic acid-type compounds, particularly chlorogenic and caffeic acids. Total polyphenol and flavonoid content were also higher in Vaccinium myrtillus (433.89 ± 8.67 mg/L GAE; 154.38 ± 3.08 mg/L QE) compared to Polygonum persicaria (269.28 ± 5.25 mg/L GAE; 132.75 ± 2.65 mg/L QE). Functionally, Vaccinium myrtillus demonstrated a significant antihyperglycemic effect from day 14 (p = 0.009) and improved lipid parameters, while Polygonum persicaria showed a delayed glycemic effect, significant only at day 35 (p = 0.014), without significant hypolipidemic activity. In contrast, Polygonum persicaria exerted a marked antioxidant effect, significantly increasing GPx activity (p = 0.025) and reducing MDA levels (p = 0.053). Conclusions: Vaccinium myrtillus showed stronger antihyperglycemic and hypolipidemic effects, while Polygonum persicaria was mainly associated with antioxidant-related biochemical changes. These differences may be influenced by phytochemical composition, but they cannot be attributed solely to total polyphenol or flavonoid content. Full article

(This article belongs to the Special Issue Antioxidants from Natural Plants: Chemistry, Bioactivity, and Applications)

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19 pages, 21598 KB

Open AccessArticle

Hierarchical Micro–Mesoporous ZnO–SiO₂/Carbon Composites: Synthesis, Structural Characterisation, and High-Capacity Adsorption of Cationic Organic Pollutants from Water

by Mariia Galaburda, Małgorzata Wasilewska, Elżbieta Grządka and Jolanta Kutkowska

Molecules 2026, 31(12), 2079; https://doi.org/10.3390/molecules31122079 (registering DOI) - 13 Jun 2026

Abstract

Hierarchical ZnO–SiO₂/carbon composites (C-Zn1, C-Zn2, C-Zn3) were synthesised via the carbonisation of resorcinol–formaldehyde gels in the presence of ZnO-modified fumed silica, and characterised by N₂ adsorption–desorption, FTIR, XRD, SEM, and zeta potential analysis. The composites exhibited hierarchical micro–mesoporous structures with [...] Read more.

Hierarchical ZnO–SiO₂/carbon composites (C-Zn1, C-Zn2, C-Zn3) were synthesised via the carbonisation of resorcinol–formaldehyde gels in the presence of ZnO-modified fumed silica, and characterised by N₂ adsorption–desorption, FTIR, XRD, SEM, and zeta potential analysis. The composites exhibited hierarchical micro–mesoporous structures with BET surface areas of 467–499 m² g⁻¹; the non-microporous volume fraction increased from 0.09 (reference carbon RFC, 545 m² g⁻¹) to 0.54–0.63 upon ZnO–SiO₂ incorporation. Adsorption of methylene blue (MB), crystal violet (CV), and rhodamine 6G (R6G) followed the Marczewski–Jaroniec isotherm model. Maximum adsorption capacities for the best-performing composite (C-Zn1) reached 1.22 mmol g⁻¹ for MB, 1.04 mmol g⁻¹ for CV, and 0.63 mmol g⁻¹ for R6G, compared to 1.32, 1.17, and 0.67 mmol g⁻¹ for unmodified RFC. Kinetic analysis revealed up to 3.5-fold faster adsorption rates for C-Zn1 relative to RFC (for CV and R6G), attributed to enhanced diffusion through mesoporous channels while preserving the micropore-driven capacity. Agar well-diffusion assays against four bacterial strains showed no inhibition zones for any composite, indicating that no biologically active concentration of zinc species was released under the assay conditions. The proposed approach yields composites with enhanced adsorption kinetics, preserved capacity, and confirmed non-leaching character, positioning them as effective candidates for water purification. Full article

(This article belongs to the Special Issue Recent Research Progress of Novel Ion Adsorbents—2nd Edition)

