Molecules

27 pages, 1053 KB

Open AccessEditor’s ChoiceReview

Critical Review Regarding the Application of Plant Extracts as Eco-Friendly Corrosion Inhibitors—A Sustainable Interdisciplinary Approach

by Catalin Alexandru Barbu, Irina Fierascu, Augustin Semenescu and Cosmin M. Cotrut

Molecules 2025, 30(18), 3722; https://doi.org/10.3390/molecules30183722 - 12 Sep 2025

Viewed by 3584

Abstract

Corrosion remains a persistent and costly issue across multiple industrial domains, including infrastructure, transportation, and marine operations. The deterioration of metals and alloys under corrosive conditions results in significant financial losses and poses considerable environmental and safety risks. Although traditional corrosion inhibitors demonstrate [...] Read more.

Corrosion remains a persistent and costly issue across multiple industrial domains, including infrastructure, transportation, and marine operations. The deterioration of metals and alloys under corrosive conditions results in significant financial losses and poses considerable environmental and safety risks. Although traditional corrosion inhibitors demonstrate high efficacy, they often contain toxic, synthetic compounds that endanger both human health and ecological systems. The increasing global focus on environmental responsibility and green chemistry has intensified the demand for alternative, non-toxic corrosion mitigation strategies. This review examines the use of plant extracts obtained through various processing methods as “environmentally friendly”, responsible corrosion inhibitors. This analysis underscores the capacity of plant-based compounds to counteract material degradation across diverse applications, from technologically advanced industrial systems to the preservation of cultural heritage. Through an interdisciplinary perspective, this review evaluates the viability of botanical approaches as sustainable substitutes for conventional inhibitors, contributing to a broader understanding of their potential across distinct fields. Full article

(This article belongs to the Special Issue Bio-Based and Natural Compounds: A Sustainable Approach for an Environmental Transition)

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16 pages, 1718 KB

Open AccessEditor’s ChoiceArticle

Development of a Generic Bio-Interface for Immuno-Biodetection on an Oxide Surface Targeting Pathogen Bacteria

by Thibaut Zwingelstein, Thérèse Leblois and Vincent Humblot

Molecules 2025, 30(18), 3681; https://doi.org/10.3390/molecules30183681 - 10 Sep 2025

Viewed by 572

Abstract

With the increase in contamination by microbial agents (bacteria, viruses, etc.) in the fields of agri-food, healthcare, and environment, it is necessary to detect and quantify these biological elements present in complex fluids in a short time with high selectivity, high sensitivity, and, [...] Read more.

With the increase in contamination by microbial agents (bacteria, viruses, etc.) in the fields of agri-food, healthcare, and environment, it is necessary to detect and quantify these biological elements present in complex fluids in a short time with high selectivity, high sensitivity, and, if possible, moderate cost. Acoustic wave biosensors, based on immuno-detection, appear to meet a certain number of these criteria. In this context, we are developing a generic antibody-based biointerface that can detect a wide range of pathogenic bacterial agents using a specific bioreceptor. Based on the silane–oxide chemistry, the process is transferable to any kind of surface that can be either oxidized in surface or activated with O₂-plasma, for instance. For this proof of concept, we have chosen to develop our biointerface on titanium and lithium niobate surfaces. The development of the biointerface consists of grafting antibodies via a self-assembled monolayer (SAM) composed of an aminopropyltriethoxysilane (APTES) and a linker (phenylene diisothiocyanate, PDITC). Two functionalization routes were tested for grafting APTES: in anhydrous toluene followed by a heating step at 110 °C or in chloroform at room temperature. The results obtained on titanium show comparable grafting efficiency between these two routes, allowing us to consider the transposition of the route at room temperature on lithium niobate. The latest route was chosen for fragile materials that do not require the heating steps necessary when using toluene for grafting aminopropyltriethoxysilane. Different surface characterization techniques were used, such as IR spectroscopy (FTIR-ATR), X-ray photoelectron spectroscopy (XPS), and contact angle (WCA), to verify the successful grafting of each layer. Biodetection experiments in static conditions were also carried out to demonstrate the specificity of pathogenic detection, testing an ideal medium with solely bacteria, with no other food sampling nutrients. This paper demonstrates the successful elaboration of a biointerface using APTES as the first anchoring layer, with chloroform as a mild solvent. The process is easily transferable to any kind of fragile surface. Moreover, following anti-L. monocytogenes antibodies, our biointerface shows a specificity of capture in static mode (at a concentration of 10⁷ CFU/mL for an incubation time of 4 h at 37 °C) of up to 98% compared to a species negative control (E. coli) and up to 85% in terms of strain specificity (L. innocua). Full article

(This article belongs to the Section Physical Chemistry)

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21 pages, 9210 KB

Open AccessEditor’s ChoiceArticle

The Influence of NaClO on the Biocorrosion of Carbon Steel Induced by Chlorella vulgaris in Artificial Seawater

by Junnan Zhang, Qi Fu and Guang-Ling Song

Molecules 2025, 30(17), 3636; https://doi.org/10.3390/molecules30173636 - 5 Sep 2025

Viewed by 1149

Abstract

Microbiologically influenced corrosion (MIC) poses a significant threat to carbon steel facilities in marine environments. Due to its environmental friendliness and excellent bactericidal effect, NaClO has been widely applied in the marine industry to inhibit MIC. In fact, algae can also cause severe [...] Read more.

Microbiologically influenced corrosion (MIC) poses a significant threat to carbon steel facilities in marine environments. Due to its environmental friendliness and excellent bactericidal effect, NaClO has been widely applied in the marine industry to inhibit MIC. In fact, algae can also cause severe biocorrosion to carbon steels. However, there are very few studies on the biocorrosion induced by algae, and thus the algicidal effect of bactericide NaClO is still unclear. In this study, the biocorrosion of 45# mild steel induced by Chlorella vulgaris (C. vulgaris) and the effect of NaClO on the biocorrosion were systematically investigated. The results showed that the corrosion rate of the steel in C. vulgaris-containing biotic artificial seawater was significantly higher than that in the abiotic solution. An increase in NaClO concentration resulted in a higher corrosion rate of the steel in general but relatively mild local corrosion penetration. The overall corrosion damage of the steel in the biofilm-covered areas was alleviated, while the corrosion penetration in the biofilm-discontinuous area became deeper after NaClO addition. The addition of 1 ppm NaClO into the biotic artificial seawater could not significantly inhibit the growth of C. vulgaris. When NaClO concentration increased to 10 ppm, the growth of C. vulgaris was markedly suppressed, resulting in a lower corrosion rate than that at 0 ppm and 1 ppm NaClO. At 100 ppm of NaClO, C. vulgaris cells were completely killed, and the overall corrosion rate in the biotic solution was close to that in the abiotic solution. Based on the experimental observations, algae-induced corrosion and its inhibition by NaClO were finally analyzed. Full article

(This article belongs to the Special Issue Corrosion Electrochemistry: A Themed Issue in Honor of the Many Contributions of Prof. Dr. Changjian Lin)

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17 pages, 856 KB

Open AccessEditor’s ChoiceArticle

Discovery of Novel Benzamide-Based Sigma-1 Receptor Agonists with Enhanced Selectivity and Safety

by Pascal Carato, Bénédicte Oxombre, Séverine Ravez, Rajaa Boulahjar, Marion Donnier-Maréchal, Amélie Barczyk, Maxime Liberelle, Patrick Vermersch and Patricia Melnyk

Molecules 2025, 30(17), 3584; https://doi.org/10.3390/molecules30173584 - 2 Sep 2025

Viewed by 1748

Abstract

Central nervous system (CNS) disorders such as neurodegenerative diseases, multiple sclerosis, or even brain ischemia represent major therapeutic challenges with limited effective treatments. The sigma-1 receptor (S1R), a unique ligand-operated molecular chaperone enriched at mitochondria-associated membranes, has emerged as a promising drug target [...] Read more.

Central nervous system (CNS) disorders such as neurodegenerative diseases, multiple sclerosis, or even brain ischemia represent major therapeutic challenges with limited effective treatments. The sigma-1 receptor (S1R), a unique ligand-operated molecular chaperone enriched at mitochondria-associated membranes, has emerged as a promising drug target due to its role in neuroprotection and neuroinflammation. Building upon our previously identified S1R ligand (compound 1), we designed and synthesized six novel benzamide derivatives through pharmacomodulation to optimize affinity, selectivity, and safety profiles. Among these, compound 2 demonstrated superior S1R affinity, improved selectivity over the sigma-2 receptor (S2R), and favorable ADME properties, including enhanced permeability and markedly reduced in vitro cardiac toxicity compared to the lead compound. Functional assays confirmed the agonist activity of key derivatives, while safety evaluations revealed low cytotoxicity and minimal off-target receptor interactions. Collectively, these findings support compound 2 as a promising candidate for further preclinical development in S1R-related CNS disorders. Full article

(This article belongs to the Special Issue Bioactive Compounds for Brain Ischemia and Neurodegenerative Disease—3rd Edition)

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47 pages, 5827 KB

Open AccessEditor’s ChoiceReview

Recent Advances in the Development of Metal-Glycoconjugates for Medicinal Applications

by Federica Brescia, Ioannis Titilas, Simona Cacciapuoti and Luca Ronconi

Molecules 2025, 30(17), 3537; https://doi.org/10.3390/molecules30173537 - 29 Aug 2025

Viewed by 1248

Abstract

Rapidly proliferating tumor cells exhibit elevated demands for nutrients and energy to support their uncontrolled growth, with glucose serving as a key metabolic substrate. Glucose is transported into cells via facilitated diffusion mediated by glucose transporters (GLUTs), after which it undergoes a series [...] Read more.

Rapidly proliferating tumor cells exhibit elevated demands for nutrients and energy to support their uncontrolled growth, with glucose serving as a key metabolic substrate. Glucose is transported into cells via facilitated diffusion mediated by glucose transporters (GLUTs), after which it undergoes a series of enzymatic reactions to generate energy. To accommodate their heightened metabolic needs, cancer cells frequently overexpress GLUTs, thereby enhancing glucose uptake. Notably, aerobic glycolysis—commonly referred to as the “Warburg effect”—has been identified as the predominant pathway of glucose metabolism within tumor tissues, even in the presence of adequate oxygen levels. Consequently, the conjugation of chemotherapeutic agents, including metallodrugs, to glucose-mimicking substrates holds significant potential for achieving tumor-specific intracellular drug delivery by exploiting the elevated glucose uptake characteristic of cancer cells. Moreover, in recent years, glycosylation of metal scaffolds has been extended to the development of bioactive metallodrugs for applications other than cancer treatment, such as potential tumor imaging, antiviral, antimicrobial, antiparasitic and anti-neurodegenerative agents. Accordingly, major advancements in the design of metal-based glycoconjugates for medicinal applications are here summarized and critically discussed, focusing on related results and discoveries published subsequently to our previous (2015) review article on the topic. Full article

(This article belongs to the Special Issue Recent Advances in Development of Small Molecules to Fight Cancer—2nd Edition)

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34 pages, 16527 KB

Open AccessEditor’s ChoiceReview

Exploration of Ruthenium(II/III/VI)–Salen Complexes: From Synthesis to Functional Applications

by Beata Cristóvão, Dariusz Osypiuk and Agata Bartyzel

Molecules 2025, 30(17), 3494; https://doi.org/10.3390/molecules30173494 - 25 Aug 2025

Viewed by 1231

Abstract

This review provides a comprehensive overview of recent advances in the synthesis, structural characterization, and applications of Ru(II), Ru(III), and Ru(VI) complexes, which bear tetradentate Schiff bases of salen type. Ruthenium complexes exhibit catalytic, electrochemical, and biological properties, serving as multifunctional platforms that [...] Read more.

This review provides a comprehensive overview of recent advances in the synthesis, structural characterization, and applications of Ru(II), Ru(III), and Ru(VI) complexes, which bear tetradentate Schiff bases of salen type. Ruthenium complexes exhibit catalytic, electrochemical, and biological properties, serving as multifunctional platforms that integrate fundamental aspects of coordination chemistry with potential practical applications. Full article

(This article belongs to the Special Issue Synthesis, Crystal Structure, and Application of Schiff Base Complexes)

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21 pages, 1126 KB

Open AccessEditor’s ChoiceArticle

Reversed-Phase (RP) and Hydrophilic Interaction (HILIC) Separation Mechanisms for the Assay of Nicotine and E-Cigarette Liquids

by Răzvan Moisi, Mircea-Alexandru Comănescu and Andrei-Valentin Medvedovici

Molecules 2025, 30(16), 3443; https://doi.org/10.3390/molecules30163443 - 21 Aug 2025

Cited by 1 | Viewed by 1327

Abstract

Nicotine is a highly used addictive substance that has recently also become available through electronic cigarettes. Here we present a study of nicotine from e-cigarette liquids through reversed-phase (RP) and hydrophilic interaction (HILIC) liquid chromatography. Multiple aqueous mobile-phase additives are considered for the [...] Read more.

