Molecules

13 pages, 6942 KiB

Open AccessArticle

Exploring the Scope of Tandem Palladium and Isothiourea Relay Catalysis for the Synthesis of α-Amino Acid Derivatives

by Jacqueline Bitai, Alexandra M. Z. Slawin, David B. Cordes and Andrew D. Smith

Molecules 2020, 25(10), 2463; https://doi.org/10.3390/molecules25102463 - 25 May 2020

Cited by 6 | Viewed by 4143

The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ [...] Read more.

The scope and limitations of a tandem N-allylation/[2,3]-rearrangement protocol are investigated through the incorporation of a variety of functional groups within an allylic phosphate precursor. This method uses readily accessible N,N-dimethylglycine aryl esters and functionalized allylic phosphates, forming quaternary ammonium salts in situ in the presence of a palladium catalyst. Subsequent enantioselective [2,3]-sigmatropic rearrangement, promoted by the chiral isothiourea tetramisole, generates α-amino acid derivatives with two contiguous stereocenters. The incorporation of electron-withdrawing ester and amide groups gave the best results, furnishing the desired products in moderate to good yields (29–70%), with low diastereocontrol (typically 60:40 dr) but high enantioselectivity (up to 90:10 er). These results indicate that substrate–catalyst interactions in the proposed transition state are sensitive to the substitution pattern of the substrates. Full article

(This article belongs to the Special Issue New Synthetic Methods for Organic Compounds)

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40 pages, 6992 KiB

Open AccessReview

The World of Cyclic Dinucleotides in Bacterial Behavior

by Aline Dias da Purificação, Nathalia Marins de Azevedo, Gabriel Guarany de Araujo, Robson Francisco de Souza and Cristiane Rodrigues Guzzo

Molecules 2020, 25(10), 2462; https://doi.org/10.3390/molecules25102462 - 25 May 2020

Cited by 21 | Viewed by 6003

Abstract

The regulation of multiple bacterial phenotypes was found to depend on different cyclic dinucleotides (CDNs) that constitute intracellular signaling second messenger systems. Most notably, c-di-GMP, along with proteins related to its synthesis, sensing, and degradation, was identified as playing a central role in [...] Read more.

The regulation of multiple bacterial phenotypes was found to depend on different cyclic dinucleotides (CDNs) that constitute intracellular signaling second messenger systems. Most notably, c-di-GMP, along with proteins related to its synthesis, sensing, and degradation, was identified as playing a central role in the switching from biofilm to planktonic modes of growth. Recently, this research topic has been under expansion, with the discoveries of new CDNs, novel classes of CDN receptors, and the numerous functions regulated by these molecules. In this review, we comprehensively describe the three main bacterial enzymes involved in the synthesis of c-di-GMP, c-di-AMP, and cGAMP focusing on description of their three-dimensional structures and their structural similarities with other protein families, as well as the essential residues for catalysis. The diversity of CDN receptors is described in detail along with the residues important for the interaction with the ligand. Interestingly, genomic data strongly suggest that there is a tendency for bacterial cells to use both c-di-AMP and c-di-GMP signaling networks simultaneously, raising the question of whether there is crosstalk between different signaling systems. In summary, the large amount of sequence and structural data available allows a broad view of the complexity and the importance of these CDNs in the regulation of different bacterial behaviors. Nevertheless, how cells coordinate the different CDN signaling networks to ensure adaptation to changing environmental conditions is still open for much further exploration. Full article

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

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18 pages, 3167 KiB

Open AccessArticle

β²-Homo-Amino Acid Scan of µ-Selective Opioid Tetrapeptide TAPP

by Dagmara Tymecka, Piotr F. J. Lipiński, Piotr Kosson and Aleksandra Misicka

Molecules 2020, 25(10), 2461; https://doi.org/10.3390/molecules25102461 - 25 May 2020

Cited by 6 | Viewed by 3960

Abstract

TAPP (H-Tyr-d-Ala-Phe-Phe-NH₂) is a potent, µ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β²-Homo-amino acid (β²hAA) scan of the TAPP sequence. To [...] Read more.

TAPP (H-Tyr-d-Ala-Phe-Phe-NH₂) is a potent, µ-selective opioid ligand. In order to gain further insights into pharmacophoric features of this tetrapeptide, we have performed a β²-Homo-amino acid (β²hAA) scan of the TAPP sequence. To this aim, 10 novel analogues have been synthesized and evaluated for µ-opioid and δ-opioid receptor affinity as well as for stability in human plasma. The derivatives included compounds in which a (R)- or (S)-β²-Homo-Homologue replaced the amino acids in the TAPP sequence. The derivatives with (R)- or (S)-β²hPhe⁴ turned out to bind µOR with affinities equal to that of the parent. β²hAAs in position 1 and 3 resulted in rather large affinity decreases, but the change differed depending on the stereochemistry. β²-Homologation in the second position gave derivatives with very poor µOR binding. According to molecular modelling, the presented α/β-peptides adopt a variety of binding poses with their common element being an ionic interaction between a protonable amine of the first residue and Asp147. A feature required for high µOR affinity seems the ability to accommodate the ring in the fourth residue in a manner similar to that found for TAPP. Contrary to what might be expected, several compounds were significantly less stable in human plasma than the parent compound. Full article

(This article belongs to the Special Issue Opioids and Their Receptors: Present and Emerging Concepts in Opioid Drug Discovery)

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15 pages, 1012 KiB

Open AccessReview

Innovations in Extractive Phases for In-Tube Solid-Phase Microextraction Coupled to Miniaturized Liquid Chromatography: A Critical Review

by Henry Daniel Ponce-Rodríguez, Jorge Verdú-Andrés, Rosa Herráez-Hernández and Pilar Campíns-Falcó

Molecules 2020, 25(10), 2460; https://doi.org/10.3390/molecules25102460 - 25 May 2020

Cited by 26 | Viewed by 3364

Abstract

Over the past years, a great effort has been devoted to the development of new sorbents that can be used to pack or to coat extractive capillaries for in-tube solid-phase microextraction (IT-SPME). Many of those efforts have been focused on the preparation of [...] Read more.

