Molecules

47 pages, 10111 KiB

Open AccessReview

Allosteric GABA_A Receptor Modulators—A Review on the Most Recent Heterocyclic Chemotypes and Their Synthetic Accessibility

by Blanca Angelica Vega Alanis, Maria Teresa Iorio, Luca L. Silva, Konstantina Bampali, Margot Ernst, Michael Schnürch and Marko D. Mihovilovic

Molecules 2020, 25(4), 999; https://doi.org/10.3390/molecules25040999 - 24 Feb 2020

Cited by 21 | Viewed by 10663

Abstract

GABA_A receptor modulators are structurally almost as diverse as their target protein. A plethora of heterocyclic scaffolds has been described as modulating this extremely important receptor family. Some made it into clinical trials and, even on the market, some were dismissed. This [...] Read more.

GABA_A receptor modulators are structurally almost as diverse as their target protein. A plethora of heterocyclic scaffolds has been described as modulating this extremely important receptor family. Some made it into clinical trials and, even on the market, some were dismissed. This review focuses on the synthetic accessibility and potential for library synthesis of GABA_A receptor modulators containing at least one heterocyclic scaffold, which were disclosed within the last 10 years. Full article

(This article belongs to the Special Issue Enabling Chemical Technologies in Medicinal Chemistry)

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17 pages, 5326 KiB

Open AccessArticle

Inclusion of the Phytoalexin trans-Resveratrol in Native Cyclodextrins: A Thermal, Spectroscopic, and X-Ray Structural Study

by Laura Catenacci, Milena Sorrenti, Maria Cristina Bonferoni, Lee Hunt and Mino R. Caira

Molecules 2020, 25(4), 998; https://doi.org/10.3390/molecules25040998 - 24 Feb 2020

Cited by 13 | Viewed by 3759

Abstract

The aim of the study was to determine the feasibility of complexation between the antioxidant trans-resveratrol (RSV) and underivatized cyclodextrins (CDs) using a variety of preparative methods, including physical mixing, kneading, microwave irradiation, co-evaporation, and co-precipitation techniques. Products were characterized using differential [...] Read more.

The aim of the study was to determine the feasibility of complexation between the antioxidant trans-resveratrol (RSV) and underivatized cyclodextrins (CDs) using a variety of preparative methods, including physical mixing, kneading, microwave irradiation, co-evaporation, and co-precipitation techniques. Products were characterized using differential scanning calorimetry (DSC), simultaneous thermogravimetric/DSC analysis (TGA/DSC), Fourier transform infrared (FT-IR) spectroscopy, and powder X-ray diffraction (PXRD). With α-CD and RSV, sample amorphization was revealed by PXRD and FT-IR, but no definitive inclusion complexation was evident. Similar results were obtained in attempts to complex RSV with β-CD. However, complex formation between γ-CD and RSV was evident from observation of an endo-/exothermic effect appearing in the DSC trace of the product from kneading and was further corroborated by FT-IR and PXRD methods. The latter technique indicated complexation unequivocally as the diffraction peak profile for the product matched that for known isostructural γ-CD complexes. Single crystal X-ray analysis followed, confirming the predicted complex between γ-CD and RSV. A combination of ¹H NMR and TGA data yielded the complex formula (γ-CD)₃·(RSV)₄·(H₂O)₆₂. However, severe disorder of the RSV molecules prevented their modeling. In contrast, our previous studies of the inclusion of RSV in methylated CDs yielded crystals with only minor guest disorder. Full article

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13 pages, 2156 KiB

Open AccessArticle

Direct Base-Assisted C‒H Cyclonickelation of 6-Phenyl-2,2′-bipyridine

by Nicolas Vogt, Vasily Sivchik, Aaron Sandleben, Gerald Hörner and Axel Klein

Molecules 2020, 25(4), 997; https://doi.org/10.3390/molecules25040997 - 24 Feb 2020

Cited by 9 | Viewed by 4585

Abstract

The organonickel complexes [Ni(Phbpy)X] (X = Br, OAc, CN) were obtained for the first time in a direct base-assisted arene C(sp²)–H cyclometalation reaction from the rather unreactive precursor materials NiX₂ and HPhbpy (6-phenyl-2,2′-bipyridine) or from the versatile precursor [Ni(HPhbpy)Br₂ [...] Read more.

