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Molecules, Volume 29, Issue 3 (February-1 2024) – 193 articles

Cover Story (view full-size image): The evolution of the central metal ion of monolayer-sandwiched clusters for constructing unique transition-metal-antimony-oxo compounds containing mixed-valence Sb(III, V) has been revealed. Experimental results on photodegradation, proton conduction, and magnetism measurements indicate that these compounds are multifunctional materials. View this paper
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12 pages, 1146 KiB  
Article
Total Synthesis of the Racemate of Laurolitsine
by Mingyu Cao, Yiming Wang, Yong Zhang, Caiyun Zhang, Niangen Chen and Xiaopo Zhang
Molecules 2024, 29(3), 745; https://doi.org/10.3390/molecules29030745 - 5 Feb 2024
Viewed by 1442
Abstract
The total synthesis of laurolitsine was achieved for the first time. This reaction was accomplished in 14 steps with a 2.3% yield (this was calculated using 3-hydroxy-4-methoxybenzaldehyde as the starting material) starting from two simple materials, 3-hydroxy-4-methoxybenzaldehyde and 2-(3-hydroxy-4-methoxyphenyl)acetic acid, and the longest [...] Read more.
The total synthesis of laurolitsine was achieved for the first time. This reaction was accomplished in 14 steps with a 2.3% yield (this was calculated using 3-hydroxy-4-methoxybenzaldehyde as the starting material) starting from two simple materials, 3-hydroxy-4-methoxybenzaldehyde and 2-(3-hydroxy-4-methoxyphenyl)acetic acid, and the longest linear sequence consisted of 11 steps. The key steps included an electrophilic addition reaction in which a nitro group was reduced to an amino group using lithium tetrahydroaluminum and a Pd-catalyzed direct biaryl coupling reaction. In this paper, many of the experimental steps were optimized, and an innovative postprocessing method in which 2-(3-(benzyloxy)-4-methoxyphenyl)ethanamine is salted with oxalic acid was proposed. Full article
(This article belongs to the Section Medicinal Chemistry)
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Figure 1

Figure 1
<p>The structure of laurolitsine.</p> Full article ">Scheme 1
<p>Retrosynthetic analysis of laurolitsine.</p> Full article ">Scheme 2
<p>Conditions: (a) K<sub>2</sub>CO<sub>3</sub>, BnCl, CH<sub>3</sub>CN, 82 °C, 83%; (b) NH<sub>4</sub>OAc, CH<sub>3</sub>NO<sub>2</sub>, HOAc, 118 °C, 89%; (c) LiAlH<sub>4</sub>, THF, 30 °C, 50%.</p> Full article ">Scheme 3
<p>Conditions: (d) EtOH, H<sub>2</sub>SO<sub>4</sub>, 78 °C, 90%; (e) K<sub>2</sub>CO<sub>3</sub>, BnCl, CH<sub>3</sub>CN, 82 °C, 82%; (f) NaOH, EtOH, 78 °C, 93%; (g) Br<sub>2</sub>, NaOAc, HOAc, 25 °C, 61%.</p> Full article ">Scheme 4
<p>Conditions: (h) DMF, HOBt, EDC, 74%; (i) POCl<sub>3</sub>, CH<sub>3</sub>CN, 82 °C, 71%; (j) NaBH<sub>4</sub>, EtOH, 25 °C, 72%; (k) (Boc)<sub>2</sub>O, Et<sub>3</sub>N, CH<sub>2</sub>Cl<sub>2</sub>, 25 °C, 80%; (l) Cs<sub>2</sub>CO<sub>3</sub>, Pd(OAc)<sub>2</sub>, (t-Bu)<sub>2</sub>PMeHBF<sub>4</sub>, 1,4-dioxane, 100 °C, 53%; (m) Pd/C, THF, HOAc, 25 °C, 82%; (n) ZnBr<sub>2</sub>, CH<sub>2</sub>Cl<sub>2</sub>, 25 °C, 49%.</p> Full article ">
15 pages, 5192 KiB  
Article
A Portable Electrochemical Dopamine Detector Using a Fish Scale-Derived Graphitized Carbon-Modified Screen-Printed Carbon Electrode
by Feng Yang, Xiao Han, Yijing Ai, Bo Shao, Weipin Ding, Kai Tang and Wei Sun
Molecules 2024, 29(3), 744; https://doi.org/10.3390/molecules29030744 - 5 Feb 2024
Cited by 4 | Viewed by 1565
Abstract
In this paper, a highly conductive alkali-activated graphitized carbon (a-GC) was prepared using tilapia fish scales as precursors through enzymolysis, activation and pyrolytic carbonization methods. The prepared a-GC was modified on the surface of a screen-printed carbon electrode to construct a flexible portable [...] Read more.
In this paper, a highly conductive alkali-activated graphitized carbon (a-GC) was prepared using tilapia fish scales as precursors through enzymolysis, activation and pyrolytic carbonization methods. The prepared a-GC was modified on the surface of a screen-printed carbon electrode to construct a flexible portable electrochemical sensing platform, which was applied to the differential pulse voltametric detection of dopamine (DA) using a U-disk electrochemical workstation combined with a smart phone and Bluetooth. The prepared a-GC possesses good electrical conductivity, a large specific surface area and abundant active sites, which are beneficial for the electrooxidation of DA molecules and result in excellent sensitivity and high selectivity for DA analysis. Under the optimal conditions, the oxidation peak current of DA increased gradually, with its concentrations in the range from 1.0 μmol/L to 1000.0 μmol/L, with the detection limit as low as 0.25 μmol/L (3S/N). The proposed sensor was further applied to the determination of DA in human sweat samples, with satisfactory results, which provided an opportunity for developing noninvasive early diagnosis and nursing equipment. Full article
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>(<b>A</b>–<b>C</b>) Scanning electron microscopy images of a-GC at 10,000×, 20,000× and 100,000× magnifications, (<b>D</b>) energy dispersive X-ray spectroscopy spectrogram of a-GC, elemental mapping of (<b>E</b>) C, (<b>F</b>) O, (<b>G</b>) Fe and (<b>H</b>) N of a-GC.</p> Full article ">Figure 2
<p>(<b>A</b>,<b>B</b>) Transmission electron microscopy images at 30,000× and 100,000× magnification, (<b>C</b>) XRD pattern, (<b>D</b>) Raman spectrum, (<b>E</b>) the N<sub>2</sub> adsorption and desorption isotherm and (<b>F</b>) the pore size distribution curve of a-GC.</p> Full article ">Figure 3
<p>Cyclic voltammograms of (<b>A</b>) different modified electrodes (a: SPCE, b: a-GC/SPCE) and (<b>B</b>) different concentrations of a-GC modified on SPCE (a–d: 0.5, 1.0, 1.5, 2.0 mg/mL) in 1.0 mmol/L [Fe(CN)<sub>6</sub>]<sup>3−</sup> and 0.5 mol/L KCl solution at a scan rate of 0.1 V/s; cyclic voltammograms of (<b>C</b>) SPCE and (<b>D</b>) a-GC/SPCE at different scan rates (0.01, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 V/s) in 1.0 mmol/L [Fe(CN)<sub>6</sub>]<sup>3−</sup> and 0.5 mol/L KCl solution, and the corresponding linear relationship between I<sub>p</sub> and υ<sup>1/2</sup> of (<b>E</b>) SPCE and (<b>F</b>) a-GC/SPCE.</p> Full article ">Figure 4
<p>Cyclic voltammograms of 0.5 mmol/L DA on (a) SPCE and (b) a-GC/SPCE in 0.1 mol/L PBS (pH 6.0); scan rate of 0.1 V/s.</p> Full article ">Figure 5
<p>(<b>A</b>) Cyclic voltammograms of a-GC/SPCE at different scan rates (a–j: 0.01, 0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5 V/s) in 0.1 mmol/L DA and PBS (pH 6.0) and (<b>B</b>) the corresponding relationship of I<sub>p</sub> versus υ<sup>1/2</sup>, (<b>C</b>) chronoamperometric response of a-GC/SPCE in 0.1 mol/L PBS (pH 6.0) in the absence (I<sub>L</sub>) and presence (I<sub>cat</sub>) of 0.1 mmol/L DA, (<b>D</b>) the corresponding relationship of I<sub>cat</sub>/I<sub>L</sub> versus t<sup>1/2</sup>.</p> Full article ">Figure 6
<p>(<b>A</b>) Cyclic voltammograms of a-GC/SPCE in 0.1 mmol/L DA with different pH values (a→f: pH 3.0, 4.0, 5.0, 6.0, 7.0, 8.0), (<b>B</b>) the plot of I<sub>pa</sub> (black line) and E<sup>0</sup>’ (red line) of DA versus pH.</p> Full article ">Figure 7
<p>(<b>A</b>) Differential pulse voltammograms of a-GC/SPCE in different concentrations of DA and (<b>B</b>) the relationships of the oxidation peak currents with the DA concentrations.</p> Full article ">Figure 8
<p>(<b>A</b>) Differential pulse voltammograms of a-GC/SPCE in 25.0 μmol/L DA solution containing 50.0 μmol/L interfering substance (inset is the corresponding selectivity), and (<b>B</b>) the oxidation current values of a-GC/SPCE in 25.0 μmol/L DA for 7 days.</p> Full article ">Scheme 1
<p>Synthesis of a-GC and electrochemical detection process for DA using a U-disk electrochemical workstation.</p> Full article ">Scheme 2
<p>Electrochemical oxidation mechanism of DA on a-GC/SPCE.</p> Full article ">
17 pages, 3144 KiB  
Article
Egg White Protein–Proanthocyanin Complexes Stabilized Emulsions: Investigation of Physical Stability, Digestion Kinetics, and Free Fatty Acid Release Dynamics
by Ting Zhang, Shanglin Li, Meng Yang, Yajuan Li, Xuanting Liu, Xiaomin Shang, Jingbo Liu, Zhiyang Du and Ting Yu
Molecules 2024, 29(3), 743; https://doi.org/10.3390/molecules29030743 - 5 Feb 2024
Cited by 6 | Viewed by 2307
Abstract
Egg white proteins pose notable limitations in emulsion applications due to their inadequate wettability and interfacial instability. Polyphenol-driven alterations in proteins serve as an effective strategy for optimizing their properties. Herein, covalent and non-covalent complexes of egg white proteins-proanthocyanins were synthesized. The analysis [...] Read more.
Egg white proteins pose notable limitations in emulsion applications due to their inadequate wettability and interfacial instability. Polyphenol-driven alterations in proteins serve as an effective strategy for optimizing their properties. Herein, covalent and non-covalent complexes of egg white proteins-proanthocyanins were synthesized. The analysis of structural alterations, amino acid side chains and wettability was performed. The superior wettability (80.00° ± 2.23°) and rigid structure (2.95 GPa) of covalent complexes established favorable conditions for their utilization in emulsions. Furthermore, stability evaluation, digestion kinetics, free fatty acid (FFA) release kinetics, and correlation analysis were explored to unravel the impact of covalent and non-covalent modification on emulsion stability, dynamic digestion process, and interlinkages. Emulsion stabilized by covalent complex exhibited exceptional stabilization properties, and FFA release kinetics followed both first-order and Korsmeyer–Peppas models. This study offers valuable insights into the application of complexes of proteins-polyphenols in emulsion systems and introduces an innovative approach for analyzing the dynamics of the emulsion digestion process. Full article
(This article belongs to the Special Issue Modifications of Biomacromolecules and Their Structure with Functional Properties)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Schematic representation of proanthocyanins’ grafting mechanism (<b>a</b>,<b>b</b>). Intrinsic fluorescence (FI) and surface hydrophobicity: 258 nm FI (<b>c</b>); 275 nm FI (<b>d</b>); 295 nm FI (<b>e</b>); and ANS FI (<b>f</b>). Alterations to protein side-chain groups: Dimeric tyrosine (<b>g</b>); Free sulfhydryl group (<b>h</b>); Free amino group (<b>i</b>). Variation in protein secondary structure content (<b>j</b>). Note: The EWP, EWP/PC, and EWP-PC correspond to egg white protein, non-covalent complex, and covalent complex, respectively. ANS (8-anilino-1-naphthalene sulfonic acid FI (fluorescence intensity)) was utilized to signify the hydrophobicity of the protein surface. small letters showed significant differences between treatments (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 2
<p>FTIR (<b>a</b>) and XRD (<b>b</b>) spectrum. Note: The PC, EWP, EWP/PC, and EWP–PC correspond to proanthocyanins, egg white protein, non-covalent complex, and covalent complex, respectively.</p> Full article ">Figure 3
<p>Contact angle (<b>a</b>–<b>c</b>), AFM images (<b>d</b>–<b>f</b>), rigidity (<b>g</b>–<b>i</b>), and height distribution (<b>j</b>–<b>l</b>). RMS is root-mean-square height. The Raw mean represents a rigid within the region. Note: The EWP, EWP/PC, and EWP–PC correspond to egg white protein, non-covalent complex, and covalent complex, respectively. The enlarged images of the dotted squares in (<b>d</b>–<b>f</b>) are presented on the right.</p> Full article ">Figure 4
<p>Optical microscopy images (<b>a</b>–<b>c</b>) and Cryo-SEM photographs (<b>d</b>–<b>f</b>). Note: The dotted colored circles in the image highlight the aggregation of large droplets.</p> Full article ">Figure 5
<p>The overall appearance of emulsion storage stability (<b>a</b>) and pH stability (<b>b</b>). The creaming index for storage stability (<b>c</b>), pH stability (<b>d</b>). Note: The dotted colored squares in the image highlight the creaming phenomenon of the emulsion.</p> Full article ">Figure 6
<p>Fitted curves for emulsion digestion kinetics (<b>a</b>) corresponding curve derivation (<b>b</b>), half−life (<b>c</b>), and maximum peptide concentration (<b>d</b>). FFA release kinetics of egg white proteins’ stabilized emulsion (<b>e</b>), non−covalent stabilized emulsion (<b>f</b>), covalent complex stabilized emulsion (<b>g</b>), and oil (<b>h</b>). small letters showed significant differences between treatments (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 7
<p>Correlation analysis.</p> Full article ">
18 pages, 664 KiB  
Article
Physicochemical Properties of Dried and Powdered Pear Pomace
by Anna Krajewska, Dariusz Dziki, Mustafa Abdullah Yilmaz and Fethi Ahmet Özdemir
Molecules 2024, 29(3), 742; https://doi.org/10.3390/molecules29030742 - 5 Feb 2024
Cited by 8 | Viewed by 2103
Abstract
Pear pomace, a byproduct of juice production, represents a valuable reservoir of bioactive compounds with potential health benefits for humans. This study aimed to evaluate the influence of drying method and temperature on pear pomace, specifically focusing on the drying kinetics, grinding characteristics, [...] Read more.
Pear pomace, a byproduct of juice production, represents a valuable reservoir of bioactive compounds with potential health benefits for humans. This study aimed to evaluate the influence of drying method and temperature on pear pomace, specifically focusing on the drying kinetics, grinding characteristics, color, phenolic profile (LC-MS/MS), and antioxidant activities of the powder. Drying using the contact method at 40 °C with microwave assistance demonstrated the shortest duration, whereas freeze-drying was briefer compared to contact-drying without microwave assistance. Freeze-drying resulted in brighter and more easily comminuted pomace. Lyophilized samples also exhibited higher total phenolic compound levels compared to contact-dried ones, correlating with enhanced antioxidant activity. Twenty-one phenolic compounds were identified, with dominant acids being quinic, chlorogenic, and protocatechuic. Flavonoids, primarily isoquercitrin, and rutin, were also presented. Pear pomace dried via contact at 60 °C contained more quinic and protocatechuic acids, while freeze-dried pomace at the same temperature exhibited higher levels of chlorogenic acid, epicatechin, and catechin. The content of certain phenolic components, such as gallic acid and epicatechin, also varied depending on the applied drying temperature. Full article
(This article belongs to the Section Food Chemistry)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Drying curves of the contact-drying process for PP. MR—moisture ratio; M—microwaves 50 W.</p> Full article ">Figure 2
<p>Drying curves of the freeze-drying process for PP. MR—moisture ratio.</p> Full article ">
13 pages, 738 KiB  
Review
Phlorizin, an Important Glucoside: Research Progress on Its Biological Activity and Mechanism
by Tongjia Ni, Shuai Zhang, Jia Rao, Jiaqi Zhao, Haiqi Huang, Ying Liu, Yue Ding, Yaqian Liu, Yuchi Ma, Shoujun Zhang, Yang Gao, Liqian Shen, Chuanbo Ding and Yunpeng Sun
Molecules 2024, 29(3), 741; https://doi.org/10.3390/molecules29030741 - 5 Feb 2024
Cited by 8 | Viewed by 3307
Abstract
Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1β/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, [...] Read more.
Phlorizin, as a flavonoid from a wide range of sources, is gradually becoming known for its biological activity. Phlorizin can exert antioxidant effects by regulating the IL-1β/IKB-α/NF-KB signaling pathway. At the same time, it exerts its antibacterial activity by reducing intracellular DNA agglutination, reducing intracellular protein and energy synthesis, and destroying intracellular metabolism. In addition, phlorizin also has various pharmacological effects such as antiviral, antidiabetic, antitumor, and hepatoprotective effects. Based on domestic and foreign research reports, this article reviews the plant sources, extraction, and biological activities of phlorizin, providing a reference for improving the clinical application of phlorizin. Full article
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Overview of the mechanism of Nrf2 activation by phlorizin [<a href="#B46-molecules-29-00741" class="html-bibr">46</a>].</p> Full article ">Figure 2
<p>The pro-apoptotic pathway activated by phlorizin in tumor cells [<a href="#B63-molecules-29-00741" class="html-bibr">63</a>].</p> Full article ">
29 pages, 12870 KiB  
Article
Multiscale Modeling of Macromolecular Interactions between Tau-Amylin Oligomers and Asymmetric Lipid Nanodomains That Link Alzheimer’s and Diabetic Diseases
by Natalia Santos, Luthary Segura, Amber Lewis, Thuong Pham and Kwan H. Cheng
Molecules 2024, 29(3), 740; https://doi.org/10.3390/molecules29030740 - 5 Feb 2024
Cited by 2 | Viewed by 2157
Abstract
The molecular events of protein misfolding and self-aggregation of tau and amylin are associated with the progression of Alzheimer’s and diabetes, respectively. Recent studies suggest that tau and amylin can form hetero-tau-amylin oligomers. Those hetero-oligomers are more neurotoxic than homo-tau oligomers. So far, [...] Read more.