Nicotine is a highly used addictive substance that has recently also become available through electronic cigarettes. Here we present a study of nicotine from e-cigarette liquids through reversed-phase (RP) and hydrophilic interaction (HILIC) liquid chromatography. Multiple aqueous mobile-phase additives are considered for the RP mechanism, focusing on chaotropic agents, mobile-phase concentrations and mixing ratios, and column temperature. Sample preparation was conducted by toluene liquid–liquid extraction of e-cigarette liquids diluted with aqueous 25 mM NaHCO₃/Na₂CO₃. Optimal RP results for retention and peak symmetry were obtained using aqueous 0.1% formic acid and 20 mM ammonium hexafluorophosphate with 0.1% formic acid in acetonitrile, using a gradient profile with a C18 column, exploited at 40 °C and a 1.5 mL/min flow rate. A dilute-and-shoot alternative with automated flow reversal after isocratic elution is presented. For HILIC, aqueous 100 mM ammonium formate and 0.1% formic acid in acetonitrile were used as mobile-phase components, using a gradient profile, on a Thermo Scientific™ Acclaim™ Mixed-Mode HILIC-1 column, operated at 25 °C with a 1 mL/min flow rate. UV detection was at 260 nm. Absolute limits of quantitation in the 1 μg/mL range were obtained for all tested alternatives, with 1 μL injection volumes. Full article

(This article belongs to the Special Issue Chromatography—The Ultimate Analytical Tool, 3rd Edition)

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20 pages, 2920 KB

Open AccessEditor’s ChoiceArticle

The Chelating Abilities of Tertiary Amines with N-O-Donors Towards Cu(II) Ions and the Catalytic Properties of the Resulting Complexes

by Martina Zonzin, Martina Chianese, Andrea Squarcina, Degnet Melese Dereje, Ambra Campofelice, Alessia Da Fermo, Federica Belluti, Nadia Marino, Filip Dębicki, Aleksandra Kotynia, Aleksandra Marciniak, Justyna Brasuń and Mauro Carraro

Molecules 2025, 30(16), 3419; https://doi.org/10.3390/molecules30163419 - 19 Aug 2025

Viewed by 1570

Abstract

Oxidative stress, driven by excess reactive oxygen species (ROS), is a key factor in the progression of neurodegenerative diseases like Alzheimer’s disease (AD). In this context, copper dysregulation can also contribute to this imbalance, being responsible for enhanced ROS production, so that copper [...] Read more.

Oxidative stress, driven by excess reactive oxygen species (ROS), is a key factor in the progression of neurodegenerative diseases like Alzheimer’s disease (AD). In this context, copper dysregulation can also contribute to this imbalance, being responsible for enhanced ROS production, so that copper scavenging has been investigated as a possible therapeutic strategy. This study investigates the behavior of two isostructural ligands, featuring an N₃O donor set, that effectively chelate Cu(II) in aqueous solution. Interestingly, their resulting mono- or dinuclear copper complexes feature a coordination environment suitable to foster antioxidant activity. By transforming copper’s oxidant potential into antioxidant action, these systems may reduce copper-induced oxidative damage. The work examines the pH-dependent metal-binding behavior of the ligands, the catalytic properties of the resulting complexes under physiological conditions, and their ability to inhibit β-amyloid peptide aggregation. Full article

(This article belongs to the Special Issue The Impact of Metal Complexes with Active Small Molecules in Biological Systems)

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32 pages, 3717 KB

Open AccessEditor’s ChoiceReview

Recent Advance in Electrochemical Chiral Recognition Based on Biomaterials (2019–2024)

by Shan Qiu, Guo-Ying Chen, Yi-Dan Qin, Ting-Ting Li and Feng-Qing Yang

Molecules 2025, 30(16), 3386; https://doi.org/10.3390/molecules30163386 - 14 Aug 2025

Cited by 1 | Viewed by 1580

Abstract

Chirality is a prevalent characteristic of natural systems that plays a significant role in the biological activities of living organisms, and the enantiomers typically exhibit different pharmacological activities. Consequently, developing methods with high selectivity and sensitivity for chiral analysis is of great importance [...] Read more.

Chirality is a prevalent characteristic of natural systems that plays a significant role in the biological activities of living organisms, and the enantiomers typically exhibit different pharmacological activities. Consequently, developing methods with high selectivity and sensitivity for chiral analysis is of great importance for pharmaceutical engineering, biomedicine, and food safety. Electrochemical chiral recognition has garnered significant attention owing to its unique advantages, including simplicity of operation, rapid response, and cost-effectiveness. The biomaterials, such as amino acids, proteins, nucleic acids, and polysaccharides, possess inherent chiral sites, excellent biocompatibility, and abundant modifiable groups, rendering them ideal candidates for constructing electrochemical chiral sensors. This review focuses on the research progress of electrochemical chiral recognition based on different biomaterials from 2019 to 2024. In addition, the distinct chiral recognition mechanisms and electrochemical analysis methods, as well as the research challenges and prospects of electrochemical chiral sensors based on biomaterials in enantiomer recognition are discussed. This review can provide a reference for further study in related fields. Full article

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

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38 pages, 3745 KB

Open AccessEditor’s ChoiceReview

Recent Advances in Microtubule Targeting Agents for Cancer Therapy

by Henrique C. Assunção, Patrícia M. A. Silva, Hassan Bousbaa and Honorina Cidade

Molecules 2025, 30(16), 3314; https://doi.org/10.3390/molecules30163314 - 8 Aug 2025

Cited by 2 | Viewed by 4296

Abstract

Cancer mortality and the development of cancer resistance present significant challenges that must be addressed to ensure global health. Among anticancer agents, microtubule-targeting agents (MTAs) represent a well-recognized therapeutic approach that disrupts microtubule dynamics, thereby inhibiting cell division, and has been widely used [...] Read more.

Cancer mortality and the development of cancer resistance present significant challenges that must be addressed to ensure global health. Among anticancer agents, microtubule-targeting agents (MTAs) represent a well-recognized therapeutic approach that disrupts microtubule dynamics, thereby inhibiting cell division, and has been widely used to treat several types of cancers. However, even though MTAs are widely regarded as effective, their potential is limited primarily due to cancer resistance and toxicity. Consequently, in the last years, the exploration of new MTAs with the aim of identifying agents with improved cytotoxicity, selectivity, and adequate pharmacokinetic profile, as well as the ability to evade drug resistance mechanisms, has remained a major concern in the development of anticancer treatment. This review highlights the discovery of new MTAs since 2020, with the goal of understanding the advancements made in this field and its future directions. Special attention is given to structure–activity relationship (SAR) studies that could be important for the discovery of more effective MTAs in the future. Full article

(This article belongs to the Special Issue Nature-Inspired Antitumor Agents, 2nd Edition)

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17 pages, 2337 KB

Open AccessEditor’s ChoiceArticle

Oxygen Reduction by Amide-Ligated Cobalt Complexes: Effect of Hydrogen Bond Acceptor

by Zahra Aghaei, Adedamola A. Opalade, Victor W. Day and Timothy A. Jackson

Molecules 2025, 30(15), 3274; https://doi.org/10.3390/molecules30153274 - 5 Aug 2025

Viewed by 1088

Abstract

The ability of earth-abundant metals to serve as catalysts for the oxygen reduction reaction is of increasing importance given the prominence of this reaction in several emerging technologies. It is now recognized that both the primary and secondary coordination environments of these catalysts [...] Read more.

The ability of earth-abundant metals to serve as catalysts for the oxygen reduction reaction is of increasing importance given the prominence of this reaction in several emerging technologies. It is now recognized that both the primary and secondary coordination environments of these catalysts can be modulated to optimize their performance. In this present work, we describe two Co^II complexes [Co^II(PaPy₂Q)](OTf) (1) and [Co^II(PaPy₂N)](OTf) (2) that catalyze chemical and electrochemical dioxygen reduction. Both 1 and 2 contain Co^II centers in a N₅⁻ coordination environment, but 2 has a naphthyridine group that places a nitrogen atom in the secondary coordination sphere. Solid-state X-ray crystallography and solution-state spectroscopic measurements reveal that, apart from this second-sphere nitrogen in 2, complexes 1 and 2 have essentially identical properties. Despite these similarities, 2 performs the chemical reduction of dioxygen ~10-fold more rapidly than 1. In addition, 2 has an enhanced performance in the electrochemical reduction of dioxygen compared to 1. Both complexes yield a significant amount of H₂O₂ in the chemical reduction of dioxygen (>25%). The enhanced catalytic performance of 2 is attributed to the presence of the second-sphere nitrogen atom, which might enable the efficient protonation of cobalt–oxygen intermediates formed during turnover. Full article

(This article belongs to the Special Issue Metal Complexes: Synthesis, Characterization and Applications)

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20 pages, 3586 KB

Open AccessEditor’s ChoiceArticle

Enhanced NiFe₂O₄ Catalyst Performance and Stability in Anion Exchange Membrane Water Electrolysis: Influence of Iron Content and Membrane Selection

by Khaja Wahab Ahmed, Aidan Dobson, Saeed Habibpour and Michael Fowler

Molecules 2025, 30(15), 3228; https://doi.org/10.3390/molecules30153228 - 1 Aug 2025

Cited by 1 | Viewed by 1827

Abstract

Anion exchange membrane (AEM) water electrolysis is a potentially inexpensive and efficient source of hydrogen production as it uses effective low-cost catalysts. The catalytic activity and performance of nickel iron oxide (NiFeO_x) catalysts for hydrogen production in AEM water electrolyzers were [...] Read more.

Anion exchange membrane (AEM) water electrolysis is a potentially inexpensive and efficient source of hydrogen production as it uses effective low-cost catalysts. The catalytic activity and performance of nickel iron oxide (NiFeO_x) catalysts for hydrogen production in AEM water electrolyzers were investigated. The NiFeO_x catalysts were synthesized with various iron content weight percentages, and at the stoichiometric ratio for nickel ferrite (NiFe₂O₄). The catalytic activity of NiFeO_x catalyst was evaluated by linear sweep voltammetry (LSV) and chronoamperometry for the oxygen evolution reaction (OER). NiFe₂O₄ showed the highest activity for the OER in a three-electrode system, with 320 mA cm⁻² at 2 V in 1 M KOH solution. NiFe₂O₄ displayed strong stability over a 600 h period at 50 mA cm⁻² in a three-electrode setup, with a degradation rate of 15 μV/h. In single-cell electrolysis using a X-37 T membrane, at 2.2 V in 1 M KOH, the NiFe₂O₄ catalyst had the highest activity of 1100 mA cm⁻² at 45 °C, which increased with the temperature to 1503 mA cm⁻² at 55 °C. The performance of various membranes was examined, and the highest performance of the tested membranes was determined to be that of the Fumatech FAA-3-50 and FAS-50 membranes, implying that membrane performance is strongly correlated with membrane conductivity. The obtained Nyquist plots and equivalent circuit analysis were used to determine cell resistances. It was found that ohmic resistance decreases with an increase in temperature from 45 °C to 55 °C, implying the positive effect of temperature on AEM electrolysis. The FAA-3-50 and FAS-50 membranes were determined to have lower activation and ohmic resistances, indicative of higher conductivity and faster membrane charge transfer. NiFe₂O₄ in an AEM water electrolyzer displayed strong stability, with a voltage degradation rate of 0.833 mV/h over the 12 h durability test. Full article

(This article belongs to the Special Issue Water Electrolysis)

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16 pages, 2009 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Incorporation and Repair of Epigenetic Intermediates as Potential Chemotherapy Agents

by Jason L. Herring, Mark L. Sowers, James W. Conrad, Linda C. Hackfeld, Bruce Chang-Gu, Rahul Dilawari and Lawrence C. Sowers

Molecules 2025, 30(15), 3239; https://doi.org/10.3390/molecules30153239 - 1 Aug 2025

Viewed by 1507

Abstract

The incorporation of nucleoside analogs into DNA by polymerases, followed by their removal through base excision repair (BER), represents a promising strategy for cancer chemotherapy. In this study, we investigated the incorporation and cytotoxic effects of several nucleoside analogs—some of which are epigenetic [...] Read more.