The organonickel complexes [Ni(Phbpy)X] (X = Br, OAc, CN) were obtained for the first time in a direct base-assisted arene C(sp²)–H cyclometalation reaction from the rather unreactive precursor materials NiX₂ and HPhbpy (6-phenyl-2,2′-bipyridine) or from the versatile precursor [Ni(HPhbpy)Br₂]₂. Different from previously necessary C‒Br oxidative addition at Ni(0), an extended scan of reaction conditions allowed quantitative access to the title compound from Ni(II) on synthetically useful timescales through base-assisted C‒H activation in nonpolar media at elevated temperature. Optimisation of the reaction conditions (various bases, solvents, methods) identified 1:2 mixtures of acetate and carbonate as unrivalled synergetic base pairs in the optimum protocol that holds promise as a readily usable and easily tuneable access to a wide range of direct nickelation products. While for the base-assisted C‒H metalation of the noble metals Ru, Ir, Rh, or Pd, this acetate/carbonate method has been established for a few years, our study represents the leap into the world of the base metals of the 3d series. Full article

(This article belongs to the Special Issue Organometallic Synthesis of Extremely Sensitive Compounds for Fundamental Investigations, Bond Activation, and Catalysis)

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19 pages, 2174 KiB

Open AccessArticle

Phytochemical Characterization and Chemotherapeutic Potential of Cinnamomum verum Extracts on the Multiplication of Protozoan Parasites In Vitro and In Vivo

by Gaber El-Saber Batiha, Amany Magdy Beshbishy, Azirwan Guswanto, Arifin Nugraha, Tserendorj Munkhjargal, Mohamed M. Abdel-Daim, Juan Mosqueda and Ikuo Igarashi

Molecules 2020, 25(4), 996; https://doi.org/10.3390/molecules25040996 - 24 Feb 2020

Cited by 28 | Viewed by 6033

Abstract

Cinnamomum verum is a commonly used herbal plant that has several documented properties against various diseases. The existing study evaluated the inhibitory effect of acetonic extract of C. verum (AECV) and ethyl acetate extract of C. verum (EAECV) against piroplasm parasites in vitro [...] Read more.

Cinnamomum verum is a commonly used herbal plant that has several documented properties against various diseases. The existing study evaluated the inhibitory effect of acetonic extract of C. verum (AECV) and ethyl acetate extract of C. verum (EAECV) against piroplasm parasites in vitro and in vivo. The drug-exposure viability assay was tested on Madin-Darby bovine kidney (MDBK), mouse embryonic fibroblast (NIH/3T3) and human foreskin fibroblast (HFF) cells. Qualitative phytochemical estimation revealed that AECV and EAECV containing multiple bioactive constituents namely alkaloids, tannins, saponins, terpenoids and remarkable amounts of polyphenols and flavonoids. AECV and EAECV inhibited B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi multiplication at half-maximal inhibitory concentrations (IC₅₀) of 23.1 ± 1.4, 56.6 ± 9.1, 33.4 ± 2.1, 40.3 ± 7.5, 18.8 ± 1.6 µg/mL, and 40.1 ± 8.5, 55.6 ± 1.1, 45.7 ± 1.9, 50.2 ± 6.2, and 61.5 ± 5.2 µg/mL, respectively. In the cytotoxicity assay, AECV and EAECV affected the viability of MDBK, NIH/3T3 and HFF cells with half-maximum effective concentrations (EC₅₀) of 440 ± 10.6, 816 ± 12.7 and 914 ± 12.2 µg/mL and 376 ± 11.2, 610 ± 7.7 and 790 ± 12.4 µg/mL, respectively. The in vivo experiment showed that AECV and EAECV were effective against B. microti in mice at 150 mg/kg. These results showed that C. verum extracts are potential antipiroplasm drugs after further studies in some clinical cases. Full article