Over the past years, a great effort has been devoted to the development of new sorbents that can be used to pack or to coat extractive capillaries for in-tube solid-phase microextraction (IT-SPME). Many of those efforts have been focused on the preparation of capillaries for miniaturized liquid chromatography (LC) due to the reduced availability of capillary columns with appropriate dimensions for this kind of system. Moreover, many of the extractive capillaries that have been used for IT-SPME so far are segments of open columns from the gas chromatography (GC) field, but the phase nature and dimensions are very limited. In particular, polar compounds barely interact with stationary GC phases. Capillary GC columns may also be unsuitable when highly selective extractions are needed. In this work, we provide an overview of the extractive capillaries that have been specifically developed for capillary LC (capLC) and nano LC (nanoLC) to enhance the overall performance of the IT-SPME, the chromatographic separation, and the detection. Different monolithic polymers, such as silica C₁₈ and C₈ polymers, molecularly imprinted polymers (MIPs), polymers functionalized with antibodies, and polymers reinforced with different types of carbon nanotubes, metal, and metal oxide nanoparticles (including magnetic nanoparticles), and restricted access materials (RAMs) will be presented and critically discussed. Full article

(This article belongs to the Special Issue Feature Review Articles in Analytical Chemistry-Part I)

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23 pages, 3909 KiB

Open AccessArticle

Dual miRNases for Triple Incision of miRNA Target: Design Concept and Catalytic Performance

by Olga Patutina, Daria Chiglintseva, Elena Bichenkova, Svetlana Gaponova, Nadezhda Mironova, Valentin Vlassov and Marina Zenkova

Molecules 2020, 25(10), 2459; https://doi.org/10.3390/molecules25102459 - 25 May 2020

Cited by 10 | Viewed by 3097

Abstract

Irreversible destruction of disease-associated regulatory RNA sequences offers exciting opportunities for safe and powerful therapeutic interventions against human pathophysiology. In 2017, for the first time we introduced miRNAses–miRNA-targeted conjugates of a catalytic peptide and oligonucleotide capable of cleaving an miRNA target. Herein, we [...] Read more.

Irreversible destruction of disease-associated regulatory RNA sequences offers exciting opportunities for safe and powerful therapeutic interventions against human pathophysiology. In 2017, for the first time we introduced miRNAses–miRNA-targeted conjugates of a catalytic peptide and oligonucleotide capable of cleaving an miRNA target. Herein, we report the development of Dual miRNases against oncogenic miR-21, miR-155, miR-17 and miR-18a, each containing the catalytic peptide placed in-between two short miRNA-targeted oligodeoxyribonucleotide recognition motifs. Substitution of adenines with 2-aminoadenines in the sequence of oligonucleotide “shoulders” of the Dual miRNase significantly enhanced the efficiency of hybridization with the miRNA target. It was shown that sequence-specific cleavage of the target by miRNase proceeded metal-independently at pH optimum 5.5–7.5 with an efficiency varying from 15% to 85%, depending on the miRNA sequence. A distinct advantage of the engineered nucleases is their ability to additionally recruit RNase H and cut miRNA at three different locations. Such cleavage proceeds at the central part by Dual miRNase, and at the 5′- and 3′-regions by RNase H, which significantly increases the efficiency of miRNA degradation. Due to increased activity at lowered pH Dual miRNases could provide an additional advantage in acidic tumor conditions and may be considered as efficient tumor-selective RNA-targeted therapeutic. Full article

(This article belongs to the Special Issue Bioconjugation Strategies in Drug Delivery and Molecular Imaging)

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12 pages, 2244 KiB

Open AccessArticle

A Direct Silanization Protocol for Dialdehyde Cellulose

by Arianna Lucia, Markus Bacher, Hendrikus W. G. van Herwijnen and Thomas Rosenau

Molecules 2020, 25(10), 2458; https://doi.org/10.3390/molecules25102458 - 25 May 2020

Cited by 28 | Viewed by 5402

Abstract

Cellulose derivatives have many potential applications in the field of biomaterials and composites, in addition to several ways of modification leading to them. Silanization in aqueous media is one of the most promising routes to create multipurpose and organic–inorganic hybrid materials. Silanization has [...] Read more.

Cellulose derivatives have many potential applications in the field of biomaterials and composites, in addition to several ways of modification leading to them. Silanization in aqueous media is one of the most promising routes to create multipurpose and organic–inorganic hybrid materials. Silanization has been widely used for cellulosic and nano-structured celluloses, but was a problem so far if to be applied to the common cellulose derivative “dialdehyde cellulose” (DAC), i.e., highly periodate-oxidized celluloses. In this work, a straightforward silanization protocol for dialdehyde cellulose is proposed, which can be readily modified with (3-aminopropyl)triethoxysilane. After thermal treatment and freeze-drying, the resulting product showed condensation and cross-linking, which was studied with infrared spectroscopy and ¹³C and ²⁹Si solid-state nuclear magnetic resonance (NMR) spectroscopy. The cross-linking involves both links of the hydroxyl group of the oxidized cellulose with the silanol groups (Si-O-C) and imine-type bonds between the amino group and keto functions of the DAC (-HC=N-). The modification was achieved in aqueous medium under mild reaction conditions. Different treatments cause different levels of hydrolysis of the organosilane compound, which resulted in diverse condensed silica networks in the modified dialdehyde cellulose structure. Full article

(This article belongs to the Special Issue Lignocellulosic Biomass)

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11 pages, 1032 KiB

Open AccessArticle

Streptavidin-Hosted Organocatalytic Aldol Addition

by Nicolò Santi, Louis C. Morrill and Louis Y. P. Luk

Molecules 2020, 25(10), 2457; https://doi.org/10.3390/molecules25102457 - 25 May 2020

Cited by 10 | Viewed by 4813

Abstract

In this report, the streptavidin-biotin technology was applied to enable organocatalytic aldol addition. By attaching pyrrolidine to the valeric motif of biotin and introducing it to streptavidin (Sav), a protein-based organocatalytic system was created, and the aldol addition of acetone with p-nitrobenzaldehyde [...] Read more.

In this report, the streptavidin-biotin technology was applied to enable organocatalytic aldol addition. By attaching pyrrolidine to the valeric motif of biotin and introducing it to streptavidin (Sav), a protein-based organocatalytic system was created, and the aldol addition of acetone with p-nitrobenzaldehyde was tested. The conversion of substrate to product can be as high as 93%. Although the observed enantioselectivity was only moderate (33:67 er), further protein engineering efforts can be included to improve the selectivity. These results have proven the concept that Sav can be used to host stereoselective aldol addition. Full article

(This article belongs to the Special Issue Hybrid Catalysts for Asymmetric Catalysis)

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17 pages, 3269 KiB

Open AccessArticle

Highly Sensitive and Selective Fluorescent Probes for Cu(II) Detection Based on Calix[4]arene-Oxacyclophane Architectures

by Alexandra I. Costa, Patrícia D. Barata, Carina B. Fialho and José V. Prata

Molecules 2020, 25(10), 2456; https://doi.org/10.3390/molecules25102456 - 25 May 2020

Cited by 12 | Viewed by 3179

Abstract

A new topological design of fluorescent probes for sensing copper ion is disclosed. The calix[4]arene-oxacyclophane (Calix-OCP) receptor, either wired-in-series in arylene-alt-ethynylene conjugated polymers or standing alone as a sole molecular probe, display a remarkable affinity and selectivity for Cu(II). The unique [...] Read more.

