Molecules

10 pages, 1825 KiB

Open AccessArticle

Stilbenes in Red Wine: Formation and Biological Potential of Resveratrol and Piceid Dimers

by Ayoub Jaa, Patricia Homobono Brito de Moura, Josep Valls-Fonayet, Grégory Da Costa, María Begoña Ruiz-Larrea, Stéphanie Krisa, José Ignacio Ruiz-Sanz and Tristan Richard

Molecules 2024, 29(24), 6067; https://doi.org/10.3390/molecules29246067 - 23 Dec 2024

Viewed by 499

Abstract

Resveratrol and its glucoside, piceid, are the primary stilbenes present in wine. These compounds are well known for their pharmaceutical properties. However, these compounds can undergo chemical transformations in wines, such as polymerization in the presence of metallic reagents. This study investigates the [...] Read more.

Resveratrol and its glucoside, piceid, are the primary stilbenes present in wine. These compounds are well known for their pharmaceutical properties. However, these compounds can undergo chemical transformations in wines, such as polymerization in the presence of metallic reagents. This study investigates the oxidative coupling of resveratrol and piceid to form dimers, including δ-viniferin and δ-viniferin-diglucoside. These dimers were synthesized using silver acetate. The formation of these stilbenes was monitored in wine model solutions and red wines. The results indicated that resveratrol and piceid underwent transformation during heat treatment, forming their respective dimers. The polymerization of both compounds is temperature-dependent, with higher conversion rates at elevated temperatures. Notably, piceid was more reactive than resveratrol in wine. Finally, the anti-inflammatory effects of these compounds were evaluated on the RAW 264.7 macrophage cell line. Full article

(This article belongs to the Special Issue Feature Papers in Food Chemistry—3rd Edition)

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10 pages, 2619 KiB

Open AccessArticle

CRISPR/Cas12a with Universal crRNA for Indiscriminate Virus Detection

by Zhenlin Shang, Sitong Liu, Dongxu Liu, Xiaojing Pei, Shujing Li, Yifan He, Yigang Tong and Guoqi Liu

Molecules 2024, 29(24), 6066; https://doi.org/10.3390/molecules29246066 - 23 Dec 2024

Viewed by 495

Abstract

Viruses, known for causing widespread biological harm and even extinction, pose significant challenges to public health. Virus detection is crucial for accurate disease diagnosis and preventing the spread of infections. Recently, the outstanding analytical performance of CRISPR/Cas biosensors has shown great potential and [...] Read more.

Viruses, known for causing widespread biological harm and even extinction, pose significant challenges to public health. Virus detection is crucial for accurate disease diagnosis and preventing the spread of infections. Recently, the outstanding analytical performance of CRISPR/Cas biosensors has shown great potential and they have been considered as augmenting methods for reverse-transcription polymerase chain reaction (RT-PCR), which was the gold standard for nucleic acid detection. We herein utilized Cas12a with universal CRISPR RNA (crRNA) for indiscriminate virus detection by attaching the target to a longer track strand for isothermal amplification. The amplified products contain a domain that is recognized by the Cas12a/crRNA complex, triggering the cleavage of surrounding reporters to produce signals, thereby escaping the target dependence of crRNA recognition. The proposed method allows the same crRNA to detect multiple viral nucleic acids with high sensitivity, including but not limited to SARS-CoV-2, human papillomaviruses (HPV), HCOV-NL63, HCOV-HKU1, and miRNA biomarkers. Taking SARS-CoV-2 and HPV16 pseudoviruses as examples, this method was proved as a versatile and sensitive platform for molecular diagnostic applications. Full article

(This article belongs to the Special Issue Analytical Chemistry Presents with State-of-the-Art Molecular Recognition and Interaction, 2nd Edition)

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14 pages, 4048 KiB

Open AccessArticle

Facile Preparation Route of Cellulose-Based Flame Retardant by Ball-Milling Mechanochemistry

by Mohamed Aaddouz, Fouad Laoutid, Jerome Mariage, Jevgenij Lazko, Bopha Yada, El Miloud Mejdoubi, Antoniya Toncheva and Philippe Dubois

Molecules 2024, 29(24), 6065; https://doi.org/10.3390/molecules29246065 - 23 Dec 2024

Viewed by 481

Abstract

In this study, a sustainable cellulose-based flame-retardant additive was developed, characterized, and incorporated into polypropylene (PP). Microcrystalline cellulose (Cel) was chemically modified with P₂O₅ using the solvent-free ball-milling mechanochemistry approach at room temperature. This modification enabled phosphorus grafting onto cellulose, [...] Read more.

In this study, a sustainable cellulose-based flame-retardant additive was developed, characterized, and incorporated into polypropylene (PP). Microcrystalline cellulose (Cel) was chemically modified with P₂O₅ using the solvent-free ball-milling mechanochemistry approach at room temperature. This modification enabled phosphorus grafting onto cellulose, significantly enhancing the cellulose charring ability and improving the thermal stability of the char as revealed by thermogravimetric analysis (TGA). The resulting product, Cel-P, containing 4.15 wt.% phosphorus, was incorporated and uniformly dispersed as a flame-retardant (FR) additive at 30 wt.% in PP through melt processing. The PP+30-Cel-P composite demonstrated improved char formation and FR properties, including reduction of both peak heat release rate (pHRR) and total heat release (THR) in mass loss cone calorimetry (MLC). Moreover, lower light absorptivity was obtained by smoke opacity tests as compared to PP filled with unmodified cellulose. Full article

(This article belongs to the Special Issue Advances in Polymer Materials Based on Lignocellulosic Biomass)

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20 pages, 2332 KiB

Open AccessArticle

Melittin-Induced Structural Transformations in DMPG and DMPS Lipid Membranes: A Langmuir Monolayer and AFM Study

by Joanna Juhaniewicz-Debinska

Molecules 2024, 29(24), 6064; https://doi.org/10.3390/molecules29246064 - 23 Dec 2024

Viewed by 415

Abstract

In this study, we explore the interactions between melittin, a cationic antimicrobial peptide, and model lipid membranes composed of the negatively charged phospholipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS). Using the Langmuir monolayer technique and atomic force microscopy (AFM), we reveal novel insights into [...] Read more.