(This article belongs to the Special Issue Biological Activities of Medicinal Plants)

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13 pages, 3069 KiB

Open AccessArticle

Potential Therapeutic Anti-Inflammatory and Immunomodulatory Effects of Dihydroflavones, Flavones, and Flavonols

by Cristina Zaragozá, Lucinda Villaescusa, Jorge Monserrat, Francisco Zaragozá and Melchor Álvarez-Mon

Molecules 2020, 25(4), 1017; https://doi.org/10.3390/molecules25041017 - 24 Feb 2020

Cited by 76 | Viewed by 6765

Abstract

Systemic inflammation, circulating immune cell activation, and endothelial cell damage play a critical role in vascular pathogenesis. Flavonoids have shown anti-inflammatory effects. In this study, we investigated the effects of different flavonoids on the production of pro-inflammatory interleukin (IL) 1β, 6, and 8, [...] Read more.

Systemic inflammation, circulating immune cell activation, and endothelial cell damage play a critical role in vascular pathogenesis. Flavonoids have shown anti-inflammatory effects. In this study, we investigated the effects of different flavonoids on the production of pro-inflammatory interleukin (IL) 1β, 6, and 8, and tumor necrosis factor α (TNF-α), in peripheral blood cells. Methods: We studied the whole blood from 36 healthy donors. Lipopolysaccharide (LPS)-stimulated (0.5 μg/mL) whole-blood aliquots were incubated in the presence or absence of different concentrations of quercetin, rutin, naringenin, naringin, diosmetin, and diosmin for 6 h. Cultures were centrifuged and the supernatant was collected in order to measure IL-1β, TNF-α, IL-6, and IL-8 production using specific immunoassay techniques. This production was significantly inhibited by quercetin, naringenin, naringin, and diosmetin, but in no case by rutin or diosmin. Flavonoids exert different effects, maybe due to the differences between aglycons and glucosides present in their chemical structures. However, these studies suggest that quercetin, naringenin, naringin, and diosmetin could have a potential therapeutic effect in the inflammatory process of cardiovascular disease. Full article

(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential)

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24 pages, 7120 KiB

Open AccessArticle

Synthesis of Fe₂SiO₄-Fe₇Co₃ Nanocomposite Dispersed in the Mesoporous SBA-15: Application as Magnetically Separable Adsorbent

by Monickarla Teixeira Pegado da Silva, Felipe Fernandes Barbosa, Marco Antonio Morales Torre, Jhonny Villarroel-Rocha, Karim Sapag, Sibele B. C. Pergher and Tiago Pinheiro Braga

Molecules 2020, 25(4), 1016; https://doi.org/10.3390/molecules25041016 - 24 Feb 2020

Cited by 9 | Viewed by 3710

Abstract

The mixture containing alloy and oxide with iron-based phases has shown interesting properties compared to the isolated species and the synergy between the phases has shown positive effect on dye adsorption. This paper describes the synthesis of Fe₂SiO₄-Fe₇ [...] Read more.

The mixture containing alloy and oxide with iron-based phases has shown interesting properties compared to the isolated species and the synergy between the phases has shown positive effect on dye adsorption. This paper describes the synthesis of Fe₂SiO₄-Fe₇Co₃-based nanocomposite dispersed in Santa Barbara Amorphous (SBA)-15 and its application in dye adsorption followed by magnetic separation. Thus, it was studied the variation of reduction temperature and amount of hydrogen used in synthesis and the effect of these parameters on the physicochemical properties of the iron and cobalt based oxide/alloy mixture, as well as the methylene blue adsorption capacity. The XRD and Mössbauer results, along with the temperature-programmed reduction (TPR) profiles, confirmed the formation of Fe₂SiO₄-Fe₇Co₃-based nanocomposites. Low-angle XRD, N₂ isotherms, and TEM images show the formation of the SBA-15 based mesoporous support with a high surface area (640 m²/g). Adsorption tests confirmed that the material reduced at 700 °C using 2% of H₂ presented the highest adsorption capacity (49 mg/g). The nanocomposites can be easily separated from the dispersion by applying an external magnetic field. The interaction between the dye and the nanocomposite occurs mainly by π-π interactions and the mixture of the Fe₂SiO₄ and Fe₇Co₃ leads to a synergistic effect, which favor the adsorption. Full article