The incorporation of nucleoside analogs into DNA by polymerases, followed by their removal through base excision repair (BER), represents a promising strategy for cancer chemotherapy. In this study, we investigated the incorporation and cytotoxic effects of several nucleoside analogs—some of which are epigenetic reprogramming intermediates—in the U87 glioblastoma cell line. We found that two analogs, 5-hydroxymethyl-2′-deoxyuridine (5HmdU) and trifluorothymidine (TFT), are both cytotoxic and are efficiently incorporated into genomic DNA. In contrast, the 5-carboxy analogs—5-carboxy-2′-deoxyuridine (5CadU) and 5-carboxycytidine (5CadC)—showed no cytotoxicity and were not incorporated into DNA. Interestingly, 5-hydroxymethyl-2′-deoxycytidine (5HmdC) was cytotoxic but was not directly incorporated into DNA. Instead, it was deaminated into 5HmdU, which was then incorporated and likely responsible for the observed toxicity. 5HmdU is actively removed from DNA through the BER pathways. In contrast, TFT remains stably incorporated and is neither excised by BER nor does it hydrolyze into 5CadU—a known substrate for the DNA glycosylase SMUG1. We also found that N⁶-benzyladenosine (BzAdo), an inhibitor of the enzyme 2′-deoxynucleoside 5′-phosphate N-hydrolase (DNPH1), enhances the cytotoxicity of 5HmdU. However, the thymidine phosphorylase inhibitor tipiracil hydrochloride (TPI) does not increase the cytotoxic effect of TFT in U87 cells. Together, these findings highlight 5HmdU and TFT as promising chemotherapeutic agents for glioblastoma, each with distinct mechanisms of action and cellular processing. Full article

(This article belongs to the Special Issue Nucleoside and Nucleotide Analogues: Chemical Synthesis and Applications)

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16 pages, 2171 KB

Open AccessEditor’s ChoiceReview

Polystyrene Upcycling via Photocatalytic and Non-Photocatalytic Degradation

by Terry Yang and Yalan Xing

Molecules 2025, 30(15), 3165; https://doi.org/10.3390/molecules30153165 - 29 Jul 2025

Viewed by 1922

Abstract

The rapid increase in polystyrene (PS) production has led to substantial growth in plastic waste, posing serious environmental and waste management challenges. Current disposal techniques are unsustainable, relying heavily on harsh conditions, high energy input, and generating environmentally harmful byproducts. This review critically [...] Read more.

The rapid increase in polystyrene (PS) production has led to substantial growth in plastic waste, posing serious environmental and waste management challenges. Current disposal techniques are unsustainable, relying heavily on harsh conditions, high energy input, and generating environmentally harmful byproducts. This review critically discusses alternative green approaches for PS treatment through photocatalytic and non-photocatalytic upcycling methods. Photocatalytic methods utilize light energy (UV, visible, or broad-spectrum irradiation) to initiate radical reactions that cleave the inert carbon backbone of PS. In contrast, non-photocatalytic strategies achieve backbone degradation without direct light activation, often employing catalysts and thermal energy. Both approaches effectively transform PS waste into higher-value compounds, such as benzoic acid and acetophenone, though yields remain moderate for most reported methods. Current limitations, including catalyst performance, low yields, and impurities in real-world PS waste, are highlighted. Future directions toward enhancing the efficiency, selectivity, and scalability of PS upcycling processes are proposed to address the growing plastic waste crisis sustainably. Full article

(This article belongs to the Special Issue Green Catalysis Technology for Sustainable Energy Conversion)

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14 pages, 1889 KB

Open AccessEditor’s ChoiceArticle

Determination of Phenylurea Herbicides in Water Samples by Magnet-Integrated Fabric Phase Sorptive Extraction Combined with High Performance Liquid Chromatography

by Natalia Manousi, Apostolia Tsiasioti, Abuzar Kabir and Erwin Rosenberg

Molecules 2025, 30(15), 3135; https://doi.org/10.3390/molecules30153135 - 26 Jul 2025

Cited by 1 | Viewed by 861

Abstract

In this study, a magnet-integrated fabric phase sorptive extraction (MI-FPSE) protocol was developed in combination with high pressure liquid chromatography—diode array detection (HPLC-DAD) for the simultaneous determination of five phenylurea pesticides (i.e., chlorbromuron, diuron, linuron, metoxuron, monuron) in environmental water samples. To produce [...] Read more.

In this study, a magnet-integrated fabric phase sorptive extraction (MI-FPSE) protocol was developed in combination with high pressure liquid chromatography—diode array detection (HPLC-DAD) for the simultaneous determination of five phenylurea pesticides (i.e., chlorbromuron, diuron, linuron, metoxuron, monuron) in environmental water samples. To produce the MI-FPSE device, two individual sol-gel coated carbowax 20 M (CW 20 M) cellulose membranes were fabricated and stitched to each other, while a magnetic rod was inserted between them to give the resulting device the ability to spin and serve as a stand-alone microextraction platform. The adsorption and desorption step of the MI-FPSE protocol was optimized to achieve high extraction efficiency and the MI-FPSE-HPLC-DAD method was validated in terms of linearity, sensitivity, selectivity, accuracy, and precision. The limits of detection (LODs) were found to be 0.3 μg L⁻¹. The relative recoveries were 85.2–110.0% for the intra-day and 87.7–103.2% for the inter-day study. The relative standard deviations were better than 13% in all cases. The green character and the practicality of the developed procedure were assessed using ComplexGAPI and Blue Analytical Grade Index metric tools, showing good method performance. Finally, the developed method was successfully used for the analysis of tap, river, and lake water samples. Full article

(This article belongs to the Special Issue Analytical Methods for Food and Environmental Pollutants: Current and Future Perspectives)

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15 pages, 2059 KB

Open AccessEditor’s ChoiceArticle

Strain Engineering of Cu₂O@C₂N for Enhanced Methane-to-Methanol Conversion

by Shuxin Kuai, Bo Li and Jingyao Liu

Molecules 2025, 30(15), 3073; https://doi.org/10.3390/molecules30153073 - 23 Jul 2025

Viewed by 715

Abstract

Inspired by the active site of methane monooxygenase, we designed a Cu₂O cluster anchored in the six-membered nitrogen cavity of a C₂N monolayer (Cu₂O@C₂N) as a stable and efficient enzyme-like catalyst. Density functional theory (DFT) [...] Read more.

Inspired by the active site of methane monooxygenase, we designed a Cu₂O cluster anchored in the six-membered nitrogen cavity of a C₂N monolayer (Cu₂O@C₂N) as a stable and efficient enzyme-like catalyst. Density functional theory (DFT) calculations reveal that the bridged Cu-O-Cu structure within C₂N exhibits strong electronic coupling, which is favorable for methanol formation. Two competing mechanisms—the concerted and radical-rebound pathways—were systematically investigated, with the former being energetically preferred due to lower energy barriers and more stable intermediate states. Furthermore, strain engineering was employed to tune the geometric and electronic structure of the Cu-O-Cu site. Biaxial strain modulates the Cu-O-Cu bond angle, adsorption properties, and d-band center alignment, thereby selectively enhancing the concerted pathway. A volcano-like trend was observed between the applied strain and the methanol formation barrier, with 1% tensile strain yielding the overall energy barrier to methanol formation (ΔG_overall) as low as 1.31 eV. N₂O effectively regenerated the active site and demonstrated strain-responsive kinetics. The electronic descriptor Δε (ε_d − ε_p) captured the structure–activity relationship, confirming the role of strain in regulating catalytic performance. This work highlights the synergy between geometric confinement and mechanical modulation, offering a rational design strategy for advanced C1 activation catalysts. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Physical Chemistry, 3rd Edition)

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19 pages, 4784 KB

Open AccessEditor’s ChoiceArticle

Investigation of the Adsorption and Reactions of Methyl Radicals on Transition Metal (M = Co, Ni, Pd, Pt) (111) Surfaces in Aqueous Suspensions

by Pankaj Kumar, Dan Meyerstein, Amir Mizrahi and Haya Kornweitz

Molecules 2025, 30(15), 3065; https://doi.org/10.3390/molecules30153065 - 22 Jul 2025

Viewed by 1060

Abstract

The DFT method was used to evaluate the adsorption of methyl radicals and the evolution of ethane on the M(111) (M = Co, Ni, Pd, Pt) surfaces, eight metal atoms, in aqueous medium. A maximum of five and four radicals can be adsorbed [...] Read more.

The DFT method was used to evaluate the adsorption of methyl radicals and the evolution of ethane on the M(111) (M = Co, Ni, Pd, Pt) surfaces, eight metal atoms, in aqueous medium. A maximum of five and four radicals can be adsorbed on Co(111) and Ni(111), respectively, and six on Pd(111) and Pt(111) (top site). The ethane evolution occurs via the Langmuir–Hinshelwood (LH) or Eley–Rideal (ER) mechanisms. The production of ethane through the interaction of two adsorbed radicals is thermodynamically feasible for high coverage ratios on the four surfaces; however, kinetically, it is feasible at room temperature only on Co(111) at a coverage of (5/5) and on Pd(111) at a coverage ratio of 4/6, 5/6, and 6/6. Ethane production occurs via the ER mechanism: a collision with solvated methyl radical produces either C₂H₆ or

{C H}_{2}^{*} + {C H}_{4 (a q)}

. On Pd(111) the product is only C₂H₆, on Pt(111), both products (C₂H₆ or

{C H}_{2}^{*}

) are plausible, and on Co(111) and Ni(111), only

{C H}_{2}^{*} + {C H}_{4 (a q)}

is produced. Further reactions of

{C H}_{2}^{*}

with

{C H}_{2}^{*}

or

{C H}_{3}^{*}

to give

C_{2} H_{4}^{*}

or

C_{2} H_{5}^{*}

are thermodynamically plausible only on Pt(111); however, they are very slow due to high energy barriers, 1.48 and 1.36 eV, respectively. Full article

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

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20 pages, 3840 KB

Open AccessEditor’s ChoiceArticle

Ketone-Assisted Alkoxysilane Condensation to Form Siloxane Bonds

by Sławomir Rubinsztajn, Marek Cypryk, Jan Kurjata, Małgorzata Kwiatkowska and Urszula Mizerska

Molecules 2025, 30(14), 3005; https://doi.org/10.3390/molecules30143005 - 17 Jul 2025

Viewed by 762

Abstract

Siloxane bond formation represents a fundamental reaction central to both silicone chemistry and its technological applications. This paper presents a novel ketone-assisted process for the condensation of alkoxy-functional silanes catalyzed by a cationic Ge(II) complex stabilized by pentamethylcyclopentadiene Cp*Ge(II)⁺. This process [...] Read more.

Siloxane bond formation represents a fundamental reaction central to both silicone chemistry and its technological applications. This paper presents a novel ketone-assisted process for the condensation of alkoxy-functional silanes catalyzed by a cationic Ge(II) complex stabilized by pentamethylcyclopentadiene Cp*Ge(II)⁺. This process leads to the formation of siloxane bonds, with dialkoxy ketal as a byproduct. Unlike the analogous reaction involving aldehydes, the ketone-assisted process is reversible, resulting in the formation of a mixture of alkoxy-functionalized silane or siloxane, along with the corresponding disiloxane product. Additionally, the introduced ketone underwent only partial conversion to the corresponding ketal. Furthermore, it was demonstrated that the siloxane bond could be cleaved to form alkoxysilane in the presence of the ketal and a cationic Cp*Ge(II) complex acting as a catalyst. Full article

(This article belongs to the Section Macromolecular Chemistry)

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13 pages, 1747 KB

Open AccessEditor’s ChoiceArticle

Decoding the Architecture of Molecular Diodes: Rational Design for Ideal Rectification

by Sara Gil-Guerrero, Nicolás Ramos-Berdullas and Marcos Mandado

Molecules 2025, 30(14), 2998; https://doi.org/10.3390/molecules30142998 - 17 Jul 2025

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Abstract

The design of nanoscale electronic components remains a major challenge because we have limited control over the chemical and physical properties of their molecular constituents. Even subtle structural or compositional modifications can significantly alter their electronic behavior. Consequently, updating a molecular component often [...] Read more.

The design of nanoscale electronic components remains a major challenge because we have limited control over the chemical and physical properties of their molecular constituents. Even subtle structural or compositional modifications can significantly alter their electronic behavior. Consequently, updating a molecular component often necessitates developing a new model from scratch. In this study, we present a comprehensive analysis of the rectification properties of a promising molecular diode initially proposed by Aviram and Van Dyck. The model has been systematically decomposed into fundamental building blocks, enabling the electron transport process to be examined both as an integrated event and as a sum of cooperative interactions. Our findings reveal that certain motifs—such as the D-σ-A architecture—play a significant role in rectification. However, achieving high-performance molecular rectifiers also requires cooperative interplay with other structural elements that contribute to rectification, such as asymmetric molecule–metal contacts. In this study, we conduct a detailed investigation of the roles these elements play in shaping the rectifying characteristics, and we further interpret their effects by analyzing the dominant transport channels under forward and backward bias conditions. This deeper understanding of the transport mechanism offers greater control over the system and opens the door for rational design strategies for improving rectification efficiency in future molecular devices. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Physical Chemistry, 3rd Edition)

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18 pages, 11863 KB

Open AccessEditor’s ChoiceArticle

Storage and Ripening Monitoring of Pecorino Cheese Through 2D ¹H-NMR Relaxation and ANOVA Simultaneous Component Analysis (ASCA): A Comparison with DSC and ATR-FTIR Characterization

by Francesca Di Donato, Francesco Gabriele, Alessandra Biancolillo, Cinzia Casieri, Angelo Antonio D’Archivio and Nicoletta Spreti

Molecules 2025, 30(14), 2916; https://doi.org/10.3390/molecules30142916 - 10 Jul 2025

Viewed by 605

Abstract

In food processing, non-destructive and non-invasive characterization is a powerful tool for monitoring processes and controlling quality. Cheeses consist of a large variety of products whose nutritional and sensory properties depend on the source materials, cheesemaking procedures, and biochemical transformations occurring during maturation [...] Read more.