In this study, we explore the interactions between melittin, a cationic antimicrobial peptide, and model lipid membranes composed of the negatively charged phospholipids 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS). Using the Langmuir monolayer technique and atomic force microscopy (AFM), we reveal novel insights into these interactions. Our key finding is the observation of the ripple phase in the DMPS bilayer on mica, a phenomenon not previously reported for negatively charged single bilayers. This discovery is significant given the critical role of phosphatidylserine (PS) in cancer biology and the potential of melittin as an anticancer agent. We also highlight the importance of subphase composition, as melittin interacts preferentially with lipids in the liquid-condensed phase; thus, selecting the appropriate subphase composition is crucial because it affects lipid behavior and consequently melittin interactions. Our results show that melittin incorporates into lipid monolayers in both liquid-expanded and liquid-condensed phases, enhancing membrane fluidity and disorder, but is expelled from DMPS in the solid phase. AFM imaging further reveals that melittin induces substantial structural changes in the DMPG membrane and forms the ripple phase in the DMPS bilayers. Despite these alterations, melittin does not cause pore formation or membrane rupture, suggesting strong electrostatic adsorption on the membrane surface that prevents penetration. These findings highlight the differential impacts of melittin on lipid monolayers and bilayers and underscore its potential for interacting with membranes without causing disruption. Full article

(This article belongs to the Section Natural Products Chemistry)

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32 pages, 8102 KiB

Open AccessReview

Porphyrin-Based Supramolecular Self-Assemblies: Construction, Charge Separation and Transfer, Stability, and Application in Photocatalysis

by Yingxu Hu, Jingfeng Peng, Rui Liu, Jing Gao, Guancheng Hua, Xiangjiang Fan and Shengjie Wang

Molecules 2024, 29(24), 6063; https://doi.org/10.3390/molecules29246063 - 23 Dec 2024

Viewed by 527

Abstract

As a key means to solve energy and environmental problems, photocatalytic technology has made remarkable progress in recent years. Organic semiconductor materials offer structural diversity and tunable energy levels and thus attracted great attention. Among them, porphyrin and its derivatives show great potential [...] Read more.

As a key means to solve energy and environmental problems, photocatalytic technology has made remarkable progress in recent years. Organic semiconductor materials offer structural diversity and tunable energy levels and thus attracted great attention. Among them, porphyrin and its derivatives show great potential in photocatalytic reactions and light therapy due to their unique large-π conjugation structure, high apparent quantum efficiency, tailorable functionality, and excellent biocompatibility. Compared to unassembled porphyrin molecules, supramolecular porphyrin assemblies facilitate the solar light absorption and improve the charge transfer and thus exhibit enhanced photocatalytic performance. Herein, the research progress of porphyrin-based supramolecular assemblies, including the construction, the regulation of charge separation and transfer, stability, and application in photocatalysis, was systematically reviewed. The construction strategy of porphyrin supramolecules, the mechanism of charge separation, and the intrinsic relationship of assembling structure-charge transfer-photocatalytic performance received special attention. Surfactants, peptide molecules, polymers, and metal ions were introduced to improve the stability of the porphyrin assemblies. Donor-acceptor structure and co-catalysts were incorporated to inhibit the recombination of the photoinduced charges. These increase the understanding of the porphyrin supramolecules and provide ideas for the design of high-performance porphyrin-based photocatalysts. Full article

(This article belongs to the Special Issue Chemical Research on Photosensitive Materials)

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25 pages, 2389 KiB

Open AccessReview

Future Prospect of Low-Molecular-Weight Prostate-Specific Membrane Antigen Radioisotopes Labeled as Theranostic Agents for Metastatic Castration-Resistant Prostate Cancer

by Ratu Ralna Ismuha, Rien Ritawidya, Isti Daruwati and Muchtaridi Muchtaridi

Molecules 2024, 29(24), 6062; https://doi.org/10.3390/molecules29246062 - 23 Dec 2024

Viewed by 558

Abstract

Prostate cancer ranks as the fourth most common cancer among men, with approximately 1.47 million new cases reported annually. The emergence of prostate-specific membrane antigen (PSMA) as a critical biomarker has revolutionized the diagnosis and treatment of prostate cancer. Recent advancements in low-molecular-weight [...] Read more.

Prostate cancer ranks as the fourth most common cancer among men, with approximately 1.47 million new cases reported annually. The emergence of prostate-specific membrane antigen (PSMA) as a critical biomarker has revolutionized the diagnosis and treatment of prostate cancer. Recent advancements in low-molecular-weight PSMA inhibitors, with their diverse chemical structures and binding properties, have opened new avenues for research and therapeutic applications in prostate cancer management. These novel agents exhibit enhanced tumor targeting and specificity due to their small size, facilitating rapid uptake and localization at the target site while minimizing the retention in non-target tissues. The primary aim of this study is to evaluate the potential of low-molecular-weight PSMA inhibitors labeled with radioisotopes as theranostic agents for prostate cancer. This includes assessing their efficacy in targeted imaging and therapy and understanding their pharmacokinetic properties and mechanisms of action. This study is a literature review focusing on in vitro and clinical research data. The in vitro studies utilize PSMA-targeted radioligands labeled with radioisotopes to assess their binding affinity, specificity, and internalization in prostate cancer cell lines. Additionally, the clinical studies evaluate the safety, effectiveness, and biodistribution of radiolabeled PSMA ligands in patients with advanced prostate cancer. The findings indicate promising outcomes regarding the safety and efficacy of PSMA-targeted radiopharmaceuticals in clinical settings. The specific accumulation of these agents in prostate tumor lesions suggests their potential for various applications, including imaging and therapy. This research underscores the promise of radiopharmaceuticals targeting PSMA in advancing the diagnosis and treatment of prostate cancer. These agents improve diagnostic accuracy and patients’ outcomes by enhancing imaging capabilities and enabling personalized treatment strategies. Full article

(This article belongs to the Special Issue New Insights into Radiopharmaceuticals)

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25 pages, 2703 KiB

Open AccessReview

In Silico Conotoxin Studies: Progress and Prospects

by Ruihan Li, Md. Mahadhi Hasan and Dan Wang

Molecules 2024, 29(24), 6061; https://doi.org/10.3390/molecules29246061 - 23 Dec 2024

Viewed by 414

Abstract

Cone snails of the genus Conus have evolved to produce structurally distinct and functionally diverse venom peptides for defensive and predatory purposes. This nature-devised delicacy enlightened drug discovery and for decades, the bioactive cone snail venom peptides, known as conotoxins, have been widely [...] Read more.

Cone snails of the genus Conus have evolved to produce structurally distinct and functionally diverse venom peptides for defensive and predatory purposes. This nature-devised delicacy enlightened drug discovery and for decades, the bioactive cone snail venom peptides, known as conotoxins, have been widely explored for their therapeutic potential, yet we know very little about them. With the augmentation of computational algorithms from the realms of bioinformatics and machine learning, in silico strategies have made substantial contributions to facilitate conotoxin studies although still with certain limitations. In this review, we made a bibliometric analysis of in silico conotoxin studies from 2004 to 2024 and then discussed in silico strategies to not only efficiently classify conotoxin superfamilies but also speed up drug discovery from conotoxins, reveal binding modes of known conotoxin–ion channel interactions at a microscopic level and relate the mechanisms of ion channel modulation to its underlying molecular structure. We summarized the current progress of studies in this field and gave an outlook on prospects. Full article

(This article belongs to the Special Issue The Role of Peptides and Peptidomimetics in Drug Discovery)

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14 pages, 3618 KiB

Open AccessArticle

Apremilast Cocrystals with Phenolic Coformers

by Yelizaveta Naumkina, Bohumil Kratochvíl, Elena Korotkova and Jan Čejka

Molecules 2024, 29(24), 6060; https://doi.org/10.3390/molecules29246060 - 23 Dec 2024

Viewed by 366

Abstract

Apremilast (APR) is an anti-inflammatory drug commonly used in the treatment of psoriasis. In efforts to enhance its solubility, several cocrystals with similar structural features have been developed. This study investigates the cocrystallization of APR with four phenolic-type coformers: phenol, catechol, pyrogallol, and [...] Read more.