The molecular events of protein misfolding and self-aggregation of tau and amylin are associated with the progression of Alzheimer’s and diabetes, respectively. Recent studies suggest that tau and amylin can form hetero-tau-amylin oligomers. Those hetero-oligomers are more neurotoxic than homo-tau oligomers. So far, the detailed interactions between the hetero-oligomers and the neuronal membrane are unknown. Using multiscale MD simulations, the lipid binding and protein folding behaviors of hetero-oligomers on asymmetric lipid nanodomains or raft membranes were examined. Our raft membranes contain phase-separated phosphatidylcholine (PC), cholesterol, and anionic phosphatidylserine (PS) or ganglioside (GM1) in one leaflet of the lipid bilayer. The hetero-oligomers bound more strongly to the PS and GM1 than other lipids via the hydrophobic and hydrophilic interactions, respectively, in the raft membranes. The hetero-tetramer disrupted the acyl chain orders of both PC and PS in the PS-containing raft membrane, but only the GM1 in the GM1-containing raft membrane as effectively as the homo-tau-tetramer. We discovered that the alpha-helical content in the heterodimer was greater than the sum of alpha-helical contents from isolated tau and amylin monomers on both raft membranes, indicative of a synergetic effect of tau-amylin interactions in surface-induced protein folding. Our results provide new molecular insights into understanding the cross-talk between Alzheimer’s and diabetes. Full article
(This article belongs to the Special Issue Soft Matter Nanostructures—Fabrication, Interactions and Applications: In Honor of Prof. Dr. Michael Rappolt’s 60th Birthday)
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Figure 1

Figure 1
<p>Modeling hetero-tau-amylin oligomer binding to raft membranes. The representative initial (0 μs) and final membrane-bound (15 μs) CG structures of 1tam/PS-raft (<b>A</b>) and 1tam/GM-raft (<b>B</b>) complexes from representative replicates in both transverse (<span class="html-italic">x</span>-<span class="html-italic">z</span>) and lateral (<span class="html-italic">x</span>-<span class="html-italic">y</span>) views are illustrated. The DPPC, DLPC, CHOL, and POPS (or GM1) lipids are shown in green, orange, black, and purple beads, and the protein structures are represented in backbone ribbon forms with chain A in blue and chain B in red. A CG-to-AA spatial transformation step converted the 15 μs-structures of CG 1tam/PS-raft and 1tam/GM-raft complexes to the corresponding AA structures. Thereafter, the 100 ns-long AA simulations were performed, and the representative final 100 ns-structures of 1tam/PS-raft (<b>C</b>) and 1tam/GM-raft (<b>D</b>) complexes are given. Other than backbone ribbons, colored AA protein surfaces of all protein atoms are shown. The AA lipids are represented in licorice with identical color assignments as the CG lipids. All CG and AA simulations were performed in 0.1 M NaCl and under physiological conditions of 1 atmosphere and 310 K. The two major hydrophobic residues at L16 and I26 of the amylin chain in the 1tam are shown in licorice. A scale bar of 1 nm is shown for each CG or AA protein/raft complex.</p> Full article ">Figure 2
<p>Minimum distance spectral analysis of hetero-tau-amylin oligomers in the PS-raft membrane. The minimum distance (<span class="html-italic">mindist</span>) spectrum, defined as time-, replicate-, and chain-averaged minimum distance between protein and lipid (or water) vs. protein residue, is shown for the 1tam/PS-raft (<b>A</b>,<b>B</b>) and 2tam/PS-raft (<b>C</b>,<b>D</b>) complexes. Each data point represents the average over the last 50 ns, across three replicates, and over the constituent chain, amylin (<b>A</b>,<b>C</b>) or tau (<b>B</b>,<b>D</b>). The error bar represents the standard error of the mean. All <span class="html-italic">mindist</span> values are color-coded, with DPPC in green, DLPC in orange, CHOL in black, POPS in purple, and water in blue. The hydrophobicity plot is given in red (see <a href="#sec4-molecules-29-00740" class="html-sec">Section 4</a>) to facilitate the identification of the hydrophobicity regions in each chain. A 5-point moving average fit is presented for the <span class="html-italic">mindist</span> spectral plots.</p> Full article ">Figure 3
<p>Minimum distance spectral analysis of hetero-tau-amylin oligomers in the GM-raft membrane. The minimum distance (<span class="html-italic">mindist</span>) spectrum, defined as time-, replicate-, and chain-averaged minimum distance between protein and lipid (or water) vs. protein residue, is shown for the 1tam/GM-raft (<b>A</b>,<b>B</b>) and 2tam/GM-raft (<b>C</b>,<b>D</b>) complexes. Each data point represents the average over the last 50 ns, across three replicates, and over the constituent chain, amylin (<b>A</b>,<b>C</b>) or tau (<b>B</b>,<b>D</b>). The error bar represents the standard error of the mean. The <span class="html-italic">mindist</span> values are color-coded, with DPPC in green, DLPC in orange, CHOL in black, GM1 in purple, and water in blue. The hydrophobicity plot is given in red (see <a href="#sec4-molecules-29-00740" class="html-sec">Section 4</a>) to facilitate the identification of the hydrophobicity residues in each chain. A 5-point moving average fit is presented for the <span class="html-italic">mindist</span> spectral plots.</p> Full article ">Figure 4
<p>Protein-protein interactions of homo-oligomers and hetero-oligomers in the PS-raft and the GM-raft. The interaction energies among interchain protein atoms of homo-amylin (1am, 2am, and 4am), homo-tau (1tau, 2tau, and 4tau), and hetero-tau-amylin (1tam and 2tam) oligomers in the PS-raft (<b>A</b>,<b>C</b>) and the GM-raft (<b>B</b>,<b>D</b>) are given. The contributions of Coulomb (Coul) and Lennard Jones (LJ) energies are shown in a stacked histogram plot format (<b>A</b>,<b>B</b>). The total energy, i.e., the sum of Coul and LJ energies, of each oligomer is also presented in a scattered plot format (<b>C</b>,<b>D</b>), where the total amino acid number of each oligomer is given in the <span class="html-italic">x</span>-axis and the homo-amylin (blue), the homo-tau (black), and the hetero-tau-amylin (red) are color-coded. Each data point represents the time- and replicate-average over the last 50 ns and across all three independent replicates of the AA simulations. The error bar indicates the standard error of the mean.</p> Full article ">Figure 5
<p>Protein-lipid interactions of homo- and hetero-oligomers in the PS-raft and the GM-raft. The interaction energies between protein and lipid atoms of homo-amylin (1am, 2am, and 4am), homo-tau (1tau, 2tau, and 4tau), and hetero-tau-amylin (1tam and 2tam) oligomers in the PS-raft (<b>A</b>–<b>D</b>) and the GM-raft (<b>E</b>–<b>H</b>) for CHOL (<b>A</b>,<b>E</b>), DPPC (<b>B</b>,<b>F</b>), DLPC (<b>C</b>,<b>G</b>), POPS (<b>D</b>), and GM1 (<b>H</b>) lipids are given. Each plot is presented in a scattered plot format where the total amino acid number of each oligomer is given in the <span class="html-italic">x</span>-axis, and the homo-amylin (blue), homo-tau (black), and hetero-tau-amylin (red) are color-coded. Each data point represents the time- and replicate average over the last 50 ns and across all three independent replicates of the AA simulations. The error bar indicates the standard error of the mean.</p> Full article ">Figure 6
<p>Lipid domain disruption by homo-oligomers and hetero-oligomers in the PS-raft. Plots of the percentages of CHOL in the Lo (<b>A</b>), Ld (<b>B</b>), and Lod (<b>C</b>) domains, and those of DPPC in the Lo domain (<b>D</b>), DLPC in the Ld domain (<b>E</b>), and the sum of DPPC and DLPC, or PC, in the Lod domain (<b>F</b>) vs. the total amino acid number of each oligomer are shown. Each percentage data point represents the time- and replicate-average over the time interval of stable membrane binding and across three independent replicates. Both homo-amylin oligomers (1am, 2am, and 4am), homo-tau oligomers (1tau, 2tau, and 4tau), and hetero-tau-amylin-oligomers (1tam and 2tam) are shown in blue circles, filled black circles, and filled red circles, respectively. The control at zero total amino acid number (open black circle) represents the percentage data without protein. The error bar indicates the standard error of the means.</p> Full article ">Figure 7
<p>Lipid domain disruption by homo-oligomers and hetero-oligomers in the GM-raft. Plots of the percentages of CHOL in the Lo (<b>A</b>), Ld (<b>B</b>), and Lod (<b>C</b>) domains, and those of DPPC in the Lo domain (<b>D</b>), DLPC in the Ld domain (<b>E</b>), and the sum of DPPC and DLPC, or PC, in the Lod domain (<b>F</b>) vs. the total amino acid number of each oligomer are shown. Each percentage data point represents the time- and replicate-average over the time interval of stable membrane binding and across three independent replicates. Both homo-amylin oligomers (1am, 2am, and 4am), homo-tau oligomers (1tau, 2tau, and 4tau), and hetero-tau-amylin-oligomers (1tam and 2tam) are shown in blue circles, filled black circles, and filled red circles, respectively. The control at zero total amino acid number (open black circle) represents the percentage data without protein. The error bar indicates the standard error of the means.</p> Full article ">Figure 8
<p>Phospholipid acyl chain order disruptions by homo-oligomers and hetero-oligomers in the PS-raft. The time- and replicate-averaged plots of the phospholipid orientational order parameter vs. lipid acyl chain carbon number, or lipid order profile, over the last 50 ns of the AA simulation and across all replicates for DPPC (<b>A</b>,<b>B</b>,<b>G</b>,<b>H</b>), DLPC (<b>C</b>,<b>D</b>,<b>I</b>,<b>J</b>), and POPS (<b>E</b>,<b>F</b>,<b>K</b>,<b>L</b>) lipids in the 0.5 nm annular lipid (AL) shell of the hetero-oligomers (1tam and 2tam) and homo-tau oligomers (1tau, 2tau, and 4tau) are shown. The lipid profiles of the lipids outside the AL shell, or non-annular lipids, are also given as controls. The data points for the <span class="html-italic">sn</span>-1 (<b>A</b>,<b>C</b>,<b>E</b>,<b>G</b>,<b>I</b>,<b>K</b>) and <span class="html-italic">sn</span>-2 (<b>B</b>,<b>D</b>,<b>F</b>,<b>H</b>,<b>J</b>,<b>L</b>) chains are shown. The error bar indicates the standard error of the mean.</p> Full article ">Figure 9
<p>Phospholipid acyl chain order disruptions by homo-oligomers and hetero-oligomers in the GM-raft. The time- and replicate-averaged plots of the phospholipid orientational order parameter vs. lipid acyl chain carbon number, or lipid order profile, over the last 50 ns of the AA simulation and across all replicates for DPPC (<b>A</b>,<b>B</b>,<b>G</b>,<b>H</b>), DLPC (<b>C</b>,<b>D</b>,<b>I</b>,<b>J</b>), and GM1 (<b>E</b>,<b>F</b>,<b>K</b>,<b>L</b>) lipids in the 0.5 nm annular lipid (AL) shell of the hetero-oligomers (1tam and 2tam) and homo-tau oligomers (1tau, 2tau, and 4tau) are shown. The lipid profiles of the lipids outside the AL shell, or non-annular lipids, are also given as controls. The data points for the <span class="html-italic">sn</span>-1 (<b>A</b>,<b>C</b>,<b>E</b>,<b>G</b>,<b>I</b>,<b>K</b>) and <span class="html-italic">sn</span>-2 (<b>B</b>,<b>D</b>,<b>F</b>,<b>H</b>,<b>J</b>,<b>L</b>) chains are presented. The error bar indicates the standard error of the mean.</p> Full article ">Figure 10
<p>Time-evolution of protein secondary structures of membrane-bound hetero-oligomers upon binding to the PS-raft. The 3D color-coded protein secondary structures as a function of residue number (vertical axis) and simulation time (horizontal axis) are given in a DSSP format (see <a href="#sec4-molecules-29-00740" class="html-sec">Section 4</a>) for the representative replicates of the 1tam and 2tam oligomers. The protein residue locations of the tau and amylin (am) chains inside the hetero-oligomers are color-coded. For 1tam (<b>A</b>), the chain A (tau) and the chain B (amylin) are shown in blue and red arrows, respectively. For the 2tam (<b>B</b>), the chain A (am), the chain B (tau), the chain C (tau), and the chain D (am) are shown in blue, red, gray, and orange arrows, respectively.</p> Full article ">Figure 11
<p>Time-evolution of protein secondary structures of membrane-bound hetero-oligomers upon binding to the GM-raft The 3D color-coded protein secondary structures as a function of residue number (vertical axis) and simulation time (horizontal axis) are given in a DSSP format (see <a href="#sec4-molecules-29-00740" class="html-sec">Section 4</a>) for the representative replicates of the 1tam and 2tam oligomers. The protein residue locations of the tau and amylin (am) chains inside the hetero-oligomers are color-coded. For 1tam (<b>A</b>), the chain A (tau) and the chain B (amylin) are shown in blue and red arrows, respectively. For the 2tam (<b>B</b>), the chain A (am), the chain B (tau), the chain C (tau), and the chain D (am) are shown in blue, red, gray, and orange arrows, respectively.</p> Full article ">Figure 12
<p>Protein secondary structures of membrane-bound homo-oligomers and hetero-oligomers in the PS-raft and GM-raft. The numbers of protein residues of the oligomers in the PS-raft (<b>A</b>–<b>D</b>) and the GM-raft (<b>E</b>–<b>H</b>) that participated in the beta (<b>A</b>,<b>E</b>), alpha-helix (<b>B</b>,<b>F</b>), turn (<b>C</b>,<b>G</b>), and random (<b>D</b>,<b>H</b>) structures are shown in a scattered-plot format where the total amino acid number of each oligomer is given in the <span class="html-italic">x</span>-axis and the homo-amylin (blue), homo-tau (black), and hetero-tau-amylin (red) are labeled in colors. Each data point represents the time- and replicate-average over the last 50 ns and across all three independent replicates of the AA simulations. The error bar indicates the standard error of the mean.</p> Full article ">Figure 13
<p>Protein secondary structures of the constituent proteins in membrane-bound homo-oligomers and hetero-oligomers. The number of residues in the PS-raft (<b>A</b>–<b>D</b>) and GM-raft (<b>E</b>–<b>H</b>) membranes that participated in the beta (<b>A</b>,<b>E</b>), alpha (<b>B</b>,<b>F</b>), turn (<b>C</b>,<b>G</b>), and random (<b>D</b>,<b>H</b>) structures is shown in a stacked histogram format. For the homo-oligomers, the sum of secondary structures from 1tau to 1am (1tau+1am) or the sum of 2tau and 2am (2tau+2am) group is directly compared alongside the secondary structure of 1tam or 2tam. Note that the total amino acid number of the (1tau+1am) or (2tau+2am) group is 167 or 334, respectively, and matches that of the 1tam or 2tam, accordingly. Each data point represents the time- and replicate-average over the last 50 ns and across all three independent replicates of the AA simulations. The error bar indicates the standard error of the mean.</p> Full article ">Figure 14
<p>Structures of the membrane-bound homo-oligomers and hetero-oligomers are surrounded by the 0.5 nm annular lipid shell in the PS-raft. The secondary structures of the homo-amylin monomer or 1am (<b>A</b>), the homo-tau monomer or 1tau (<b>B</b>), the hetero-tau-amylin dimer or 1tam (<b>C</b>), the homo-amylin-dimer or 2am (<b>D</b>), the homo-tau dimer or 2tau (<b>E</b>), and the hetero-tau-amylin tetramer or 2tam (<b>F</b>) are shown. All protein structures are presented in color-coded backbone ribbons. For the homo-oligomers, chains A and B are labeled in blue and red, respectively. For the 1tam (<b>C</b>), chain A (tau) and chain B (am) are labeled in blue and red, respectively. For the 2tam (<b>F</b>), chain A (am), chain B (tau), chain C (tau), and chain D (am) are labeled in blue, red, gray, and orange, respectively. The 0.5 nm annular lipids within are color-coded in licorice, with DPPC in green, DLPC in orange, cholesterol in black, and POPS in purple. A scale bar of 1 nm is shown.</p> Full article ">Figure 15
<p>Structures of the membrane-bound homo-oligomers and hetero-oligomers surrounded by the 0.5 nm annular lipid shell in the GM-raft. The secondary structures of the homo-amylin monomer or 1am (<b>A</b>), the homo-tau monomer or 1tau (<b>B</b>), the hetero-tau-amylin dimer or 1tam (<b>C</b>), the homo-amylin-dimer or 2am (<b>D</b>), the homo-tau dimer or 2tau (<b>E</b>), and the hetero-tau-amylin tetramer or 2tam (<b>F</b>) are shown. All protein structures are presented in color-coded backbone ribbons. For the homo-oligomers, chains A and B are labeled in blue and red, respectively. For the 1tam (<b>C</b>), chain A (tau) and chain B (am) are labeled in blue and red, respectively. For the 2tam (<b>F</b>), chain A (am), chain B (tau), chain C (tau), and chain D (am) are labeled in blue, red, gray, and orange, respectively. The 0.5 nm annular lipids within are color-coded in licorice, with DPPC in green, DLPC in orange, cholesterol in black, and GM1 in purple. A scale bar of 1 nm is shown.</p> Full article ">
15 pages, 1461 KiB  
Review
Hyaluronan: Sources, Structure, Features and Applications
by Katarína Valachová, Mohamed E. Hassan and Ladislav Šoltés
Molecules 2024, 29(3), 739; https://doi.org/10.3390/molecules29030739 - 5 Feb 2024
Cited by 13 | Viewed by 5460
Abstract
Hyaluronan (HA) is a non-sulfated glycosaminoglycan that is present in a variety of body tissues and organs. Hyaluronan has a wide range of biological activities that are frequently influenced by molar mass; however, they also depend greatly on the source, purity, and kind [...] Read more.