(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Inorganic Chemistry)

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16 pages, 1680 KiB

Open AccessReview

DEAD-box RNA Helicase DDX3: Functional Properties and Development of DDX3 Inhibitors as Antiviral and Anticancer Drugs

by Marina K. Kukhanova, Inna L. Karpenko and Alexander V. Ivanov

Molecules 2020, 25(4), 1015; https://doi.org/10.3390/molecules25041015 - 24 Feb 2020

Cited by 53 | Viewed by 8191

Abstract

This short review is focused on enzymatic properties of human ATP-dependent RNA helicase DDX3 and the development of antiviral and anticancer drugs targeting cellular helicases. DDX3 belongs to the DEAD-box proteins, a large family of RNA helicases that participate in all aspects of [...] Read more.

This short review is focused on enzymatic properties of human ATP-dependent RNA helicase DDX3 and the development of antiviral and anticancer drugs targeting cellular helicases. DDX3 belongs to the DEAD-box proteins, a large family of RNA helicases that participate in all aspects of cellular processes, such as cell cycle progression, apoptosis, innate immune response, viral replication, and tumorigenesis. DDX3 has a variety of functions in the life cycle of different viruses. DDX3 helicase is required to facilitate both the Rev-mediated export of unspliced/partially spliced human immunodeficiency virus (HIV) RNA from nucleus and Tat-dependent translation of viral genes. DDX3 silencing blocks the replication of HIV, HCV, and some other viruses. On the other hand, DDX displays antiviral effect against Dengue virus and hepatitis B virus through the stimulation of interferon beta production. The role of DDX3 in different types of cancer is rather controversial. DDX3 acts as an oncogene in one type of cancer, but demonstrates tumor suppressor properties in other types. The human DDX3 helicase is now considered as a new attractive target for the development of novel pharmaceutical drugs. The most interesting inhibitors of DDX3 helicase and the mechanisms of their actions as antiviral or anticancer drugs are discussed in this short review. Full article

(This article belongs to the Special Issue Discovery of New Antiviral Substances)

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10 pages, 2830 KiB

Open AccessArticle

Free-standing Reduced Graphene Oxide/Carbon Nanotube Paper for Flexible Sodium-ion Battery Applications

by Yong Hao and Chunlei Wang

Molecules 2020, 25(4), 1014; https://doi.org/10.3390/molecules25041014 - 24 Feb 2020

Cited by 21 | Viewed by 3970

Abstract

We propose a flexible, binder-free and free-standing carbonaceous paper fabricated via electrostatic spray deposition using reduced graphene oxide/carbon nanotube (rGO/CNT) as a promising electrode material for flexible sodium-ion batteries (NIBs). The as-prepared rGO/CNT paper exhibits a three-dimensional (3D) layered structure by employing rGO [...] Read more.

We propose a flexible, binder-free and free-standing carbonaceous paper fabricated via electrostatic spray deposition using reduced graphene oxide/carbon nanotube (rGO/CNT) as a promising electrode material for flexible sodium-ion batteries (NIBs). The as-prepared rGO/CNT paper exhibits a three-dimensional (3D) layered structure by employing rGO as conductive frameworks to provide sodium-storage active sites and CNT as spacer to increase rGO interlayer distance and benefit the diffusion kinetics of sodium ions. Consequently, the rGO/CNT paper delivers an enhanced sodium ion storage capacity of 166.8 mAh g⁻¹ at 50 mA g⁻¹, retaining an average capacity of 101.4 mAh g⁻¹ when current density sets back 100 mA g⁻¹ after cycling at various current rates. An average capacity of 50 mAh g⁻¹ at 200 mA g⁻¹ was stabilized when cycling up to 300 cycles. The well-maintained electrochemical performance of free-standing rGO/CNT paper is due to the well-established hybrid 3D nanostructures, which demonstrates our carbon based material fabricated by a facile approach can be applied as one of the high-performance and low-cost electrode materials for applications in flexible energy storage devices. Full article