Apremilast (APR) is an anti-inflammatory drug commonly used in the treatment of psoriasis. In efforts to enhance its solubility, several cocrystals with similar structural features have been developed. This study investigates the cocrystallization of APR with four phenolic-type coformers: phenol, catechol, pyrogallol, and hydroxyquinol. These coformers differ in the number and position of their hydroxyl groups, with their melting points varying by as much as 100 °C. Four novel cocrystal forms were synthesized, purified, and characterized using X-Ray diffraction and thermal analysis techniques. Surprisingly, the resulting cocrystals exhibited minimal differences in their melting points. The molecular packing of APR appears to limit the network-forming potential of the hydroxyl groups, a conclusion supported by the solved crystal structures, Hirshfeld surface analysis, and differential scanning calorimetry (DSC) results. Full article

(This article belongs to the Special Issue Covalent and Noncovalent Interactions in Crystal Chemistry, 2nd Edition)

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15 pages, 2173 KiB

Open AccessArticle

Synergistic Effects Between Mixed Plastics and Their Impact on Pyrolysis Behavior and Pyrolysis Products

by Yong Li, Shengming Kang, Wenwen Han and Fengfu Yin

Molecules 2024, 29(24), 6059; https://doi.org/10.3390/molecules29246059 - 23 Dec 2024

Viewed by 497

Abstract

Pyrolysis is recognized as a promising technology for waste plastics management. Although there have been many studies on pyrolysis of waste plastics, there is still a lack of in-depth research on the mechanism of synergistic effect between mixed plastics and the mechanism of [...] Read more.

Pyrolysis is recognized as a promising technology for waste plastics management. Although there have been many studies on pyrolysis of waste plastics, there is still a lack of in-depth research on the mechanism of synergistic effect between mixed plastics and the mechanism of product formation. In this paper, based on the pyrolysis characteristics of Polystyrene, Polyethylene, and mixed plastics (Polystyrene/Polyethylene), it is demonstrated that a synergistic effect exists in the co-pyrolysis of Polystyrene/Polyethylene and affects the pyrolysis behavior and pyrolysis products. It was found that polystyrene chain segments containing C=C double bonds, generated from the pyrolysis of polystyrene, initiated the pyrolysis of polyethylene during the polystyrene/polyethylene co-pyrolysis, resulting in the termination pyrolysis temperature of the co-pyrolysis being advanced by 19.8 K. Due to the reduction in the termination pyrolysis temperature by 19.8 K, the average activation energy of the co-pyrolysis was reduced by about 14%. Compared with the weighted values of single-component plastics (Polystyrene and Polyethylene), the actual oil production of co-pyrolysis increased by 9.7% to 89.80%. At the same time, the content of low molecular weight Styrene and Toluene in pyrolysis oil increased by 12.3% and 1.65%, respectively. This study provides a useful and comprehensive reference for realizing the closed cycle of “from plastics to plastics”. Full article

(This article belongs to the Special Issue Solid Waste and Fly Ash Chemical Treatment Methods)

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16 pages, 12429 KiB

Open AccessArticle

Enhancement of Thermochemical Energy Storage by Alkali Metal Chloride Salts-Doped Ca-Based Sorbents: A Combined DFT and Experimental Study

by Dehao Kong, Nan He, Qicheng Chen, Binjian Nie, Yingjin Zhang, Nan An, Liang Yao and Zhihui Wang

Molecules 2024, 29(24), 6058; https://doi.org/10.3390/molecules29246058 - 23 Dec 2024

Viewed by 358

Abstract

In this paper, the enhancement of thermochemical energy storage by alkali metal chloride salts-doped Ca-based sorbents is revealed by experiments and DFT calculations. The results indicate that NaCl and KCl doping increases the reaction rate and cycle stability. Compared to CaO, the conversion [...] Read more.

In this paper, the enhancement of thermochemical energy storage by alkali metal chloride salts-doped Ca-based sorbents is revealed by experiments and DFT calculations. The results indicate that NaCl and KCl doping increases the reaction rate and cycle stability. Compared to CaO, the conversion of NaCl-CaO and KCl-CaO after one cycle is increased by 59.1% and 61.9%, respectively. This enhancement originates from the oxygen vacancies generated by Na₂O and K₂O and the significantly increased surface area by CaCl₂ as well as the sintering delay. The synergistic effect between Na₂O, K₂O, and CaCl₂ increases the reaction rate of calcium-based materials. Meanwhile, the penetration of low-viscosity molten NaCl and KCl into the calcium-based materials successfully segregates the CaO grains and allows the calcium-based material to maintain the porous structure after 80 cycles, thus exhibiting a high effective conversion rate. In addition, the KCl-CaO composites show the best combined performance in terms of effective conversion and averaged thermal energy density. This work paves the way for the application of chloride salts-doped calcium-based materials. Full article

(This article belongs to the Special Issue Theoretical Study of Inorganic Complexes: Recent Advances and Future Perspectives)

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25 pages, 6923 KiB

Open AccessArticle

Important Aspects of the Design of Experiments and Data Treatment in the Analytical Quality by Design Framework for Chromatographic Method Development

by Bianca F. G. Passerine and Márcia C. Breitkreitz

Molecules 2024, 29(24), 6057; https://doi.org/10.3390/molecules29246057 - 23 Dec 2024

Viewed by 406

Abstract

In the analytical quality by design (AQbD) framework, the design of experiments (DOE) plays a very important role, as it provides information about how experimental input variables influence critical method attributes. Based on the information obtained from the DOE, mathematical models are generated [...] Read more.

In the analytical quality by design (AQbD) framework, the design of experiments (DOE) plays a very important role, as it provides information about how experimental input variables influence critical method attributes. Based on the information obtained from the DOE, mathematical models are generated and used to build the method operable design region (MODR), which is a robust region of operability. Data treatment steps are usually carried out in software such as Fusion QbD, Minitab, or StaEase 360, among others. Although there are many studies in the literature that use the DOE, none of them address important aspects of data treatment for optimization and MODR generation and compare different software calculations. The purpose of this study is to contribute to a better understanding of data treatment aspects that are frequently misread or not fully understood, such as model selection, ANOVA results, and residual analysis. The discussion will be guided by the separation of curcuminoids, using ultra-high performance liquid chromatography and eight quality attributes as responses. This study highlights the importance of carefully selecting and evaluating models, as they significantly influence the generation of the MODR. Moreover, the findings emphasize that it is essential to incorporate uncertainties into the contour plots to accurately determine the MODR in compliance with the ICH Q14 guidelines and USP General Chapter <1220>. Full article

(This article belongs to the Section Analytical Chemistry)

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11 pages, 23880 KiB

Open AccessArticle

Density Functional Theory Insights into Conduction Mechanisms in Perovskite-Type RCoO₃ Nanofibers for Future Resistive Random-Access Memory Applications

by Quanli Hu, Hanqiong Luo, Chao Song, Yin Wang, Bin Yue and Jinghai Liu

Molecules 2024, 29(24), 6056; https://doi.org/10.3390/molecules29246056 - 23 Dec 2024

Viewed by 399

Abstract

In the era of artificial intelligence and Internet of Things, data storage has an important impact on the future development direction of data analysis. Resistive random-access memory (RRAM) devices are the research hotspot in the era of artificial intelligence and Internet of Things. [...] Read more.