Hyaluronan (HA) is a non-sulfated glycosaminoglycan that is present in a variety of body tissues and organs. Hyaluronan has a wide range of biological activities that are frequently influenced by molar mass; however, they also depend greatly on the source, purity, and kind of impurities in hyaluronan. High-molar-mass HA has anti-inflammatory, immunosuppressive, and antiangiogenic properties, while low-molar-mass HA has opposite properties. A number of chemical modifications have been performed to enhance the stability of HA and its applications in medical practice. Hyaluronan is widely applied in medicine, such as viscosupplementation, ophthalmology, otolaryngology, wound healing, cosmetics, and drug delivery. In this review, we summarized several medical applications of polymers based on the hyaluronan backbone. Full article
(This article belongs to the Special Issue Hyaluronan, 2nd Edition)
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<p>Hyaluronic acid chemical structure.</p> Full article ">Figure 2
<p>(<b>a</b>) Annual number of HA articles indexed in Pubmed database over the last 20 years. (<b>b</b>) Types of HA articles indexed in Science Direct database during the last 20 years.</p> Full article ">Figure 3
<p>The impact of HA at wound sites throughout the stages of wound healing includes hemostasis, inflammation, proliferation, and remodeling (adapted from Sudhakar et al. [<a href="#B76-molecules-29-00739" class="html-bibr">76</a>]).</p> Full article ">Figure 4
<p>Drug delivery formulations using HA and its derivatives (adapted from Juhaščik et al. [<a href="#B89-molecules-29-00739" class="html-bibr">89</a>]).</p> Full article ">Figure 5
<p>Application of hyaluronan in nasal drug delivery.</p> Full article ">
16 pages, 2667 KiB  
Article
Efficient Scavenging of TEMPOL Radical by Ascorbic Acid in Solution and Related Prolongation of 13C and 1H Nuclear Spin Relaxation Times of the Solute
by Václav Římal, Eleonora I. Bunyatova and Helena Štěpánková
Molecules 2024, 29(3), 738; https://doi.org/10.3390/molecules29030738 - 5 Feb 2024
Cited by 1 | Viewed by 1418
Abstract
Dynamic nuclear polarization for nuclear magnetic resonance (NMR) spectroscopy and imaging uses free radicals to strongly enhance the NMR signal of a compound under investigation. At the same time, the radicals shorten significantly its nuclear spin relaxation times which reduces the time window [...] Read more.
Dynamic nuclear polarization for nuclear magnetic resonance (NMR) spectroscopy and imaging uses free radicals to strongly enhance the NMR signal of a compound under investigation. At the same time, the radicals shorten significantly its nuclear spin relaxation times which reduces the time window available for the experiments. Radical scavenging can overcome this drawback. Our work presents a detailed study of the reduction of the TEMPOL radical by ascorbic acid in solution by high-resolution NMR. Carbon-13 and hydrogen-1 nuclear spin relaxations are confirmed to be restored to their values without TEMPOL. Reaction mechanism, kinetics, and the influence of pD and viscosity are thoroughly discussed. The detailed investigation conducted in this work should help with choosing suitable concentrations in the samples for dynamic nuclear polarization and optimizing the measurement protocols. Full article
(This article belongs to the Special Issue Stable Radicals: Synthesis and Applications)
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<p>Schemes of (<b>a</b>) TEMPOL; (<b>b</b>) TEMPOL-H; (<b>c</b>) glycine with carbon numbering; and (<b>d</b>) ascorbic acid (AA).</p> Full article ">Figure 2
<p>1H NMR spectra of solutions with 200 mM [1-<sup>13</sup>C]-glycine at 25 °C (500 MHz, 4 scans acquired). Additional solution components and scaling are indicated in the figure. The sample with TEMPOL and AA was measured more than 2 h after preparation. Major peaks: TMSP: 0 ppm; TEMPOL-H methyl protons: 1.5 ppm; glycine: doublet (caused by coupling with <sup>13</sup>C) at 3.6 ppm; AA: multiplets at 3.7 ppm and 4.1 ppm and the singlet at 4.9 ppm; H4 of TEMPOL-H and DHA: multiplets at 4.3–4.4 ppm; HDO: 4.7–4.8 ppm.</p> Full article ">Figure 3
<p>Time course of TEMPOL-H increase in 200 mM glycine, 2 mM TEMPOL, and 10 mM AA at 25 °C. The points are obtained from integral intensities of <sup>1</sup>H NMR resonance of TEMPOL-H methyl groups, the solid line is fit by Equation (6).</p> Full article ">Figure 4
<p>TEMPOL-H concentration in time in 200 mM Gly, 25 mM TEMPOL, and 5 mM AA at 25 °C. The points are obtained from integral intensities of <sup>1</sup>H NMR resonance of TEMPOL-H methyl groups, the fits correspond to kinetic models described in <a href="#app1-molecules-29-00738" class="html-app">Supporting Information</a>. Top: the initial part of the reaction. Bottom: the full experimental run with the region shown in the top panel indicated by dashed lines.</p> Full article ">Figure 5
<p>Longitudinal (<span class="html-italic">R</span><sub>1</sub>) and transverse (<span class="html-italic">R</span><sub>2</sub>) <sup>13</sup>C relaxation rates of 200 mM [1-<sup>13</sup>C]- (<b>left</b>) and [2-<sup>13</sup>C]-glycine (<b>right</b>) versus TEMPOL concentration at 25 °C (blue) and 37 °C (red). Filled symbols: without AA; empty symbols: with 200 mM AA. Lines are linear fits.</p> Full article ">Figure 6
<p>Longitudinal (<span class="html-italic">R</span><sub>1</sub>) and transverse (<span class="html-italic">R</span><sub>2</sub>) 1H relaxation rates in natural-abundance (<b>left</b>), [1-<sup>13</sup>C]- (<b>centre</b>), and [2-<sup>13</sup>C]-glycine (<b>right</b>) versus TEMPOL concentration at 25 °C (blue) and 37 °C (red). Filled symbols: without AA; empty symbols: with 200 mM AA. Lines are linear fits.</p> Full article ">Figure 7
<p>Experimental (horizontal axis) and calculated pD (vertical axis) of the solutions containing 200 mM AA and variable TEMPOL concentrations (<a href="#molecules-29-00738-t001" class="html-table">Table 1</a>). Method described in <a href="#app1-molecules-29-00738" class="html-app">Supporting Information</a>.</p> Full article ">Figure 8
<p>Longitudinal <sup>13</sup>C relaxation times versus dynamic viscosities of mixtures containing 200 mM [2-<sup>13</sup>C]-glycine (25 °C). Open symbols: samples without TEMPOL; filled symbols: samples with AA and TEMPOL-H.</p> Full article ">
15 pages, 3339 KiB  
Article
Combination of a Deep Eutectic Solvent and Macroporous Resin for Green Recovery of Iridoids, Chlorogenic Acid, and Flavonoids from Eucommia ulmoides Leaves
by Yunhui Liao, Feng Chen, Haishan Tang, Wubliker Dessie and Zuodong Qin
Molecules 2024, 29(3), 737; https://doi.org/10.3390/molecules29030737 - 5 Feb 2024
Cited by 5 | Viewed by 1674
Abstract
To increase the effectiveness of using typical biomass waste as a resource, iridoids, chlorogenic acid, and flavonoids from the waste biomass of Eucommia ulmoides leaves (EULs) were extracted by deep eutectic solvents (DESs) in conjunction with macroporous resin. To optimize the extract conditions, [...] Read more.
To increase the effectiveness of using typical biomass waste as a resource, iridoids, chlorogenic acid, and flavonoids from the waste biomass of Eucommia ulmoides leaves (EULs) were extracted by deep eutectic solvents (DESs) in conjunction with macroporous resin. To optimize the extract conditions, the experiment of response surface was employed with the single-factor of DES composition molar ratio, liquid–solid ratio, water percentage, extraction temperature, and extraction time. The findings demonstrated that the theoretical simulated extraction yield of chlorogenic acid (CGA), geniposidic acid (GPA), aucubin (AU), geniposide (GP), rutin (RU), and isoquercetin (IQU) were 42.8, 137.2, 156.7, 5.4, 13.5, and 12.8 mg/g, respectively, under optimal conditions (hydrogen bond donor–hydrogen bond acceptor molar ratio of 1.96, liquid–solid ratio of 28.89 mL/g, water percentage of 38.44%, temperature of 317.36 K, and time of 55.59 min). Then, 12 resins were evaluated for their adsorption and desorption capabilities for the target components, and the HPD950 resin was found to operate at its optimum. Additionally, the HPD950 resin demonstrated significant sustainability and considerable potential in the recyclability test. Finally, the hypoglycemic in vitro, hypolipidemic in vitro, immunomodulatory, and anti-inflammatory effects of EUL extract were evaluated, and the correlation analysis of six active components with biological activity and physicochemical characteristics of DESs by heatmap were discussed. The findings of this study can offer a theoretical foundation for the extraction of valuable components by DESs from waste biomass, as well as specific utility benefits for the creation and development of natural products. Full article
(This article belongs to the Special Issue Biomass-Based Value-Added Bioactive Products: Recovery and Valorization)
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<p>The effect of different DESs on iridoids, chlorogenic acid, and flavonoids yield (<b>a</b>) and single-factor analysis of the extraction procedure (<b>b</b>–<b>f</b>). Extraction conditions: (<b>a</b>) the HBA-HBD molar ratio was 1:2, the liquid–solid ratio was 30 mL/g, the water percentage was 40%, the temperature was 318.15 K, and the time was 60 min; (<b>b</b>) the liquid–solid ratio was 30 mL/g, the water percentage was 40%, the temperature was 318.15 K, and the time was 60 min; (<b>c</b>) the HBA-HBD molar ratio was 1:2, the water percentage was 40%, the temperature was 318.15 K, and the time was 60 min; (<b>d</b>) the HBA-HBD molar ratio was 1:2, the liquid–solid ratio was 30 mL/g, the temperature was 318.15 K, and the time was 60 min; (<b>e</b>) the HBA-HBD molar ratio was 1:2, the liquid–solid ratio was 30 mL/g, the water percentage was 40%, and the time was 60 min; (<b>f</b>) the HBA-HBD molar ratio was 1:2, the liquid–solid ratio was 30 mL/g, the water percentage was 40%, and the temperature was 318.15 K.</p> Full article ">Figure 2
<p>Heatmap analysis for different DESs on the yield of iridoids, chlorogenic acid, and flavonoids.</p> Full article ">Figure 3
<p>Adsorption (<b>a</b>) desorption (<b>b</b>), and recovery (<b>c</b>) of target components in resins.</p> Full article ">Figure 4
<p>Recyclability results of HPD950 resins on adsorption (<b>a</b>), desorption (<b>b</b>), and recovery (<b>c</b>).</p> Full article ">Figure 5
<p>In vitro hypoglycemic and lipid-lowering activity of EUL extract: (<b>a</b>) α-glucosidase inhibition; (<b>b</b>) α-amylase inhibition; (<b>c</b>) sodium glycinate binding capacity; and (<b>d</b>) sodium taurocholate binding capacity.</p> Full article ">Figure 6
<p>The impact of EUL extract on cell viability (<b>a</b>) and anti-inflammatory (<b>b</b>–<b>d</b>).</p> Full article ">Figure 7
<p>The correlation matrix of six active components with the biological activity of EUL extract and the physicochemical characteristics of DESs by a heatmap. The significant correlation at <span class="html-italic">p</span> &lt; 0.05 and <span class="html-italic">p</span> &lt; 0.01 levels is indicated by the * and **, respectively.</p> Full article ">
13 pages, 1829 KiB  
Article
Organophosphate Triesters and Their Transformation Products in Sediments of Mangrove Wetlands in the Beibu Gulf, South China Sea
by Li Zhang, Yongze Xing, Peng Zhang, Xin Luo and Zengyuan Niu
Molecules 2024, 29(3), 736; https://doi.org/10.3390/molecules29030736 - 5 Feb 2024
Viewed by 1442
Abstract
As emerging pollutants, organophosphate esters (OPEs) have been reported in coastal environments worldwide. Nevertheless, information on the occurrence and ecological risks of OPEs, especially the related transformation products, in mangrove wetlands is scarce. For the first time, the coexistence and distribution of OP [...] Read more.
As emerging pollutants, organophosphate esters (OPEs) have been reported in coastal environments worldwide. Nevertheless, information on the occurrence and ecological risks of OPEs, especially the related transformation products, in mangrove wetlands is scarce. For the first time, the coexistence and distribution of OP triesters and their transformation products in three mangrove wetlands in the Beibu Gulf were investigated using ultrasonication and solid-phase extraction, followed by UHPLC-MS/MS detection. The studied OPEs widely existed in all the sampling sites, with the total concentrations ranging from 6.43 ng/g dry weight (dw) to 39.96 ng/g dw and from 3.33 ng/g dw to 22.50 ng/g dw for the OP triesters and transformation products, respectively. Mangrove wetlands tend to retain more OPEs than the surrounding coastal environment. Pearson correlation analysis revealed that the TOC was not the sole factor in determining the OPEs’ distribution, and degradation was not the main source of the transformation products in mangrove sediments in the Beibu Gulf. The ecological risks of selected OPEs for different organisms were also assessed, revealing a medium to high risk posed by OP diesters to organisms. The levels or coexistence of OPEs and their metabolites in mangroves need constant monitoring, and more toxicity data should be further studied to assess the effect on normal aquatic organisms. Full article
(This article belongs to the Special Issue Analysis of Residues in Environmental Samples II)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Occurrence and distribution of OP triesters and their degradation products in mangrove surface sediment in the Beibu Gulf.</p> Full article ">Figure 2
<p>Concentration percentage of individual OPEs in surface sediment.</p> Full article ">Figure 3
<p>The ecological risk of individual OP triester (HQ<sub>I-OPtri</sub>) and transformation product (HQ<sub>I-OPtp</sub>).</p> Full article ">Figure 4
<p>Sampling stations for surface sediments in three mangrove wetlands.</p> Full article ">
20 pages, 6080 KiB  
Article
Enhancement of Female Rat Fertility via Ethanolic Extract from Nigella sativa L. (Black Cumin) Seeds Assessed via HPLC-ESI-MS/MS and Molecular Docking
by Ahmed M. Nagy, Mohamed F. Abdelhameed, Asmaa S. Abd Elkarim, Tushar C. Sarker, Ahmed M. Abd-ElGawad, Abdelsamed I. Elshamy and Abdelmohsen M. Hammam
Molecules 2024, 29(3), 735; https://doi.org/10.3390/molecules29030735 - 5 Feb 2024
Cited by 5 | Viewed by 2368
Abstract
The characteristic chemical composition of Nigella seeds is directly linked to their beneficial properties. This study aimed to investigate the phytochemical composition of Nigella sativa seeds using a 100% ethanolic extract using HPLC-ESI-MS/MS. Additionally, it explored the potential biological effects of the extract [...] Read more.
The characteristic chemical composition of Nigella seeds is directly linked to their beneficial properties. This study aimed to investigate the phytochemical composition of Nigella sativa seeds using a 100% ethanolic extract using HPLC-ESI-MS/MS. Additionally, it explored the potential biological effects of the extract on female rat reproduction. Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estrogen (E2), and Progesterone (P4) hormone levels were also assessed, along with the morphological and histological effects of the extract on ovarian, oviductal, and uterine tissues. Molecular docking was performed to understand the extract’s activity and its role in regulating female reproduction by assessing its binding affinity to hormonal receptors. Twenty metabolites, including alkaloids, saponins, terpenes, flavonoids, phenolic acids, and fatty acids, were found in the ethanolic extract of N. sativa seeds through the HPLC-ESI-MS/MS study. The N. sativa seed extract exhibited strong estrogenic and LH-like activities (p < 0.05) with weak FSH-like activity. Furthermore, it increased the serum levels of LH (p < 0.05), P4 hormones (p < 0.001), and E2 (p < 0.0001). Molecular docking results displayed a strong interaction with Erβ, LH, GnRH, and P4 receptors, respectively. Based on these findings, N. sativa seeds demonstrated hormone-like activities, suggesting their potential as a treatment for improving female fertility. Full article
(This article belongs to the Special Issue Extraction and Analysis of Natural Product in Food)
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<p>Weight of the genitalia and the ovaries of rats showing (<b>A</b>,<b>B</b>) the FSH-like activity of <span class="html-italic">N. sativa</span> seeds. (<b>C</b>,<b>D</b>) The LH-like activity of <span class="html-italic">N. sativa</span> seeds. (<b>E</b>) Weight of the uterine tissue/g, showing the Estrogen-like activity of <span class="html-italic">N. sativa</span> seeds (mean ± SEM, <sup>ns</sup> non-significant, * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01, *** <span class="html-italic">p</span> ≤ 0.001, **** <span class="html-italic">p</span> ≤ 0.0001).</p> Full article ">Figure 2
<p>Female immature rats. (<b>A</b>) Control -ve group treated with saline; the uterus is elongated and thin, and the ovaries are small and contain small numbers of follicles (the arrows). (<b>B</b>) Control FSH +ve group treated with 20 IU of PMSG. The uterine body and horns are wide in diameter and filled with large quantities of fluids, and the ovaries are large and contain large numbers of large follicles (the arrows). (<b>C</b>) Control LH +ve group treated with 20 IU of PMSG followed by 20 IU of hCG 3 days later. The uteri were short and contained a large amount of secretions. The ovaries contained numerous corpora lutea (the arrows). (<b>D</b>,<b>E</b>) The uterine body and horns in the <span class="html-italic">N. sativa</span>-treated group were short, large in diameter, and filled with uterine secretions. The ovaries contained a large number of corpora lutea (CLs) (the arrows).</p> Full article ">Figure 3
<p>Cross-sections of the ovarian, oviductal, and uterine tissues (magnification 40×) of (<b>A1</b>–<b>A3</b>) control –ve group. (<b>B1</b>–<b>B3</b>) Control +ve FSH-like activity (PMSG) showing different stages of follicular maturation and large number of mature follicles (arrow). (<b>C1</b>–<b>C3</b>) Control +ve LH-like activity (PMSG + LH) showing strong luteal activity in the ovaries (arrow), characterized by the presence of multiple adjacent well-developed CLs and potential endometrial activity (arrow), including an increase in endometrial epithelium height.</p> Full article ">Figure 4
<p>Cross-sections of the ovarian, oviductal, and uterine tissues (magnification 40× and 100×) revealed (<b>A1</b>–<b>A3</b>) FSH-like activity of <span class="html-italic">N. sativa</span> characterized by the presence of multiple active follicles at different developmental stages (arrow). (<b>B1</b>–<b>B3</b>) LH-like activity of <span class="html-italic">N. sativa</span> showing multiple CLs and progestational proliferation, characterized by columnar lining epithelium and folding of endometrial villi (arrow).</p> Full article ">Figure 5
<p>Ovariectomized female rats. (<b>A</b>) Control (–ve) group treated with saline. The uterus is thin and elongated. (<b>B</b>) Control (+ve) group treated with Folone<sup>®</sup> (E2). The uterus is short, thin, and filled with large amounts of fluid, showing estrogenic activity. (<b>C</b>) <span class="html-italic">N. sativa</span>-treated group. The uterus is short and filled with medium amounts of secretions, showing estrogenic activity. The arrows showing the difference of uterine thickness between the groups.</p> Full article ">Figure 6
<p>Cross-sections of the uterine tissues (magnification 40× and 100×) revealed the estrogenic activity of (<b>A1</b>,<b>A2</b>) control ovariectomized rats. (<b>B1</b>,<b>B2</b>) E2-like activity of Folone-injected group. showing strong uterine activity in the reference group, characterized by active endometrial hyperplasia and dilation of uterine glands (arrow). (<b>C1</b>,<b>C2</b>) E2-like activity of <span class="html-italic">N. sativa</span>-treated group showing good estrogenic activity, as evidenced by the presence of active endometrial hyperplasia (arrow).</p> Full article ">Figure 7
<p>Concentrations of the gonadotropins and steroidal hormones in the serum of rats. (<b>A</b>) FSH serum concentration (mIU/mL). (<b>B</b>) LH concentration (mIU/mL). (<b>C</b>) Estrogen (E2) concentration (pg/mL). (<b>D</b>) Progesterone (P4) concentration (pg/mL), (mean ± SEM, <sup>ns</sup> non-significant, * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤ 0.01,*** <span class="html-italic">p</span> ≤ 0.001, **** <span class="html-italic">p</span> ≤ 0.0001).</p> Full article ">Figure 8
<p>2D and 3D representations of (<b>A</b>,<b>B</b>) octadecadienoic acid with Estrogen β Receptor (ER β), (<b>C</b>,<b>D</b>) hederagenin pentoside with Human Gonadotropin-Releasing Hormone Receptor (GnRHR), (<b>E</b>,<b>F</b>) hymoquinol glucoside with Luteinizing Hormone receptor (LHR), and (<b>G</b>,<b>H</b>) magnoflorine with Progesterone Receptor (PR).</p> Full article ">
16 pages, 4422 KiB  
Article
Porous Electropolymerized Films of Ruthenium Complex: Photoelectrochemical Properties and Photoelectrocatalytic Synthesis of Hydrogen Peroxide
by Hong-Ju Yin and Ke-Zhi Wang
Molecules 2024, 29(3), 734; https://doi.org/10.3390/molecules29030734 - 5 Feb 2024
Cited by 1 | Viewed by 1324
Abstract
The photoelectrochemical cells (PECs) performing high-efficiency conversions of solar energy into both electricity and high value-added chemicals are highly desirable but rather challenging. Herein, we demonstrate that a PEC using the oxidatively electropolymerized film of a heteroleptic Ru(II) complex of [Ru(bpy)(L) [...] Read more.