(This article belongs to the Special Issue Materials for Electrochemical Energy Storage:Lithium Ion Batteries and Beyond)

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20 pages, 2446 KiB

Open AccessArticle

Production of Methane, Hydrogen and Ethanol from Secale cereale L. Straw Pretreated with Sulfuric Acid

by Jarosław Domański, Olga Marchut-Mikołajczyk, Weronika Cieciura-Włoch, Piotr Patelski, Urszula Dziekońska-Kubczak, Bartłomiej Januszewicz, Bolin Zhang and Piotr Dziugan

Molecules 2020, 25(4), 1013; https://doi.org/10.3390/molecules25041013 - 24 Feb 2020

Cited by 12 | Viewed by 3180

Abstract

The study describes sulfuric acid pretreatment of straw from Secale cereale L. (rye straw) to evaluate the effect of acid concentration and treatment time on the efficiency of biofuel production. The highest ethanol yield occurred after the enzyme treatment at a dose of [...] Read more.

The study describes sulfuric acid pretreatment of straw from Secale cereale L. (rye straw) to evaluate the effect of acid concentration and treatment time on the efficiency of biofuel production. The highest ethanol yield occurred after the enzyme treatment at a dose of 15 filter paper unit (FPU) per gram of rye straw (subjected to chemical hydrolysis with 2% sulfuric acid (SA) at 121 °C for 1 h) during 120 h. Anaerobic digestion of rye straw treated with 10% SA at 121 °C during 1 h allowed to obtain 347.42 L methane/kg volatile solids (VS). Most hydrogen was released during dark fermentation of rye straw after pretreatment of 2% SA, 121 °C, 1 h and 1% SA, 121 °C, 2 h—131.99 and 134.71 L hydrogen/kg VS, respectively. If the rye straw produced in the European Union were processed into methane, hydrogen, ethanol, the annual electricity production in 2018 could reach 9.87 TWh (terawatt-hours), 1.16 TWh, and 0.60 TWh, respectively. Full article

(This article belongs to the Special Issue Lignocellulosic Biomass to Biofuels and Biochemicals)

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11 pages, 1378 KiB

Open AccessArticle

High Density Supercritical Carbon Dioxide for the Extraction of Pesticide Residues in Onion with Multivariate Response Surface Methodology

by Teshome Tolcha, Tura Gemechu, Said Al-Hamimi, Negussie Megersa and Charlotta Turner

Molecules 2020, 25(4), 1012; https://doi.org/10.3390/molecules25041012 - 24 Feb 2020

Cited by 13 | Viewed by 3887

Abstract

The excessive use of pesticides is a serious health problem due to their toxicity and bioaccumulation through the food chain. Due to the complexity of foods, the analysis of pesticides is challenging often giving large matrix effects and co-extracted compounds. To overcome this [...] Read more.

The excessive use of pesticides is a serious health problem due to their toxicity and bioaccumulation through the food chain. Due to the complexity of foods, the analysis of pesticides is challenging often giving large matrix effects and co-extracted compounds. To overcome this problem, a selective and “green” supercritical fluid extraction method was developed, using neat carbon dioxide as a solvent at pressures of up to 800 bars. A Box–Behnken response surface experimental design was used, with the independent variables of density (0.70−1.0 g mL⁻¹), temperature (40−70 °C), and volume (10−40 mL) of solvent, and the dependent variable of extracted amount of pesticides. The optimum extraction condition was found at the use of 29 mL of supercritical CO₂ at 0.90 g mL⁻¹ and 53 °C (corresponding to 372 bars of pressure). It was observed that increasing the density of CO₂ significantly increased the extraction recovery of endrin and 2,4′-dichlorodiphenyldichloroethane. Matrix-matched calibration curves showed satisfactory linearity (R² ≥ 0.994), and LODs ranged from 0.2 to 2.0 ng g⁻¹. Precision was lower than 11% and recoveries between 80%–103%. Thus, the developed method could efficiently be used for trace analysis of pesticides in complex food matrices without the use of organic solvents. Full article