In the era of artificial intelligence and Internet of Things, data storage has an important impact on the future development direction of data analysis. Resistive random-access memory (RRAM) devices are the research hotspot in the era of artificial intelligence and Internet of Things. Perovskite-type rare-earth metal oxides are common functional materials and considered promising candidates for RRAM devices because their interesting electronic properties depend on the interaction between oxygen ions, transition metals, and rare-earth metals. LaCoO₃, NdCoO₃, and SmCoO₃ are typical rare-earth cobaltates (RCoO₃). These perovskite materials were fabricated by electrospinning and the calcination method. The aim of this study was to investigate the resistive switching effect in the RCoO₃ structure. The oxygen vacancies in RCoO₃ are helpful to form conductive filaments, which dominates the resistance transition mechanism of Pt/RCoO₃/Pt. The electronic properties of RCoO₃ were investigated, including the barrier height and the shape of the conductive filaments. This study confirmed the potential application of LaCoO₃, NdCoO₃, and SmCoO₃ in memory storage devices. Full article

(This article belongs to the Special Issue Application of Computer Simulation in Materials Science of Molecules, 2nd Edition)

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10 pages, 5636 KiB

Open AccessArticle

Synthesis of a Cholesterol Derivative and Its Application in Gel Emulsion Preparation

by Yang Liu, Shuaihua Liu, Qiang Zhang and Guanghui Tian

Molecules 2024, 29(24), 6055; https://doi.org/10.3390/molecules29246055 - 23 Dec 2024

Viewed by 412

Abstract

As a small-molecule gelator used as a stabilizer in gel emulsions, it has numerous advantages, such as low dosage, independence from phase ratios, and ease of control. In this study, a cholesterol derivative (CSA) was designed and synthesized to be used as a [...] Read more.

As a small-molecule gelator used as a stabilizer in gel emulsions, it has numerous advantages, such as low dosage, independence from phase ratios, and ease of control. In this study, a cholesterol derivative (CSA) was designed and synthesized to be used as a stabilizer for gel emulsions. Gelation experiments demonstrated that this small molecule could gelate various organic solvents, including linear alkanes, toluene, isoamyl alcohol, and acetone. Based on these gelation experiments, a series of gel emulsions were prepared with water as the dispersed phase and an organic solvent immiscible with water as the continuous phase. Finally, the gelation behavior of the gelator/water/toluene and gelator/water/cyclohexane systems was investigated, exploring the effects of different systems and varying water content within the same system on the structure and stability of the gel emulsions. Studies have shown that the gel emulsion prepared from the gelator/water/toluene system exhibits superior stability, likely due to the molecular self-assembly behavior of this cholesterol derivative exhibited in the water/toluene biphasic system. The research results provide a basis for using gel emulsions as templates to prepare porous materials and adjust their internal structure, ultimately laying a solid foundation for applying these porous materials in fields such as adsorption and catalysis. Full article

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16 pages, 9222 KiB

Open AccessArticle

Chemical Modification of Acrylonitrile-Divinylbenzene Polymer Supports with Aminophosphonate Groups and Their Antibacterial Activity Testing

by Ileana Nichita, Lavinia Lupa, Aurelia Visa, Ecaterina-Stela Dragan, Maria Valentina Dinu and Adriana Popa

Molecules 2024, 29(24), 6054; https://doi.org/10.3390/molecules29246054 - 23 Dec 2024

Viewed by 377

Abstract

Bacterial contamination is a major public health concern on a global scale. Treatment resistance in bacterial infections is becoming a significant problem that requires solutions. We were interested in obtaining new polymeric functionalized compounds with antibacterial properties. Three components (polymeric amine, aldehyde, and [...] Read more.

Bacterial contamination is a major public health concern on a global scale. Treatment resistance in bacterial infections is becoming a significant problem that requires solutions. We were interested in obtaining new polymeric functionalized compounds with antibacterial properties. Three components (polymeric amine, aldehyde, and phosphite) were used in the paper in a modified “one-pot” Kabachnik–Fields reaction, in tetrahydrofuran at 60 °C, to create the N-C-P skeleton in aminophosphonate groups. Two copolymers were thus prepared starting from an acrylonitriledivinylbenzene (AN-15%DVB) copolymer containing pendant primary amine groups modified by grafting aminophosphonate groups, i.e., aminobenzylphosphonate (Bz-DVB-AN) and aminoethylphosphonate (Et-DVB-AN). The two copolymers were characterized by FT-IR spectroscopy, SEM-EDX, TGA, and antibacterial properties. It was shown that the novel products have antibacterial qualities against S. aureus and E. coli bacteria. The sample with the strongest antibacterial activity was Et-DVB-AN. We assessed how well the Weibull model and the first-order kinetic model represent the inactivation of microbial cells in our samples. The main advantage of the new antibacterial agents developed in this work is their easy recovery, which helps to avoid environmental contamination. Full article

(This article belongs to the Section Green Chemistry)

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12 pages, 2056 KiB

Open AccessArticle

Three-Dimensional Zeolitic Imidazolate Framework-8 as Sorbent Integrated with Active Capillary Plasma Mass Spectrometry for Rapid Assessment of Low-Level Wine and Grape Quality-Related Volatiles

by Morphy C. Dumlao, Liang Jiang, Saroj Kumar Bhattacharyya, William A. Donald, Christopher C. Steel and Leigh M. Schmidtke

Molecules 2024, 29(24), 6053; https://doi.org/10.3390/molecules29246053 - 23 Dec 2024

Viewed by 366

Abstract

The most commonly used methods to chemically assess grape and wine quality with high sensitivity and selectivity require lengthy analysis time and can be resource intensive. Here, we developed a rapid and non-destructive method that would help in grading and decision support. In [...] Read more.

The most commonly used methods to chemically assess grape and wine quality with high sensitivity and selectivity require lengthy analysis time and can be resource intensive. Here, we developed a rapid and non-destructive method that would help in grading and decision support. In this work, we demonstrate that integrating a three-dimensional (3D) material for volatile sampling with mass spectrometry detection can be used to sample grapes for phytosanitary, quality or smoke-taint assessments at low levels of marker compounds. An efficient zeolitic imidazolate framework-8 (ZIF-8) material was synthesised in situ on nickel foam (NF), taking advantage of its ultrahigh surface area, structural diversity, and functionality as an emerging nanostructured material for preconcentrating low-level wine and grape quality-related volatiles. When used as a sorbent in thermal desorption tubes and coupled directly to active capillary mass spectrometry, the average signal across the selected analytes increased by ~50% as compared to Tenax TA, a commercially available polymer, in a measurement that takes less than two minutes. The first integration of 3D materials into mass spectrometry opens new possibilities for developing new material architecture with enhanced selectivity of next-generation multifunctional instrumentation for volatile analysis and product quality assessment. Full article

(This article belongs to the Special Issue Metal Organic Frameworks: Synthesis and Application, 3rd Edition)

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13 pages, 979 KiB

Open AccessArticle

DFT Approach for Predicting ¹³C NMR Shifts of Atoms Directly Coordinated to Pt: Scopes and Limitations

by Svetlana A. Kondrashova and Shamil K. Latypov

Molecules 2024, 29(24), 6052; https://doi.org/10.3390/molecules29246052 - 23 Dec 2024

Viewed by 344

Abstract

In this study, comparative analysis of calculated and experimental ¹³C NMR shifts for a wide range of model platinum complexes showed that, on the whole, the theory reproduces the experimental data well. The chemical shifts of carbon atoms directly bonded to Pt [...] Read more.