The photoelectrochemical cells (PECs) performing high-efficiency conversions of solar energy into both electricity and high value-added chemicals are highly desirable but rather challenging. Herein, we demonstrate that a PEC using the oxidatively electropolymerized film of a heteroleptic Ru(II) complex of [Ru(bpy)(L)2](PF6)2 Ru1 {bpy and L stand for 2,2′-bipyridine and 1-phenyl-2-(4-vinylphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline respectively}, polyRu1, as a working electrode performed both efficient in situ synthesis of hydrogen peroxide and photocurrent generation/switching. Specifically, when biased at −0.4 V vs. saturated calomel electrode and illuminated with 100 mW·cm−2 white light, the PEC showed a significant cathodic photocurrent density of 9.64 μA·cm−2. Furthermore, an increase in the concentrations of quinhydrone in the electrolyte solution enabled the photocurrent polarity to switch from cathodic to anodic, and the anodic photocurrent density reached as high as 11.4 μA·cm−2. Interestingly, in this single-compartment PEC, the hydrogen peroxide yield reached 2.63 μmol·cm−2 in the neutral electrolyte solution. This study will serve as a guide for the design of high-efficiency metal-complex-based molecular systems performing photoelectric conversion/switching and photoelectrochemical oxygen reduction to hydrogen peroxide. Full article
(This article belongs to the Special Issue Synthesis and Applications of Transition Metal Complexes)
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Figure 1
<p>(<b>a</b>) UV–Vis absorption, excitation and emission spectra of <b>Ru1</b> in acetonitrile (<span class="html-italic">λ</span><sub>ex</sub>/<span class="html-italic">λ</span><sub>em</sub> = 459 nm/608 nm, <span class="html-italic">c</span> = 5 × 10<sup>−6</sup> M); (<b>b</b>) UV–Vis absorption, excitation and emission spectra of poly(<b>Ru1</b>)<sub>8</sub>@ITO (<span class="html-italic">λ</span><sub>ex</sub>/<span class="html-italic">λ</span><sub>em</sub> = 456 nm/620 nm); and (<b>c</b>) UV–Vis absorption spectra of films poly(<b>Ru1</b>)<span class="html-italic"><sub>n</sub></span> (<span class="html-italic">n</span> = 3, 5, 8, 10, 13)@ITO. The inset shows the linear relationship between the absorbances at 300 and 457 nm and the number of scan cycles <span class="html-italic">n</span>.</p> Full article ">Figure 2
<p>Side-view (<b>a</b>) and top-view (<b>b</b>,<b>c</b>) SEM images of poly(<b>Ru1</b>)<sub>20</sub>@ITO.</p> Full article ">Figure 3
<p>(<b>a</b>) Cyclic voltammograms of the poly(<b>Ru1</b>)<sub>3</sub> films in CH<sub>2</sub>Cl<sub>2</sub> solution that were recorded upon increasing the scan rate (ν) from 0.04 to 0.4 V/s—the inset shows linear dependence of the peak current on ν. The dependence of the anodic (circle) and cathodic (square) overpotentials without (<b>b</b>) and with (<b>c</b>) corrections of ohmic drop on the logarithm of the potential scan rate (log ν); and (<b>d</b>) nyquist diagrams obtained in 0.1 M Na<sub>2</sub>SO<sub>4</sub> and 5 mM [Fe(CN)<sub>6</sub>]<sup>3−/4−</sup> electrolyte solution at 0.123 V in the range from 100 kHz to 1 Hz for poly(<b>Ru1</b>)<span class="html-italic"><sub>n</sub></span> (<span class="html-italic">n</span> = 3, 5, 8, 10, 13) films.</p> Full article ">Figure 4
<p>(<b>a</b>) Photocurrent responses for bare ITO and poly(<b>Ru1</b>)<span class="html-italic"><sub>n</sub></span> (<span class="html-italic">n</span> = 3, 5, 8, 10, 13) films biased at −0.4 V vs. SCE—the inset shows a plot of photocurrent vs. potential scan cycles number <span class="html-italic">n</span>; (<b>b</b>) photocurrent responses for poly(<b>Ru1</b>)<sub>8</sub> film biased at −0.4, −0.3, −0.2, −0.1, 0, +0.1 and 0.2 V vs. SCE—the inset shows a plot of photocurrent vs. potential; (<b>c</b>) photocurrent responses for poly(<b>Ru1</b>)<sub>8</sub> film in N<sub>2</sub>−, air−, and O<sub>2</sub>−equilibrated electrolyte solutions biased at −0.4 V vs. SCE; (<b>d</b>) effect of quinhydrone on photocurrent density of poly(<b>Ru1</b>)<sub>8</sub> biased at 0 V vs. SCE in 0.1 M Na<sub>2</sub>SO<sub>4</sub> aqueous solution; and (<b>e</b>) photocurrent switching behavior induced by changes in quinhydrone concentrations.</p> Full article ">Figure 5
<p>(<b>a</b>) Comparison of photocurrent action spectrum (scattered) and UV–Vis absorption spectrum (solid line) of poly(<b>Ru1</b>)<sub>8</sub> film at zaro applied potential vs. SCE in 0.1 M Na<sub>2</sub>SO<sub>4</sub> aqueous solution containing 0.73 mM quinhydrone; and (<b>b</b>) the proposed mechanism of cathodic and anodic photocurrent generation.</p> Full article ">Figure 6
<p>UV–Visible absorption spectra of iodide−molybdate indicator solution containing varying concentrations of H<sub>2</sub>O<sub>2</sub>. Inset shows a linear fitting of the absorbances at 350 nm vs. H<sub>2</sub>O<sub>2</sub> concentrations.</p> Full article ">Figure 7
<p>(<b>a</b>) Cyclic voltammograms of poly(<b>Ru1</b>)<sub>8</sub> film and blank ITO in O<sub>2</sub>− and Ar− equilibrated 0.1 M Na<sub>2</sub>SO<sub>4</sub> aqueous solution at pH 7.0 with and without 60 mWcm<sup>−2</sup> of white light illumination; (<b>b</b>) the corresponding <span class="html-italic">i</span>−t curve; (<b>c</b>) H<sub>2</sub>O<sub>2</sub> production during the photoelectrocatalytic process; and (<b>d</b>) changes in H<sub>2</sub>O<sub>2</sub> production Faradaic efficiencies for poly(<b>Ru1</b>)<sub>8</sub> film over 10 h photoelectrocatalysis under 60 mWcm<sup>−2</sup> white light irradiation at a biased potential of −0.4 V vs. SCE in O<sub>2</sub>-equilibrated 0.1 M Na<sub>2</sub>SO<sub>4</sub> aqueous solution at a pH of 7.0.</p> Full article ">Figure 8
<p>Cyclic voltammograms (<b>a</b>) of pTTh film and blank ITO in O<sub>2</sub>−equilibrated 0.1 M Na<sub>2</sub>SO<sub>4</sub> aqueous solution at pH 7.0 with and without 60 mWcm<sup>−2</sup> of white light illumination; photocurrent–time curve (<b>b</b>); changes in H<sub>2</sub>O<sub>2</sub> concentrations (<b>c</b>); and Faradaic efficiencies (<b>d</b>) vs. duration of photoelectrocatalysis of PECs based on pTTh photocathode in O<sub>2</sub>-equilibrated 0.1 M Na<sub>2</sub>SO<sub>4</sub> aqueous solution (pH 7.0) when the photocathode was biased at a potential of −0.4 V vs. SCE and irradiated with 60 mWcm<sup>−2</sup> of white light.</p> Full article ">Scheme 1
<p>Synthetic route to <b>Ru1</b>.</p> Full article ">Scheme 2
<p>The proposed electropolymerization mechanism of <b>Ru1</b><sup>2+</sup>.</p> Full article ">
21 pages, 7224 KiB  
Article
African Under-Utilized Medicinal Leafy Vegetables Studied by Microtiter Plate Assays and High-Performance Thin-Layer Chromatography–Planar Assays
by Ibukun O. Oresanya, Ilkay Erdogan Orhan, Julia Heil and Gertrud E. Morlock
Molecules 2024, 29(3), 733; https://doi.org/10.3390/molecules29030733 - 5 Feb 2024
Viewed by 1887
Abstract
Biological activities of six under-utilized medicinal leafy vegetable plants indigenous to Africa, i.e., Basella alba, Crassocephalum rubens, Gnetum africanum, Launaea taraxacifolia, Solanecio biafrae, and Solanum macrocarpon, were investigated via two independent techniques. The total phenolic content (TPC) [...] Read more.
Biological activities of six under-utilized medicinal leafy vegetable plants indigenous to Africa, i.e., Basella alba, Crassocephalum rubens, Gnetum africanum, Launaea taraxacifolia, Solanecio biafrae, and Solanum macrocarpon, were investigated via two independent techniques. The total phenolic content (TPC) was determined, and six microtiter plate assays were applied after extraction and fractionation. Three were antioxidant in vitro assays, i.e., ferric reducing antioxidant power (FRAP), cupric reduction antioxidant capacity (CUPRAC), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, and the others were enzyme (acetylcholinesterase, butyrylcholinesterase, and tyrosinase) inhibition assays. The highest TPC and antioxidant activity from all the methods were obtained from polar and medium polar fractions of C. rubens, S. biafrae, and S. macrocarpon. The highest acetyl- and butyrylcholinesterase inhibition was exhibited by polar fractions of S. biafrae, C. rubens, and L. taraxacifolia, the latter comparable to galantamine. The highest tyrosinase inhibition was observed in the n-butanol fraction of C. rubens and ethyl acetate fraction of S. biafrae. In vitro assay results of the different extracts and fractions were mostly in agreement with the bioactivity profiling via high-performance thin-layer chromatography–multi-imaging–effect-directed analysis, exploiting nine different planar assays. Several separated compounds of the plant extracts showed antioxidant, α-glucosidase, α-amylase, acetyl- and butyrylcholinesterase-inhibiting, Gram-positive/-negative antimicrobial, cytotoxic, and genotoxic activities. A prominent apolar bioactive compound zone was tentatively assigned to fatty acids, in particular linolenic acid, via electrospray ionization high-resolution mass spectrometry. The detected antioxidant, antimicrobial, antidiabetic, anticholinesterase, cytotoxic, and genotoxic potentials of these vegetable plants, in particular C. rubens, S. biafrae, and S. macrocarpon, may validate some of their ethnomedicinal uses. Full article
(This article belongs to the Special Issue Discovery of New Functional Foods with Bioactive Compounds)
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<p>HPTLC fingerprints (<b>A</b>–<b>D</b>) and radical scavenging autogram (<b>E</b>) of <span class="html-italic">Basella alba</span> (BA), <span class="html-italic">Crassocephalum rubens</span> (CR), <span class="html-italic">Gnetum africanum</span> (GA), <span class="html-italic">Launaea taraxacifolia</span> (LT), <span class="html-italic">Solanecio biafrae</span> (SB), and <span class="html-italic">Solanum macrocarpon</span> (SM) along with solvent blank (<b>B</b>), all 5 µL/band, developed on HPTLC plates silica gel 60 F<sub>254</sub> with ethyl acetate–toluene–methanol–water (4:1:1:0.4, <span class="html-italic">V/V/V/V</span>) and detected under (<b>A</b>) white light illumination (Vis), (<b>B</b>) UV 254 nm, and (<b>C</b>) FLD 366 nm as well as (<b>D</b>) white light illumination and FLD 366 nm after the <span class="html-italic">Aliivibrio fischeri</span> bioassay, followed by derivatization with the anisaldehyde sulfuric acid reagent; also shown with a slightly less polar mobile phase in the ratios (4:1:0.75:0.375, <span class="html-italic">V/V/V/V;</span> color changes due to reagent stored too long) and (<b>E</b>) white light illumination after the DPPH• assay (only 3 µL/band applied) instantly and after 1 day; zone 1 marked was recorded by HRMS.</p> Full article ">Figure 2
<p>HPTLC–enzyme inhibition–Vis autograms of <span class="html-italic">Basella alba</span> (BA), <span class="html-italic">Crassocephalum rubens</span> (CR), <span class="html-italic">Gnetum africanum</span> (GA), <span class="html-italic">Launaea taraxacifolia</span> (LT), <span class="html-italic">Solanecio biafrae</span> (SB), and <span class="html-italic">Solanum macrocarpon</span> (SM) along with solvent blank (<b>B</b>), all 5 µL/band, developed on HPTLC plates silica gel 60 F<sub>254</sub> with ethyl acetate–toluene–methanol–water (4:1:1:0.4, <span class="html-italic">V/V/V/V</span>), or apolar mobile phase toluene–ethyl acetate (7:3, <span class="html-italic">V/V</span>), and detected under white light illumination (Vis) after the (<b>A</b>) AChE, (<b>B</b>) BChE, (<b>C</b>) α-glucosidase, and (<b>D</b>) α-amylase assays; zone 1 marked was recorded by HRMS.</p> Full article ">Figure 3
<p>HPTLC–biological assays–Vis/BL/FLD bioautograms of <span class="html-italic">Basella alba</span> (BA), <span class="html-italic">Crassocephalum rubens</span> (CR), <span class="html-italic">Gnetum africanum</span> (GA), <span class="html-italic">Launaea taraxacifolia</span> (LT), <span class="html-italic">Solanecio biafrae</span> (SB), and <span class="html-italic">Solanum macrocarpon</span> (SM) along with solvent blank (<b>B</b>), all 5 µL/band (except 15 µL for SOS-Umu-C and cytotoxicity bioassays), developed on HPTLC plates silica gel 60 F<sub>254</sub> (for C/D on HPTLC plates silica gel 60) with ethyl acetate–toluene–methanol–water (4:1:1:0.4, <span class="html-italic">V/V/V/V</span>) and detected after the (<b>A</b>) <span class="html-italic">Bacillus subtilis</span> bioassay under white light illumination (Vis), (<b>B</b>) <span class="html-italic">Aliivibrio fischeri</span> bioassay as bioluminescence (BL) depicted as greyscale image, (<b>C</b>) cytotoxicity bioassay using the <span class="html-italic">Salmonella</span> Typhimurium cells with thiazol blue tetrazolium bromide substrate under white light illumination, and (<b>D</b>) SOS-Umu-C genotoxicity bioassay with fluorescein-digalactoside substrate, and for comparison, on a separate plate, the same with metabolization via the S9 liver enzyme system detected at FLD 254 nm; zone 1 (marked) was recorded by HRMS.</p> Full article ">Figure 4
<p>HPTLC–UV/Vis/FLD–HESI-HRMS spectra in the (<b>A</b>) negative and (<b>B</b>) positive ionization mode of the prominent multi-potent bioactive compound zone 1 (marked in <a href="#molecules-29-00733-f001" class="html-fig">Figure 1</a>, <a href="#molecules-29-00733-f002" class="html-fig">Figure 2</a> and <a href="#molecules-29-00733-f003" class="html-fig">Figure 3</a>) exemplarily recorded from <span class="html-italic">Basella alba</span> (5 µL/band applied and developed on silica gel 60 F<sub>254</sub> HPTLC plate with toluene–ethyl acetate 7:3, <span class="html-italic">V/V</span>); post-HRMS performance of the α-amylase inhibition assay and respective autogram under white light illumination (Vis) as proof of the proper positioning on the active zone 1, which was originally not UV-active, not fluorescent and not visible.</p> Full article ">
14 pages, 2294 KiB  
Article
Ameliorative Effects of Zingiber officinale Rosc on Antibiotic-Associated Diarrhea and Improvement in Intestinal Function
by Sung Jin Kim, Myoung-Sook Shin and You-Kyung Choi
Molecules 2024, 29(3), 732; https://doi.org/10.3390/molecules29030732 - 5 Feb 2024
Cited by 5 | Viewed by 1713
Abstract
The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Zingiber officinale Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated [...] Read more.
The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Zingiber officinale Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated for the expression of lysozyme, claudin-1, and α-defensin-1, which are associated with intestinal homeostasis. The cecum was analyzed to assess the concentration of short-chain fatty acids (SCFAs). The chemical properties analysis of ZO extracts revealed the levels of total neutral sugars, acidic sugars, proteins, and polyphenols to be 86.4%, 8.8%, 4.0%, and 0.8%, respectively. Furthermore, the monosaccharide composition of ZO was determined to include glucose (97.3%) and galactose (2.7%). ZO extract administration ameliorated the impact of AAD and associated weight loss, and water intake also returned to normal. Moreover, treatment with ZO extract restored the expression levels of lysozyme, α-defensin-1, and claudin-1 to normal levels. The decreased SCFA levels due to induced AAD showed a return to normal levels. The results indicate that ZO extract improved AAD, strengthened the intestinal barrier, and normalized SCFA levels, showing that ZO extract possesses intestinal-function strengthening effects. Full article
(This article belongs to the Special Issue Research on Natural Products for Intestinal Disorders)
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<p>Effect of ZO extraction on changes in body weight, diarrhea status score, and water intake in the AAD model using BALB/c mice. AAD models were established by treatment with or without lincomycin via oral administration for ten days in mice. After diarrhea induction was completed, ZO extracts were orally administered at concentrations of 100 mg/kg or 300 mg/kg for ten days. Mouse body weight was measured every two days (<b>A</b>). Changes in the water intake of mice were recorded every other day (<b>B</b>). Diarrhea status scores of mice were observed once every 2 days (<b>C</b>).</p> Full article ">Figure 1 Cont.