(This article belongs to the Special Issue Analytical methods and Green chemistry: A Themed Issue in Honor of Professor Jacek Namieśnik)

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12 pages, 2059 KiB

Open AccessArticle

Effect of Different Durations of Solid-Phase Fermentation for Fireweed (Chamerion angustifolium (L.) Holub) Leaves on the Content of Polyphenols and Antioxidant Activity In Vitro

by Marius Lasinskas, Elvyra Jariene, Nijole Vaitkeviciene, Ewelina Hallmann and Katarzyna Najman

Molecules 2020, 25(4), 1011; https://doi.org/10.3390/molecules25041011 - 24 Feb 2020

Cited by 21 | Viewed by 3412

Abstract

Fireweed has recently been recognized as a plant with high antioxidant potential and phenolic content. Its leaves can be fermented to prepare an infusion with ideal antioxidant activity. The aim of this study was to investigate and to determine the influence of solid-phase [...] Read more.

Fireweed has recently been recognized as a plant with high antioxidant potential and phenolic content. Its leaves can be fermented to prepare an infusion with ideal antioxidant activity. The aim of this study was to investigate and to determine the influence of solid-phase fermentation of different durations on the variation of polyphenols in the leaves of fireweed. Laboratory experiments were conducted in 2017–2018. The leaves of fireweed, naturally growing, were fermented for different periods of time: not fermented (control) and fermented for 24 and 48 h. The evaluation of polyphenols and antioxidant activity in leaves was performed using high- performance liquid chromatography (HPLC). Additionally, principal component analysis was used to characterize differences in bioactive compounds between fireweed samples fermented at different durations. Solid-phase fermented leaves were characterized by higher contents of oenothein B, quercetin and benzoic acid but had lower contents of quercetin-3-O-rutinoside, luteolin and chlorogenic and gallic acids. Antioxidant activity in short- (24 h) and long-term (48 h) fermentation (compared to control) gave the highest level of regression in 2017, but in 2018 the effect was observed only with short-term fermentation and control. In conclusion, solid-phase fermentation can be used to modulate biologically active compounds in fireweed leaves. Full article

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19 pages, 1499 KiB

Open AccessFeature PaperArticle

Synthesis and Cytotoxic Activity of New Vindoline Derivatives Coupled to Natural and Synthetic Pharmacophores

by András Keglevich, Leonetta Dányi, Alexandra Rieder, Dorottya Horváth, Áron Szigetvári, Miklós Dékány, Csaba Szántay, Jr., Ahmed Dhahir Latif, Attila Hunyadi, István Zupkó, Péter Keglevich and László Hazai

Molecules 2020, 25(4), 1010; https://doi.org/10.3390/molecules25041010 - 24 Feb 2020

Cited by 14 | Viewed by 4655

Abstract

New Vinca alkaloid derivatives were synthesized to improve the biological activity of the natural alkaloid vindoline. To this end, experiments were performed to link vindoline with various structural units, such as amino acids, a 1,2,3-triazole derivative, morpholine, piperazine and N-methylpiperazine. The structure of [...] Read more.