A new topological design of fluorescent probes for sensing copper ion is disclosed. The calix[4]arene-oxacyclophane (Calix-OCP) receptor, either wired-in-series in arylene-alt-ethynylene conjugated polymers or standing alone as a sole molecular probe, display a remarkable affinity and selectivity for Cu(II). The unique recognition properties of Calix-OCP system toward copper cation stem from its pre-organised cyclic array of O-ligands at the calixarene narrow rim, which is kept in a conformational rigid arrangement by a tethered oxacyclophane sub-unit. The magnitude of the binding constants (K_a = 5.30 − 8.52 × 10⁴ M⁻¹) and the free energy changes for the inclusion complexation (−ΔG = 27.0 − 28.1 kJmol⁻¹), retrieved from fluorimetric titration experiments, revealed a high sensitivity of Calix-OCP architectures for Cu(II) species. Formation of supramolecular inclusion complexes was evidenced from UV-Vis spectroscopy. The new Calix-OCP-conjugated polymers (polymers 4 and 5), synthesized in good yields by Sonogashira–Hagihara methodologies, exhibit high fluorescence quantum yields (Φ_F = 0.59 − 0.65). Density functional theory (DFT) calculations were used to support the experimental findings. The fluorescence on–off behaviour of the sensing systems is tentatively explained by a photoinduced electron transfer mechanism. Full article

(This article belongs to the Special Issue Calixarene Complexes: Synthesis, Properties and Applications)

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13 pages, 3544 KiB

Open AccessArticle

Evaluation of Organosolv Lignin as an Oxidation Inhibitor in Bitumen

by Yi Zhang, Xueyan Liu, Panos Apostolidis, Ruxin Jing, Sandra Erkens, Natascha Poeran and Athanasios Skarpas

Molecules 2020, 25(10), 2455; https://doi.org/10.3390/molecules25102455 - 25 May 2020

Cited by 14 | Viewed by 3111

Abstract

Organosolv lignin, a natural polymer, has been used in this study as an oxidation inhibitor in bitumen. Particularly, the effect of oxidative aging on the chemical compositional changes and on the rheology of bituminous binders with organosolv lignin and the impact to inhibit [...] Read more.

Organosolv lignin, a natural polymer, has been used in this study as an oxidation inhibitor in bitumen. Particularly, the effect of oxidative aging on the chemical compositional changes and on the rheology of bituminous binders with organosolv lignin and the impact to inhibit oxidation in bitumen were evaluated. Firstly, after analyzing the microstructure and surface characteristics of utilized organosolv lignin, a high shear mixing procedure was followed to produce binders of different proportions of lignin in bitumen. Pressure aging vessel conditioning was applied to these binders to simulate in-field aging and a series of tests were performed. Fourier transform infrared spectroscopy was used to track the compositional changes of lignin–bitumen systems before and after aging respectively. The rheological changes due to oxidative aging in the different lignin–bitumen systems were studied by means of dynamic shear rheometer tests. Based on the spectroscopic laboratory analyses, certain proportions of organosolv lignin in bitumen have shown a potential oxidation retardation effect in bitumen since a reduction of carbonyl and sulfoxide compounds was observed. However, the addition of lignin reduced the fatigue life of bitumen and potentially led to an increase in brittle fracture sensitivity at low and medium temperatures. Nevertheless, lignin improved the rutting resistance at high temperatures. Overall, it can be concluded that organosolv lignin can suppress the oxidation of sulfur and carbon compounds in bitumen either by direct deceleration of oxidation reaction or interaction with compounds that otherwise are oxidizable, without seriously degrading the mechanical properties. Full article

(This article belongs to the Special Issue Chemistry in Pavement Materials)

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13 pages, 3738 KiB

Open AccessArticle

The Synergistic Anti-Cancer Effects of NVP-BEZ235 and Regorafenib in Hepatocellular Carcinoma

by Cheng-Chan Yu, Sung-Ying Huang, Shu-Fang Chang, Kuan-Fu Liao and Sheng-Chun Chiu

Molecules 2020, 25(10), 2454; https://doi.org/10.3390/molecules25102454 - 25 May 2020

Cited by 13 | Viewed by 4038

Abstract

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual [...] Read more.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual PI3K/mTOR inhibitor BEZ235 in the human HCC cell lines (n = 3). The combined treatment with BEZ235 and regorafenib enhanced the inhibition of cell proliferation and increased the expression of cleaved caspase-3 and cleaved PARP in HCC cells. Moreover, the combined treatment suppressed HCC cell migration and invasion in the transwell assay. Further, the Western blot analyses confirmed the involvement of epithelial-mesenchymal transition (EMT)-related genes such as slug, vimentin, and matrix metalloproteinase (MMP)-9/-2. Additionally, the proteinase activity of MMP-9/-2 was analyzed using gelatin zymography. Furthermore, the inhibition of phosphorylation of the Akt, mTOR, p70S6K, and 4EBP1 after combined treatment was validated using Western blot analysis. Therefore, these results suggest that the combined treatment with BEZ235 and regorafenib benefits patients with HCC. Full article

(This article belongs to the Special Issue Recent Advances in Anticancer Drugs II)

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11 pages, 3379 KiB

Open AccessArticle

Antiobesity Effects of Gentiana lutea Extract on 3T3-L1 Preadipocytes and a High-Fat Diet-Induced Mouse Model

by Eunkuk Park, Chang Gun Lee, Junho Kim, Subin Yeo, Ji Ae Kim, Chun Whan Choi and Seon-Yong Jeong

Molecules 2020, 25(10), 2453; https://doi.org/10.3390/molecules25102453 - 25 May 2020

Cited by 17 | Viewed by 7097

Abstract

Obesity is one of the most common metabolic diseases resulting in metabolic syndrome. In this study, we investigated the antiobesity effect of Gentiana lutea L. (GL) extract on 3T3-L1 preadipocytes and a high-fat-diet (HFD)-induced mouse model. For the induction of preadipocytes into adipocytes, [...] Read more.

Obesity is one of the most common metabolic diseases resulting in metabolic syndrome. In this study, we investigated the antiobesity effect of Gentiana lutea L. (GL) extract on 3T3-L1 preadipocytes and a high-fat-diet (HFD)-induced mouse model. For the induction of preadipocytes into adipocytes, 3T3-L1 cells were induced by treatment with 0.5 mM 3-isobutyl-1-methylxanthine, 1 mM dexamethasone, and 1 μg/mL insulin. Adipogenesis was assessed based on the messenger ribonucleic acid expression of adipogenic-inducing genes (adiponectin (Adipoq), CCAAT/enhancer-binding protein alpha (Cebpa), and glucose transporter type 4 (Slc2a4)) and lipid accumulation in the differentiated adipocytes was visualized by Oil Red O staining. In vivo, obese mice were induced with HFD and coadministered with 100 or 200 mg/kg/day of GL extract for 12 weeks. GL extract treatment inhibited adipocyte differentiation by downregulating the expression of adipogenic-related genes in 3T3-L1 cells. In the obese mouse model, GL extract prevented HFD-induced weight gain, fatty hepatocyte deposition, and adipocyte size by decreasing the secretion of leptin and insulin. In conclusion, GL extract shows antiobesity effects in vitro and in vivo, suggesting that this extract can be beneficial in the prevention of obesity. Full article

(This article belongs to the Special Issue Phytochemicals in Medicine and Food)

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17 pages, 3897 KiB

Open AccessArticle

Experimental Data Based Machine Learning Classification Models with Predictive Ability to Select in Vitro Active Antiviral and Non-Toxic Essential Oils

by Manuela Sabatino, Marco Fabiani, Mijat Božović, Stefania Garzoli, Lorenzo Antonini, Maria Elena Marcocci, Anna Teresa Palamara, Giovanna De Chiara and Rino Ragno

Molecules 2020, 25(10), 2452; https://doi.org/10.3390/molecules25102452 - 25 May 2020

Cited by 18 | Viewed by 4229

Abstract

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor [...] Read more.