<p>Effect of ZO extraction on changes in body weight, diarrhea status score, and water intake in the AAD model using BALB/c mice. AAD models were established by treatment with or without lincomycin via oral administration for ten days in mice. After diarrhea induction was completed, ZO extracts were orally administered at concentrations of 100 mg/kg or 300 mg/kg for ten days. Mouse body weight was measured every two days (<b>A</b>). Changes in the water intake of mice were recorded every other day (<b>B</b>). Diarrhea status scores of mice were observed once every 2 days (<b>C</b>).</p> Full article ">Figure 2
<p>The effect of oral administration of ZO extract on lysozyme and claudin-1 expression in the AAD model. AAD mice were orally administered the ZO extract (100 mg/kg or 300 mg/kg) daily for ten days. The intestinal tissue was extracted using a radioimmunoprecipitation assay buffer. Lysozyme and claudin-1 protein expression were determined by immunoblotting. β-actin was used as an internal loading control (<b>A</b>). Lysozyme and claudin-1 expression were analyzed using Image J software (<b>B</b>). Data are presented as the mean ± standard deviation (SD) of triplicate experiments. ***, <span class="html-italic">p</span> &lt; 0.0001 and **, <span class="html-italic">p</span> &lt; 0.001 vs. the AAD group.</p> Full article ">Figure 3
<p>Effects of oral administration of ZO extract on lysozyme and claudin-1 mRNA expression in the AAD model. AAD mice were orally administered ZO extracts (100 mg/kg or 300 mg/kg) daily for 10 days. Intestinal RNA was extracted and claudin-1 (<b>A</b>), α-defensin1 (<b>B</b>), and lysozyme (<b>C</b>) mRNA expressions were determined by RT-qPCR. Data are presented as the mean ± standard deviation (SD) of triplicate experiments. ***, <span class="html-italic">p</span> &lt; 0.0001 vs. the AAD group.</p> Full article ">Figure 4
<p>Effects of ZO extract on short-chain fatty acids in the cecum of lincomycin-induced AAD mice. AAD mice were orally administered the ZO extract (100 mg/kg or 300 mg/kg) daily for ten days. Acetic acid (<b>A</b>), butyric acid (<b>B</b>), propionic acid (<b>C</b>), and total SCFA content (<b>D</b>) in the mouse cecum were determined using flame ionization detector–gas chromatography. Data are presented as the mean±standard deviation (SD) of triplicate experiments. #, <span class="html-italic">p</span> &lt; 0.05 vs. the normal group; ***, <span class="html-italic">p</span> &lt; 0.05 vs. the AAD group and *, <span class="html-italic">p</span> &lt; 0.01 vs. the AAD group.</p> Full article ">Figure 4 Cont.
<p>Effects of ZO extract on short-chain fatty acids in the cecum of lincomycin-induced AAD mice. AAD mice were orally administered the ZO extract (100 mg/kg or 300 mg/kg) daily for ten days. Acetic acid (<b>A</b>), butyric acid (<b>B</b>), propionic acid (<b>C</b>), and total SCFA content (<b>D</b>) in the mouse cecum were determined using flame ionization detector–gas chromatography. Data are presented as the mean±standard deviation (SD) of triplicate experiments. #, <span class="html-italic">p</span> &lt; 0.05 vs. the normal group; ***, <span class="html-italic">p</span> &lt; 0.05 vs. the AAD group and *, <span class="html-italic">p</span> &lt; 0.01 vs. the AAD group.</p> Full article ">Figure 5
<p>Oral administration schedule for ZO extraction in the lincomycin-induced AAD model. AAD models were induced by the administration of 3 g/kg lincomycin for ten days. CMC solutions were administered to the control groups. The ZO extraction group was orally administered 100 or 300 mg/kg lincomycin for ten days.</p> Full article ">
20 pages, 15030 KiB  
Article
Angelica Sinensis Polysaccharide-Based Nanoparticles for Liver-Targeted Delivery of Oridonin
by Henglai Sun, Jijuan Nai, Biqi Deng, Zhen Zheng, Xuemei Chen, Chao Zhang, Huagang Sheng and Liqiao Zhu
Molecules 2024, 29(3), 731; https://doi.org/10.3390/molecules29030731 - 5 Feb 2024
Cited by 5 | Viewed by 2186
Abstract
The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to [...] Read more.
The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors. Full article
(This article belongs to the Special Issue Drug Delivery Systems Based on Polysaccharides: Second Edition)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>The design principle of ORI/ASP-DOCA NPs and its anti-liver tumor effect. Reprinted/adapted with permission from Ref. [<a href="#B23-molecules-29-00731" class="html-bibr">23</a>]. 2021, Dan Zheng.</p> Full article ">Figure 2
<p>(<b>A</b>) UV absorption spectrum scanning results of ASP; (<b>B</b>) FT-IR spectrum of ASP; (<b>C</b>) Dextran corresponding molecular weight standard curve; (<b>D</b>) HPLC chromatogram of monosaccharide standard solution mixture; (<b>E</b>) HPLC chromatogram of ASP solution. (1: PMP; 2: <span class="html-small-caps">d</span>-mannose; 3: Rhamnose; 4: <span class="html-small-caps">d</span>-galacturonic acid; 5: <span class="html-small-caps">d</span>-glucose; 6: <span class="html-small-caps">d</span>-galactose; 7: Arabinose).</p> Full article ">Figure 3
<p>Synthetic route of the ASP-DOCA compound.</p> Full article ">Figure 4
<p>FT-IR (<b>A</b>) and <sup>1</sup>H-NMR Spectra (<b>B</b>) of ASP, DOCA and the ASP-DOCA compound; (<b>C</b>) CAC of the ASP-DOCA compound.</p> Full article ">Figure 5
<p>(<b>A</b>) ORI/ASP-DOCA NPs solution and its freeze-dried powder; (<b>B</b>) The relationship between the particle size and dispersion coefficient of ORI/ASP-DOCA NPs and storage time; (<b>C</b>) Particle size distribution of ORI/ASP-DOCA NPs; (<b>D</b>) The drug release curves of free ORI and ORI/ASP-DOCA NPs at different pH values.</p> Full article ">Figure 6
<p>TEM images of ASP-DOCA NPs (<b>Aa</b>) and ORI/ASP-DOCA NPs (<b>Ab</b>); SEM images of ASP-DOCA NPs (<b>Ba</b>) and ORI/ASP-DOCA NPs (<b>Bb</b>); (<b>C</b>) XRD patterns of ORI, ORI/ASP-DOCA NPs, ASP-DOCA NPs, ORI and ASP-DOCA NPs physical mixture; (<b>D</b>) DSC spectrum of ORI, ORI/ASP-DOCA NPs, ASP-DOCA NPs, ORI and ASP-DOCA NPs physical mixture.</p> Full article ">Figure 7
<p>Cytotoxicity of ASP-DOCA NPs on HepG2 cells for 24 h (<b>Aa</b>) and 48 h (<b>Ab</b>); Cytotoxicity of ASP-DOCA NPs on HeLa cells for 24 h (<b>Ba</b>) and 48 h (<b>Bb</b>).</p> Full article ">Figure 8
<p>Cytotoxicity of free ORI and ORI/ASP DOCA NPs on HepG2 cells for 24 h (<b>Aa</b>) and 48 h (<b>Ab</b>); Cytotoxicity of free ORI and ORI/ASP DOCA NPs on HeLa cells for 24 h (<b>Ba</b>) and 48 h (<b>Bb</b>). (Note: compared with ORI group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01).</p> Full article ">Figure 9
<p>The in vitro targeting effect of ORI/ASP-DOCA NPs and ASP + ORI/ASP-DOCA NPs on HepG2 after 1 h (<b>a</b>), 2 h (<b>b</b>), 4 h (<b>c</b>) and 24 h (<b>d</b>). (Note: compared with ASP + ORI/ASP-DOCA NPs group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01).</p> Full article ">Figure 10
<p>Cellular uptake of ORI, ORI/ASP-DOCA, ORI/DEX-DOCA and ASP + ORI/ASP-DOCA by HepG2 (<b>Aa</b>) and HeLa (<b>Ab</b>) cells; (<b>B</b>) Cellular uptake of C6, C6/ASP-DOCA and C6/DEX-DOCA NPs detected by flow cytometry.</p> Full article ">Figure 11
<p>(<b>A</b>) CLSM images of HepG2 cells incubated with C6/ASP-DOCA NPs for different times of 2, 4, 6 h. (<b>B</b>) CLSM images of HepG2 cells incubated with different drugs for 6 h. (<b>C</b>) CLSM images of HeLa cells incubated with different drugs for 6 h.</p> Full article ">Figure 12
<p>(<b>A</b>) Fluorescence images of DIR obtained by free DIR, DIR/ASP-DOCA and DIR/DEX-DOCA NPs at different time points of tumor-bearing mice in vivo; (<b>B</b>) DIR fluorescence imaging of the main isolated organs of tumor-bearing mice; (<b>C</b>) Tumor tissue images of tumor-bearing mice in each group; (<b>D</b>) Changes in the body weight of tumor-bearing mice in each group; (Note: compared with the ORI/ASP-DOCA NPs group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01); (<b>E</b>) Changes in the tumor volume of tumor-bearing mice in each group; (<b>F</b>) Tumor tissue weight of tumor-bearing mice in each group (Note: compared with control group, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01).</p> Full article ">Figure 13
<p>H &amp; E staining on sections of hearts, spleens, lungs, kidneys and tumors in tumor-bearing mice in each group (200×).</p> Full article ">Figure 14
<p>H &amp; E staining of mouse liver sections in each group (200×).</p> Full article ">
14 pages, 2345 KiB  
Article
Aminoquinoline-Based Tridentate (NNN)-Copper Catalyst for C–N Bond-Forming Reactions from Aniline and Diazo Compounds
by Mohsen Teimouri, Selvam Raju, Edward Acheampong, Allison N. Schmittou, Bruno Donnadieu, David O. Wipf, Brad S. Pierce, Sean L. Stokes and Joseph P. Emerson
Molecules 2024, 29(3), 730; https://doi.org/10.3390/molecules29030730 - 5 Feb 2024
Cited by 1 | Viewed by 1778
Abstract
A new tridentate Cu2+ complex based on (E)-1-(pyridin-2-yl)-N-(quinolin-8-yl)methanimine (PQM) was generated and characterized to support the activation of diazo compounds for the formation of new C–N bonds. This neutral Schiff base ligand was structurally characterized to coordinate with [...] Read more.
A new tridentate Cu2+ complex based on (E)-1-(pyridin-2-yl)-N-(quinolin-8-yl)methanimine (PQM) was generated and characterized to support the activation of diazo compounds for the formation of new C–N bonds. This neutral Schiff base ligand was structurally characterized to coordinate with copper(II) in an equatorial fashion, yielding a distorted octahedral complex. Upon characterization, this copper(II) complex was used to catalyze an efficient and cost-effective protocol for C–N bond formation between N-nucleophiles and copper carbene complexes arising from the activation of diazo carbonyl compounds. A substrate scope of approximately 15 different amine-based substrates was screened, yielding 2° or 3° amine products with acceptable to good yields under mild reaction conditions. Reactivity towards phenol and thiophenol were also screened, showing relatively weak C–O or C–S bond formation under optimized conditions. Full article
(This article belongs to the Special Issue Featured Papers in Organometallic Chemistry)
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Graphical abstract
Full article ">Figure 1
<p>The copper complex of the Cu<sup>2+</sup>(PQM) crystal structure is shown as a 50% thermal ellipsoid plot. The H-atoms are removed for clarity. (Note: O<sub>W</sub> = water, O<sub>L</sub> = triflate anions, black = carbon, red = oxygen, blue = nitrogen, green = fluorine, yellow = sulfur).</p> Full article ">Figure 2
<p>(<b>A</b>) UV–visible absorption spectrum of the Cu<sup>2+</sup>(PQM) at 5.0 µM in methanol (blue line) and the inset at 5.0 mM in methanol (red line), highlighting the low-intensity d→d transition. (<b>B</b>) X-band EPR spectrum of 4.0 mM Cu<sup>2+</sup>(PQM) shown as an experiment (black) and simulated (blue) data recorded at 10K.</p> Full article ">Figure 3
<p>Cyclic voltammograms of solvent/acetonitrile (gray), 1.0 mM solution of Cu<sup>2+</sup>(PQM) complex (blue), and Cu<sup>2+</sup>(PQM) with ferrocene (red) at a scan rate of 0.1 V/s.</p> Full article ">Figure 4
<p>Proposed catalytic cycle for the carbene transfer reactions.</p> Full article ">Scheme 1
<p>Previous work and our findings on the construction of C–N bonds [<a href="#B29-molecules-29-00730" class="html-bibr">29</a>,<a href="#B32-molecules-29-00730" class="html-bibr">32</a>,<a href="#B41-molecules-29-00730" class="html-bibr">41</a>]. * represent a chiral center formed in product.</p> Full article ">Scheme 2
<p>The synthesis of a Schiff base <span class="html-italic">NNN</span>-PQM ligand ligated with Cu(OTf)<sub>2</sub>.</p> Full article ">Scheme 3
<p>Substrate scopes of Cu<sup>2+</sup>(PQM)-catalyzed N–H insertion products. Reaction conditions: <b>1a</b> (0.5 mmol), <b>2a</b> (1.0 mmol), and Cu<sup>2+</sup>(PQM) (0.05 mmol) in 2.0 mL of DCM at 0 °C to RT for 4 h. The reaction conversions were determined through crude <sup>1</sup>H-NMR spectroscopy using mesitylene as an internal standard. * represent a newly formed chiral centers in products, where reported conversions are a racemic mixture of both enantiomers.</p> Full article ">Scheme 4
<p>Control experiments for the carbene transfer reactions. Reaction conditions: <b>1</b> (0.5 mmol), <b>2a</b> (1.0 mmol), and Cu<sup>2+</sup>(PQM) (0.05 mmol) in 2.0 mL of DCM at 0 °C to RT for 4 h. The reaction conversations were determined through crude <sup>1</sup>H-NMR spectroscopy using mesitylene as an internal standard.</p> Full article ">
15 pages, 6560 KiB  
Article
In Vivo Wound Healing Potential and Molecular Pathways of Amniotic Fluid and Moringa Olifera-Loaded Nanoclay Films
by Akram Ashames, Munaza Ijaz, Manal Buabeid, Haya Yasin, Sidra Yaseen, Richie R. Bhandare and Ghulam Murtaza
Molecules 2024, 29(3), 729; https://doi.org/10.3390/molecules29030729 - 5 Feb 2024
Cited by 2 | Viewed by 1915
Abstract
Cutaneous wounds pose a significant health burden, affecting millions of individuals annually and placing strain on healthcare systems and society. Nanofilm biomaterials have emerged as promising interfaces between materials and biology, offering potential for various biomedical applications. To explore this potential, our study [...] Read more.
Cutaneous wounds pose a significant health burden, affecting millions of individuals annually and placing strain on healthcare systems and society. Nanofilm biomaterials have emerged as promising interfaces between materials and biology, offering potential for various biomedical applications. To explore this potential, our study aimed to assess the wound healing efficacy of amniotic fluid and Moringa olifera-loaded nanoclay films by using in vivo models. Additionally, we investigated the antioxidant and antibacterial properties of these films. Using a burn wound healing model on rabbits, both infected and non-infected wounds were treated with the nanoclay films for a duration of twenty-one days on by following protocols approved by the Animal Ethics Committee. We evaluated wound contraction, proinflammatory mediators, and growth factors levels by analyzing blood samples. Histopathological changes and skin integrity were assessed through H&E staining. Statistical analysis was performed using SPSS software (version 2; Chicago, IL, USA) with significance set at p < 0.05. Our findings demonstrated a significant dose-dependent increase in wound contraction in the 2%, 4%, and 8% AMF-Me.mo treatment groups throughout the study (p < 0.001). Moreover, macroscopic analysis revealed comparable effects (p > 0.05) between the 8% AMF-Me.mo treatment group and the standard treatment. Histopathological examination confirmed the preservation of skin architecture and complete epidermal closure in both infected and non-infected wounds treated with AMF-Me.mo-loaded nanofilms. RT-PCR analysis revealed elevated concentrations of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF), along with decreased levels of tumor necrosis factor-alpha (TNF-α) in AMF-Me.mo-loaded nanofilm treatment groups. Additionally, the antimicrobial activity of AMF-Me.mo-loaded nanofilms contributed to the decontamination of the wound site, positioning them as potential candidates for effective wound healing. However, further extensive clinical trials-based studies are necessary to confirm these findings. Full article
(This article belongs to the Special Issue Polysaccharide-Based Biopolymer: Recent Development and Applications)
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<p>Antibacterial effect of amikacin, <span class="html-italic">Moringa olifera</span> extract, and 2%, 4%, and 8% AMF solution against <span class="html-italic">Staphylococcus aureus</span> and <span class="html-italic">Escherichia coli</span> bacteria.</p> Full article ">Figure 2
<p>Macroscopic analysis of burn infected wound healing model.</p> Full article ">Figure 3
<p>Graphical representation of percent wound contraction in infected wounds. Values shown are Mean ± SEM (<span class="html-italic">n</span> = 4). Where ** = <span class="html-italic">p</span> ˂ 0.01, *** = <span class="html-italic">p</span> ˂ 0.001. Violet, green, and blue color stars show comparison of 2%, 4%, and 8% nanoclay-based AMF-<span class="html-italic">Moringa</span>-loaded nanofilm treatment groups with diseased control. While red color stars show comparison of standard (Quench<sup>®</sup>) with diseased control.</p> Full article ">Figure 4
<p>Macroscopic analysis of burn non-infected wound healing model.</p> Full article ">Figure 5
<p>Graphical representation of percent wound contraction in non-infected wounds. Values shown are Mean ± SEM (<span class="html-italic">n</span> = 4). Where ** = <span class="html-italic">p</span> ˂ 0.01, *** = <span class="html-italic">p</span> ˂ 0.001. Violet, green, and blue color stars show comparison of 2%, 4%, and 8% nanoclay-based AMF-<span class="html-italic">Moringa</span>-loaded nanofilms treatment groups with diseased control, while red color stars show comparison of standard (Quench<sup>®</sup>) with diseased control, respectively.</p> Full article ">Figure 6
<p>Histopathological analysis of infected burn wound healing animals treated with Quench<sup>®</sup> (<b>a</b>,<b>b</b>) and 8% (<b>c</b>,<b>d</b>), 4% (<b>e</b>–<b>g</b>), and 2% (<b>h</b>,<b>i</b>) AMF-<span class="html-italic">Me.mo</span>-loaded nanocomposites and diseased control (<b>j</b>–<b>l</b>) group, respectively. The arrows in this figure represent the above-mentioned processes (granulation tissue formation, occurrence of blood vessel growth, development of fibroblasts, scab formation, hypertrophy, atrophy, and the infiltration of macrophages and neutrophils in various images) as indicated by arrows.</p> Full article ">
39 pages, 3914 KiB  
Review
Natural Compounds in Non-Melanoma Skin Cancer: Prevention and Treatment
by Szymon Kowalski, Julia Karska, Maciej Tota, Katarzyna Skinderowicz, Julita Kulbacka and Małgorzata Drąg-Zalesińska
Molecules 2024, 29(3), 728; https://doi.org/10.3390/molecules29030728 - 4 Feb 2024
Cited by 6 | Viewed by 4474
Abstract
The elevated occurrence of non-melanoma skin cancer (NMSC) and the adverse effects associated with available treatments adversely impact the quality of life in multiple dimensions. In connection with this, there is a necessity for alternative approaches characterized by increased tolerance and lower side [...] Read more.