In food processing, non-destructive and non-invasive characterization is a powerful tool for monitoring processes and controlling quality. Cheeses consist of a large variety of products whose nutritional and sensory properties depend on the source materials, cheesemaking procedures, and biochemical transformations occurring during maturation and storage. In this study, proton magnetic resonance relaxation time correlation maps (2D ¹H-NMR T₁–T₂) are used to investigate the effect of the ripening degree on Pecorino cheese and evaluate its evolution during storage in a refrigerator under vacuum-packaging conditions. NMR relaxometry has allowed for non-invasive monitoring of packaged Pecorino cheese slices, and the results were compared with those obtained with the two widely used techniques, i.e., Differential Scanning Calorimetry (DSC) and Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy (ATR-FTIR). The analysis of variance and simultaneous component analysis (ASCA), separately applied to 2D ¹H-NMR T₁–T₂ correlation maps, DSC, and ATR-FTIR data, suggests that the results obtained with the NMR approach are consistent with those obtained using the two benchmark techniques. In addition, it can distinguish cheeses stored for different durations (storage time) irrespective of their original moisture content (ripening degree), and vice versa, without opening the vacuum-package, which could compromise the integrity of the samples. Full article

(This article belongs to the Special Issue Application of Analytical Methods in Food, Drug, and Natural Products Research: Volume II)

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18 pages, 5167 KB

Open AccessEditor’s ChoiceArticle

Highly Efficient Photocatalytic Degradation of Tetracycline Antibiotics by BiPO₄/g-C₃N₄: A Novel Heterojunction Nanocomposite with Nanorod/Stacked-like Nanosheets Structure

by Xin Zhu, Moye Luo, Cheng Sun, Jinlin Jiang and Yang Guo

Molecules 2025, 30(14), 2905; https://doi.org/10.3390/molecules30142905 - 9 Jul 2025

Viewed by 801

Abstract

The use of semiconductors for photocatalytic degradation of organic pollutants has garnered considerable attention as a promising solution to environmental challenges. Compared to TiO₂, BiPO₄ exhibits superior photocatalytic activity. However, its large band gap restricts its light absorption to the [...] Read more.

The use of semiconductors for photocatalytic degradation of organic pollutants has garnered considerable attention as a promising solution to environmental challenges. Compared to TiO₂, BiPO₄ exhibits superior photocatalytic activity. However, its large band gap restricts its light absorption to the UV region. One effective technique for extending BiPO₄’s absorption wavelength into the visible spectrum is the construction of the heterostructure. This study aimed to synthesize monodisperse BiPO₄ nanorods via a solvothermal approach and fabricate BiPO₄/g-C₃N₄ heterojunctions with varying loadings through in situ deposition. Tetracyclines were employed as the target pollutant to evaluate the photocatalytic performance and stability of the prepared materials. The results indicated that 5 wt% of composite exhibited better photocatalytic performance than single catalysts, which showed the highest photodegradation efficiency of approximately 98% for tetracyclines. The prepared bi-photocatalyst presented favorable stability under sunlight irradiation, the photocatalytic activity of which remained almost unchanged after four cycles. The enhanced photocatalytic activity was attributed to the synergistic effect. Additionally, the possible degradation mechanism was elucidated utilizing the semiconductor energy band theory. Overall, this work presents new perspectives on synthesizing innovative and efficient visible-light-driven photocatalysts. It also offers a mechanistic analysis approach by integrating theoretical calculations with experimental observations. Full article

(This article belongs to the Special Issue Advances in Photocatalytic Degradation of Organic Pollutants)

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15 pages, 3934 KB

Open AccessEditor’s ChoiceArticle

Methyl Viologen@β-Zeolite with Absorption/Fluorescence Dual-Mode and Photo/Chemical Synergistic Stimuli-Responsive Chromism

by Jingxuan Han, Shaoning Li, Huihui Li, Yu Li, Jiaqiao Qin, Fuxiang Wang and Qinhe Pan

Molecules 2025, 30(13), 2872; https://doi.org/10.3390/molecules30132872 - 6 Jul 2025

Cited by 1 | Viewed by 1077

Abstract

In this work, methyl viologen (MV) was adsorbed into the nanopores of Si/Al H-β-zeolite via cation exchange. The resulting MV@β-zeolite possessed absorption/fluorescence dual-mode and photo/chemical synergistic stimuli-responsive chromism. Owing to the acidic surrounding provided by β-zeolite, the chromism of MV required the synergistic [...] Read more.

In this work, methyl viologen (MV) was adsorbed into the nanopores of Si/Al H-β-zeolite via cation exchange. The resulting MV@β-zeolite possessed absorption/fluorescence dual-mode and photo/chemical synergistic stimuli-responsive chromism. Owing to the acidic surrounding provided by β-zeolite, the chromism of MV required the synergistic stimuli of UV irradiation and a chemical reductant (such as Na₂SO₃). UV irradiation induced single electron transfer from the chemical reductant to MV@β-zeolite, leading to enhanced absorption at 610 nm together with a daylight color change from pale yellow to blue. Meanwhile, the nanopores of β-zeolite inhibited aggregation-caused quenching of MV, enabling MV to emit cyan fluorescence at 500 nm. After the single electron transfer of the chemical reductant under UV irradiation, the cyan fluorescence of MV@β-zeolite was quenched. Additionally, MV@β-zeolite exhibited a short stimulus response time (250 s) and good color change reversibility. These findings in this work provide valuable insights into the design of multi-mode and synergistic stimuli-responsive viologen-based chromic materials, particularly for applications in secure high-throughput information storage, high-level anti-counterfeiting and multi-target multi-mode sensing. Full article

(This article belongs to the Special Issue Novel Organic-Inorganic Hybrid Porous Photochromic Materials)

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25 pages, 2976 KB

Open AccessEditor’s ChoiceArticle

Dual Opioid–Neuropeptide FF Small Molecule Ligands Demonstrate Analgesia with Reduced Tolerance Liabilities

by Marco Mottinelli, V. Blair Journigan, Samuel Obeng, Victoria L. C. Pallares, Christophe Mѐsangeau, Coco N. Kapanda, Stephen J. Cutler, Janet A. Lambert, Shainnel O. Eans, Michelle L. Ganno, Wanhui Sheng, Tamara King, Abhisheak Sharma, Catherine Mollereau, Bonnie A. Avery, Jay P. McLaughlin and Christopher R. McCurdy

Molecules 2025, 30(13), 2851; https://doi.org/10.3390/molecules30132851 - 3 Jul 2025

Viewed by 1024

Abstract

Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the [...] Read more.

Neuropeptide FF (NPFF) receptor antagonists prevent morphine-mediated antinociceptive tolerance, and compounds with dual mu opioid receptor (MOR) agonist and NPFF antagonist activity produce antinociception without tolerance. Compounds synthesized showed affinities in radioligand competition binding assays in the nM and µM range at the opioid and NPFF receptors, respectively, and displayed substitution-dependent functional profiles in the [³⁵S]GTPγS functional assay. From six compounds screened in vivo for antinociception and ability to prevent NPFF-induced hyperalgesia in mouse warm water tail withdrawal tests, compound 22b produced dose-dependent MOR-mediated antinociception with an ED₅₀ value (and 95% confidence interval) of 6.88 (4.71–9.47) nmol, i.c.v., and also prevented NPFF-induced hyperalgesia. Meanwhile, 22b did not demonstrate the respiratory depression, hyperlocomotion, or impaired intestinal transit of morphine. Moreover, repeated treatment with 22b produced a 1.6-fold rightward shift in antinociceptive dose response, significantly less acute antinociceptive tolerance than morphine. Evaluated for microsomal stability in vitro and in vivo pharmacokinetic profile, 22b showed suitable microsomal stability paired in vivo with a large apparent volume of distribution and a clearance smaller than the hepatic flow in rats, suggesting no extra-hepatic metabolism. In conclusion, the present study confirms that dual-action opioid–NPFF ligands may offer therapeutic promise as analgesics with fewer liabilities of use. Full article

(This article belongs to the Special Issue New Strategies for Drug Development)

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17 pages, 3836 KB

Open AccessEditor’s ChoiceArticle

Anticancer Quinolinol Small Molecules Target Multiple Pathways to Promote Cell Death and Eliminate Melanoma Cells Resistant to BRAF Inhibitors

by Xinjiang Wang, Rati Lama, Alexis D. Kelleher, Erika C. Rizzo, Samuel L. Galster, Chao Xue, Yali Zhang, Jianmin Wang, Jun Qu and Sherry R. Chemler

Molecules 2025, 30(13), 2696; https://doi.org/10.3390/molecules30132696 - 22 Jun 2025

Viewed by 1238

Abstract

Small molecule inhibitors that target the E3 ligase activity of MDM2-MDM4 have been explored to inhibit the oncogenic activity of MDM2-MDM4 complex. MMRi62 is a small molecule that was identified using an MDM2-MDM4 E3 ligase-based high throughput screen and a cell-death-based secondary screen. [...] Read more.

Small molecule inhibitors that target the E3 ligase activity of MDM2-MDM4 have been explored to inhibit the oncogenic activity of MDM2-MDM4 complex. MMRi62 is a small molecule that was identified using an MDM2-MDM4 E3 ligase-based high throughput screen and a cell-death-based secondary screen. Our previous studies showed that MMRi62 promotes MDM4 degradation in cells and induces p53-independent apoptosis in cancer cells. However, MMRi62 activity in solid tumor cells such as melanoma cells, especially in BRAF inhibitor resistant melanoma cells, have not been explored. Although its promotion of MDM4 degradation is clear, the direct MMRi62 targets in cells are unknown. In this report, we show that MMRi62 is a much more potent p53-independent apoptosis inducer than conventional MDM2 inhibitors in melanoma cells. A brief structure-activity study led to development of SC-62-1 with improved activity. SC-62-1 potently inhibits and eliminates clonogenic growth of melanoma cells that acquired resistance to BRAF inhibitors. We developed a pair of active and inactive SC-62-1 probes and profiled the cellular targets of SC-62-1 using a chemical biology approach coupled with IonStar/nano-LC/MS analysis. We found that SC-62-1 covalently binds to more than 15 hundred proteins in cells. Pathways analysis showed that SC-62-1 significantly altered several pathways including carbon metabolism, RNA metabolism, amino acid metabolism, translation and cellular response to stress. This study provides mechanistic insights into the mechanisms of action for MMRi62-like quinolinols. This study also suggests multi-targeting compounds like SC-62-1 might be useful for overcoming resistance to BRAF inhibitors for improved melanoma treatment. Full article

(This article belongs to the Special Issue Small-Molecule Modulators Targeting Emerging Therapeutic Pathways: Design, Synthesis and Biological Evaluation)

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18 pages, 4031 KB

Open AccessEditor’s ChoiceArticle

On the Question of the Course of the Hetero Diels–Alder Reactions Between N-(2,2,2-Trichloroethylidene)Carboxamides and Dicyclohexylcarbodiimide: A New Case of the Stepwise Zwitterionic Cycloaddition Process

by Przemysław Woliński, Karolina Zawadzińska-Wrochniak, Ewa Dresler and Radomir Jasiński

Molecules 2025, 30(13), 2692; https://doi.org/10.3390/molecules30132692 - 21 Jun 2025

Cited by 4 | Viewed by 1515

Abstract

The regioselectivity and the molecular mechanism of the Diels–Alder reactions between N-(2,2,2-trichloroethylidene)carboxamides and dicyclohexylcarbodiimide were explored based on the ωB97xd/6-311G(d) (PCM) calculations. It was found that the reaction course is determined by polar local interactions. It is interesting that the most favored [...] Read more.

The regioselectivity and the molecular mechanism of the Diels–Alder reactions between N-(2,2,2-trichloroethylidene)carboxamides and dicyclohexylcarbodiimide were explored based on the ωB97xd/6-311G(d) (PCM) calculations. It was found that the reaction course is determined by polar local interactions. It is interesting that the most favored reaction channel is realized not via classical single-step Diels–Alder mechanism, but according to the stepwise scheme with the intervention of the zwitterionic intermediate. The details of the electron density redistribution along the reaction coordinate were explained using the ELF technique. Full article

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17 pages, 3516 KB

Open AccessEditor’s ChoiceArticle

Is the Greener Approach Better? Application of Electrochemistry in the Synthesis of Perylenediimides

by Patrycja Filipek, Agata Szlapa-Kula, Stanisław Krompiec, Krzysztof Zemlak, Bartłomiej Kula, Karol Erfurt and Michał Filapek

Molecules 2025, 30(13), 2683; https://doi.org/10.3390/molecules30132683 - 21 Jun 2025

Viewed by 800

Abstract

Perylenediimides are an interesting group of compounds that are finding more and more applications. However, the synthetic route of obtaining and modifying them is usually very complicated, costly, and time-consuming. Therefore, the conducted research aimed to develop new, greener, electrochemical methods of obtaining [...] Read more.