New Vinca alkaloid derivatives were synthesized to improve the biological activity of the natural alkaloid vindoline. To this end, experiments were performed to link vindoline with various structural units, such as amino acids, a 1,2,3-triazole derivative, morpholine, piperazine and N-methylpiperazine. The structure of the new compounds was characterized by NMR spectroscopy and mass spectrometry (MS). Several compounds exhibited in vitro antiproliferative activity against human gynecological cancer cell lines with IC₅₀ values in the low micromolar concentration range. Full article

(This article belongs to the Special Issue Organic Chemistry Including Heteroatoms)

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29 pages, 5236 KiB

Open AccessEditor’s ChoiceReview

Reactive & Efficient: Organic Azides as Cross-Linkers in Material Sciences

by Marvin Schock and Stefan Bräse

Molecules 2020, 25(4), 1009; https://doi.org/10.3390/molecules25041009 - 24 Feb 2020

Cited by 53 | Viewed by 13137

Abstract

The exceptional reactivity of the azide group makes organic azides a highly versatile family of compounds in chemistry and the material sciences. One of the most prominent reactions employing organic azides is the regioselective copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition with alkynes yielding 1,2,3-triazoles. Other [...] Read more.

The exceptional reactivity of the azide group makes organic azides a highly versatile family of compounds in chemistry and the material sciences. One of the most prominent reactions employing organic azides is the regioselective copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition with alkynes yielding 1,2,3-triazoles. Other named reactions include the Staudinger reduction, the aza-Wittig reaction, and the Curtius rearrangement. The popularity of organic azides in material sciences is mostly based on their propensity to release nitrogen by thermal activation or photolysis. On the one hand, this scission reaction is accompanied with a considerable output of energy, making them interesting as highly energetic materials. On the other hand, it produces highly reactive nitrenes that show extraordinary efficiency in polymer crosslinking, a process used to alter the physical properties of polymers and to boost efficiencies of polymer-based devices such as membrane fuel cells, organic solar cells (OSCs), light-emitting diodes (LEDs), and organic field-effect transistors (OFETs). Thermosets are also suitable application areas. In most cases, organic azides with multiple azide functions are employed which can either be small molecules or oligo- and polymers. This review focuses on nitrene-based applications of multivalent organic azides in the material and life sciences. Full article

(This article belongs to the Special Issue Organic Azides 2019)

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11 pages, 2438 KiB

Open AccessArticle

In Silico, Ex Vivo and In Vivo Studies of Roflumilast as a Potential Antidiarrheal and Antispasmodic agent: Inhibition of the PDE-4 Enzyme and Voltage-gated Ca++ ion Channels

by Najeeb Ur Rehman, Mohd Nazam Ansari and Abdul Samad

Molecules 2020, 25(4), 1008; https://doi.org/10.3390/molecules25041008 - 24 Feb 2020

Cited by 19 | Viewed by 4409

Abstract

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated [...] Read more.

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration–response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast. Full article

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15 pages, 2239 KiB

Open AccessArticle

Pharmacological Blockade of PPAR Isoforms Increases Conditioned Fear Responding in the Presence of Nociceptive Tone

by Jessica C. Gaspar, Bright N. Okine, Alvaro Llorente-Berzal, Michelle Roche and David P. Finn

Molecules 2020, 25(4), 1007; https://doi.org/10.3390/molecules25041007 - 24 Feb 2020

Cited by 10 | Viewed by 3741

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPARα, PPARβ/δ, PPARγ) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR [...] Read more.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors with three isoforms (PPARα, PPARβ/δ, PPARγ) and can regulate pain, anxiety, and cognition. However, their role in conditioned fear and pain-fear interactions has not yet been investigated. Here, we investigated the effects of systemically administered PPAR antagonists on formalin-evoked nociceptive behaviour, fear-conditioned analgesia (FCA), and conditioned fear in the presence of nociceptive tone in rats. Twenty-three and a half hours following fear conditioning to context, male Sprague-Dawley rats received an intraplantar injection of formalin and intraperitoneal administration of vehicle, PPARα (GW6471), PPARβ/δ (GSK0660) or PPARγ (GW9662) antagonists, and 30 min later were re-exposed to the conditioning arena for 15 min. The PPAR antagonists did not alter nociceptive behaviour or fear-conditioned analgesia. The PPARα and PPARβ/δ antagonists prolonged context-induced freezing in the presence of nociceptive tone without affecting its initial expression. The PPARγ antagonist potentiated freezing over the entire trial. In conclusion, pharmacological blockade of PPARα and PPARβ/δ in the presence of formalin-evoked nociceptive tone, impaired short-term, within-trial fear-extinction in rats without affecting pain response, while blockade of PPARγ potentiated conditioned fear responding. These results suggest that endogenous signalling through these three PPAR isoforms may reduce the expression of conditioned fear in the presence of nociceptive tone. Full article