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23 pages, 22420 KB

Open AccessArticle

Hydrostaticity-Sensitive Structural Phase Transition and High-Pressure Phase Diagram in Fluorite: Evidence of Raman Spectroscopy and Electrical Conductivity

by Mingyu Wu, Lidong Dai, Haiying Hu, Wenqing Sun, Meiling Hong and Chuang Li

Molecules 2026, 31(12), 2078; https://doi.org/10.3390/molecules31122078 (registering DOI) - 13 Jun 2026

Abstract

Raman spectroscopic analysis of fluorite was conducted in a diamond anvil cell (DAC) over a pressure range of 0.5–20.5 GPa under different hydrostatic environments, whereas the electrical conductivity was measured at 298–873 K and 1.2–19.6 GPa. High-resolution transmission electron microscopy (HRTEM) observations were [...] Read more.

Raman spectroscopic analysis of fluorite was conducted in a diamond anvil cell (DAC) over a pressure range of 0.5–20.5 GPa under different hydrostatic environments, whereas the electrical conductivity was measured at 298–873 K and 1.2–19.6 GPa. High-resolution transmission electron microscopy (HRTEM) observations were performed on both the initial and recovered samples after recovery to ambient conditions. Three representative pressure-transmitting media (PTMs), including silicone oil, the mixture of methanol and ethanol (4:1 volume ratio, ME), and helium, were employed to control the degree of hydrostaticity within the DAC sample chamber. Experimental results indicate that the pressure-induced abrupt change in A_1g, A_3g, B_1g and B_2g Raman modes, together with the discontinuities in pressure-dependent Raman shifts, Grüneisen parameters, and electrical conductivity, can efficiently characterize the α (cubic structure, space group

F m \bar{3} m

, No 225)-to-γ (cotunnite structure, PbCl₂-type, space group Pnma, No 62) phase transition in fluorite. The transition pressures are determined to be 10.4, 9.6, 8.9 and 7.5 GPa under conditions of no PTM, silicone oil, ME and helium, respectively, demonstrating that the structural phase transition of fluorite is highly sensitive to hydrostaticity. Raman spectroscopy and electrical conductivity measurements upon decompression reveal that the phase transition is reversible, which is further confirmed by the HRTEM microstructural observation on both the initial and recovered samples. The linear relationships between electrical current and sinusoidal voltage, with the nonlinearity factors close to 1.00, manifest the Ohmic response of fluorite under high pressure. Finally, our high-temperature and high-pressure electrical conductivity results revealed the negative dependence of transition temperature on pressure, and the phase boundary between cubic and PbCl₂-type fluorite was determined as: P (GPa) = 13.057 (±1.008) − 0.008 (±0.001) T (K). The obtained phase diagram of fluorite can be employed to deeply explore the high-pressure phase stability and structural transitions of other similar binary halide family minerals. Full article

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15 pages, 2152 KB

Open AccessArticle

Feature Down-Selection to Improve Supervised Classification by Machine Learning on Mass Spectrometry Imaging Data

by Braysen Miller, Aleesa E. Chua, Madeline Isom, Eden P. Go, Emily R. Sekera, Amanda B. Hummon and Heather Desaire

Molecules 2026, 31(12), 2077; https://doi.org/10.3390/molecules31122077 (registering DOI) - 13 Jun 2026

Abstract

The advancements made in the mass spectrometry imaging (MSI) field have allowed for the generation of very large-scale data sets. These data are often interrogated by machine learning (ML), although storing and handling data sets of this size can be difficult. To aid [...] Read more.