Perylenediimides are an interesting group of compounds that are finding more and more applications. However, the synthetic route of obtaining and modifying them is usually very complicated, costly, and time-consuming. Therefore, the conducted research aimed to develop new, greener, electrochemical methods of obtaining unknown perylenediimides (containing 2-ethylhexyl at the nitrogen atom). For the products obtained in this way, optical and electrochemical studies were conducted and compared with DFT results (i.e., energy gaps and HOMO and LUMO levels). Asa result of optical studies, different emission wavelengths of two isomers originating from the same excitation wavelength were observed. Electrochemical studies also confirmed significant differences in properties between the obtained isomers. Spectroelectrochemical measurements were also performed; they revealed the electrochromic properties of the obtained isomers in the visible and near-infrared range. Considering all the properties (optical and (spectro)electrochemical), the obtained compounds have a high potential for use in optoelectronic devices. Moreover, unprecedented pi-expansion of cis-DBPDI via 1,2-bis(p-bromophenyl)acetylene Diels–Alder cycloaddition into the bay region was also realized successfully. Summing up, electrosynthesis and further pi-expansion via cycloaddition offer a sea of opportunities for obtaining nanographenes. Full article

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21 pages, 4310 KB

Open AccessEditor’s ChoiceArticle

Evaluating Triazole-Substituted Pyrrolopyrimidines as CSF1R Inhibitors

by Srinivasulu Cherukupalli, Jan Eickhoff, Carsten Degenhart, Peter Habenberger, Anke Unger, Bård Helge Hoff and Eirik Sundby

Molecules 2025, 30(12), 2641; https://doi.org/10.3390/molecules30122641 - 18 Jun 2025

Viewed by 1389

Abstract

6-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines have promising properties as colony-stimulating factor 1 receptor (CSF1R) inhibitors. Inspired by these antagonists, two series of 1,2,3-triazole analogues (28 compounds) were synthesized and evaluated as CSF1R inhibitors. Enzymatic IC₅₀ profiling showed that 27 of the 28 [...] Read more.

6-Aryl-7H-pyrrolo[2,3-d]pyrimidin-4-amines have promising properties as colony-stimulating factor 1 receptor (CSF1R) inhibitors. Inspired by these antagonists, two series of 1,2,3-triazole analogues (28 compounds) were synthesized and evaluated as CSF1R inhibitors. Enzymatic IC₅₀ profiling showed that 27 of the 28 derivatives had lower IC₅₀ than the reference drug PLX-3397. Three derivatives displayed CSF1R Ba/F3 cellular IC₅₀ well below 1 µM. Profiling of the most promising triazole analogue (compound 27a) toward a panel of kinases reveals a high selectivity for CSF1R with respect to its family kinases, but 27a also inhibits ABL, SRC, and YES kinases. Molecular docking of 27a toward two CSF1R X-ray structures identified two different ligand-inverted binding poses, which triggers interest for further investigations. Full article

(This article belongs to the Special Issue Heterocycles: Design, Synthesis and Biological Evaluation, 3rd Edition)

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25 pages, 6878 KB

Open AccessEditor’s ChoiceArticle

Multifunctional Evaluation of Graphene Oxide–Sulfonamide Nanoconjugates: Antimicrobial, Antibiofilm, Cytocompatibility and Xenobiotic Metabolism Gene Expression Insight

by Irina Zarafu, Irina Mușat, Carmen Limban, Diana C. Nuță, Ioana Daniela Dulama, Cristiana Radulescu, Raluca Maria Stirbescu, Arnaud Tatibouet, Carmen M. Chifiriuc, Luminita Marutescu, Marcela Popa, Laura D. Dragu, Elena Radu, Ioana Nicolau, Coralia Bleotu and Petre Ionita

Molecules 2025, 30(12), 2585; https://doi.org/10.3390/molecules30122585 - 13 Jun 2025

Cited by 2 | Viewed by 1057

Abstract

The clinical utility of sulfonamide antibiotics is increasingly challenged by antimicrobial resistance and pharmacokinetic limitations. In this study, we synthesized five graphene oxide–sulfonamide nanoconjugates (GO–S1 to GO–S5) via covalent functionalization, comprehensively characterized them by IR, Raman, SEM, EDS, etc., and evaluated their antimicrobial, [...] Read more.

The clinical utility of sulfonamide antibiotics is increasingly challenged by antimicrobial resistance and pharmacokinetic limitations. In this study, we synthesized five graphene oxide–sulfonamide nanoconjugates (GO–S1 to GO–S5) via covalent functionalization, comprehensively characterized them by IR, Raman, SEM, EDS, etc., and evaluated their antimicrobial, antibiofilm, cytotoxic, apoptotic, hemolytic and gene expression-modulating effects. While the free sulfonamides (S1–S5) exhibited superior antimicrobial activity in planktonic cultures (MICs as low as 19 μg/mL), their GO-functionalized counterparts demonstrated enhanced antibiofilm efficacy, particularly against Pseudomonas aeruginosa (MBIC: 78–312 μg/mL). Cytotoxicity studies using CellTiter assays and Incucyte live-cell imaging revealed low toxicity for all compounds below 250 μg/mL. Morphological and gene expression analyses indicated mild pro-apoptotic effects, predominantly via caspase-9 and caspase-7 activation, with minimal caspase-3 involvement. Hemolysis assays confirmed the improved blood compatibility of GO–Sx conjugates compared to GO alone. Furthermore, qRT-PCR analysis showed that GO–Sx modulated the expression of key xenobiotic metabolism genes (CYPs and NATs), highlighting potential pharmacokinetic implications. Among all tested formulations, GOS3, GOS4 and GOS5 emerged as the most promising candidates, balancing low cytotoxicity, high hemocompatibility and strong antibiofilm activity. These findings support the use of graphene oxide nanocarriers to enhance the therapeutic potential of sulfonamides, particularly in the context of biofilm-associated infections. Full article

(This article belongs to the Section Nanochemistry)

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29 pages, 15607 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Visible-Light-Driven Co₃O₄/Nb₂O₅ Heterojunction Nanocomposites for Efficient Photocatalytic and Antimicrobial Performance in Wastewater Treatment

by Anil Pandey, Santu Shrestha, Rupesh Kandel, Narayan Gyawali, Subas Acharya, Pujan Nepal, Binod Gaire, Vince Fualo and Jae Ryang Hahn

Molecules 2025, 30(12), 2561; https://doi.org/10.3390/molecules30122561 - 12 Jun 2025

Cited by 4 | Viewed by 2204

Abstract

The development of high-performance photocatalysts is vital for combating water pollution and microbial contamination. In this study, visible-light-active Z-scheme heterojunction nanocomposites composed of Co₃O₄ and Nb₂O₅ (CNNC) were synthesized via co-crystallization and subsequent high-pressure annealing to enhance [...] Read more.

The development of high-performance photocatalysts is vital for combating water pollution and microbial contamination. In this study, visible-light-active Z-scheme heterojunction nanocomposites composed of Co₃O₄ and Nb₂O₅ (CNNC) were synthesized via co-crystallization and subsequent high-pressure annealing to enhance photocatalytic and antimicrobial performance. Structural and optical analyses via XRD, FESEM, TEM, XPS, and PL confirmed the heterojunction formation between porous Co₃O₄ nanoparticles (CONP) and columnar orthorhombic Nb₂O₅ nanoparticles (NONP). The CNNC exhibited significantly improved photocatalytic activity, achieving degradation efficiencies of 95.1% for methylene blue, 72.6% for tetracycline, and 90.0% for Congo red within 150 min. Kinetic studies showed that CNNC’s rate constants were 367% and 466% of those of CONP and NONP, respectively. Moreover, CNNC demonstrated a strong antibacterial effect on Staphylococcus aureus and Escherichia coli with ZOI values of 9.3 mm and 6.8 mm, respectively. Mechanistic analysis revealed that the Z-scheme charge-transfer pathway improved charge separation and reduced electron–hole recombination, contributing to the promoted photocatalytic efficiency. The nanocomposite also showed robust stability and recyclability over five times. These results highlight the promise of CNNC as a bifunctional, visible-light-driven photocatalyst for pollutant decomposition and microbial control. Full article

(This article belongs to the Special Issue Wastewater Treatment: Functional Materials and Advanced Technology, 2nd Edition)

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15 pages, 1936 KB

Open AccessEditor’s ChoiceArticle

Studying the Formation of Fullerenes During Catagenesis

by Jens Dreschmann and Wolfgang Schrader

Molecules 2025, 30(12), 2516; https://doi.org/10.3390/molecules30122516 - 9 Jun 2025

Viewed by 829

Abstract

The formation of polycyclic aromatic hydrocarbons (PAHs) during catagenesis does not exclusively lead to planar structures. The inclusion of five-ring elements increases the curvature of PAHs and yields bent molecules. These bowl-like configurations may end in the formation of spherical carbon allotropes as [...] Read more.

The formation of polycyclic aromatic hydrocarbons (PAHs) during catagenesis does not exclusively lead to planar structures. The inclusion of five-ring elements increases the curvature of PAHs and yields bent molecules. These bowl-like configurations may end in the formation of spherical carbon allotropes as fullerenes or nanotubes, as recently shown. The presence of fullerenes in crude oil raises the question of why the reaction is feasible under catagenic conditions although the laboratory synthesis of fullerenes commonly requires high-energy environments. This study focuses on the feasibility of the simulation of catagenesis under laboratory conditions and the question of which building blocks may lead to spherical structures. Possible educts, reaction mechanisms, and conditions such as temperature are discussed and related to experimental outcomes. For the simulation under laboratory conditions, a light gas condensate was fractionated by distillation in order to reduce the number of compounds per fraction and make them distinguishable. The characterization of the resulting fractions was performed through GC-MS and GC-FID measurements before heat application in a closed reactor. High-resolution mass spectrometry (HRMS) measurements of the products indicated PAH growth and, more importantly, the formation of fullerenes. Interestingly, the characterized fullerenes mostly comprised the range of non-IPR (isolated pentagon rule) fullerenes. Full article

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24 pages, 1714 KB

Open AccessEditor’s ChoiceReview

Engineering and Exploiting Immobilized Peptide Organocatalysts for Modern Synthesis

by Marco Francescato, Hang Liao and Luca Gentilucci

Molecules 2025, 30(12), 2517; https://doi.org/10.3390/molecules30122517 - 9 Jun 2025

Viewed by 1628

Abstract

Short- and medium-sized peptides have long been used as effective and versatile organocatalysts. In the early 80s, Inoue used diketopiperazines in the Strecker reaction, while Juliá and Colonna reported the epoxidation of chalcone catalyzed by poly-L-Ala. Since then, a variety of peptide-catalyzed reactions [...] Read more.

Short- and medium-sized peptides have long been used as effective and versatile organocatalysts. In the early 80s, Inoue used diketopiperazines in the Strecker reaction, while Juliá and Colonna reported the epoxidation of chalcone catalyzed by poly-L-Ala. Since then, a variety of peptide-catalyzed reactions have been described. However, peptide synthesis typically implicates the use of toxic reagents and generates wastes; therefore, peptide recycling is expected to significantly improve the overall sustainability of the process. Easy recovery and recycling of peptide catalysts can be expediently attained by covalent binding, inclusion, or adsorption. In addition, immobilization can significantly accelerate the screening of new peptide catalysts. For these reasons, diverse supports have been tested, including natural or synthetic polymers, porous polymeric networks, inorganic porous materials, organic-inorganic hybrid materials, and finally metal–organic frame-works. Full article

(This article belongs to the Special Issue Organocatalysis: Past, Present, and Future Perspectives)

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67 pages, 16344 KB

Open AccessEditor’s ChoiceReview

Enantiomerically Pure ansa-η⁵-Complexes of Transition Metals as an Effective Tool for Chirality Transfer

by Pavel V. Kovyazin, Leonard M. Khalilov and Lyudmila V. Parfenova

Molecules 2025, 30(12), 2511; https://doi.org/10.3390/molecules30122511 - 8 Jun 2025

Cited by 2 | Viewed by 1506

Abstract

Chiral ansa-η⁵-complexes of transition metals have shown remarkable efficacy in organometallic synthesis and catalysis. Additionally, enantiomerically pure ansa-complexes hold promise for the development of novel chiral materials and pharmaceuticals. The discovery and synthesis of a diverse range of [...] Read more.