The elevated occurrence of non-melanoma skin cancer (NMSC) and the adverse effects associated with available treatments adversely impact the quality of life in multiple dimensions. In connection with this, there is a necessity for alternative approaches characterized by increased tolerance and lower side effects. Natural compounds could be employed due to their safety profile and effectiveness for inflammatory and neoplastic skin diseases. These anti-cancer drugs are often derived from natural sources such as marine, zoonotic, and botanical origins. Natural compounds should exhibit anti-carcinogenic actions through various pathways, influencing apoptosis potentiation, cell proliferation inhibition, and metastasis suppression. This review provides an overview of natural compounds used in cancer chemotherapies, chemoprevention, and promotion of skin regeneration, including polyphenolic compounds, flavonoids, vitamins, alkaloids, terpenoids, isothiocyanates, cannabinoids, carotenoids, and ceramides. Full article
(This article belongs to the Section Medicinal Chemistry)
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<p>Chemical structures of selected polyphenolic compounds showing anti-NMSC effect.</p> Full article ">Figure 2
<p>Mechanisms of resveratrol action [<a href="#B97-molecules-29-00728" class="html-bibr">97</a>,<a href="#B98-molecules-29-00728" class="html-bibr">98</a>,<a href="#B99-molecules-29-00728" class="html-bibr">99</a>,<a href="#B100-molecules-29-00728" class="html-bibr">100</a>,<a href="#B101-molecules-29-00728" class="html-bibr">101</a>,<a href="#B102-molecules-29-00728" class="html-bibr">102</a>,<a href="#B103-molecules-29-00728" class="html-bibr">103</a>,<a href="#B104-molecules-29-00728" class="html-bibr">104</a>,<a href="#B105-molecules-29-00728" class="html-bibr">105</a>,<a href="#B106-molecules-29-00728" class="html-bibr">106</a>] (parts of the figure were drawn by using pictures from Servier Medical Art).</p> Full article ">Figure 3
<p>Chemical structures of selected flavonoids showing an anti-NMSC effect. EGCG—epigallocatechin gallate.</p> Full article ">Figure 4
<p>Chemical structures of selected vitamins showing anti-NMSC effect.</p> Full article ">Figure 5
<p>Chemical structures of selected alkaloids showing anti-NMSC effect.</p> Full article ">Figure 6
<p>Chemical structures of selected terpenoids showing anti-NMSC effect.</p> Full article ">Figure 7
<p>Chemical structures of selected isothiocyanates showing anti-NMSC effect.</p> Full article ">Figure 8
<p>In SCC, exposure to SFN hinders cancer progression and in vivo metastasis by diminishing arginine methylation at histone 3 (H3). This reduction involves SFN-induced proteasomal degradation of arginine N-methyltransferase 5 (PRMT5) and methylosome protein 50 (MEP50). Both enzymes are responsible for arginine methylation at H3 and H4, respectively, leading to decreased levels of dimethylated arginine 3 at H4 (H4R3me2) [<a href="#B193-molecules-29-00728" class="html-bibr">193</a>]. Moreover, using a biotin-tagged SFN analog (Biotin-ITC) and kinetic analysis, it was showed that SFN covalently binds to recombinant type 2 transglutaminase (TG2), irreversibly inhibiting its transamidase activity. This induces an open/extended conformation and partially inhibits GTP binding, which is crucial for maintaining the aggressive SCC phenotype [<a href="#B194-molecules-29-00728" class="html-bibr">194</a>].</p> Full article ">Figure 9
<p>Chemical structures of selected cannabinoids showing anti-NMSC effect.</p> Full article ">Figure 10
<p>Chemical structures of selected carotenoids showing anti-NMSC effect.</p> Full article ">Figure 11
<p>Chemical structures of C2 ceramide showing anti-NMSC effect.</p> Full article ">
18 pages, 9567 KiB  
Review
Recent Developments in Functional Polymers via the Kabachnik–Fields Reaction: The State of the Art
by Rui Yuan, Xianzhe He, Chongyu Zhu and Lei Tao
Molecules 2024, 29(3), 727; https://doi.org/10.3390/molecules29030727 - 4 Feb 2024
Cited by 1 | Viewed by 1811
Abstract
Recently, multicomponent reactions (MCRs) have attracted much attention in polymer synthesis. As one of the most well-known MCRs, the Kabachnik–Fields (KF) reaction has been widely used in the development of new functional polymers. The KF reaction can efficiently introduce functional groups into polymer [...] Read more.
Recently, multicomponent reactions (MCRs) have attracted much attention in polymer synthesis. As one of the most well-known MCRs, the Kabachnik–Fields (KF) reaction has been widely used in the development of new functional polymers. The KF reaction can efficiently introduce functional groups into polymer structures; thus, polymers prepared via the KF reaction have unique α-aminophosphonates and show important bioactivity, metal chelating abilities, and flame-retardant properties. In this mini-review, we mainly summarize the latest advances in the KF reaction to synthesize functional polymers for the preparation of heavy metal adsorbents, multifunctional hydrogels, flame retardants, and bioimaging probes. We also discuss some emerging applications of functional polymers prepared by means of the KF reaction. Finally, we put forward our perspectives on the further development of the KF reaction in polymer chemistry. Full article
(This article belongs to the Section Organic Chemistry)
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<p>(<b>a</b>) Mechanism of the KF reaction. (<b>b</b>) Scheme of the KF reaction synthesizing functional polymers for multiple applications.</p> Full article ">Figure 2
<p>Exploration of safe and efficient polymer chelators by combining the KF reaction, chelator, and polymer chemistry for preventing acute and chronic heavy metal poisoning in mice. Reprinted with permission from ref. [<a href="#B8-molecules-29-00727" class="html-bibr">8</a>]. Copyright 2022 American Chemical Society. All rights reserved.</p> Full article ">Figure 3
<p>(<b>a</b>) Polymers used in the Cd<sup>2+</sup> chelating tests. (<b>b</b>) Color change and (<b>b’</b>) concentrations of Cd<sup>2+</sup>/5-Br-PADAP (absorbance at 520 nm) in the presence of different polymers. Water serves as a blank. The data are presented as the mean ± SD (n = 5). (<b>c</b>) H&amp;E staining of the liver tissues of mice after different treatments. Yellow arrows: hepatocyte steatosis. Reprinted with permission from ref. [<a href="#B8-molecules-29-00727" class="html-bibr">8</a>]. Copyright 2022 American Chemical Society. All rights reserved.</p> Full article ">Figure 4
<p>(<b>a</b>) Metal cation positively charges selective layer membranes for heavy metal ion rejection. (<b>b</b>) Rejection performance of heavy metal ions by the membranes. (<b>c</b>) Comparative salt retention performance with the existing literature. Testing conditions: salt solutions concentration = 1.0 g L<sup>−1</sup>, mixed salt solutions concentration, i.e., Co<sup>II</sup>/Zn<sup>II</sup> = 0.5/0.5 g L<sup>−1</sup>, 21 °C, pH = 3.25, 0.8 MPa. Error bars are the standard deviations of three repeat experiments. Reprinted with permission from ref. [<a href="#B41-molecules-29-00727" class="html-bibr">41</a>]. Copyright © 2019 American Chemical Society. All rights reserved.</p> Full article ">Figure 5
<p>Preparation of mussel-inspired LDH through the modification of the functional polymer prepared by the KF reaction for highly efficient adsorption. Reprinted with permission from ref. [<a href="#B42-molecules-29-00727" class="html-bibr">42</a>]. Copyright © 2019 Elsevier Ltd. All rights reserved.</p> Full article ">Figure 6
<p>Fabrication of CNT-based polymer composites through DA cycloaddition and KF reactions for the removal of Eu<sup>3+</sup> ions from wastewater. Reprinted with permission from ref. [<a href="#B46-molecules-29-00727" class="html-bibr">46</a>]. Copyright 2020 Elsevier B.V. All rights reserved.</p> Full article ">Figure 7
<p>A polyanion self-healing hydrogel for the controlled release of cisplatin in a 3D cell culture through the KF reaction. Reprinted with permission from ref. [<a href="#B47-molecules-29-00727" class="html-bibr">47</a>]. Copyright 2020 Elsevier Ltd. All rights reserved.</p> Full article ">Figure 8
<p>(<b>a</b>) Preparation of P1 and the P1–IONPs complex. (<b>b</b>) Temperature of P1–PVA hydrogels containing different amounts of IONPs vs. time in an AMF (f = 285 kHz, H = 201.2 Oe). Data are presented as the mean ± SD, n = 5. (<b>c</b>) MRI images and T<sub>2</sub> values of P1–PVA hydrogels containing different amounts of IONPs. Reprinted with permission from ref. [<a href="#B9-molecules-29-00727" class="html-bibr">9</a>]. Copyright 2022 American Chemical Society. All rights reserved.</p> Full article ">Figure 9
<p>A novel ternary metal–silicon–phosphorus intramolecular hybrid flame retardant based on Ti-embedded and DOPO-functionalized POSS for the modification of EP. (<b>a</b>) The interior layer of EP-0. (<b>b</b>) The interior layer of EP-3. (<b>a’</b>) The exterior layer of EP-0. (<b>b’</b>) The exterior layer of EP-3. The Reprinted with permission from ref. [<a href="#B51-molecules-29-00727" class="html-bibr">51</a>]. Copyright 2019 Elsevier B.V. All rights reserved.</p> Full article ">Figure 10
<p>(<b>a</b>) Preparation process of the organophosphorus-modified hollow bimetallic organic framework. (<b>b</b>) Flame retardancy mechanisms for the EP mixed with the organic frameworks. Reprinted with permission from ref. [<a href="#B27-molecules-29-00727" class="html-bibr">27</a>]. Copyright 2021 Elsevier B.V. All rights reserved.</p> Full article ">Figure 11
<p>(<b>a</b>) Preparation process and cell imaging properties of the AIE-active FNPs. (<b>b</b>) TEM image of the AIE-active FNPs dispersed in water. (<b>c</b>) Fluorescent imaging under excitation with a 405 nm laser. Reprinted with permission from ref. [<a href="#B52-molecules-29-00727" class="html-bibr">52</a>]. Copyright 2016 Elsevier B.V. All rights reserved.</p> Full article ">Figure 12
<p>(<b>a</b>) Preparation of PEG-DP-PhE FPNs by MCP based on a microwave-assisted KF reaction. (<b>b</b>) TEM image of the PEG-DP-PhE FPNs. (<b>c</b>) Bright field images of L929 cells co-cultured with the PEG-DP-PhE FPNs. (<b>d</b>) Fluorescent imaging under excitation with a 458 nm laser. Reprinted with permission from ref. [<a href="#B53-molecules-29-00727" class="html-bibr">53</a>]. Copyright 2017 Elsevier B.V. All rights reserved.</p> Full article ">Figure 13
<p>(<b>a</b>) Preparation of the PEGMA-TPE FPNs through an efficient post-modification method through a microwave-assisted KF reaction for biological imaging applications. (<b>b</b>) Fluorescent imaging under excitation with a 405 nm laser. (<b>c</b>) TEM image of the PEGMA-TPE FPNs. (<b>d</b>) Excitation (Ex) and emission (Em) fluorescent spectra of the PEGMA-TPE FPNs dispersed in water. Ex = 368 nm, Em = 500 nm. Reprinted with permission from ref. [<a href="#B54-molecules-29-00727" class="html-bibr">54</a>]. Copyright 2017 Elsevier B.V. All rights reserved.</p> Full article ">Figure 14
<p>(<b>a</b>) Preparation of polyApp through “one pot” KF-RAFT polymerization. (<b>b</b>) Mechanisms for compatibility enhancement of Pglass/polymer composites by adding polyAPP. Reprinted with permission from ref. [<a href="#B55-molecules-29-00727" class="html-bibr">55</a>]. Copyright 2018 Elsevier Ltd. All rights reserved.</p> Full article ">Figure 15
<p>Structure of the PCH as an environmentally friendly scale inhibitor and the DFT simulation of descaling mechanisms. Reprinted with permission from ref. [<a href="#B56-molecules-29-00727" class="html-bibr">56</a>]. Copyright 2021 The Authors. Published by the American Chemical Society. This publication is licensed under CC-BY 4.0. All rights reserved.</p> Full article ">
10 pages, 2293 KiB  
Article
Improved Process for the Continuous Acylation of 1,3-Benzodioxole
by Davide Pollon, Francesca Annunziata, Stefano Paganelli, Lucia Tamborini, Andrea Pinto, Sabrina Fabris, Maria Antonietta Baldo and Oreste Piccolo
Molecules 2024, 29(3), 726; https://doi.org/10.3390/molecules29030726 - 4 Feb 2024
Viewed by 1736
Abstract
The acylation of 1,3-benzodioxole was studied in a continuous process using a recyclable heterogeneous substoichiometric catalyst. In a short time period (30 min), at 100 °C, the conversion rate was 73%, with a selectivity of 62% of the desired acylated product; the reaction [...] Read more.
The acylation of 1,3-benzodioxole was studied in a continuous process using a recyclable heterogeneous substoichiometric catalyst. In a short time period (30 min), at 100 °C, the conversion rate was 73%, with a selectivity of 62% of the desired acylated product; the reaction was run continuously for 6 h, showing excellent stability and selectivity. Moreover, the unreacted starting material, 1,3-benzodioxole, can be easily separated by distillation and recycled. Full article
(This article belongs to the Special Issue Research on Heterogeneous Catalysis)
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<p>Picture of Aquivion SO<sub>3</sub>H<sup>®</sup> after its use under continuous flow conditions at 140 °C.</p> Full article ">Figure 2
<p>The structure of bis(benzo[<span class="html-italic">d</span>][1,3]dioxol-5-yl)methane formed in the presence of MDB and Zn-Aquivion at 120 °C after a residence time of 15 min.</p> Full article ">Figure 3
<p>GC chromatogram of a reaction crude. Reaction conditions: propionic anhydride 1:1 and Aquivion SO<sub>3</sub>H<sup>®</sup>, temperature reaction 100 °C, residence time 30 min; internal standard mesitylene, 25 mg L<sup>−1</sup>.</p> Full article ">Figure 4
<p>Identification of the retention times of MDB and product (<b>1</b>), 1-(benzo[<span class="html-italic">d</span>][1,3]dioxol-5-yl)propan-1-one.</p> Full article ">Scheme 1
<p>A schematic representation of the flow set up for the synthesis of compound (<b>1</b>).</p> Full article ">
18 pages, 3908 KiB  
Article
Discovery of Novel Antitumor Small-Molecule Agent with Dual Action of CDK2/p-RB and MDM2/p53
by Zhaofeng Liu, Yifei Yang, Xiaohui Sun, Runchen Ma, Wenjing Zhang, Wenyan Wang, Gangqiang Yang, Hongbo Wang, Jianzhao Zhang, Yunjie Wang and Jingwei Tian
Molecules 2024, 29(3), 725; https://doi.org/10.3390/molecules29030725 - 4 Feb 2024
Cited by 2 | Viewed by 2219
Abstract
Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is [...] Read more.