In the last decade essential oils have attracted scientists with a constant increase rate of more than 7% as witnessed by almost 5000 articles. Among the prominent studies essential oils are investigated as antibacterial agents alone or in combination with known drugs. Minor studies involved essential oil inspection as potential anticancer and antiviral natural remedies. In line with the authors previous reports the investigation of an in-house library of extracted essential oils as a potential blocker of HSV-1 infection is reported herein. A subset of essential oils was experimentally tested in an in vitro model of HSV-1 infection and the determined IC₅₀s and CC₅₀s values were used in conjunction with the results obtained by gas-chromatography/mass spectrometry chemical analysis to derive machine learning based classification models trained with the partial least square discriminant analysis algorithm. The internally validated models were thus applied on untested essential oils to assess their effective predictive ability in selecting both active and low toxic samples. Five essential oils were selected among a list of 52 and readily assayed for IC₅₀ and CC₅₀ determination. Interestingly, four out of the five selected samples, compared with the potencies of the training set, returned to be highly active and endowed with low toxicity. In particular, sample CJM1 from Calaminta nepeta was the most potent tested essential oil with the highest selectivity index (IC₅₀ = 0.063 mg/mL, SI > 47.5). In conclusion, it was herein demonstrated how multidisciplinary applications involving machine learning could represent a valuable tool in predicting the bioactivity of complex mixtures and in the near future to enable the design of blended essential oil possibly endowed with higher potency and lower toxicity. Full article

(This article belongs to the Special Issue Chemoinformatics of Natural Products Chemistry)

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50 pages, 6084 KiB

Open AccessReview

Peculiar Structural Effects in Pure and Doped Functional Single Crystals of Complex Compositions

by Galina Kuz’micheva and Irina Kaurova

Molecules 2020, 25(10), 2451; https://doi.org/10.3390/molecules25102451 - 25 May 2020

Cited by 5 | Viewed by 4271

Abstract

Results of a detailed structural characterization of nominally pure and doped single crystals of scheelite, eulytin, and perovskite families obtained by melt methods were considered and analyzed. The influence of growth and post-growth annealing conditions on actual compositions of crystals is shown. The [...] Read more.

Results of a detailed structural characterization of nominally pure and doped single crystals of scheelite, eulytin, and perovskite families obtained by melt methods were considered and analyzed. The influence of growth and post-growth annealing conditions on actual compositions of crystals is shown. The reasons for the coloration of the crystals are explained. A change in crystal symmetry due to crystal–chemical and growth reasons is considered. The use of structural analysis and X-ray absorption spectroscopy is substantiated to reveal the role of activator ions in the formation of statistical and local structures, respectively. A relationship between the distribution of activator ions over crystallographic sites and photoluminescent parameters of materials is established, which allows selecting optimal systems for the application. The combined results of studying single-crystal compounds of other classes (huntite, sillenite, whitlockite, garnet, tetragonal bronzes) allow formulating and summarizing structural effects that appeared in the systems and caused by various factors and, in many cases, due to the local environment of cations. A principal difference in the structural behavior of solid solutions and doped compounds is shown. The methodology developed for single-crystal samples of complex compositions can be recommended for the systematic structural studies of functional materials of different compositions. Full article

(This article belongs to the Special Issue Crystallography and Crystal Chemistry)

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26 pages, 3317 KiB

Open AccessReview

Crystal Chemistry of High-Temperature Borates

by Nikolay I. Leonyuk, Victor V. Maltsev and Elena A. Volkova

Molecules 2020, 25(10), 2450; https://doi.org/10.3390/molecules25102450 - 25 May 2020

Cited by 18 | Viewed by 4819

Abstract

In recent years borate-based crystals has attracted substantial interest among the research community. The overall importance of this family of materials is reflected in miscellaneous articles and several reviews that have been published over the years. Crystalline borate materials exhibit numerous interesting physical [...] Read more.

In recent years borate-based crystals has attracted substantial interest among the research community. The overall importance of this family of materials is reflected in miscellaneous articles and several reviews that have been published over the years. Crystalline borate materials exhibit numerous interesting physical properties, which make them promising for further practical applications. Diversity of functional characteristics results from their high structural flexibility caused in the linkage of planar/non–planar BO₃ groups and BO₄ tetrahedra, which can occur as isolated or condensed structural units. This report is a brief review on crystal chemistry and structure features of anhydrous/high-temperature borates. Polymorphism of boron-oxygen radicals has been considered basing on cations’ nature and synthesis conditions. Analysis of the laws governing borates structures and general principles of their systematics was discussed. As a result, an alternative classification of anhydrous compounds has been considered. It is based on four orders of their subdivision: (1) by the variety of anion formers, (2) by the cation charge, (3) by the N = N_M:N_B, i.e., ratio of metal atoms number to the ratio of boron atoms number (N-factor) value indicating the borate structural type (if it is known), (4) by the cation type and size. Full article

(This article belongs to the Special Issue Crystallography and Crystal Chemistry)

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17 pages, 3985 KiB

Open AccessArticle

Influence of Harvest Time and Malaxation Conditions on the Concentration of Individual Phenols in Extra Virgin Olive Oil Related to Its Healthy Properties

by Panagiotis Diamantakos, Triada Giannara, Maria Skarkou, Eleni Melliou and Prokopios Magiatis

Molecules 2020, 25(10), 2449; https://doi.org/10.3390/molecules25102449 - 24 May 2020

Cited by 37 | Viewed by 4710

Abstract

The phenolic fraction of the extra virgin olive oil (EVOO) has been studied over the past two decades because of its important health protective properties. Numerous studies have been performed in order to clarify the most crucial factors that affect the concentration of [...] Read more.

The phenolic fraction of the extra virgin olive oil (EVOO) has been studied over the past two decades because of its important health protective properties. Numerous studies have been performed in order to clarify the most crucial factors that affect the concentration of the EVOO’s phenolic fraction and many contradictory results have been reported. Having as target to maximize the phenolic content of EVOO and its healthy properties we investigated the impact of harvest time, malaxation temperature, and malaxation duration on the concentration of individual phenols in extra virgin olive oil. Olive oil was prepared in a lab-scale olive mill from different varieties in Greece. The extraction process for cultivar (cv) Koroneiki samples was performed at five different harvest periods from the same trees with three different malaxation temperatures and five different malaxation duration times (N = 75). Similar types of experiments were also performed for other varieties: cv Athenolia (N = 20), cv Olympia (N = 3), cv Kalamata (N = 3), and cv Throubolia Aegean (N=3) in order to compare the changes in the phenolic profile during malaxation. The quantitative analysis of the olive oil samples with NMR showed that the total phenolic content has a negative correlation with the ripening degree and the malaxation time. The NMR data we collected helped us to quantitate not only the total phenolic content but also the concentration of the major phenolic compounds such as oleocanthal, oleacein, oleokoronal, and oleomissional. We noticed different trends for the concentration of these phenols during malaxation process and for different malaxation temperatures. The different trends of the concentration of the individual phenols during malaxation and the completely different behavior of each variety revealed possible biosynthetic formation steps for oleocanthal and oleacein and may explain the discrepancies reported from previous studies. Full article