The advancements made in the mass spectrometry imaging (MSI) field have allowed for the generation of very large-scale data sets. These data are often interrogated by machine learning (ML), although storing and handling data sets of this size can be difficult. To aid impacted researchers, we seek to evaluate feature reduction strategies that will minimize the amount of data stored while still maintaining the ability to correctly classify the data. Two different feature selection strategies are tested on six different data sets, leveraging XGBoost as the machine learning algorithm. The study provides evidence that selecting features based on the greatest average abundance across all samples is best suited to scale down the feature set at a more modest trimming level, while selecting features based on statistical analysis via a Student’s t-test is better suited for a more aggressive trimming level. These trends were present regardless of training set size or cross-validation strategy. The results from this work provide insight into when these feature filtering steps can be used effectively and when another data reduction strategy, including not restricting the data set, should be considered. Full article

(This article belongs to the Section Analytical Chemistry)

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13 pages, 8024 KB

Open AccessArticle

Computational Insights into the Effect of Noncovalent S···S Interaction on the Excited-State Characteristics of Multiresonant Fluorophore

by Sunwoo Kang and Taekyung Kim

Molecules 2026, 31(12), 2076; https://doi.org/10.3390/molecules31122076 (registering DOI) - 13 Jun 2026

Abstract

The photophysical properties of the designed molecules were investigated by theoretical calculations. The introduction of thiophene units into the DABNA-1 core reduces both S₁ and T₁ energies, whereas the derived ∆E_ST values become larger. As revealed by normal mode [...] Read more.

The photophysical properties of the designed molecules were investigated by theoretical calculations. The introduction of thiophene units into the DABNA-1 core reduces both S₁ and T₁ energies, whereas the derived ∆E_ST values become larger. As revealed by normal mode analysis for all designed molecules, the designed molecule, including the S···S interaction, exhibits the lowest reorganization energy during the excitation and de-excitation. Vibrationally resolved emission spectra further show that S···S interaction plays a pivotal role in reducing the spectrum width. Comprehensively, it is evident that the S···S interaction is a useful chemical design strategy to suppress the k_nr and enhance the color purity for OLED emitter. Full article

(This article belongs to the Special Issue Advances in Density Functional Theory (DFT) Calculation, 2nd Edition)

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20 pages, 3853 KB

Open AccessArticle

Study on Regulatory Mechanism of Gastrodia elata Specific microRNA Targeting JNK3 in Alzheimer’s Disease

by Hongyao Li, Zhongteng Lu, Ke Gao, Jianjun Guo, Zuoming Nie and Qing Sheng

Molecules 2026, 31(12), 2075; https://doi.org/10.3390/molecules31122075 (registering DOI) - 12 Jun 2026

Abstract

Alzheimer’s disease (AD) is characterized by Tau hyperphosphorylation, β-amyloid (Aβ) accumulation, and progressive neuronal loss. Gastrodia elata (G. elata), a traditional Chinese medicine with well-established neuroprotective properties, was investigated. Two G. elata-derived miRNAs, Gas-miR04-3p and Gas-miR19-5p, were identified as regulators [...] Read more.

Alzheimer’s disease (AD) is characterized by Tau hyperphosphorylation, β-amyloid (Aβ) accumulation, and progressive neuronal loss. Gastrodia elata (G. elata), a traditional Chinese medicine with well-established neuroprotective properties, was investigated. Two G. elata-derived miRNAs, Gas-miR04-3p and Gas-miR19-5p, were identified as regulators of JNK3. By means of Western blot, RT-qPCR, and assessments of antioxidant indices, it was demonstrated that Gas-miR04-3p and Gas-miR19-5p can suppress JNK3 expression, reduce Tau phosphorylation at Ser202 and Ser396, enhance antioxidant capacity, and attenuate apoptosis in AD-related cellular and molecular pathology models. These miRNAs were also detectable in murine brain tissues following oral administration of total RNA extracted from G. elata. Their administration was associated with decreased JNK3 activation, alleviated Tau hyperphosphorylation, and improved expression of apoptosis-related proteins in AD mouse models. These results suggest that G. elata miRNAs may exert neuroprotective effects through regulation of JNK3 signaling, thereby attenuating Tau-related pathological changes and neuronal injury in AD-related models. Full article

(This article belongs to the Section Medicinal Chemistry)

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