Cell cycle-dependent kinase 2 (CDK2) is located downstream of CDK4/6 in the cell cycle and regulates cell entry into S-phase by binding to Cyclin E and hyper-phosphorylating Rb. Proto-oncogene murine double minute 2 (MDM2) is a key negative regulator of p53, which is highly expressed in tumors and plays an important role in tumorigenesis and progression. In this study, we identified a dual inhibitor of CDK2 and MDM2, III-13, which had good selectivity for inhibiting CDK2 activity and significantly reduced MDM2 expression. In vitro results showed that III-13 inhibited proliferation of a wide range of tumor cells, regardless of whether Cyclin E1 (CCNE1) was overexpressed or not. The results of in vivo experiments showed that III-13 significantly inhibited proliferation of tumor cells and did not affect body weight of mice. The results of the druggability evaluation showed that III-13 was characterized by low bioavailability and poor membrane permeability when orally administered, suggesting the necessity of further structural modifications. Therefore, this study provided a lead compound for antitumor drugs, especially those against CCNE1-amplified tumor proliferation. Full article
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<p>Structure modification, synthesis, and CDK inhibitory activity of III-13. (<b>A</b>) Molecular docking of PF-4091 and CDK2. (<b>B</b>) Design structure of III-13. (<b>C</b>) III-13 synthesis step. (<b>D</b>–<b>H</b>) Summary of the inhibitory effect of III-13 on CDKs. Conditions and Reagents. Letters: (a) 4-Chlorobutyryl chloride, Et3N, DCM, 0−20 °C, 16 h; (b) NaH, THF, 0−25 °C, 2 h; (c) NaOH, THF/EtOH, 60 °C, 1 h; (d) 4, TCFH, NMI, DMF, 20−70 °C, 3 h; (e) 1M HCl, MeOH, THF (10.0 V), 20 °C, 16 h; (f) 4-nitrophenyl carbonochloridate, Py, DMAP, THF, 75 °C, 22 h; (g) 2,2-dimethylazetidine, DIEA, 50 °C, 14 h; (h) TFA, DCM, 80 °C, 14 h.</p> Full article ">Figure 2
<p>Antitumor effects of III-13 and its effect on CDK2 pathway. (<b>A</b>) <span class="html-italic">CCNE1</span> mRNA expression in TOV-21G, HCT116, and OVCAR3 cells. Results are expressed as mean ± SD, n = 3. * <span class="html-italic">p</span> &lt; 0.05 vs. TOV-21G cells. (<b>B</b>,<b>C</b>) Inhibition of TOV-21G, HCT116, and OVCAR3 cell proliferation by III-13. (<b>D</b>,<b>E</b>) Effect of III-13 on p-Rb, Rb, p-CDK2, and CDK2 protein expression in HCT116 and OVCAR3 cells. Results are expressed as mean ± SD, n = 4. *** <span class="html-italic">p</span> &lt; 0.001 vs. control group.</p> Full article ">Figure 3
<p>Transcriptome sequencing and related validation. (<b>A</b>) RNA sequencing cluster analysis chart. OVCAR3 cells were treated with III-13 or DMSO for 12 h. Orange color indicates gene up-regulation (<span class="html-italic">p</span> &lt; 0.05 and fold change &gt; 2) and blue color indicates gene down-regulation (<span class="html-italic">p</span> &lt; 0.05 and fold change &lt; 0.5). (<b>B</b>) KEGG signaling pathway that was significantly changed by III-13 treatment. Different colors of bubbles represent different <span class="html-italic">p</span> values, and different sizes of bubbles represent the number of genes in the signaling pathway. (<b>C</b>,<b>D</b>) q-PCR was performed to detect changes in mRNA after 12 h of III-13 treatment. (<b>E</b>) Changes in MDM2 and p53 protein levels after III-13-treated cells were detected by Western blot. (<b>F</b>) PF-4091 did not affect MDM2 and p53 expression in OVCAR3 cells. Results are expressed as mean ± SD, n = 3 or 4. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group.</p> Full article ">Figure 4
<p>III-13 blocked cycle progression and inhibited cell migration and colony formation in HCT116 and OVCAR3 cells. (<b>A</b>,<b>B</b>) Effect of III-13 on the cell cycle of HCT116 and OVCAR3 cells detected by flow cytometry. (<b>C</b>,<b>D</b>) The effect of III-13 on cell migration was detected by scratch test. (<b>E</b>,<b>F</b>) Detection of the effect of III-13 on colony formation. Results are expressed as mean ± SD, n = 3. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. control group.</p> Full article ">Figure 5
<p>Antitumor activity of III-13 in vivo. (<b>A</b>) Comparison of nude mice and tumor volumes between groups after 14 days of compound treatment. (<b>B</b>–<b>E</b>) Quantitative plot of tumor volume, tumor weight, and body weight change. Results are expressed as mean ± SD, n = 7. (<b>F</b>,<b>G</b>) Changes in p-Rb, Rb, p-CDK2, CDK2, MDM2, and p53 protein levels in transplanted tumors in each group. Results are expressed as mean ± SD, n = 4. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 vs. vehicle group.</p> Full article ">Figure 6
<p>Schematic diagram. III-13 exerts antitumor effects by inhibiting the hyper-phosphorylation of Rb by CDK2, arresting tumor cells in the G0/G1 phase and significantly inhibiting the expression of MDM2, thereby increasing the expression of p53.</p> Full article ">
22 pages, 4389 KiB  
Article
Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells
by Vital Ugirinema, Frank Odei-Addo, Carminita L. Frost and Zenixole R. Tshentu
Molecules 2024, 29(3), 724; https://doi.org/10.3390/molecules29030724 - 4 Feb 2024
Cited by 1 | Viewed by 1860
Abstract
The reaction of the vanadyl ion (VO2+) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and phosphate (Phos)] and high-molecular-weight (HMW) human serum proteins [...] Read more.
The reaction of the vanadyl ion (VO2+) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and phosphate (Phos)] and high-molecular-weight (HMW) human serum proteins [albumin (HSA) and transferrin (hTf)] were studied in aqueous solution using potentiometric acid–base titrations. The species distribution diagrams for the high-molecular-mass (HMM) proteins with oxidovanadium(IV) under physiological pH were dominated by VO(HMM)2, VOL(HMM) for unsubstituted ligands (L− = Im4COO− and Im2COO−). However, for the N-substituted MeIm2COOH, the species distribution diagrams under physiological pH were dominated by VOL2, VO(HMM)2 and VO2L2(HMM). These species were further confirmed by LC-MS, MALDI-TOF-MS and EPR studies. The glucose-stimulated insulin secretion (GSIS) action of the complexes was investigated using INS-1E cells at a 1 µM concentration, which was established through cytotoxicity studies via the MTT assay. The neutral complexes, especially VO(MeIm2COO)2, showed promising results in the stimulation of insulin secretion than the cationic [VO(MeIm2CH2OH)2]2+ complex and the vanadium salt. Oxidovanadium(IV) complexes reduced insulin stimulation significantly under normoglycaemic levels but showed positive effects on insulin secretion under hyperglycaemic conditions (33.3 mM glucose media). The islets exposed to oxidovanadium(IV) complexes under hyperglycaemic conditions displayed a significant increase in the stimulatory index with 1.19, 1.75, 1.53, 1.85, 2.20 and 1.29 observed for the positive control (sulfonylurea:gliclazide), VOSO4, VO(Im4COO)2, VO(Im2COO)2, VO(MeIm2COO)2 and VO(MeIm2CH2OH)22+, respectively. This observation showed a potential further effect of vanadium complexes towards type 2 diabetes and has been demonstrated for the first time in this study. Full article
(This article belongs to the Special Issue Advances in Vanadium Complexes)
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<p>Chemical structures of the oxidovanadium(IV) complexes used in this study.</p> Full article ">Figure 2
<p>Species distribution diagram for the complexation of VO(IV) with MeIm2COOH (LH) and citric acid (Cit), <span class="html-italic">C<sub>VO</sub></span> = 0.002 mol·L<sup>−1</sup>, VO:L:Cit (1:2:2).</p> Full article ">Figure 3
<p>Species distribution diagram for the complexation of VO(IV) with Im4COOH and oxalic acid (Ox), C<sub>VO</sub> = 0.002 mol·L<sup>−1</sup>, VO:L:Ox (1:2:2).</p> Full article ">Figure 4
<p>Species distribution diagram for the complexation of VO(IV) with Im4COOH (LH) and human serum albumin (HSA), <span class="html-italic">C<sub>VO</sub></span> = 0.002 mol·L<sup>−1</sup>, VO:L:HSA (1:2:2).</p> Full article ">Figure 5
<p>Species distribution diagram for the complexation of VO(IV) with MeIm2COOH (LH) and human serum albumin (HSA), CVO = 0.002 mol·L<sup>−1</sup>, VO:L:HSA (1:2:2).</p> Full article ">Figure 6
<p>Species distribution diagram for the complexation of VO(IV) with MeIm2COOH (LH) and human serum transferrin (hTf), C<sub>VO</sub> = 0.002 mol·L<sup>−1</sup>, VO:L:hTf (1:2:2).</p> Full article ">Figure 7
<p>EPR spectra of VO(IV) with Im4COOH (LH) and low-molecular-weight bioligands of human plasma, pH = 7.4.</p> Full article ">Figure 8
<p>EPR spectra of VO(IV) with Im2COOH (LH) and high-molecular-weight ligands of human plasma, pH = 7.4.</p> Full article ">Figure 9
<p>Cell viability of Im2COOH, Im4COOH, MeIm2COOH and MeImCH<sub>2</sub>OH at 20, 10, 1, 0.1, 0.1 and 0.01 µM on INS-1E cells. Error bars indicate SEM (n = 3).</p> Full article ">Figure 10
<p>Cell viability of VOSO<sub>4</sub>, VO(Im4COO)<sub>2,</sub> VO(Im2COO)<sub>2</sub>, VO(MeIm2COO)<sub>2</sub> and VO(MeImCH<sub>2</sub>O)<sub>2</sub><sup>2+</sup> at 20, 10, 1, 0.1, 0.1 and 0.01 µM on INS-1E cells. Error bars indicate SEM (n = 3), * (<span class="html-italic">p</span> &lt; 0.05) relative to the control.</p> Full article ">Figure 11
<p>Chronic insulin release after 48 h exposure to the oxidovanadium(IV) complexes (1 µM) in RPMI media containing 11.1 mM and 33.3 mM glucose. * <span class="html-italic">p</span> &lt; 0.01 and # <span class="html-italic">p</span> &lt; 0.05, indicating significance relative to the 11.1 mM and 33.3 mM glucose control, respectively; error bars indicate SEM (n = 3).</p> Full article ">Figure 12
<p>Basal insulin after 48 h exposure to the oxidovanadium(IV) complexes (1 µM) in RPMI media containing 11.1 mM and 33.3 mM glucose. * <span class="html-italic">p</span> &lt; 0.01 and # <span class="html-italic">p</span> &lt; 0.05, indicating significance relative to the 11.1 mM glucose control and 33.3 mM glucose control, respectively; error bars indicate SEM (n = 3).</p> Full article ">Figure 13
<p>Stimulated insulin secretion after 48 h exposure to the oxidovanadium(IV) complexes (1 µM) in RPMI media containing 11.1mM and 33.3 mM glucose. * <span class="html-italic">p</span> &lt; 0.01 and # <span class="html-italic">p</span> &lt; 0.05, indicating significance relative to the 11.1mM and 33.3mM glucose control, respectively; error bars indicate SEM (n = 3).</p> Full article ">Figure 14
<p>The insulin content of the islets after 48 h exposure to the oxidovanadium(IV) complexes (1 µM) in RPMI media containing 11.1 mM and 33.3 mM glucose (* <span class="html-italic">p</span> &lt; 0.01 and # <span class="html-italic">p</span> &lt; 0.05), indicating significance relative to the 11.1 mM glucose control and 33.3 mM glucose control, respectively; error bars indicate SEM (n = 3).</p> Full article ">Figure 15
<p>The stimulatory index of the islets after 48 h exposure to the oxidovanadium(IV) complexes (1 µM) in RPMI media containing 11.1 mM and 33.3 mM glucose (* <span class="html-italic">p</span> &lt; 0.01 and # <span class="html-italic">p</span> &lt; 0.05), indicating significance relative to the 11.1 mM glucose control and 33.3 mM glucose control, respectively; error bars indicate SEM (n = 3).</p> Full article ">
17 pages, 19240 KiB  
Article
Influence of the Tensile Strain on Electron Transport of Ultra-Thin SiC Nanowires
by Qin Tan, Jie Li, Kun Liu, Rukai Liu and Vladimir Skuratov
Molecules 2024, 29(3), 723; https://doi.org/10.3390/molecules29030723 - 4 Feb 2024
Cited by 1 | Viewed by 1286
Abstract
The influence of nanomechanical tensile behavior on electron transport is especially interesting for ultra-thin SiC nanowires (NWs) with different diameters. Our studies theoretically show that these NWs can hold stable electron transmission in some strain ranges and that stretching can enhance the electron [...] Read more.
The influence of nanomechanical tensile behavior on electron transport is especially interesting for ultra-thin SiC nanowires (NWs) with different diameters. Our studies theoretically show that these NWs can hold stable electron transmission in some strain ranges and that stretching can enhance the electron transmission around the Fermi level (EF) at the strains over 0.5 without fracture for a single-atom SiC chain and at the strains not over 0.5 for thicker SiC NWs. For each size of SiC NW, the tensile strain has a tiny effect on the number of device density of states (DDOSs) peaks but can increase the values. Freshly broken SiC NWs also show certain values of DDOSs around EF. The maximum DDOS increases significantly with the diameter, but interestingly, the DDOS at EF shows little difference among the three sizes of devices in the late stage of the stretching. Essentially, high electron transmission is influenced by high DDOSs and delocalized electronic states. Analysis of electron localization functions (ELFs) indicates that appropriate tensile stress can promote continuous electronic distributions to contribute electron transport, while excessively large stretching deformation of SiC NWs would split electronic distributions and consequently hinder the movement of electrons. These results provide strong theoretical support for the use of ultra-thin SiC NWs in nano-sensors for functional and controllable electronic devices. Full article
(This article belongs to the Special Issue Recent Advancements in Density Functional Theory (DFT) and beyond for Computational Chemistry)
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<p>Schematic diagram of SiC NW initial devices with three cross-sectional areas. The inset shows the detailed connection between the electrode and SiC NW of Device 2 × 2.</p> Full article ">Figure 2
<p>(<b>a</b>–<b>g</b>) Equilibrium electron transmission spectrum of Device 1 × 1 around the Fermi level at representative strains, respectively. (<b>h</b>) Equilibrium electron transmission coefficient of Device 1 × 1 at the Fermi level under typical strains.</p> Full article ">Figure 3
<p>(<b>a</b>–<b>g</b>) Equilibrium electron transmission spectrum of Device 2 × 2 around the Fermi level at representative strains, respectively; the inset shows the transmission spectrum in a narrower possibility range. (<b>h</b>) Equilibrium electron transmission coefficient of Device 2 × 2 at the Fermi level under typical strains.</p> Full article ">Figure 4
<p>(<b>a–n</b>) Equilibrium electron transmission spectrum of Device 3 × 3 around the Fermi level at representative strains, respectively. (<b>o</b>) Equilibrium electron transmission coefficient of Device 3 × 3 at the Fermi level under typical strains. (p) Comparison of equilibrium electron transmission coefficient at the Fermi level under typical strains among Device 1 × 1, Device 2 × 2 and Device 3 × 3.</p> Full article ">Figure 5
<p>(<b>a</b>–<b>g</b>) Equilibrium device density of states of Device 1 × 1 around the Fermi level at representative strains, respectively. (<b>h</b>) Equilibrium device density of states of Device 1 × 1 at the Fermi level under typical strains. (<b>i–j</b>) Equilibrium electronic states of Device 1 × 1 at strain 0.0896 and 0.2112, respectively.</p> Full article ">Figure 6
<p>(<b>a</b>–<b>g</b>) Equilibrium device density of states of Device 2 × 2 around the Fermi level at representative strains, respectively. (<b>h</b>) Equilibrium device density of states of Device 2 × 2 at the Fermi level under typical strains. (<b>i–j</b>) Equilibrium electronic states of Device 2 × 2 at strain 0.1584 and 0.8112, respectively.</p> Full article ">Figure 7
<p>(<b>a–n</b>) Equilibrium device density of states of Device 3 × 3 around the Fermi level at representative strains, respectively. (<b>o</b>) Comparison of equilibrium device density of states at the Fermi level under typical strains among Device 1 × 1, Device 2 × 2 and Device 3 × 3, respectively. (<b>p–q</b>) Equilibrium electronic states of Device 3 × 3 at strain 0.4752 and 1.0136, respectively.</p> Full article ">Figure 8
<p>(<b>a1</b>–<b>c14</b>) ELF maps of the devices with Wire 1 × 1, Wire 2 × 2, and Wire 3 × 3 at representative strains, respectively.</p> Full article ">
26 pages, 2900 KiB  
Review
Early Diagnosis of Neurodegenerative Diseases: What Has Been Undertaken to Promote the Transition from PET to Fluorescence Tracers
by Nicolò Bisi, Luca Pinzi, Giulio Rastelli and Nicolò Tonali
Molecules 2024, 29(3), 722; https://doi.org/10.3390/molecules29030722 - 4 Feb 2024
Cited by 3 | Viewed by 2770
Abstract
Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble β-sheet-rich fibrils, which ultimately lead to neurotoxicity [...] Read more.
Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) represent two among the most frequent neurodegenerative diseases worldwide. A common hallmark of these pathologies is the misfolding and consequent aggregation of amyloid proteins into soluble oligomers and insoluble β-sheet-rich fibrils, which ultimately lead to neurotoxicity and cell death. After a hundred years of research on the subject, this is the only reliable histopathological feature in our hands. Since AD and PD are diagnosed only once neuronal death and the first symptoms have appeared, the early detection of these diseases is currently impossible. At present, there is no effective drug available, and patients are left with symptomatic and inconclusive therapies. Several reasons could be associated with the lack of effective therapeutic treatments. One of the most important factors is the lack of selective probes capable of detecting, as early as possible, the most toxic amyloid species involved in the onset of these pathologies. In this regard, chemical probes able to detect and distinguish among different amyloid aggregates are urgently needed. In this article, we will review and put into perspective results from ex vivo and in vivo studies performed on compounds specifically interacting with such early species. Following a general overview on the three different amyloid proteins leading to insoluble β-sheet-rich amyloid deposits (amyloid β1–42 peptide, Tau, and α-synuclein), a list of the advantages and disadvantages of the approaches employed to date is discussed, with particular attention paid to the translation of fluorescence imaging into clinical applications. Furthermore, we also discuss how the progress achieved in detecting the amyloids of one neurodegenerative disease could be leveraged for research into another amyloidosis. As evidenced by a critical analysis of the state of the art, substantial work still needs to be conducted. Indeed, the early diagnosis of neurodegenerative diseases is a priority, and we believe that this review could be a useful tool for better investigating this field. Full article
(This article belongs to the Section Medicinal Chemistry)
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<p>Schematic representation of two different diagnostic approaches in neurodegeneration through PET (Positron Emission Tomography) and Near-Infrared (NIR) fluorescent imaging (NIRF), discussed in this review.</p> Full article ">Figure 2
<p>Representation of the different molecular scaffolds employed for the design of NIR probes detecting Aβ aggregates: (<b>A</b>) (Styril scaffold), (<b>B</b>) (Oxazine scaffold), (<b>C</b>) (Biothiophene scaffold), (<b>D</b>) (Curcumin scaffold), (<b>E</b>) (Chalcone scaffold), (<b>F</b>) (Naphtoquinone scaffold), (<b>G</b>) (Bodipy scaffold), (<b>H</b>) (DANIR scaffold).</p> Full article ">Figure 3
<p>Chemical structure of PET, MRI, and fluorophore probes detecting Tau, discussed in the review.</p> Full article ">Figure 4
<p>Probes for the detection of αSyn aggregation discussed in the review.</p> Full article ">
19 pages, 792 KiB  
Review
The Role of the PTEN Tumor Suppressor Gene and Its Anti-Angiogenic Activity in Melanoma and Other Cancers
by Jacqueline Maphutha, Danielle Twilley and Namrita Lall
Molecules 2024, 29(3), 721; https://doi.org/10.3390/molecules29030721 - 4 Feb 2024
Cited by 4 | Viewed by 2608
Abstract
Human malignant melanoma and other solid cancers are largely driven by the inactivation of tumor suppressor genes and angiogenesis. Conventional treatments for cancer (surgery, radiation therapy, and chemotherapy) are employed as first-line treatments for solid cancers but are often ineffective as monotherapies due [...] Read more.