In this study, comparative analysis of calculated and experimental ¹³C NMR shifts for a wide range of model platinum complexes showed that, on the whole, the theory reproduces the experimental data well. The chemical shifts of carbon atoms directly bonded to Pt can be calculated well only within the framework of the fully relativistic matrix Dirac−Kohn−Sham (mDKS) level (R² = 0.9973, RMSE = 3.7 ppm); however, for carbon atoms not bonded to metal, a more simple, non-relativistic approach can be used. Effective locally dense basis set schemes were developed for practical applications. The efficiency of the protocol is demonstrated using the example of the isomeric structure determination in case of several possible coordination modes. Full article

(This article belongs to the Special Issue Exclusive Feature Papers on Molecular Structure)

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8 pages, 1412 KiB

Open AccessArticle

Insights into the C-Cl Bond Breaking in Epichlorohydrin Induced by Low Energy (<10 eV) Electrons

by Hassan Abdoul-Carime, Louisa Castel and Franck Rabilloud

Molecules 2024, 29(24), 6051; https://doi.org/10.3390/molecules29246051 - 23 Dec 2024

Viewed by 325

Abstract

Epichlorohydrin is used as an intermediate for the synthesis of polymers and, more particularly, epoxy adhesives. The traditional process involves the cleavage of the carbon-chlorine bond in an alkaline solution. Here, we investigate the breakage of this bond induced by low-energy (<10 eV) [...] Read more.

Epichlorohydrin is used as an intermediate for the synthesis of polymers and, more particularly, epoxy adhesives. The traditional process involves the cleavage of the carbon-chlorine bond in an alkaline solution. Here, we investigate the breakage of this bond induced by low-energy (<10 eV) electrons. We show the production of the chlorine anion via a resonant process at different energies. The experimental observations are completed by quantum chemistry calculations of the involved molecular orbitals in the formation of the precursor temporary anions, and their decay mechanisms are discussed in terms of the complex potential energy curve crossing network. The gained information may potentially contribute to a strategy of synthesis by other means where low-energy electrons are implicated, i.e., cold plasmas or even scanning tunnelling microscope for which the bond breakage can be controlled by the energy of the colliding electrons. Full article

(This article belongs to the Section Physical Chemistry)

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18 pages, 4915 KiB

Open AccessArticle

Novel 4-alkoxy Meriolin Congeners Potently Induce Apoptosis in Leukemia and Lymphoma Cells

by Karina S. Krings, Tobias R. Wassenberg, Pablo Cea-Medina, Laura Schmitt, Ilka Lechtenberg, Tanya R. Llewellyn, Nan Qin, Holger Gohlke, Sebastian Wesselborg and Thomas J. J. Müller

Molecules 2024, 29(24), 6050; https://doi.org/10.3390/molecules29246050 - 23 Dec 2024

Viewed by 585

Abstract

Meriolins (3-(pyrimidin-4-yl)-7-azaindoles) are synthetic hybrids of the naturally occurring alkaloids variolin and meridianin and display a strong cytotoxic potential. We have recently shown that the novel derivative meriolin 16 is highly cytotoxic in several lymphoma and leukemia cell lines as well as [...] Read more.

Meriolins (3-(pyrimidin-4-yl)-7-azaindoles) are synthetic hybrids of the naturally occurring alkaloids variolin and meridianin and display a strong cytotoxic potential. We have recently shown that the novel derivative meriolin 16 is highly cytotoxic in several lymphoma and leukemia cell lines as well as in primary patient-derived lymphoma and leukemia cells and predominantly targets cyclin-dependent kinases (CDKs). Here, we efficiently synthesized nine novel 2-aminopyridyl meriolin congeners (3a–3i), i.e., pyrimeriolins, using a one-pot Masuda borylation-Suzuki coupling (MBSC) sequence, with eight of them bearing lipophilic alkoxy substituents of varying length, to systematically determine the influence of the alkoxy sidechain length on the biological activity. All the synthesized derivatives displayed a pronounced cytotoxic potential, with six compounds showing IC₅₀ values in the nanomolar range. Derivatives 3b–3f strongly induced apoptosis and activated caspases with rapid kinetics within 3–4 h in Jurkat leukemia and Ramos lymphoma cells. The induction of apoptosis by the most potent derivative 3e was mediated by the intrinsic mitochondrial death pathway, as it was blocked in caspase-9 deficient and Apaf-1 knockdown Jurkat cells. However, as recently shown for meriolin 16, derivative 3e was able to induce apoptosis in the Jurkat cells overexpressing the antiapoptotic protein Bcl-2. Since tumor cells often inactivate the intrinsic mitochondrial apoptosis pathway (e.g., by overexpression of Bcl-2), these meriolin congeners represent promising therapeutic agents for overcoming therapeutic resistance. Full article

(This article belongs to the Special Issue Synthesis, Characterization, and Biological Evaluation of Alkaloids)

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16 pages, 6174 KiB

Open AccessArticle

Raman Spectroscopic Analysis of Molecular Structure and Mechanical Properties of Hypophosphatasia Primary Tooth

by Hayata Imamura, Tetsuya Adachi, Wenliang Zhu, Toshiro Yamamoto, Narisato Kanamura, Hiroaki Onoda, Aki Nakamura-Takahashi, Masataka Kasahara, Masaru Nakada, Hideo Sato and Giuseppe Pezzotti

Molecules 2024, 29(24), 6049; https://doi.org/10.3390/molecules29246049 - 22 Dec 2024

Viewed by 636

Abstract

Mild hypophosphatasia (HPP) can be difficult to distinguish from other bone disorders in the absence of typical symptoms such as the premature loss of primary teeth. Therefore, this study aimed to analyze the crystallinity of hydroxyapatite (HAp) and the three-dimensional structure of collagen [...] Read more.