(This article belongs to the Special Issue Olive Oil: From Processing to Health Benefits)

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27 pages, 3996 KiB

Open AccessReview

Second-Generation Androgen Receptor Antagonists as Hormonal Therapeutics for Three Forms of Prostate Cancer

by Pravien Rajaram, Alyssa Rivera, Kevin Muthima, Nicholas Olveda, Hubert Muchalski and Qiao-Hong Chen

Molecules 2020, 25(10), 2448; https://doi.org/10.3390/molecules25102448 - 24 May 2020

Cited by 38 | Viewed by 9410

Abstract

Enzalutamide is the first second-generation nonsteroidal androgen receptor (AR) antagonist with a strong binding affinity to AR. Most significantly, enzalutamide can prolong not only overall survival time and metastatic free survival time for patients with lethal castration-resistant prostate cancer (CRPC), but also castration-resistant [...] Read more.

Enzalutamide is the first second-generation nonsteroidal androgen receptor (AR) antagonist with a strong binding affinity to AR. Most significantly, enzalutamide can prolong not only overall survival time and metastatic free survival time for patients with lethal castration-resistant prostate cancer (CRPC), but also castration-resistant free survival time for patients with castration-sensitive prostate cancer (CSPC). Enzalutamide has thus been approved by the US Food and Drug Administration (FDA) for the treatment of both metastatic (in 2012) and non-metastatic (in 2018) CRPC, as well as CSPC (2019). This is an inspiring drug discovery story created by an amazing interdisciplinary collaboration. Equally important, the successful clinical use of enzalutamide proves the notion that the second-generation AR antagonists can serve as hormonal therapeutics for three forms of advanced prostate cancer. This has been further verified by the recent FDA approval of the other two second-generation AR antagonists, apalutamide and darolutamide, for the treatment of prostate cancer. This review focuses on the rational design and discovery of these three second-generation AR antagonists, and then highlights their syntheses, clinical studies, and use. Strategies to overcome the resistance to the second-generation AR antagonists are also reviewed. Full article

(This article belongs to the Special Issue Anticancer Agents: Design, Synthesis and Evaluation)

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19 pages, 4478 KiB

Open AccessFeature PaperArticle

Climate and Processing Effects on Tea (Camellia sinensis L. Kuntze) Metabolome: Accurate Profiling and Fingerprinting by Comprehensive Two-Dimensional Gas Chromatography/Time-of-Flight Mass Spectrometry

by Federico Stilo, Giulia Tredici, Carlo Bicchi, Albert Robbat, Jr., Joshua Morimoto and Chiara Cordero

Molecules 2020, 25(10), 2447; https://doi.org/10.3390/molecules25102447 - 24 May 2020

Cited by 24 | Viewed by 4282

Abstract

This study applied an untargeted–targeted (UT) fingerprinting approach, based on comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOF MS), to assess the effects of rainfall and temperature (both seasonal and elevational) on the tea metabolome. By this strategy, the same compound found in multiple [...] Read more.

This study applied an untargeted–targeted (UT) fingerprinting approach, based on comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOF MS), to assess the effects of rainfall and temperature (both seasonal and elevational) on the tea metabolome. By this strategy, the same compound found in multiple samples need only to be identified once, since chromatograms and mass spectral features are aligned in the data analysis process. Primary and specialized metabolites of leaves from two Chinese provinces, Yunnan (pu′erh) and Fujian (oolong), and a farm in South Carolina (USA, black tea) were studied. UT fingerprinting provided insight into plant metabolism activation/inhibition, taste and trigeminal sensations, and antioxidant properties, not easily attained by other analytical approaches. For example, pu′erh and oolong contained higher relative amounts of amino acids, organic acids, and sugars. Conversely, black tea contained less of all targeted compounds except fructose and glucose, which were more similar to oolong tea. Findings revealed compounds statistically different between spring (pre-monsoon) and summer (monsoon) in pu′erh and oolong teas as well as compounds that exhibited the greatest variability due to seasonal and elevational differences. The UT fingerprinting approach offered unique insights into how differences in growing conditions and commercial processing affect the nutritional benefits and sensory characteristics of tea beverages. Full article

(This article belongs to the Special Issue Recent Advances in Food and Natural Product Analysis)

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37 pages, 7742 KiB

Open AccessReview

Polymers and Plastics Modified Electrodes for Biosensors: A Review

by Sonia Lanzalaco and Brenda G. Molina

Molecules 2020, 25(10), 2446; https://doi.org/10.3390/molecules25102446 - 24 May 2020

Cited by 27 | Viewed by 5194

Abstract

Polymer materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. The present study reviews the field of electrochemical biosensors fabricated on modified plastics and polymers, focusing the attention, in the [...] Read more.

Polymer materials offer several advantages as supports of biosensing platforms in terms of flexibility, weight, conformability, portability, cost, disposability and scope for integration. The present study reviews the field of electrochemical biosensors fabricated on modified plastics and polymers, focusing the attention, in the first part, on modified conducting polymers to improve sensitivity, selectivity, biocompatibility and mechanical properties, whereas the second part is dedicated to modified “environmentally friendly” polymers to improve the electrical properties. These ecofriendly polymers are divided into three main classes: bioplastics made from natural sources, biodegradable plastics made from traditional petrochemicals and eco/recycled plastics, which are made from recycled plastic materials rather than from raw petrochemicals. Finally, flexible and wearable lab-on-a-chip (LOC) biosensing devices, based on plastic supports, are also discussed. This review is timely due to the significant advances achieved over the last few years in the area of electrochemical biosensors based on modified polymers and aims to direct the readers to emerging trends in this field. Full article

(This article belongs to the Special Issue Polymer Biosensor for Electrochemical Detection)

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13 pages, 1907 KiB

Open AccessArticle

Dilute-and-Shoot HPLC-UV Method for Determination of Urinary Creatinine as a Normalization Tool in Mycotoxin Biomonitoring in Pigs

by Agnieszka Tkaczyk and Piotr Jedziniak

Molecules 2020, 25(10), 2445; https://doi.org/10.3390/molecules25102445 - 24 May 2020

Cited by 15 | Viewed by 4757

Abstract

A simple, rapid, and accurate HPLC-UV method was developed for the determination of creatinine in pig urine. Usually, it is determined in urine in biomonitoring of xenobiotics to correct for variations in dilutions of urine samples. The colorimetric method (based on Jaffe reaction), [...] Read more.