Human malignant melanoma and other solid cancers are largely driven by the inactivation of tumor suppressor genes and angiogenesis. Conventional treatments for cancer (surgery, radiation therapy, and chemotherapy) are employed as first-line treatments for solid cancers but are often ineffective as monotherapies due to resistance and toxicity. Thus, targeted therapies, such as bevacizumab, which targets vascular endothelial growth factor, have been approved by the US Food and Drug Administration (FDA) as angiogenesis inhibitors. The downregulation of the tumor suppressor, phosphatase tensin homolog (PTEN), occurs in 30–40% of human malignant melanomas, thereby elucidating the importance of the upregulation of PTEN activity. Phosphatase tensin homolog (PTEN) is modulated at the transcriptional, translational, and post-translational levels and regulates key signaling pathways such as the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) pathways, which also drive angiogenesis. This review discusses the inhibition of angiogenesis through the upregulation of PTEN and the inhibition of hypoxia-inducible factor 1 alpha (HIF-1-α) in human malignant melanoma, as no targeted therapies have been approved by the FDA for the inhibition of angiogenesis in human malignant melanoma. The emergence of nanocarrier formulations to enhance the pharmacokinetic profile of phytochemicals that upregulate PTEN activity and improve the upregulation of PTEN has also been discussed. Full article
(This article belongs to the Special Issue Molecular Targets and Mechanisms of Action of Anti-cancer Agents)
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<p>Depiction of the phosphatase tensin homolog (PTEN) gene, comprised of the N-terminal domain, PIP<sub>2</sub> binding motif, phosphatase domain, C2 domain, PDZ binding motif, and C-terminal domain.</p> Full article ">Figure 2
<p>Depiction of the pro-angiogenic factors that lead to the transition from normal vasculature to abnormal vasculature. Anti-angiogenic factors and anti-angiogenic drugs (Bevacizumab) revert abnormal vasculature to normal vasculature.</p> Full article ">
11 pages, 1915 KiB  
Article
Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein
by Thao Thi Phuong Tran, Ni Ngoc Thi Huynh, Ninh Thi Pham, Dung Thi Nguyen, Chien Van Tran, Uyen Quynh Nguyen, Anh Ngoc Ho, Joo-Won Suh, Jinhua Cheng, Thao Kim Nu Nguyen, Sung Van Tran and Duc Minh Nguyen
Molecules 2024, 29(3), 720; https://doi.org/10.3390/molecules29030720 - 4 Feb 2024
Viewed by 1623
Abstract
Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, [...] Read more.
Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1–3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein. Full article
(This article belongs to the Section Bioorganic Chemistry)
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<p>Colony morphology of <span class="html-italic">Streptomyces aureus</span> VTCC43181.</p> Full article ">Figure 2
<p>The structures, HMBC, and COSY correlations of the isolated compounds (<b>1–3</b>) from <span class="html-italic">Streptomyces aureus</span>.</p> Full article ">Figure 3
<p>Purification of recombinant <span class="html-italic">Mycobacterium tuberculosis</span> ClpC1: electrophoretic analysis of affinity chromatography using Ni-TED resin. M: maker; 1: non-induced pET28a(+)/ClpC1; 2: induced pET28a(+)/ClpC1; 3, 4: washing fractions; and 5, 6, 7: elution fractions.</p> Full article ">Figure 4
<p>(<b>a</b>) Evaluation of ATPase activity. (<b>b</b>) Evaluation of ATPase stability.</p> Full article ">Figure 5
<p>Affection of compounds <b>1</b>, <b>2</b>, <b>3</b>, rufomycin, and ecumicin to ATPase activity.</p> Full article ">
12 pages, 5995 KiB  
Communication
Keto-Adamantane-Based Macrocycle Crystalline Supramolecular Assemblies Showing Selective Vapochromism to Tetrahydrofuran
by Zunhua Li, Yingzi Tan, Manhua Ding, Linli Tang and Fei Zeng
Molecules 2024, 29(3), 719; https://doi.org/10.3390/molecules29030719 - 4 Feb 2024
Cited by 3 | Viewed by 1348
Abstract
Here, we report the synthesis of adamantane-based macrocycle 2 by combining adamantane building blocks with π-donor 1,3-dimethoxy-benzene units. An unpredictable keto-adamantane-based macrocycle 3 was obtained by the oxidation of 2 using DDQ as an oxidant. Moreover, a new type of macrocyclic molecule-based CT [...] Read more.
Here, we report the synthesis of adamantane-based macrocycle 2 by combining adamantane building blocks with π-donor 1,3-dimethoxy-benzene units. An unpredictable keto-adamantane-based macrocycle 3 was obtained by the oxidation of 2 using DDQ as an oxidant. Moreover, a new type of macrocyclic molecule-based CT cocrystal was prepared through exo-wall CT interactions between 3 and DDQ. The cocrystal material showed selective vapochromism behavior towards THF, specifically, among nine volatile organic solvents commonly used in the laboratory. Powder X-ray diffraction; UV-Vis diffuse reflectance spectroscopy; 1H NMR; and single crystal X-ray diffraction analyses revealed that color changes are attributed to the vapor-triggered decomplexation of cocrystals. Full article
(This article belongs to the Special Issue Macrocyclic Compounds: Derivatives and Applications)
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<p>Chemical structures of <b>3</b> and DDQ.</p> Full article ">Figure 2
<p>Partial <sup>1</sup>H NMR spectra (400 MHz, CDCl<sub>3</sub>, 298 K) of (<b>a</b>) <b>3</b> and 1.0 equiv. of DDQ, and (<b>b</b>) free <b>3</b>. [3]<sub>0</sub> = 4.0 mM. Inset: photograph showing colors of <b>3</b>, <b>3</b> + DDQ and DDQ in CHCl<sub>3</sub>.</p> Full article ">Figure 3
<p>Single crystal structures of <b>2</b> (<b>a</b>,<b>b</b>); single crystal structures of <b>3</b> (<b>c</b>,<b>d</b>).</p> Full article ">Figure 4
<p>Single crystal structures of <b>3</b>@DDQ (<b>a</b>,<b>b</b>); stacking mode of <b>3</b>@DDQ (<b>c</b>).</p> Full article ">Figure 5
<p>Photographs of <b>3</b>, <b>3</b>@DDQ and DDQ (<b>a</b>); PXRD patterns of <b>3</b>, <b>3</b>@DDQ and DDQ (<b>b</b>). I: <b>3</b>, II: DDQ, III: <b>3</b>@DDQ, IV: simulated from <b>3</b>@DDQ; (<b>c</b>) diffuse reflectance spectra of <b>3</b>, <b>3</b>@DDQ and DDQ.</p> Full article ">Figure 6
<p>Photographs of <b>3</b>@DDQ after exposure to various vapors (<b>a</b>,<b>b</b>); (<b>c</b>) PXRD patterns of <b>3</b>@DDQ before (I) and after (II) exposure to CH<sub>2</sub>Cl<sub>2</sub>, (III) CHCl<sub>3</sub>, (IV) THF, (V) 1,4-dioxane, (VI) EtOAc, (VII) benzene, (VIII) <span class="html-italic">n</span>-hexane, (IX) EtOH and (X) ClCH<sub>2</sub>CH<sub>2</sub>Cl; (<b>d</b>) diffuse reflectance spectra of <b>3</b>@DDQ before and after exposure to various vapors.</p> Full article ">Scheme 1
<p>The synthesis route of macrocyclic molecules <b>2</b> and <b>3</b>.</p> Full article ">
31 pages, 3425 KiB  
Review
Traditional Uses, Chemical Constituents and Pharmacological Activities of the Toona sinensis Plant
by Mengyao Zhao, Huiting Li, Rongshen Wang, Shuying Lan, Yuxin Wang, Yuhua Zhang, Haishan Sui and Wanzhong Li
Molecules 2024, 29(3), 718; https://doi.org/10.3390/molecules29030718 - 4 Feb 2024
Cited by 1 | Viewed by 2363
Abstract
Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use [...] Read more.
Toona sinensis (A. Juss.) Roem., which is widely distributed in China, is a homologous plant resource of medicine and food. The leaves, seeds, barks, buds and pericarps of T. sinensis can be used as medicine with traditional efficacy. Due to its extensive use in traditional medicine in the ancient world, the T. sinensis plant has significant development potential. In this review, 206 compounds, including triterpenoids (1–133), sesquiterpenoids (134–135), diterpenoids (136–142), sterols (143–147), phenols (148–167), flavonoids (168–186), phenylpropanoids (187–192) and others (193–206), are isolated from the T. sinensis plant. The mass spectrum cracking laws of representative compounds (64, 128, 129, 154–156, 175, 177, 179 and 183) are reviewed, which are conducive to the discovery of novel active substances. Modern pharmacological studies have shown that T. sinensis extracts and their compounds have antidiabetic, antidiabetic nephropathy, antioxidant, anti-inflammatory, antitumor, hepatoprotective, antiviral, antibacterial, immunopotentiation and other biological activities. The traditional uses, chemical constituents, compound cracking laws and pharmacological activities of different parts of T. sinensis are reviewed, laying the foundation for improving the development and utilization of its medicinal value. Full article
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Figure 1
<p>Different parts of the <span class="html-italic">T. sinensis</span> plant and its chemical constituents and pharmacological activities.</p> Full article ">Figure 2
<p>Main skeleton structures of tetracyclic triterpenoids from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 3
<p>Structure of dammarane and tirucallane triterpenoids from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 4
<p>Structure of <span class="html-italic">apo</span>-tirucallane triterpenoids from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 5
<p>Structure of limonoid triterpenoids from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 6
<p>Structure of cycloartane triterpenoids, other triterpenoids, sesquiterpenoids, diterpenoids and sterols from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 7
<p>Structure of phenols, flavonoids, phenylpropanoids and other compounds from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 8
<p>The proposed fragmentation pathway of gedunin (<b>64</b>) [<a href="#B48-molecules-29-00718" class="html-bibr">48</a>].</p> Full article ">Figure 9
<p>Antidiabetic and antidiabetic nephropathy activities of extracts or compounds from <span class="html-italic">T. sinensis</span>.</p> Full article ">Figure 10
<p>Antioxidant and anti-inflammatory activities of extracts or compounds from <span class="html-italic">T. sinensis</span> via Nrf-2/NF-κB pathway.</p> Full article ">
13 pages, 3231 KiB  
Article
TLC-Bioautography-Guided Isolation and Assessment of Antibacterial Compounds from Manuka (Leptospermum scoparium) Leaf and Branch Extracts
by Wenliang Xu, Danxia Shi, Kuanmin Chen and David G. Popovich
Molecules 2024, 29(3), 717; https://doi.org/10.3390/molecules29030717 - 4 Feb 2024
Cited by 2 | Viewed by 2079
Abstract
A rapid procedure for the targeted isolation of antibacterial compounds from Manuka (Leptospermum scoparium) leaf and branch extracts was described in this paper. Antibacterial compounds from three different Manuka samples collected from New Zealand and China were compared. The active compounds [...] Read more.
A rapid procedure for the targeted isolation of antibacterial compounds from Manuka (Leptospermum scoparium) leaf and branch extracts was described in this paper. Antibacterial compounds from three different Manuka samples collected from New Zealand and China were compared. The active compounds were targeted by TLC-bioautography against S. aureus and were identified by HR-ESI-MS, and -MS/MS analysis in conjunction with Compound Discoverer 3.3. The major antibacterial component, grandiflorone, was identified, along with 20 β-triketones, flavonoids, and phloroglucinol derivatives. To verify the software identification, grandiflorone underwent purification via column chromatography, and its structure was elucidated through NMR analysis, ultimately confirming its identity as grandiflorone. This study successfully demonstrated that the leaves and branches remaining after Manuka essential oil distillation serve as excellent source for extracting grandiflorone. Additionally, we proposed an improved TLC-bioautography protocol for evaluating the antibacterial efficacy on solid surfaces, which is suitable for both S. aureus and E. coli. The minimum effective dose (MED) of grandiflorone was observed to be 0.29–0.59 μg/cm2 against S. aureus and 2.34–4.68 μg/cm2 against E. coli, respectively. Furthermore, the synthetic plant growth retardant, paclobutrazol, was isolated from the samples obtained in China. It is hypothesized that this compound may disrupt the synthesis pathway of triketones, consequently diminishing the antibacterial efficacy of Chinese Manuka extract in comparison to that of New Zealand. Full article
(This article belongs to the Special Issue Selected Scholars' Exclusive Papers on Natural Products Chemistry)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Bioautography assay of Manuka hexane extract (1 mg/mL, 3 μL spotting) against <span class="html-italic">S. aureus</span> at 37 °C, 16 h. Sample I: untreated CN Manuka; Sample II: untreated NZ Manuka; Sample III: steam-distilled NZ Manuka. Compounds <b>1</b>–<b>4</b> are β-triketones detected from the corresponding inhibition zones, including: a pair of isomers leptospermone (<b>1a</b>) and isoleptospermone (<b>1b</b>); flavesone (<b>2</b>); grandiflorone (<b>3</b>); myrigalone A (<b>4</b>).</p> Full article ">Figure 2
<p>Negative mode base peak chromatogram of untreated (<b>A</b>) and steam-distilled (<b>B</b>) NZ Manuka hexane extract. Compound (<b>1</b>): a pair of isomers, leptospermone (<b>a</b>) and isoleptospermone (<b>b</b>); Compounds <b>2</b>–<b>4</b>: flavesone (<b>2</b>); grandiflorone (<b>3</b>); myrigalone A (<b>4</b>).</p> Full article ">Figure 3
<p>Bioautography assay of steam-distilled NZ Manuka ((<b>A</b>), 0.5 mg/mL, 3 μL spotting) and untreated CN Manuka ((<b>B</b>), 1 mg/mL, 3 × 3 μL spotting) extract against <span class="html-italic">S. aureus</span> at 37 °C, 24 h. Sample I: hexane extract; Sample II: untreated NZ Manuka. Compounds <b>3</b>–<b>12</b> are chemicals detected from the corresponding inhibition zones including β-triketones (<b>3</b>) and (<b>4</b>); phloroglucinol derivative (<b>7</b>); synthetic plant growth retardant, paclobutrazol (<b>10</b>); flavonoids (<b>5</b>, <b>6</b>, <b>8</b>, <b>9</b>, <b>11</b> and <b>12</b>).</p> Full article ">Figure 4
<p>Positive mode base peak chromatogram of NZ (<b>A</b>) and CN (<b>B</b>) Manuka dichloromethane extract. Compounds <b>5</b>–<b>12</b>: chemicals detected from the corresponding inhibition zones shown in <a href="#molecules-29-00717-f003" class="html-fig">Figure 3</a>. Compounds <b>13</b>–<b>21</b>: flavonoids and phloroglucinol derivatives identified that have not been collected from bioautography assay, structures shown in <a href="#molecules-29-00717-f005" class="html-fig">Figure 5</a>.</p> Full article ">Figure 5
<p>Chemical structures of low-content or inactive flavonoids (<b>13</b>,<b>14</b>, <b>16</b>–<b>20</b>) and phloroglucinol derivatives (<b>15</b> and <b>21</b>) identified from NZ Manuka dichloromethane extract.</p> Full article ">Figure 6
<p><sup>13</sup>C NMR spectrum (1D, 125 MHz, CDCl<sub>3</sub>) of grandiflorone isolated from steam-distilled NZ Manuka leaves and branches.</p> Full article ">Figure 7
<p>Direct bioautography-based minimum effective dose (MED) determination. Spots 1–8 on each plate were two-fold diluted samples with constant 3 μL spotting to control an approximately 0.16 cm<sup>2</sup> sample area. Visualized under 254 nm UV light (<b>A</b>), inhibition effect against <span class="html-italic">S. aureus</span> ((<b>B</b>), 37 °C, 16 h; (<b>D</b>), 37 °C, 40 h) and <span class="html-italic">E. coli</span> ((<b>C</b>), 37 °C, 16 h; (<b>E</b>), 37 °C, 40 h). Sample I: grandiflorone, initial concentration 1 mg/mL; Sample II: tetracycline, initial concentration 0.1 mg/mL.</p> Full article ">
15 pages, 8436 KiB  
Article
Study on the Physical and Rheological Characterisation of Low-Density Polyethylene (LDPE)/Recycled Crumb Rubber (RCR) on Asphalt Binders
by Shibo Zhang, Yong Yan, Yang Yang and Rongxin Guo
Molecules 2024, 29(3), 716; https://doi.org/10.3390/molecules29030716 - 4 Feb 2024
Cited by 1 | Viewed by 1603
Abstract
Recycled crumb rubber (RCR) is considered a reliable asphalt modifier and a solution to the problem of scrap tyre recycling. RCR-modified asphalt (RCRMA) typically has good low-temperature performance and storage stability. However, the pre-treatment of crumb rubber (CR) impairs its physical properties, resulting [...] Read more.
Recycled crumb rubber (RCR) is considered a reliable asphalt modifier and a solution to the problem of scrap tyre recycling. RCR-modified asphalt (RCRMA) typically has good low-temperature performance and storage stability. However, the pre-treatment of crumb rubber (CR) impairs its physical properties, resulting in poor high-temperature performance, which limits the industrial application of RCRMA. In this study, low-density polyethylene (LDPE) composite RCR was used to modify asphalt, and LDPE/RCR-composite-modified asphalt (L-RCRMA) was produced to compensate for the deficiencies in the high-temperature performance of RCRMA. The comprehensive physical properties of L-RCRMA were elucidated using tests such as the conventional properties, rotational viscosity, and rheological tests. The results showed that the incorporation of LDPE improved the high-temperature stability and rutting resistance of the asphalt, but an excessive amount of LDPE impaired the low-temperature performance and storage stability of L-RCRMA. Therefore, it is necessary to control the amount of LDPE to balance the performance of the asphalt. On this basis, we recommend a dosage of 20% for RCR and 1.5% for LDPE. Full article
(This article belongs to the Section Materials Chemistry)
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Graphical abstract

Graphical abstract
Full article ">Figure 1
<p>Conventional physical properties of modified asphalt: (<b>a</b>) penetration, (<b>b</b>) softening point, and (<b>c</b>) 5 °C ductility.</p> Full article ">Figure 2
<p>Viscosity–temperature curve.</p> Full article ">Figure 3
<p>(<b>a</b>) Rutting factor. (<b>b</b>) Fatigue factor.</p> Full article ">Figure 4
<p>Complex modulus master curve.</p> Full article ">Figure 5
<p>Han curve.</p> Full article ">Figure 5 Cont.
<p>Han curve.</p> Full article ">Figure 6
<p>Time–strain curves: (<b>a</b>) 0.1 kPa and (<b>b</b>) 3.2 kPa.</p> Full article ">Figure 7
<p>MSCR-based assessment of modified asphalt: (<b>a</b>) R and (<b>b</b>) <span class="html-italic">J<sub>nr</sub></span>.</p> Full article ">Figure 8
<p>Creep recovery rate difference (R<sub>diff</sub>/%) and unrecoverable creep flexibility difference (J<sub>nr-diff</sub>/%).</p> Full article ">Figure 9
<p>BBR-based assessment of (<b>a</b>) bending beam creep modulus of strength (S) and (<b>b</b>) bending beam creep rate (m).</p> Full article ">Figure 9 Cont.
<p>BBR-based assessment of (<b>a</b>) bending beam creep modulus of strength (S) and (<b>b</b>) bending beam creep rate (m).</p> Full article ">Figure 10
<p>SEM images: (<b>a</b>) CR and (<b>b</b>) RCR.</p> Full article ">Figure 11
<p>Preparation flow chart.</p> Full article ">
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