Mild hypophosphatasia (HPP) can be difficult to distinguish from other bone disorders in the absence of typical symptoms such as the premature loss of primary teeth. Therefore, this study aimed to analyze the crystallinity of hydroxyapatite (HAp) and the three-dimensional structure of collagen in HPP teeth at the molecular level and to search for new biomarkers of HPP. Raman spectroscopy was used to investigate the molecular structure, composition, and mechanical properties of primary teeth from healthy individuals and patients with HPP. The results showed that the crystallinity of HAp decreased and the carbonate apatite content increased in the region near the dentin–enamel junction (DEJ) of HPP primary teeth. X-ray diffraction (XRD) analyses confirmed a decrease in HAp crystallinity near the DEJ, and micro-computed tomography (CT) scanning revealed a decrease in mineral density in this region. These results suggest incomplete calcification in HPP primary dentin and may contribute to the development of diagnostic and therapeutic agents. Full article

(This article belongs to the Special Issue Synthesis of Nanomaterials and Their Applications in Biomedicine)

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16 pages, 4225 KiB

Open AccessArticle

Direct Synthesis of 2-(4-Hydroxyphenoxy)benzamide Derivatives from 2-Aryloxybenzamide via PhIO-Mediated Oxidation Reaction

by Zhenhua Shang, Dechen Jiao, Haoran Cheng and Daowei Huang

Molecules 2024, 29(24), 6048; https://doi.org/10.3390/molecules29246048 - 22 Dec 2024

Viewed by 519

Abstract

The 2-(4-hydroxyphenoxy)benzamide scaffold is frequently found in a variety of bioactive compounds, displaying a broad spectrum of properties, such as antibacterial and antitumor effects. In this study, we developed a new method for synthesizing 2-(4-hydroxyphenoxy)benzamide derivatives from 2-aryloxybenzamide via a PhIO-mediated oxidation reaction. [...] Read more.

The 2-(4-hydroxyphenoxy)benzamide scaffold is frequently found in a variety of bioactive compounds, displaying a broad spectrum of properties, such as antibacterial and antitumor effects. In this study, we developed a new method for synthesizing 2-(4-hydroxyphenoxy)benzamide derivatives from 2-aryloxybenzamide via a PhIO-mediated oxidation reaction. The optimal reaction conditions were established as follows: TFA was used as the solvent, PhIO served as the oxidant with a substrate-to-oxidant ratio of 1:2, and the reaction was conducted at room temperature. This method, characterized by mild reaction conditions, broad applicability, and a metal-free nature, considerably improves the accessibility of 2-(4-hydroxyphenoxy)benzamide derivatives, which have been challenging to prepare using previously reported methods. Full article

(This article belongs to the Section Organic Chemistry)

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43 pages, 10073 KiB

Open AccessReview

Benzylic C–H Oxidation: Recent Advances and Applications in Heterocyclic Synthesis

by Nonhlelo Majola and Vineet Jeena

Molecules 2024, 29(24), 6047; https://doi.org/10.3390/molecules29246047 - 22 Dec 2024

Viewed by 633

Abstract

Benzylic C–H oxidation to form carbonyl compounds, such as ketones, is a fundamental transformation in organic synthesis as it allows for the preparation of versatile intermediates. In this review, we highlight the synthesis of aromatic ketones via catalytic, electrochemical, and photochemical oxidation of [...] Read more.

Benzylic C–H oxidation to form carbonyl compounds, such as ketones, is a fundamental transformation in organic synthesis as it allows for the preparation of versatile intermediates. In this review, we highlight the synthesis of aromatic ketones via catalytic, electrochemical, and photochemical oxidation of alkylarenes using different catalysts and oxidants in the past 5 years. Additionally, we also discuss the synthesis of heterocyclic molecules using benzylic C–H oxidation as a key step. These methods can potentially be used in medicinal, synthetic, and inorganic chemistry. Full article

(This article belongs to the Special Issue Recent Advances in C–H Functionalization)

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24 pages, 11860 KiB

Open AccessArticle

Phytosome-Encapsulated 6-Gingerol- and 6-Shogaol-Enriched Extracts from Zingiber officinale Roscoe Protect Against Oxidative Stress-Induced Neurotoxicity

by Nootchanat Mairuae, Parinya Noisa and Nut Palachai

Molecules 2024, 29(24), 6046; https://doi.org/10.3390/molecules29246046 - 22 Dec 2024

Viewed by 570

Abstract

The rising prevalence of neurodegenerative disorders underscores the urgent need for effective interventions to prevent neuronal cell death. This study evaluates the neuroprotective potential of phytosome-encapsulated 6-gingerol- and 6-shogaol-enriched extracts from Zingiber officinale Roscoe (6GS), bioactive compounds renowned for their antioxidant and anti-inflammatory [...] Read more.

The rising prevalence of neurodegenerative disorders underscores the urgent need for effective interventions to prevent neuronal cell death. This study evaluates the neuroprotective potential of phytosome-encapsulated 6-gingerol- and 6-shogaol-enriched extracts from Zingiber officinale Roscoe (6GS), bioactive compounds renowned for their antioxidant and anti-inflammatory properties. The novel phytosome encapsulation technology employed enhances the bioavailability and stability of these compounds, offering superior therapeutic potential compared to conventional formulations. Additionally, the study investigates the role of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-signaling pathway, a key mediator of the neuroprotective effects of 6GS. Neurotoxicity was induced in SH-SY5Y cells (a human neuroblastoma cell line) using 200 μM of hydrogen peroxide (H₂O₂), following pretreatment with 6GS at concentrations of 15.625 and 31.25 μg/mL. Cell viability was assessed via the MTT assay alongside evaluations of reactive oxygen species (ROS), antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]), oxidative stress markers (malondialdehyde [MDA]), and molecular mechanisms involving the PI3K/Akt pathway, apoptotic factors (B-cell lymphoma-2 [Bcl-2] and caspase-3), and inflammatory markers (tumor necrosis factor-alpha [TNF-α]). The results demonstrated that 6GS significantly improved cell viability, reduced ROS, MDA, TNF-α, and caspase-3 levels, and enhanced antioxidant enzyme activities. Furthermore, 6GS treatment upregulated PI3K, Akt, and Bcl-2 expression while suppressing caspase-3 activation. Activation of the PI3K/Akt pathway by 6GS led to phosphorylated Akt-mediated upregulation of Bcl-2, promoting neuronal survival and attenuating oxidative stress and inflammation. Moreover, Bcl-2 inhibited ROS generation, further mitigating neurotoxicity. These findings suggest that phytosome encapsulation enhances the bioavailability of 6GS, which through activation of the PI3K/Akt pathway, exhibits significant neuroprotective properties. Incorporating these compounds into functional foods or dietary supplements could offer a promising strategy for addressing oxidative stress and neuroinflammation associated with neurodegenerative diseases. Full article

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16 pages, 4109 KiB

Open AccessArticle

Diluting Ionic Liquids with Small Functional Molecules of Polypropylene Carbonate to Boost the Photovoltaic Performance of Perovskite Solar Cells

by Shuo Yang, Shaohua Chi, Youshuai Qi, Kaiyue Li, Xiang Zhang, Xinru Gao, Lili Yang and Jinghai Yang

Molecules 2024, 29(24), 6045; https://doi.org/10.3390/molecules29246045 - 22 Dec 2024

Viewed by 520

Abstract

It is necessary to overcome the relatively low conductivity of ionic liquids (ILs) caused by steric hindrance effects to improve their ability to passivate defects and inhibit ion migration to boost the photovoltaic performance of perovskite solar cells (PSCs). Herein, we designed and [...] Read more.