A simple, rapid, and accurate HPLC-UV method was developed for the determination of creatinine in pig urine. Usually, it is determined in urine in biomonitoring of xenobiotics to correct for variations in dilutions of urine samples. The colorimetric method (based on Jaffe reaction), which was mainly used for this purpose in mycotoxin biomonitoring, is not a reliable approach for pig urine. Therefore, a novel and accurate HPLC method for creatinine determination was developed. The sample preparation was based on the dilute and shoot approach. An HPLC separation was performed with a porous graphitic carbon column with an aqueous mobile phase to achieve satisfactory retention time for creatinine. The method has been successfully validated, applied for the determination of creatinine in pig urine, and compared with other methods commonly used for that purpose—a colorimetric method based on Jaffe reaction and commercial ELISA test. The developed HPLC method shows the highest precision and accuracy for pig urine samples. Finally, the method was applied as a normalization tool in LC-MS/MS mycotoxin biomarkers analysis. The standardization to a constant creatinine level (0.5 mg/mL) enables similar matrix effects for eleven mycotoxin biomarkers for pig urine samples with different creatinine levels. Full article

(This article belongs to the Section Analytical Chemistry)

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19 pages, 1205 KiB

Open AccessReview

Anti-aggregation Effects of Phenolic Compounds on α-synuclein

by Kenjiro Ono, Mayumi Tsuji, Tritia R. Yamasaki and Giulio M. Pasinetti

Molecules 2020, 25(10), 2444; https://doi.org/10.3390/molecules25102444 - 24 May 2020

Cited by 22 | Viewed by 5960

Abstract

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there [...] Read more.

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies. Full article

(This article belongs to the Special Issue Synthesis and Identification of Small Compounds Active in Neurodegeneration)

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11 pages, 4267 KiB

Open AccessArticle

Study on Different Water-Based Binders for Li₄Ti₅O₁₂ Electrodes

by Christina Toigo, Catia Arbizzani, Karl-Heinz Pettinger and Maurizio Biso

Molecules 2020, 25(10), 2443; https://doi.org/10.3390/molecules25102443 - 24 May 2020

Cited by 17 | Viewed by 4102

Abstract

In this study, Li₄Ti₅O₁₂ (LTO) electrodes with different types of water-soluble binders are successfully coated upon aluminum foil. Electrodes containing solely sodium alginate (SA) as a binder or a mixed PVDF/carboxymethyl cellulose (CMC) binder show the most stable [...] Read more.

In this study, Li₄Ti₅O₁₂ (LTO) electrodes with different types of water-soluble binders are successfully coated upon aluminum foil. Electrodes containing solely sodium alginate (SA) as a binder or a mixed PVDF/carboxymethyl cellulose (CMC) binder show the most stable performance in 1 M LiPF₆ in EC/DMC 1:1 in half cell vs. Li, with respect to cycle stability over 100 cycles at 1 C. The electrodes processed with a mixture of PVDF/SA show considerable fading and slightly worse values for rate capability. Each one of the different binders used is eco-friendly, and the whole processing can be performed without the use of organic solvents. Further advantages covering the whole production and recycling process, as well as safety issues during operation, encourage deeper research in this area. Full article

(This article belongs to the Special Issue Next Generation Electrode Material)

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19 pages, 3508 KiB

Open AccessArticle

Cross-Linked Microencapsulation of CO₂ Supercritical Extracted Oleoresins from Sea Buckthorn: Evidence of Targeted Functionality and Stability

by Corina Neagu, Liliana Mihalcea, Elena Enachi, Vasilica Barbu, Daniela Borda, Gabriela Elena Bahrim and Nicoleta Stănciuc

Molecules 2020, 25(10), 2442; https://doi.org/10.3390/molecules25102442 - 23 May 2020

Cited by 12 | Viewed by 3351

Abstract

Oleoresin supercritical extracts from sea buckthorn were microencapsulated in whey proteins isolate and casein, in two states: native (N) and cross-linked mediated by transglutaminase (TG). The encapsulation efficiency showed values higher than 92% for total carotenoids and lycopene. Phytochemicals content was 352.90 ± [...] Read more.

Oleoresin supercritical extracts from sea buckthorn were microencapsulated in whey proteins isolate and casein, in two states: native (N) and cross-linked mediated by transglutaminase (TG). The encapsulation efficiency showed values higher than 92% for total carotenoids and lycopene. Phytochemicals content was 352.90 ± 1.02 mg/g dry weight (DW) for total carotenoids in TG and 302.98 ± 2.30 mg/g DW in N, with antioxidant activity of 703.13 ± 23.60 mMol Trolox/g DW and 608.74 ± 7.12 mMol Trolox/g DW, respectively. Both powders had an inhibitory effect on α-glucosidase, of about 40% for N and 35% for TG. The presence of spherosomes was highlighted, with sizes ranging between 15.23–73.41 µm and an agglutination tendency in N, and lower sizes, up to 35 µm in TG. The in vitro digestibility revealed a prolonged release in an intestinal environment, up to 65% for TG. Moisture sorption isotherms were studied at 20 °C and the shape of curves corresponds to sigmoidal type II model. The presence of cross-linked mediated aggregates in TG powders improved stability and flowability. Our results can be used as evidence that cross-linked aggregates mediated by transglutaminase applied for microencapsulation of oleoresins have the potential to become new delivery systems, for carotenoids and lycopene, being valuable in terms of their attractive color and biological and bioaccessibility properties. Full article

(This article belongs to the Special Issue Recent Advances in Micro- and Nanoencapsulation of Bioactive Compounds)

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14 pages, 1839 KiB

Open AccessArticle

Effects of Intra- and Interchain Interactions on Exciton Dynamics of PTB7 Revealed by Model Oligomers

by Thomas J. Fauvell, Zhengxu Cai, Matthew S. Kirschner, Waleed Helweh, Pyosang Kim, Tianyue Zheng, Richard D. Schaller, Luping Yu and Lin X. Chen

Molecules 2020, 25(10), 2441; https://doi.org/10.3390/molecules25102441 - 23 May 2020

Cited by 5 | Viewed by 3715

Abstract

Recent studies have shown that molecular aggregation structures in precursor solutions of organic photovoltaic (OPV) polymers have substantial influence on polymer film morphology, exciton and charge carrier transport dynamics, and hence, the resultant device performance. To distinguish photophysical impacts due to increasing π-conjugation [...] Read more.

Recent studies have shown that molecular aggregation structures in precursor solutions of organic photovoltaic (OPV) polymers have substantial influence on polymer film morphology, exciton and charge carrier transport dynamics, and hence, the resultant device performance. To distinguish photophysical impacts due to increasing π-conjugation from chain lengthening and π–π stacking from single/multi chain aggregation in solution and film, we used oligomers of a well-studied charge transfer polymer PTB7 with different lengths as models to reveal intrinsic photophysical properties of a conjugated segment in the absence of inter-segment aggregation. In comparison with previously studied photophysical properties in polymeric PTB7, we found that oligomer dynamics are dominated by a process of planarization of the conjugated backbone into a quinoidal structure that resembles the self-folded polymer and that, when its emission is isolated, this quinoidal excited state resembling the planar polymer chain exhibits substantial charge transfer character via solvent-dependent emission shifts. Furthermore, the oligomers distinctly lack the long-lived charge separated species characteristic of PTB7, suggesting that the progression from charge transfer character in isolated chains to exciton splitting in neat polymer solution is modulated by the interchain interactions enabled by self-folding. Full article

(This article belongs to the Special Issue Nanomaterials and Interfaces for Next Generation Photovoltaics)

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13 pages, 1225 KiB

Open AccessArticle

Co-Occurrence of Moniliformin and Regulated Fusarium Toxins in Maize and Wheat Grown in Italy

by Terenzio Bertuzzi, Paola Giorni, Silvia Rastelli, Patrizia Vaccino, Chiara Lanzanova and Sabrina Locatelli

Molecules 2020, 25(10), 2440; https://doi.org/10.3390/molecules25102440 - 23 May 2020

Cited by 13 | Viewed by 3893

Abstract

The co-occurrence of moniliformin (MON), fumonisins (FBs), and deoxynivalenol (DON) was evaluated in maize, durum, and common wheat grown in different experimental fields located in several Italian regions. MON was quantified using a LC-MS/MS method adding lanthanum ions in the mobile phase. In [...] Read more.