Chiral ansa-η⁵-complexes of transition metals have shown remarkable efficacy in organometallic synthesis and catalysis. Additionally, enantiomerically pure ansa-complexes hold promise for the development of novel chiral materials and pharmaceuticals. The discovery and synthesis of a diverse range of group IVB and IIIB metal complexes represents a significant milestone in the advancement of stereoselective catalytic methods for constructing metal-C, C-C, C-H, and C-heteroatom bonds. The synthesis of enantiomerically pure metallocenes can be accomplished through several strategies: utilizing optically active precursors of η⁵-ligands, separation of diastereomers of complexes with enantiomerically pure agents, and synthesis via the stereocontrolled reactions of enantiomerically pure σ-complexes with prochiral anions of η⁵-ligands. This review focuses on the analysis of various nuances of the synthesis of enantiomerically pure ansa-η⁵-complexes of titanium and lanthanum families. Their applicability as effective catalysts in asymmetric carbomagnesiation, carbo- and cycloalumination, oligo- and polymerization, Diels–Alder cycloaddition, reactions of zirconaaziridines, cyclization, hydrosilylation, hydrogenation, hydroamination, and other processes are highlighted as well. Full article

(This article belongs to the Special Issue Advances in Metallocene Chemistry)

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11 pages, 465 KB

Open AccessEditor’s ChoiceArticle

Rapid Enantiomeric Ratio Determination of Multiple Amino Acids Using Ion Mobility-Mass Spectrometry

by Wenqing Xu, Estelle Rathahao-Paris and Sandra Alves

Molecules 2025, 30(12), 2497; https://doi.org/10.3390/molecules30122497 - 6 Jun 2025

Cited by 1 | Viewed by 911

Abstract

Chiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric ratio (er) of seven pairs of [...] Read more.

Chiral analysis is becoming increasingly important across various scientific fields, including chemistry, pharmaceuticals, biosciences, and more recently, metabolomics. In this context, a high-resolution and high-throughput method was developed for the simultaneous determination of the enantiomeric ratio (er) of seven pairs of amino acid (AA) enantiomers (Arg, Gln, His, Met, Pro, Tyr, and Trp) using flow injection analysis coupled with ion mobility-mass spectrometry (FIA-IM-MS) technology. Specifically, the Single Ion Mobility Monitoring (SIM²) mode on a TIMS-Tof^TM instrument enabled the rapid relative quantification of chiral compound mixtures. A linear model accurately described the relationship between enantiomeric ratio and IM-MS response for Arg, Gln, and Pro enantiomers, as evidenced by high R² values and unbiased residuals. In contrast, non-linear trends were observed for His, Tyr, and Trp, where a quadratic model significantly improved the fit. However, the linear model was retained for Met, despite an R² of about 0.98, due to its comparable performance and simplicity. Measurement accuracy was confirmed with very good recovery rates for er values of 0.95 and 0.99 across all AAs. Finally, the potential of the FIA-SIM²-MS approach in chiral analysis was demonstrated, particularly its ability to provide a reliable and efficient high-throughput tool for accurate er determination. Full article

(This article belongs to the Special Issue Enantioselective Synthesis, Enantiomeric Separations and Chiral Recognition: 3rd Edition)

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16 pages, 1650 KB

Open AccessEditor’s ChoiceArticle

Application of VUV/Sulfite Defluorination System for the Simple Detection of Perfluoroalkyl Substances

by Shiyong Tao, Yilin Chen, Xiao Mei, Luyao Jin, Feng Wu and Jing Xu

Molecules 2025, 30(11), 2475; https://doi.org/10.3390/molecules30112475 - 5 Jun 2025

Cited by 1 | Viewed by 1651

Abstract

This study investigated the defluorination of PFOA and PFOS using a vacuum ultraviolet (VUV)/sulfite system, and evaluated its potential application in quantifying individual perfluoroalkyl substances (PFAS). Results showed that 81.9% and 87.5% defluorination of PFOA and PFOS were achieved after 120 min of [...] Read more.

This study investigated the defluorination of PFOA and PFOS using a vacuum ultraviolet (VUV)/sulfite system, and evaluated its potential application in quantifying individual perfluoroalkyl substances (PFAS). Results showed that 81.9% and 87.5% defluorination of PFOA and PFOS were achieved after 120 min of photoreaction under conditions of pH 12 and 20 mM of sulfite. Higher pH and sulfite dosage facilitated the reaction, while competing ions could suppress the defluorination efficiency. Based on the optimized defluorination conditions for individual PFAS, the potential of fluoride release amount, as an indirect quantification indicator, was further assessed. A strong linearity between the fluoride release and initial PFAS concentration (R² > 0.999) was observed in the PFAS concentration range of 2–100 μM, and such linearity was also shown in the presence of sediment leachates. This correlation enabled the estimation of individual PFAS concentrations by measuring fluoride release after defluorination treatment. The approach was further demonstrated in an adsorption experiment, where calculated distribution coefficients (K_oc) for PFAS–sediment interactions were consistent with previously reported values, supporting the analytical validity of the method under controlled conditions. Overall, this work presents a simple and cost-effective indirect analytical strategy of applying a VUV/sulfite defluorination system for individual PFAS quantitative detection in complex environmental matrices. Full article

(This article belongs to the Section Green Chemistry)

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19 pages, 1937 KB

Open AccessEditor’s ChoiceReview

Current Approaches to Microplastics Detection and Plastic Biodegradation

by Paula Przygoda-Kuś, Katarzyna E. Kosiorowska, Aneta K. Urbanek and Aleksandra M. Mirończuk

Molecules 2025, 30(11), 2462; https://doi.org/10.3390/molecules30112462 - 4 Jun 2025

Cited by 4 | Viewed by 5177

Abstract

Environmental concerns about the widespread use of non-biodegradable plastic have generated interest in developing quick and effective methods to degrade synthetic polymers. With millions of tons of plastic waste generated annually, biodegradation by microorganisms presents a promising and eco-friendly solution. However, a bottleneck [...] Read more.

Environmental concerns about the widespread use of non-biodegradable plastic have generated interest in developing quick and effective methods to degrade synthetic polymers. With millions of tons of plastic waste generated annually, biodegradation by microorganisms presents a promising and eco-friendly solution. However, a bottleneck has arisen due to the lack of standardized methods for verification of the biodegradation process. Based on this literature review, he techniques most commonly employed for this purpose currently include measuring mass loss, examining the surface of plastic fragments by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and using analytical methods such as Fourier transform infrared spectroscopy (FTIR), pyrolysis–gas chromatography–mass spectrometry (Pyr-GC/MS) or high-performance liquid chromatography (HPLC). Each of these methods has its advantages and disadvantages. Nevertheless, currently, there is no universal approach to accurately assess the ability of individual microorganisms to degrade plastics. In this review, we summarize the latest advances in techniques for detecting biodegradation of synthetic polymers and future directions in the development of sustainable strategies for mitigating plastic pollution. Full article

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14 pages, 1353 KB

Open AccessEditor’s ChoiceArticle

One-Pot Syntheses and Characterization of Group VI Carbonyl NHC Coordination Compounds

by Zala Stopar, Evelin Gruden, Melita Tramšek and Gašper Tavčar

Molecules 2025, 30(11), 2433; https://doi.org/10.3390/molecules30112433 - 2 Jun 2025

Viewed by 986

Abstract

The reactions of N-heterocyclic carbenes (IMesNHC and IPrNHC) with transition metal carbonyls of group VI (Cr(CO)₆, Mo(CO)₆, and W(CO)₆) were carried out in acetonitrile in simple one-pot syntheses and led to the formation of the coordination [...] Read more.

The reactions of N-heterocyclic carbenes (IMesNHC and IPrNHC) with transition metal carbonyls of group VI (Cr(CO)₆, Mo(CO)₆, and W(CO)₆) were carried out in acetonitrile in simple one-pot syntheses and led to the formation of the coordination compounds IMesNHC–Cr(CO)₅ (1a), IMesNHC–Mo(CO)₅ (2a), IMesNHC–W(CO)₅ (3a), IPrNHC–Cr(CO)₅ (1b), IPrNHC–Mo(CO)₅ (2b), and IPrNHC–W(CO)₅ (3b). With the exception of 1b, the coordination compounds were formed selectively and in high yields. The method represents an effective and easy-to-perform alternative to the previously described methods for NHC–M(CO)₅ (M = Cr, Mo, W). All prepared compounds were characterized by NMR and Raman spectroscopy. Compounds 1a, 2a, 3a, and 2b were also crystallized and structurally characterized by X-ray structure analysis. Finally, the structural features of all compounds were compared with DFT calculations of structurally optimized coordination compounds. Full article

(This article belongs to the Special Issue Featured Papers in Organometallic Chemistry—2nd Edition)

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18 pages, 2229 KB

Open AccessEditor’s ChoiceArticle

The Puzzle of the New Type of Intermediate in the Course of [2 + 2] Cycloaddition with the Participation of Conjugated Nitroalkenes: MEDT Computational Study

by Radomir Jasiński and Agnieszka Kącka-Zych

Molecules 2025, 30(11), 2410; https://doi.org/10.3390/molecules30112410 - 30 May 2025

Cited by 1 | Viewed by 1695

Abstract

The phenomena of regio- and stereoselectivity and the molecular mechanism of the [2 + 2] cycloaddition reaction between (E)-2-arylnitroethenes and the ynamine molecular system were analyzed using wb97xd/6-311 + G(d) (PCM) quantumchemical calculations. It was found that, independently of the stepwise nature of [...] Read more.

The phenomena of regio- and stereoselectivity and the molecular mechanism of the [2 + 2] cycloaddition reaction between (E)-2-arylnitroethenes and the ynamine molecular system were analyzed using wb97xd/6-311 + G(d) (PCM) quantumchemical calculations. It was found that, independently of the stepwise nature of the cycloaddition, the full retention of the stereoconfiguration of the nitroalkene can be interpreted and explained. Next, the analysis of the electronic properties of the localized reaction intermediate suggests its possible zwitterionic nature. Additionally, the solvent and the substituent effect on the reaction course were also evaluated. In consequence, the proposed mechanism can be treated as general for some groups of [2 + 2] cycloaddition processes. Lastly, for the model process, the full Bonding Evolution Theory (BET) analysis along the reaction coordinate was performed. It was found that the [2 + 2] cycloaddition reaction between (E)-2-phenylonitroethene and ynamine begins with the formation of two pseudoradical centers at the C2 and C3 atoms. First, a C2-C3 single bond is formed in phase V by combining two pseudoradical centers, while the formation of a second C4-C1 single bond begins at the last, eleventh phase of the reaction path. A BET analysis of intermediate (I) allows it to be classified as a compound with a pseudoradical structure. Next to zwitterions and biradicals, it is evidently new type of intermediate on the path of the [2 + 2] cycloaddition reaction. Full article

(This article belongs to the Section Organic Chemistry)

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33 pages, 4695 KB

Open AccessEditor’s ChoiceReview

CO₂-Responsive Vinyl Polymers: From Synthesis to Application

by Mahshab Sheraz and Rui Wang

Molecules 2025, 30(11), 2350; https://doi.org/10.3390/molecules30112350 - 28 May 2025

Cited by 1 | Viewed by 1754

Abstract

CO₂-responsive polymers have emerged as a significant class of smart materials, distinguished by their ability to reversibly alter their properties upon exposure to CO₂. Due to CO₂’s abundant availability, low cost, non-toxicity, energy efficiency, and excellent biocompatibility, [...] Read more.

CO₂-responsive polymers have emerged as a significant class of smart materials, distinguished by their ability to reversibly alter their properties upon exposure to CO₂. Due to CO₂’s abundant availability, low cost, non-toxicity, energy efficiency, and excellent biocompatibility, these polymers offer remarkable environmental and practical advantages. This review succinctly explores recent advancements in the synthesis, mechanisms, and applications of CO₂-responsive polymers, emphasizing the pivotal roles of specific acidic and basic functional groups such as carboxylic acids, phenolic groups, amines, amidines, guanidines, and imidazoles. Advanced polymerization techniques including free radical polymerization (FRP), atom transfer radical polymerization (ATRP), reversible addition-fragmentation chain transfer (RAFT), and nitroxide-mediated polymerization (NMP) are critically evaluated for their precision and flexibility in polymer design. Significant applications in smart separation, carbon capture, drug delivery, desalination, emulsions, tissue engineering, and sensing technologies are discussed comprehensively. Although substantial progress has been made, ongoing challenges include enhancing response speed, durability, sustainability, and economic viability. Future research is recommended to focus on innovative polymer structures, computational modeling, hybrid materials, and greener synthesis methods. This review aims to inspire continued exploration and practical utilization of CO₂-responsive polymers to address pressing environmental and technological needs. Full article

(This article belongs to the Special Issue 30th Anniversary of Molecules: Recent Advances and the Next in Macromolecular Chemistry)

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15 pages, 2709 KB

Open AccessEditor’s ChoiceArticle

Design, Synthesis, and Biological Evaluations of a Novel Resveratrol-Type Analogue Against VEGF

by Shengying Lin, Maggie Suisui Guo, Roy Wai-Lun Tang, Yutong Ye, Jiahui Wu, Yuen Man Ho, Ran Duan, Ka Wing Leung, Tina Ting-Xia Dong and Karl Wah-Keung Tsim

Molecules 2025, 30(11), 2345; https://doi.org/10.3390/molecules30112345 - 27 May 2025

Viewed by 3260

Abstract

Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been reported to mediate various diseases, including cancer and wet age-related macular degeneration (wAMD). Despite the fact that VEGF inhibitors are commercially available and appear to be effective in clinical applications, adverse effects [...] Read more.

Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been reported to mediate various diseases, including cancer and wet age-related macular degeneration (wAMD). Despite the fact that VEGF inhibitors are commercially available and appear to be effective in clinical applications, adverse effects have been caused by these treatments. There is an unmet need for developing novel VEGF-targeted treatments against these diseases. Resveratrol, a phytochemical derived from fruits and vegetables, has shown promising potency in suppressing VEGF-mediated bioactivities through a series of in vitro and in vivo testing models. Herein, we report that RE-1, a synthetic resveratrol-type analog, displays robust inhibitory activities against VEGF and its downstream signaling pathways, surpassing its parental molecule, resveratrol. In addition, the drug capabilities of RE-1 were evaluated. As a newly synthesized chemical, RE-1 could be considered for subsequent pharmacological development targeting VEGF-related diseases. Full article

(This article belongs to the Special Issue Design, Synthesis and Biological Evaluation of Medicinal Potential Compounds)

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25 pages, 4306 KB

Open AccessEditor’s ChoiceArticle

Design and Evaluation of a Crosslinked Chitosan-Based Scaffold Containing Hyaluronic Acid for Articular Cartilage Reconstruction

by Salim Hamidi, Mickael Maton, Feng Hildebrand, Valérie Gaucher, Cédric Bossard, Frédéric Cazaux, Jean Noel Staelens, Nicolas Blanchemain and Bernard Martel

Molecules 2025, 30(10), 2202; https://doi.org/10.3390/molecules30102202 - 17 May 2025

Cited by 1 | Viewed by 2046

Abstract

Polymeric scaffolds are promising in tissue engineering due to their structural similarity to extracellular matrix components. This study aimed to design freeze-dried hydrogels based on chitosan (CHT) and hyaluronic acid (HA). Chitosan-based gels were crosslinked with oxidized maltodextrin (MDo) before the freeze-drying step, [...] Read more.

Polymeric scaffolds are promising in tissue engineering due to their structural similarity to extracellular matrix components. This study aimed to design freeze-dried hydrogels based on chitosan (CHT) and hyaluronic acid (HA). Chitosan-based gels were crosslinked with oxidized maltodextrin (MDo) before the freeze-drying step, resulting in spongy porous scaffolds. Based on the state-of-the-art, our hypothesis was that crosslinking would increase scaffold stiffness and delay the degradation of the CHT:HA resorbable scaffolds swelled in a hydrated physiological environment. The physicochemical and mechanical properties of crosslinked CHT- and CHT:HA-based scaffolds were analyzed. Hygroscopic and swelling behavior were assessed using dynamic vapor sorption analysis and batch studies. Degradation was evaluated under different conditions, including in phosphate-buffered saline (PBS), PBS with lysozyme, and lactic acid solutions, to investigate scaffold resistance against enzymatic and acidic degradation. The porosity of the spongy materials was characterized using scanning electron microscopy, while dynamic mechanical analysis provided information on the mechanical properties. Crosslinked scaffolds showed reduced swelling, slower degradation rates, and increased stiffness, confirming MDo as an effective crosslinking agent. Scaffolds loaded with ciprofloxacin (CFX) demonstrated their ability to deliver therapeutic agents, as the CFX loading capacity was promoted by CHT–CFX interactions. Microbiologic investigation confirmed the results. Finally, cytotoxicity tests displayed no toxicity. In conclusion, MDo-crosslinked CHT and CHT:HA scaffolds exhibit enhanced stability, functionality, and mechanical performance, making them promising for cartilage tissue engineering. Full article

(This article belongs to the Special Issue Chitosan, Chitosan Derivatives, Polysaccharides and Their Applications—2nd Edition)

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14 pages, 3464 KB

Open AccessFeature PaperEditor’s ChoiceArticle

Dual-Engineering Tailored Co₃O₄ Hollow Microspheres Assembled by Nanosheets for Boosting Oxygen Evolution Reaction

by Yinghan Cui, Shiduo Yang, Jianqiang Zhu, Zaidong Wang, Sen Chen, Jian Qi and Huan Wang

Molecules 2025, 30(10), 2181; https://doi.org/10.3390/molecules30102181 - 16 May 2025

Cited by 3 | Viewed by 928

Abstract

The development of efficient, low-cost electrocatalysts for the oxygen evolution reaction (OER) is crucial for advancing sustainable hydrogen production through water splitting. This study presents a dual-engineering strategy to enhance the OER performance of Co₃O₄ by synthesizing hollow microspheres assembled [...] Read more.

The development of efficient, low-cost electrocatalysts for the oxygen evolution reaction (OER) is crucial for advancing sustainable hydrogen production through water splitting. This study presents a dual-engineering strategy to enhance the OER performance of Co₃O₄ by synthesizing hollow microspheres assembled from nanosheets (HMNs) with abundant oxygen vacancies and highly active crystal facet exposure. Through a modified one-step hydrothermal process, Co₃O₄ HMNs with exposed (111) and (100) crystal facets were successfully fabricated, demonstrating superior OER activity compared to Co₃O₄ nanocubes (NCs) with only (100) facet exposure. The optimized Co₃O₄-5% HMNs exhibited a low overpotential of 330 mV at 10 mA cm⁻² and a Tafel slope of 69 mV dec⁻¹. The enhanced performance was attributed to the synergistic effects of crystal facet engineering and defect engineering, which optimized the Co-O bond energy, increased the number of active sites, and improved conductivity. The unique hollow structure further facilitated mass transport and prevented nanosheet stacking, exposing more edge sites for catalytic reactions. This work highlights the potential of geometric and electronic structure modulation in designing high-performance OER catalysts for sustainable energy applications. Full article

(This article belongs to the Special Issue Synthesis and Applications of Novel Low-Dimensional Nanomaterials in Catalysis)

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25 pages, 3752 KB

Open AccessEditor’s ChoiceArticle

Synthesis of 3-Carboxy-6-sulfamoylquinolones and Mefloquine-Based Compounds as Panx1 Blockers: Molecular Docking, Electrophysiological and Cell Culture Studies

by Letizia Crocetti, Maria Paola Giovannoni, Tengis S. Pavlov, Veniamin Ivanov, Fabrizio Melani and Gabriella Guerrini

Molecules 2025, 30(10), 2171; https://doi.org/10.3390/molecules30102171 - 15 May 2025

Cited by 1 | Viewed by 1290

Abstract

The membrane channel protein Panx1 is a promising therapeutic target since its involvement was demonstrated in a variety of pathologies such as neuropathic pain, ischemic stroke and cancer. As a continuation of our previous work in this field, we report here the synthesis [...] Read more.

The membrane channel protein Panx1 is a promising therapeutic target since its involvement was demonstrated in a variety of pathologies such as neuropathic pain, ischemic stroke and cancer. As a continuation of our previous work in this field, we report here the synthesis and biological evaluation of two classes of compounds as Panx1 blockers: 3-carboxy-6-sulphonamidoquinolone derivatives and new Mefloquine analogs. The series of 3-carboxy-6-sulphonamidoquinolones gave interesting results, affording powerful Panx1 channel blockers with 73.2 < I% < 100 at 50 µM. In particular, 12f was a more potent Panx1 blocker than the reference compound CBX (IC₅₀ = 2.7 µM versus IC₅₀ = 7.1 µM), and its profile was further investigated in a cell culture model of polycystic kidney disease. Finally, interesting results have been highlighted by new molecular modeling studies. Full article

(This article belongs to the Special Issue The Design, Synthesis, and Biological Activity of New Drug Candidates, 2nd Edition)

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21 pages, 1526 KB

Open AccessEditor’s ChoiceArticle

Strawberry Tree Fruit Residue as Carbon Source Towards Sustainable Fuel Biodesulfurization by Gordonia alkanivorans Strain 1B

by Susana M. Paixão, Tiago P. Silva, Francisco Salgado and Luís Alves

Molecules 2025, 30(10), 2137; https://doi.org/10.3390/molecules30102137 - 13 May 2025

Viewed by 782

Abstract

Biodesulfurization (BDS) is a clean technology that uses microorganisms to efficiently remove sulfur from recalcitrant organosulfur compounds present in fuels (fossil fuels or new-generation fuels resulting from pyrolysis and hydrothermal liquefaction). One of the limitations of this technology is the low desulfurization rates. [...] Read more.

Biodesulfurization (BDS) is a clean technology that uses microorganisms to efficiently remove sulfur from recalcitrant organosulfur compounds present in fuels (fossil fuels or new-generation fuels resulting from pyrolysis and hydrothermal liquefaction). One of the limitations of this technology is the low desulfurization rates. These result in the need for greater amounts of biocatalyst and lead to increased production costs. To mitigate this issue, several approaches have been pursued, such as the use of alternative carbon sources (C-sources) from agro-industrial waste streams or the co-production of high-added-value products by microorganisms. The main goal of this work is to assess the potential of strawberry tree fruit residue (STFr) as an alternative C-source for a BDS biorefinery using Gordonia alkanivorans strain 1B, a well-known desulfurizing bacterium with high biotechnological potential. Hence, the first step was to produce sugar-rich liquor from the STFr and employ it in shake-flask assays to evaluate the influence of different pretreatments (treatments with 1–4% activated charcoal for prior phenolics removal) on metabolic parameters and BDS rates. Afterwards, the liquor was used as the C-source in chemostat assays, compared to commercial sugars, to develop and optimize the use of STFr-liquor as a viable C-source towards cost-effective biocatalyst production. Moreover, the high-market-value bioproducts simultaneously produced during microbial growth were also evaluated. In this context, the best results, considering both the production of biocatalysts with BDS activity and simultaneous bioproduct production (carotenoids and gordofactin biosurfactant/bioemulsifier) were achieved when strain 1B was cultivated in a chemostat with untreated STFr-liquor (5.4 g/L fructose + glucose, 6:4 ratio) as the C-source and in a sulfur-free mineral-minimized culture medium at a dilution rate of 0.04 h⁻¹. Cells from this steady-state culture (STFr L1) achieved the highest desulfurization with 250 mM of dibenzothiophene as a reference organosulfur compound, producing a maximum of ≈213 mM of 2-hydroxibyphenil (2-HBP) with a corresponding specific rate (q_2-HBP) of 6.50 µmol/g(_DCW)/h (where DCW = dry cell weight). This demonstrates the potential of STFr as a sustainable alternative C-source for the production of cost-effective biocatalysts without compromising BDS ability. Additionally, cells grown in STFr L1 also presented the highest production of added-value products (338 ± 15 µg/g_(DCW) of carotenoids and 8 U/mL of gordofactin). These results open prospects for a future G. alkanivorans strain 1B biorefinery that integrates BDS, waste valorization, and the production of added-value products, contributing to the global economic viability of a BDS process and making BDS scale-up a reality in the near future. Full article

(This article belongs to the Special Issue Advances in Biomass Chemicals: Transformation and Valorization)

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19 pages, 6348 KB

Open AccessEditor’s ChoiceArticle

Synthesis, Characterisation, Biological Evaluation and In Silico Studies of Quinoline–1,2,3-Triazole–Anilines as Potential Antitubercular and Anti-HIV Agents

by Snethemba S. Magwaza, Darian Naidu, Oluwatoba E. Oyeneyin, Sibusiso Senzani, Nompumelelo P. Mkhwanazi and Matshawandile Tukulula

Molecules 2025, 30(10), 2119; https://doi.org/10.3390/molecules30102119 - 10 May 2025

Cited by 5 | Viewed by 2016

Abstract

HIV/AIDS and Mycobacterial tuberculosis (Mtb) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate [...] Read more.