It is necessary to overcome the relatively low conductivity of ionic liquids (ILs) caused by steric hindrance effects to improve their ability to passivate defects and inhibit ion migration to boost the photovoltaic performance of perovskite solar cells (PSCs). Herein, we designed and prepared a kind of low-concentration 1-butyl-3-methylimidazolium tetrafluoroborate (BMIMBF₄) diluted with propylene carbonate (PC) via an ultrasonic technique (PC/IL). The decrease in the decomposition temperature related to the IL part and the increase in the sublimation temperature related to the PC part facilitated the use of PC/IL to effectively delay the crystallization process and passivate the defects in multiple ways to obtain high-quality perovskite films. Moreover, the increased conductivity of PC/IL and the more matched band alignment accelerated electron transport and collection. Finally, the MAPbI₃- and CsMAFA-based PSCs achieved PCE values of 20.87% and 23.29%, respectively, and their stabilities were greatly improved. This work provides a promising approach to optimizing ILs to achieve multiple functions and boost the performance of PSCs. Full article

(This article belongs to the Special Issue Electrochemical Materials: Design and Energy Storage Applications)

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16 pages, 3126 KiB

Open AccessArticle

Lavender Essential Oil and Its Terpenic Components Negatively Affect Tumor Properties in a Cell Model of Glioblastoma

by Miriam Russo, Noemi Martella, Deborah Gargano, Francesca Fantasma, Chiara Marcovecchio, Veronica Russo, Maria Antonietta Oliva, Marco Segatto, Gabriella Saviano, Sabrina Di Bartolomeo and Antonietta Arcella

Molecules 2024, 29(24), 6044; https://doi.org/10.3390/molecules29246044 - 22 Dec 2024

Viewed by 528

Abstract

Glioblastoma (GBM) is the most common and aggressive form of brain cancer in adults, characterized by extensive growth, a high recurrence rate, and resistance to treatment. Growing research interest is focusing on the biological roles of natural compounds due to their potential beneficial [...] Read more.

Glioblastoma (GBM) is the most common and aggressive form of brain cancer in adults, characterized by extensive growth, a high recurrence rate, and resistance to treatment. Growing research interest is focusing on the biological roles of natural compounds due to their potential beneficial effects on health. Our research aimed to investigate the effects of lavender essential oil (LEO) on a GBM cell model. Chemical characterization using GC-MS analysis indicated that LEO contains several terpenes, compounds that have been found to exhibit anticancer properties by interfering with key cancer-related pathways in several cancer models. By means of cell biology assays, we demonstrated that LEO impairs cell proliferation and migration, and also reduces oxidative stress in U87 cells. We further observed that Terpinen-4-ol, contained in LEO, was capable of reproducing the effects of the oil on GBM cells. Our results suggest that the terpenic molecules present in LEO could be considered valuable allies alongside conventional therapies against GBM. Full article

(This article belongs to the Special Issue Essential Oils in Human Health)

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16 pages, 13054 KiB

Open AccessArticle

Multi-Analytical and Non-Invasive Approach for Characterising Blackened Areas of Originally Blue Paints

by Maria Labate, Maurizio Aceto, Giacomo Chiari, Simone Baiocco, Lorenza Operti and Angelo Agostino

Molecules 2024, 29(24), 6043; https://doi.org/10.3390/molecules29246043 - 22 Dec 2024

Viewed by 450

Abstract

Azurite, a natural mineral pigment consisting of basic copper carbonate (2CuCO₃·Cu(OH)₂), is one of the Middle Ages’ most common blue pigments. Why paintings originally coated with azurite appear blackened today remains debated. Using a non-invasive multi-analytical approach, the study [...] Read more.

Azurite, a natural mineral pigment consisting of basic copper carbonate (2CuCO₃·Cu(OH)₂), is one of the Middle Ages’ most common blue pigments. Why paintings originally coated with azurite appear blackened today remains debated. Using a non-invasive multi-analytical approach, the study analysed several unexpectedly black-appearing details (objects such as books or clothing such as veils, robes, or mantles) in Antoine de Lonhy’s works. The aim was to investigate if the black colour was due to intentional iconographic reasons, incautious restoration work, or painting deterioration. The analytical results displayed the presence of the blue pigment azurite, therefore, the expected original colour of various areas should be blue. To shed light on the discussion regarding the blackening, several other Renaissance paintings with similar black details were analysed, all from the same period and geographic area as de Lonhy’s works and conserved under identical conditions. The reasons why the blackening takes place are still unclear. However, the combined use of X-ray fluorescence spectrometry (XRF), UV-visible diffuse reflectance spectrophotometry with optical fibres (FORS), portable X-ray diffraction (XRD), and the elemental mapping based on the XRF data revealed that these blackened areas were originally painted with azurite, suggesting they were once blue. This finding significantly changes the overall appreciation of these artworks. Full article

(This article belongs to the Special Issue Advances in Analytical Strategies to Study Cultural Heritage Samples, 2nd Edition)

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13 pages, 1666 KiB

Open AccessArticle

The Use of a Penta-Deuterophenyl Substituent to Improve the Metabolic Stability of a Tyrosine Kinase Inhibitor

by Júlia Dulsat, Raimon Puig de la Bellacasa and José I. Borrell

Molecules 2024, 29(24), 6042; https://doi.org/10.3390/molecules29246042 - 22 Dec 2024

Viewed by 587

Abstract

In cases in which a rapid metabolism is the cause of an unfavorable pharmacokinetic profile, it is important to determine the Sites of Metabolism (SoMs) of a molecule to introduce the necessary modifications to improve the stability of the compound. The substitution of [...] Read more.

In cases in which a rapid metabolism is the cause of an unfavorable pharmacokinetic profile, it is important to determine the Sites of Metabolism (SoMs) of a molecule to introduce the necessary modifications to improve the stability of the compound. The substitution of hydrogen atoms by deuterium atoms has been proposed to ameliorate such properties due to the greater stability of the C-D bonds. IQS016, bearing a 2-phenylamino substituent, is a compound previously described by our group with good biological activity as a discoidin domain receptor (DDR2) inhibitor but suffers from low metabolic stability determined in a test with rat-liver microsomes (less than 50% of the initial compound after 60 min). We have obtained the corresponding 2-(penta-deuterophenyl) analog (IQS016-d₅) from aniline-2,3,4,5,6-d₅ showing that it has a better metabolic stability than IQS016 and a higher inhibitory effect on isolated tyrosine kinase receptors but not a better 2D in vitro effect. Full article

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

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12 pages, 5169 KiB

Open AccessArticle

Phosphorescent Sensor Based on Iridium(III) Complex with Aggregation-Induced Emission Activity for Facile Detection of Volatile Acids

by Yu Pei, Yan Sun and Dongxia Zhu

Molecules 2024, 29(24), 6041; https://doi.org/10.3390/molecules29246041 - 22 Dec 2024

Viewed by 542

Abstract

Phosphorescent sensors are essential for rapid visual sensing of volatile acids, due to their profound impact on ecosystems and human health. However, solid phosphorescent materials for acid-base stimulus response are still rare, and it is important to achieve real-time monitoring of volatile acids. [...] Read more.