The co-occurrence of moniliformin (MON), fumonisins (FBs), and deoxynivalenol (DON) was evaluated in maize, durum, and common wheat grown in different experimental fields located in several Italian regions. MON was quantified using a LC-MS/MS method adding lanthanum ions in the mobile phase. In maize, MON contamination was widespread and considerable; the toxin was detected in almost all the samples (95.1%) and exceeded 500 and 1000 µg kg⁻¹ in 42.0% and in 18.5% of samples, respectively. Significant positive correlation was found between MON and FB contamination levels. When there were not droughty climate conditions, a positive significant correlation was found between growing degree days (GDD) and MON values. In wheat, MON contamination was not widespread like in maize and it was lower in common wheat than in durum wheat. In durum wheat, MON was detected in 45.0% of the samples with only 6 samples (7.5%) exceeding 500 µg kg⁻¹, while in common wheat the toxin was detected above the LOD in 18.7% of samples exceeding 100 µg kg⁻¹ in only two samples (2.5%). No correlation was found with DON contamination. Climate conditions influenced both MON and DON occurrence. Full article

(This article belongs to the Special Issue Analytical Methods for Mycotoxin Analysis)

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33 pages, 4702 KiB

Open AccessReview

The Positive Side of the Alzheimer’s Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1

by Lidia Ciccone, Chenghui Shi, Davide di Lorenzo, Anne-Cécile Van Baelen and Nicolo Tonali

Molecules 2020, 25(10), 2439; https://doi.org/10.3390/molecules25102439 - 23 May 2020

Cited by 40 | Viewed by 6156

Abstract

Alzheimer’s disease (AD) represents a progressive amyloidogenic disorder whose advancement is widely recognized to be connected to amyloid-β peptides and Tau aggregation. However, several other processes likely contribute to the development of AD and some of them might be related to protein-protein interactions. [...] Read more.

Alzheimer’s disease (AD) represents a progressive amyloidogenic disorder whose advancement is widely recognized to be connected to amyloid-β peptides and Tau aggregation. However, several other processes likely contribute to the development of AD and some of them might be related to protein-protein interactions. Amyloid aggregates usually contain not only single type of amyloid protein, but also other type of proteins and this phenomenon can be rationally explained by the process of protein cross-seeding and co-assembly. Amyloid cross-interaction is ubiquitous in amyloid fibril formation and so a better knowledge of the amyloid interactome could help to further understand the mechanisms of amyloid related diseases. In this review, we discuss about the cross-interactions of amyloid-β peptides, and in particular Aβ1-42, with other amyloids, which have been presented either as integrated part of Aβ neurotoxicity process (such as Tau) or conversely with a preventive role in AD pathogenesis by directly binding to Aβ (such as transthyretin, cystatin C and apolipoprotein A1). Particularly, we will focus on all the possible therapeutic strategies aiming to rescue the Aβ toxicity by taking inspiration from these protein-protein interactions. Full article

(This article belongs to the Special Issue Understanding Protein/Peptide Self-Assembly using Structural and Biophysical Chemistry)

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9 pages, 3274 KiB

Open AccessArticle

3D Micro/Nanopatterning of a Vinylferrocene Copolymer

by Dennis Löber, Subhayan Dey, Burhan Kaban, Fabian Roesler, Martin Maurer, Hartmut Hillmer and Rudolf Pietschnig

Molecules 2020, 25(10), 2438; https://doi.org/10.3390/molecules25102438 - 23 May 2020

Cited by 4 | Viewed by 2802

Abstract

In nanoimprint lithography (NIL), a pattern is created by mechanical deformation of an imprint resist via embossing with a stamp, where the adhesion behavior during the filling of the imprint stamp and its subsequent detachment may impose some practical challenges. Here we explored [...] Read more.

In nanoimprint lithography (NIL), a pattern is created by mechanical deformation of an imprint resist via embossing with a stamp, where the adhesion behavior during the filling of the imprint stamp and its subsequent detachment may impose some practical challenges. Here we explored thermal and reverse NIL patterning of polyvinylferrocene and vinylferrocene-methyl methacrylate copolymers to prepare complex non-spherical objects and patterns. While neat polyvinylferrocene was found to be unsuitable for NIL, freshly-prepared vinylferrocene-methyl methacrylate copolymers, for which identity and purity were established, have been structured into 3D-micro/nano-patterns using NIL. The cross-, square-, and circle-shaped columnar structures form a 3 × 3 mm arrangement with periodicity of 3 µm, 1 µm, 542 nm, and 506 nm. According to our findings, vinylferrocene-methyl methacrylate copolymers can be imprinted without further additives in NIL processes, which opens the way for redox-responsive 3D-nano/micro-objects and patterns via NIL to be explored in the future. Full article

(This article belongs to the Special Issue Metal-Containing Polymers and Dendrimers)

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37 pages, 11335 KiB

Open AccessEditor’s ChoiceReview

Stereochemistry of Simple Molecules inside Nanotubes and Fullerenes: Unusual Behavior of Usual Systems

by Valerij Kuznetsov

Molecules 2020, 25(10), 2437; https://doi.org/10.3390/molecules25102437 - 23 May 2020

Cited by 16 | Viewed by 5489

Abstract

Over the past three decades, carbon nanotubes and fullerenes have become remarkable objects for starting the implementation of new models and technologies in different branches of science. To a great extent, this is defined by the unique electronic and spatial properties of nanocavities [...] Read more.