HIV/AIDS and Mycobacterial tuberculosis (Mtb) are the leading cause of deaths worldwide. Thus, better medicaments are required to manage these diseases. Quinolines have shown great potential due to their broad spectrum of biological activity. Thus, quinoline–1,2,3-triazole–aniline hybrids were synthesised in moderate to good yields. Compounds 11g (IC₅₀ = 0.388 µM), 11h (IC₅₀ = 0.01032 µM) and 11i (IC₅₀ = 0.167 µM) exhibited the most promising in vitro activities against the wild-type HIV-1 subtype B, with 11h being 9-fold more active than AZT (IC₅₀ = 0.0909 µM), the reference drug. Furthermore, compound 11h displayed moderate activity, with a MIC₉₀ of 88μM against Mtb’s H37Rv strain. Cytotoxicity studies on TZM-bl cell lines revealed that most of the tested compounds were generally non-cytotoxic; the selectivity index (SI) for 11h, the front runner, is >2472. Molecular docking studies revealed that 11h interacted with Phe112, Tyr108, Glu283 and Trp86 amino acid residues in the active site of HIV-1. DFT studies revealed that 11h has the ability to donate and accept electrons to and from available orbitals. The predicted ADMET studies showed that these compounds possess drug-likeness, and 11h has the potential for further optimisation as an anti-HIV-1 agent. Full article

(This article belongs to the Special Issue Heterocyclic Compounds: Synthesis and Medicinal Chemistry Applications)

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12 pages, 1656 KB

Open AccessEditor’s ChoiceArticle

Organophotoredox-Catalyzed Stereoselective Synthesis of Bicyclo[3.2.0]heptanes via [2+2] Photocycloaddition

by Tommaso Benettin, Simonetta Resta, Alessandra Forni, Laura Raimondi, Alessandra Puglisi and Sergio Rossi

Molecules 2025, 30(10), 2090; https://doi.org/10.3390/molecules30102090 - 8 May 2025

Viewed by 1446

Abstract

The stereoselective synthesis of bicyclo[3.2.0]heptanes via an anion radical [2+2] photocycloaddition of aryl bis-enone derivatives was investigated. By employing chiral oxazolidinone auxiliaries bound to aryl bis-enone substrates, enantioenriched, highly substituted bicyclo[3.2.0]heptanes have been synthesized. The reaction, mediated by Eosin Y and promoted by [...] Read more.

The stereoselective synthesis of bicyclo[3.2.0]heptanes via an anion radical [2+2] photocycloaddition of aryl bis-enone derivatives was investigated. By employing chiral oxazolidinone auxiliaries bound to aryl bis-enone substrates, enantioenriched, highly substituted bicyclo[3.2.0]heptanes have been synthesized. The reaction, mediated by Eosin Y and promoted by LiBr under visible light irradiation, has been studied both experimentally and computationally to elucidate the mechanism and stereoselective outcomes. The process proceeds via a syn-closure pathway, leading to the formation of the corresponding cis-anti diastereoisomers as major products isolated and characterized by X-ray analysis; DFT calculations provided useful insights and computational support which allow a plausible reaction mechanism to be proposed that agrees with the collected experimental data. Full article

(This article belongs to the Special Issue Cyclization Reactions in Organic Synthesis: Recent Developments)

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25 pages, 8081 KB

Open AccessEditor’s ChoiceArticle

Discovery, Biological Evaluation and Binding Mode Investigation of Novel Butyrylcholinesterase Inhibitors Through Hybrid Virtual Screening

by Lizi Li, Puchen Zhao, Can Yang, Qin Yin, Na Wang, Yan Liu and Yanfang Li

Molecules 2025, 30(10), 2093; https://doi.org/10.3390/molecules30102093 - 8 May 2025

Cited by 2 | Viewed by 1600

Abstract

Butyrylcholinesterase (BChE), plays a critical role in alleviating the symptoms of Alzheimer’s disease (AD) by regulating acetylcholine levels, emerging as an attractive target for AD treatment. This study employed a quantitative structure–activity relationship (QSAR) model based on ECFP4 molecular fingerprints with several machine [...] Read more.

Butyrylcholinesterase (BChE), plays a critical role in alleviating the symptoms of Alzheimer’s disease (AD) by regulating acetylcholine levels, emerging as an attractive target for AD treatment. This study employed a quantitative structure–activity relationship (QSAR) model based on ECFP4 molecular fingerprints with several machine learning algorithms (XGBoost, RF, SVM, KNN), among which the XGBoost model showed the best performance (AUC = 0.9740). A hybrid strategy integrating ligand- and structure-based virtual screening identified 12 hits from the Topscience core database, three of which were identified for the first time. Among them, piboserod and Rotigotine demonstrated the best BChE inhibitory potency (IC₅₀ = 15.33 μM and 12.76 μM, respectively) and exhibited favorable safety profiles as well as neuroprotective effects in vitro. Notably, Rotigotine, a marketed drug, was newly recognized for its anti-AD potential, with further enzyme kinetic analyses revealing that it acts as a mixed-type inhibitor in a non-competitive mode. Fluorescence spectroscopy, molecular docking, and molecular dynamics simulations further clarified their binding modes and stability. This study provides an innovative screening strategy for the discovery of BChE inhibitors, which not only identifies promising drug candidates for the treatment of AD but also demonstrates the potential of machine learning in drug discovery. Full article

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18 pages, 2382 KB

Open AccessEditor’s ChoiceArticle

Synthesis of Diversely Substituted Diethyl (Pyrrolidin-2-Yl)Phosphonates

by Andrea Bagán, Alba López-Ruiz, Sònia Abás, Elies Molins, Belén Pérez, Itziar Muneta-Arrate, Luis F. Callado and Carmen Escolano

Molecules 2025, 30(9), 2078; https://doi.org/10.3390/molecules30092078 - 7 May 2025

Viewed by 1717

Abstract

Imidazoline I₂ receptors (I₂-IR) are untapped therapeutic targets lacking a structural description. Although the levels of I₂-IR are dysregulated in a plethora of illnesses, the arsenal of ligands that can modulate I₂-IR is limited. In this [...] Read more.

Imidazoline I₂ receptors (I₂-IR) are untapped therapeutic targets lacking a structural description. Although the levels of I₂-IR are dysregulated in a plethora of illnesses, the arsenal of ligands that can modulate I₂-IR is limited. In this framework, we have reported several new structural families embodying the iminophosphonate functional group that have an excellent affinity and selectivity for I₂-IR, and selected members have demonstrated relevant pharmacological properties in murine models of neurodegeneration and Alzheimer’s disease. Starting with these iminophosphonates, we continued to exploit their high degree of functionalization through a short and efficient synthesis to access unprecedented 2,3-di, 2,2,3-tri, 2,3,4-tri, and 2,2,3,4-tetrasubstituted diethyl (pyrrolidine-2-yl) phosphonates. The stereochemistry of the new compounds was unequivocally characterized by X-ray crystallographic analyses. Two selected compounds with structural features shared with the starting products were pharmacologically evaluated, allowing us to deduce the required key structural motifs for biologically active aminophosphonate derivatives. Full article

(This article belongs to the Special Issue Heterocycles: Design, Synthesis and Biological Evaluation, 3rd Edition)

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15 pages, 1754 KB

Open AccessEditor’s ChoiceArticle

Capillary Electrophoresis Electrospray Ionization Mass Spectrometry Reveals Metabolic Perturbations During Nematode Infection in Drosophila melanogaster

by Yayra T. Tuani, Navid J. Ayon, Rosemary M. Onjiko, Sam B. Choi, Shruti Yadav, Ioannis Eleftherianos and Peter Nemes

Molecules 2025, 30(9), 2023; https://doi.org/10.3390/molecules30092023 - 1 May 2025

Viewed by 1138

Abstract

Drosophila melanogaster is broadly used to model host–pathogen interactions. Entomopathogenic nematodes are excellent research tools for dissecting the molecular and functional basis of parasitism and the host’s anti-parasitic response. In this work, we used discovery metabolomics to explore the differences in the metabolome [...] Read more.

Drosophila melanogaster is broadly used to model host–pathogen interactions. Entomopathogenic nematodes are excellent research tools for dissecting the molecular and functional basis of parasitism and the host’s anti-parasitic response. In this work, we used discovery metabolomics to explore the differences in the metabolome composition of wild type D. melanogaster larvae that were infected with symbiotic nematodes (Steinernema carpocapsae carrying Xenorhabdus nematophila mutualistic bacteria) or axenic nematodes (S. carpocapsae lacking their bacterial partners). Benefiting from their high separation power, sensitivity, and compatibility with low amounts of the starting metabolome, we leveraged microanalytical capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS) to profile the small (<500 Da) polar portion of the metabolome among these experimental treatments. We detected and quantified 122 different small molecules, of which 50 were identified with high confidence. Supervised multivariate analysis revealed that the infection was paralleled with changes in amino acid biosynthesis (arginine, phenylalanine, tryptophan, and tyrosine), metabolism (alanine, arginine, aspartate, glutamate, glycine, proline, serine, and threonine), and classical signalling (aspartate, γ-aminobutyrate, glutamate, and pyridoxine). This study demonstrates the ability of high-sensitivity CE-ESI-MS to uncover metabolic perturbations during infection. The results from the metadata may facilitate the design of targeted studies to explore small biomolecules and their functions during host–pathogen interaction. Full article

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14 pages, 1555 KB

Open AccessEditor’s ChoiceArticle

Synthesis of 1,4-Benzodiazepines via Intramolecular C–N Bond Coupling and Ring Opening of Azetidines

by Xin-Ming Xu, Sen Chen, Shao-Lei Duan, Xiang-Min Wang, Qian Liu and Kai Sun

Molecules 2025, 30(9), 2014; https://doi.org/10.3390/molecules30092014 - 30 Apr 2025

Viewed by 3124

Abstract

A facile and efficient synthesis of functionalized 1,4-benzodiazepine derivatives under mild conditions was developed. The CuI/N,N-dimethylglycine-catalyzed intramolecular cross-coupling reaction of 1-(2-bromobenzyl)azetidine-2-carboxamides proceeded smoothly under mild conditions to provide 1,4,9,10a-tetrahydroazeto[1,2-a]benzo[e][1,4]diazepin-10(2H)-ones. The resulting azetidine-fused 1,4-benzodiazepine compounds underwent [...] Read more.

A facile and efficient synthesis of functionalized 1,4-benzodiazepine derivatives under mild conditions was developed. The CuI/N,N-dimethylglycine-catalyzed intramolecular cross-coupling reaction of 1-(2-bromobenzyl)azetidine-2-carboxamides proceeded smoothly under mild conditions to provide 1,4,9,10a-tetrahydroazeto[1,2-a]benzo[e][1,4]diazepin-10(2H)-ones. The resulting azetidine-fused 1,4-benzodiazepine compounds underwent consecutive N-methylation with methyl triflate and the opening of the four-membered heterocyclic ring by NaN₃, KCN and PhSNa to produce diverse 1,4-benzodiazepine derivatives in good to excellent yields. Upon treatment with methyl chloroformate, on the other hand, the 1,4,9,10a-tetrahydroazeto[1,2-a]benzo[e][1,4]diazepin-10(2H)-ones were straightforwardly converted into 2-chloroethyl-substituted 1,4-benzodiazepine derivatives. Full article

(This article belongs to the Special Issue Synthesis, Modification and Application of Heterocyclic Compounds)

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18 pages, 7203 KB

Open AccessEditor’s ChoiceArticle

Study on the Catalytic Performance of Nickel(II) Complexes with Distinct Triazine Support Structures in Ethylene Oligomerization via Different Experiment Designs

by Xiaobing Wei, Jiahui Li, Dan Li, Lijun Guo, Yanling Xiao and Cuiqin Li

Molecules 2025, 30(9), 1977; https://doi.org/10.3390/molecules30091977 - 29 Apr 2025

Cited by 3 | Viewed by 907

Abstract

Covalent organic frameworks hold great promise for heterogeneous catalysis because of their porous structure for gas adsorption and tunable functionality. Two triazine support materials (MAmPA-COF and MAoPA-COF) were prepared by using melamine as the linked monomer and meta-phthalaldehyde (MPA) [...] Read more.

Covalent organic frameworks hold great promise for heterogeneous catalysis because of their porous structure for gas adsorption and tunable functionality. Two triazine support materials (MAmPA-COF and MAoPA-COF) were prepared by using melamine as the linked monomer and meta-phthalaldehyde (MPA) or ortho-phthalaldehyde (OPA) as the sub-construction monomer. Two nickel(II) complexes (Ni@MAmPA-COF and Ni@MAoPA-COF) based on the synthesized COFs were prepared to use for ethylene oligomerization. The nickel(II) complexes had good catalytic activities in ethylene oligomerization. Moreover, the substituent position of the aldehyde group in the sub-construction monomer had a certain influence on the specific surface area, morphology and catalytic activity. The morphology of Ni@MAmPA-COF was spherical, while Ni@MAoPA-COF exhibited layered stacking shapes and had a large specific surface area. Ni@MAoPA-COF has a higher catalytic activity and higher selectivity for low-carbon olefins in ethylene oligomerization due to its larger specific surface area and smaller pore width. Ni@MAoPA-COF has good recyclability and still had excellent catalytic activity after three cycles. Based on the gray correlation analysis and single factor experiment, the reaction pressure was the most important factor affecting the activity of Ni@MAoPA-COF in ethylene oligomerization, and the molar ratio of Al/Ni was the main important factor affecting the selectivity. Full article

(This article belongs to the Special Issue Exclusive Feature Papers in Macromolecular Chemistry)

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