Phosphorescent sensors are essential for rapid visual sensing of volatile acids, due to their profound impact on ecosystems and human health. However, solid phosphorescent materials for acid-base stimulus response are still rare, and it is important to achieve real-time monitoring of volatile acids. In order to obtain an efficient and rapid response to volatile acid stimulation, N-H and -NH₂ substituents are introduced into an auxiliary ligand to synthesize a new cationic Ir(III) complex (Ir-NH). The AIE property of Ir-NH leads to enhanced emission in the aggregated state, which facilitates the construction of solid-state acid-base sensors. More importantly, due to the introduction of -NH₂ and N-H in the molecular structure, reversible switching of the emission color of Ir-NH under acid-base stimulation was successfully achieved. A convenient and efficient sensing device for volatile acid monitoring was prepared using Ir-NH as the active material. Our results provide a new strategy for designing phosphorescent materials with AIE and acid-base stimulus-responsive properties. Full article

(This article belongs to the Special Issue Advances in Coordination Chemistry 2.0)

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21 pages, 4921 KiB

Open AccessArticle

In Silico Design of Dual Estrogen Receptor and Hsp90 Inhibitors for ER-Positive Breast Cancer Through a Mixed Ligand/Structure-Based Approach

by Gabriele La Monica, Federica Alamia, Alessia Bono, Francesco Mingoia, Annamaria Martorana and Antonino Lauria

Molecules 2024, 29(24), 6040; https://doi.org/10.3390/molecules29246040 - 21 Dec 2024

Viewed by 614

Abstract

Breast cancer remains one of the most prevalent and lethal malignancies in women, particularly the estrogen receptor-positive (ER+) subtype, which accounts for approximately 70% of cases. Traditional endocrine therapies, including aromatase inhibitors, selective estrogen receptor degraders/antagonists (SERDs), and selective estrogen receptor modulators (SERMs), [...] Read more.

Breast cancer remains one of the most prevalent and lethal malignancies in women, particularly the estrogen receptor-positive (ER+) subtype, which accounts for approximately 70% of cases. Traditional endocrine therapies, including aromatase inhibitors, selective estrogen receptor degraders/antagonists (SERDs), and selective estrogen receptor modulators (SERMs), have improved outcomes for metastatic ER+ breast cancer. However, resistance to these agents presents a significant challenge. This study explores a novel therapeutic strategy involving the simultaneous inhibition of the estrogen receptor (ER) and the chaperone protein Hsp90, which is crucial for the stabilization of various oncoproteins, including ER itself. We employed a hybrid, hierarchical in silico virtual screening approach to identify new dual ER/Hsp90 inhibitors, utilizing the Biotarget Predictor Tool (BPT) for efficient multitarget screening of a large compound library. Subsequent structure-based studies, including molecular docking analyses, were conducted to further evaluate the interaction of the top candidates with both ER and Hsp90. Supporting this, molecular dynamics simulations demonstrate the high stability of the multitarget inhibitor 755435 in complex with ER and Hsp90. Our findings suggest that several small molecules, particularly compound 755435, exhibit promising potential as dual inhibitors, representing a new avenue to overcome resistance in ER+ breast cancer. Full article

(This article belongs to the Special Issue Anticancer Computational Drug Discovery: New Approaches, New Targets, and New Treatments)

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13 pages, 1628 KiB

Open AccessArticle

Study on Preparation Process of Anticoagulant BAY2433334

by Yanqun Zeng, Guodong Cen, Guanglin Zhou, Xucheng Zhu, Long Huang and Xiaoyu Wang

Molecules 2024, 29(24), 6039; https://doi.org/10.3390/molecules29246039 - 21 Dec 2024

Viewed by 397

Abstract

A new process route suitable for the industrial production of BAY2433334 has been developed in this paper, which avoids the patent limitations of the originator company of BAY2433334 to the preparation of BAY2433334. BAY2433334 is obtained from (2R)-2-aminobutyric acid by esterification, [...] Read more.

A new process route suitable for the industrial production of BAY2433334 has been developed in this paper, which avoids the patent limitations of the originator company of BAY2433334 to the preparation of BAY2433334. BAY2433334 is obtained from (2R)-2-aminobutyric acid by esterification, diazotization, condensation reactions, deacetyl deprotection, activation reactions, and Mitsunobu reactions. This method is simple to operate, and the raw materials are inexpensive and readily available. Simultaneously, the product quality is very high; few O-alkylated impurities are generated during the reaction, with a high N-alkylated product/O-alkylated product ratio (above 35–45:1). As a result, the ee value is greater than 99%, which means that there are very few isomers present such that no chiral resolution is required, which greatly reduces the cost. Full article

(This article belongs to the Section Medicinal Chemistry)

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18 pages, 6186 KiB

Open AccessArticle

Nanoconfined Chlorine-Substituted Monomethine Cyanine Dye with a Propionamide Function Based on the Thiazole Orange Scaffold—Use of a Fluorogenic Probe for Cell Staining and Nucleic Acid Visualization

by Nikolay Ishkitiev, Maria Micheva, Marina Miteva, Stefaniya Gaydarova, Christo Tzachev, Vesela Lozanova, Valentin Lozanov, Diana Cheshmedzhieva, Meglena Kandinska, Sonia Ilieva, Raimundo Gargallo, Stanislav Baluschev, Stoyno Stoynov, Teodora Dyankova-Danovska, Marina Nedelcheva-Veleva, Katharina Landfester, Zornitsa Mihaylova and Aleksey Vasilev

Molecules 2024, 29(24), 6038; https://doi.org/10.3390/molecules29246038 - 21 Dec 2024

Viewed by 627

Abstract

The development of fluorescence-based methods for bioassays and medical diagnostics requires the design and synthesis of specific markers to target biological microobjects. However, biomolecular recognition in real cellular systems is not always as selective as desired. A new concept for creating fluorescent biomolecular [...] Read more.

The development of fluorescence-based methods for bioassays and medical diagnostics requires the design and synthesis of specific markers to target biological microobjects. However, biomolecular recognition in real cellular systems is not always as selective as desired. A new concept for creating fluorescent biomolecular probes, utilizing a fluorogenic dye and biodegradable, biocompatible nanomaterials, is demonstrated. The synthesis of a new dicationic asymmetric monomethine cyanine dye with benzo[d]thiazolium-N-propionamide and chloroquinoline end groups is presented. The photophysical properties of the newly synthesized dye were examined through the combined application of spectroscopic and theoretical methods. The applicability of the dye as a fluorogenic nucleic acid probe was proven by UV-VIS spectroscopy and fluorescence titration. The dye–nucleic acid interaction mode was investigated by UV-Vis and CD spectroscopy. The newly synthesized dicationic dye, like other similar fluorogenic structures, limited permeability, which restricts its use as a probe for RNA and DNA. To enhance cellular delivery, we utilized a patented technology that employs solid, insoluble lipid nanoparticles. This method ensures the complete introduction of the dye into cells while minimizing activity outside the cells. In our study involving two human cell lines, we observed improved penetration through the cell membrane and distinctive selectivity in visualizing nucleic acids within the cytoplasm and nucleus. Full article

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Molecules, Volume 29, Issue 24 (December-2 2024) – 252 articles

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