Over the past three decades, carbon nanotubes and fullerenes have become remarkable objects for starting the implementation of new models and technologies in different branches of science. To a great extent, this is defined by the unique electronic and spatial properties of nanocavities due to the ramified π-electron systems. This provides an opportunity for the formation of endohedral complexes containing non-covalently bonded atoms or molecules inside fullerenes and nanotubes. The guest species are exposed to the force field of the nanocavity, which can be described as a combination of electronic and steric requirements. Its action significantly changes conformational properties of even relatively simple molecules, including ethane and its analogs, as well as compounds with C−O, C−S, B−B, B−O, B−N, N−N, Al−Al, Si−Si and Ge−Ge bonds. Besides that, the cavity of the host molecule dramatically alters the stereochemical characteristics of cyclic and heterocyclic systems, affects the energy of pyramidal nitrogen inversion in amines, changes the relative stability of cis and trans isomers and, in the case of chiral nanotubes, strongly influences the properties of R- and S-enantiomers. The present review aims at primary compilation of such unusual stereochemical effects and initial evaluation of the nature of the force field inside nanotubes and fullerenes. Full article

(This article belongs to the Special Issue Structure and Conformational Analysis of Heterocyclic Compounds)

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21 pages, 2121 KiB

Open AccessReview

Sphingosine 1-Phosphate Signaling and Metabolism in Chemoprevention and Chemoresistance in Colon Cancer

by Petra Grbčić and Mirela Sedić

Molecules 2020, 25(10), 2436; https://doi.org/10.3390/molecules25102436 - 23 May 2020

Cited by 17 | Viewed by 4605

Abstract

Colorectal carcinoma (CRC) is the leading cause of cancer-related deaths worldwide. Despite advances in prevention and treatment modalities for CRC, rapidly developing resistance to chemotherapy limits its effectiveness. For that reason, it is important to better understand the mechanisms that undergird the process [...] Read more.

Colorectal carcinoma (CRC) is the leading cause of cancer-related deaths worldwide. Despite advances in prevention and treatment modalities for CRC, rapidly developing resistance to chemotherapy limits its effectiveness. For that reason, it is important to better understand the mechanisms that undergird the process of chemoresistance to enable design of novel anticancer agents specifically targeting malignant properties of cancer cells. Over recent decades, bioactive sphingolipid species have come under the spotlight for their recognized role in cancer development and progression, and the evidence has surfaced to support their role as regulators of anti-cancer drug resistance. Colon cancer is characterized by a shift in sphingolipid balance that favors the production and accumulation of oncogenic species such as sphingosine 1-phosphate (S1P). S1P is known to govern the processes that facilitate cancer cell growth and progression including proliferation, survival, migration, invasion and inflammation. In this review paper, we will give a comprehensive overview of current literature findings on the molecular mechanisms by which S1P turnover, transport and signaling via receptor-dependent and independent pathways shape colon cancer cell behavior and influence treatment outcome in colon cancer. Combining available modulators of S1P metabolism and signaling with standard chemotherapy drugs could provide a rational approach to achieve enhanced therapeutic response, diminish chemoresistance development and improve the survival outcome in CRC patients. Full article

(This article belongs to the Special Issue Translational Approach to Antitumor Drugs)

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20 pages, 4751 KiB

Open AccessArticle

Thermotropic Liquid-Crystalline and Light-Emitting Properties of Bis(4-aalkoxyphenyl) Viologen Bis(triflimide) Salts

by Pradip K. Bhowmik, Muhammed Kareem M. Al-Karawi, Shane T. Killarney, Erenz J. Dizon, Anthony Chang, Jongin Kim, Si L. Chen, Ronald Carlo G. Principe, Andy Ho, Haesook Han, Hari D. Mandal, Raymond G. Cortez, Bryan Gutierrez, Klarissa Mendez, Lewis Sharpnack, Deña M. Agra-Kooijman, Michael R. Fisch and Satyendra Kumar

Molecules 2020, 25(10), 2435; https://doi.org/10.3390/molecules25102435 - 23 May 2020

Cited by 11 | Viewed by 5563

Abstract

A series of bis(4-alkoxyphenyl) viologen bis(triflimide) salts with alkoxy chains of different lengths were synthesized by the metathesis reaction of respective bis(4-alkoxyphenyl) viologen dichloride salts, which were in turn prepared from the reaction of Zincke salt with the corresponding 4-n-alkoxyanilines, with lithium triflimide [...] Read more.

A series of bis(4-alkoxyphenyl) viologen bis(triflimide) salts with alkoxy chains of different lengths were synthesized by the metathesis reaction of respective bis(4-alkoxyphenyl) viologen dichloride salts, which were in turn prepared from the reaction of Zincke salt with the corresponding 4-n-alkoxyanilines, with lithium triflimide in methanol. Their chemical structures were characterized by ¹H and ¹³C nuclear magnetic resonance spectra and elemental analysis. Their thermotropic liquid-crystalline (LC) properties were examined by differential scanning calorimetry, polarizing optical microscopy, and variable temperature X-ray diffraction. Salts with short length alkoxy chains had crystal-to-liquid transitions. Salts of intermediate length alkoxy chains showed both crystal-to-smectic A (SmA) transitions, T_ms, and SmA-to-isotropic transitions, T_is. Those with longer length of alkoxy chains had relatively low T_ms at which they formed the SmA phases that persisted up to the decomposition at high temperatures. As expected, all of them had excellent thermal stabilities in the temperature range of 330–370 °C. Their light-emitting properties in methanol were also included. Full article

(This article belongs to the Special Issue Current Advances in Liquid Crystals)

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12 pages, 1014 KiB

Open AccessArticle

Inhibitory Effects of AF-343, a Mixture of Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on Compound 48/80-Mediated Allergic Responses in RBL-2H3 Cells

by Eun Kyeong Lee, Jeongah Song, Youjin Seo, Eun Mi Koh, Seon-Hee Kim and Kyung Jin Jung

Molecules 2020, 25(10), 2434; https://doi.org/10.3390/molecules25102434 - 22 May 2020

Cited by 7 | Viewed by 3599

Abstract

The purpose of this study was to determine the antiallergic effects of AF-343, a mixture of natural plant extracts from Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on rat basophilic leukemia (RBL-2H3) cells. The inhibitory effects on cell degranulation, proinflammatory [...] Read more.

The purpose of this study was to determine the antiallergic effects of AF-343, a mixture of natural plant extracts from Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on rat basophilic leukemia (RBL-2H3) cells. The inhibitory effects on cell degranulation, proinflammatory cytokine secretion, and reactive oxygen species (ROS) production were studied in compound 48/80-treated RBL-2H3 cells. The bioactive compounds in AF-343 were also identified by HPLC–UV. AF-343 was found to effectively suppress compound 48/80-induced β-hexosaminidase release, and interleukin (IL)-4 and tumor necrosis factor-α (TNF-α) production in RBL-2H3 cells. In addition, AF-343 exhibited DPPH free radical scavenging effects in vitro (half-maximal inhibitory concentration (IC₅₀) = 105 μg/mL) and potently inhibited compound 48/80-induced cellular ROS generation in a 2′,7′-dichlorofluorescein diacetate (DCFH-DA) assay. Specifically, treatment with AF-343 exerted stronger antioxidant effects in vitro and antiallergic effects in cells than treatment with three single natural plant extracts. Furthermore, AF-343 was observed to contain bioactive compounds, including catechin, aurantio-obtusin, and chicoric acid, which have been reported to elicit antiallergic responses. This study reveals that AF-343 attenuates allergic responses via suppression of β-hexosaminidase release, IL-4 and TNF-α secretion, and ROS generation, perhaps through mechanisms related to catechin, aurantio-obtusin, and chicoric acid. The results indicate that AF-343 can be considered a treatment for various allergic diseases. Full article

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