(This article belongs to the Special Issue Role of Cannabinoids in Inflammation)

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12 pages, 1412 KiB

Open AccessFeature PaperReview

Computational Studies of Molecular Materials for Unconventional Energy Conversion: The Challenge of Light Emission by Thermally Activated Delayed Fluorescence

by Javier Sanz-Rodrigo, Yoann Olivier and Juan-Carlos Sancho-García

Molecules 2020, 25(4), 1006; https://doi.org/10.3390/molecules25041006 - 24 Feb 2020

Cited by 18 | Viewed by 5059

Abstract

In this paper we describe the mechanism of light emission through thermally activated delayed fluorescence (TADF)—a process able to ideally achieve 100% quantum efficiencies upon fully harvesting the energy of triplet excitons, and thus minimizing the energy loss of common (i.e., fluorescence and [...] Read more.

In this paper we describe the mechanism of light emission through thermally activated delayed fluorescence (TADF)—a process able to ideally achieve 100% quantum efficiencies upon fully harvesting the energy of triplet excitons, and thus minimizing the energy loss of common (i.e., fluorescence and phosphorescence) luminescence processes. If successful, this technology could be exploited for the manufacture of more efficient organic light-emitting diodes (OLEDs) made of only light elements for multiple daily applications, thus contributing to the rise of a sustainable electronic industry and energy savings worldwide. Computational and theoretical studies have fostered the design of these all-organic molecular emitters by disclosing helpful structure–property relationships and/or analyzing the physical origin of this mechanism. However, as the field advances further, some limitations have also appeared, particularly affecting TD-DFT calculations, which have prompted the use of a variety of methods at the molecular scale in recent years. Herein we try to provide a guide for beginners, after summarizing the current state-of-the-art of the most employed theoretical methods focusing on the singlet–triplet energy difference, with the additional aim of motivating complementary studies revealing the stronger and weaker aspects of computational modelling for this cutting-edge technology. Full article

(This article belongs to the Special Issue Molecular Materials for Energy Conversion and Storage Technologies)

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15 pages, 2269 KiB

Open AccessArticle

Study on Cecropin B2 Production via Construct Bearing Intein Oligopeptide Cleavage Variants

by Yi-Ting Fang, Si-Yu Li, Nien-Jen Hu, Jie Yang, Jyung-Hurng Liu and Yung-Chuan Liu

Molecules 2020, 25(4), 1005; https://doi.org/10.3390/molecules25041005 - 24 Feb 2020

Cited by 3 | Viewed by 3284

Abstract

In this study, genetic engineering was applied to the overexpression of the antimicrobial peptide (AMP) cecropin B2 (cecB2). pTWIN1 vector with a chitin-binding domain (CBD) and an auto-cleavage Ssp DnaB intein (INT) was coupled to the cecB2 to form a fusion protein construct [...] Read more.

In this study, genetic engineering was applied to the overexpression of the antimicrobial peptide (AMP) cecropin B2 (cecB2). pTWIN1 vector with a chitin-binding domain (CBD) and an auto-cleavage Ssp DnaB intein (INT) was coupled to the cecB2 to form a fusion protein construct and expressed via Escherichia coli ER2566. The cecB2 was obtained via the INT cleavage reaction, which was highly related to its adjacent amino acids. Three oligopeptide cleavage variants (OCVs), i.e., GRA, CRA, and SRA, were used as the inserts located at the C-terminus of the INT to facilitate the cleavage reaction. SRA showed the most efficient performance in accelerating the INT self-cleavage reaction. In addition, in order to treat the INT as a biocatalyst, a first-order rate equation was applied to fit the INT cleavage reaction. A possible inference was proposed for the INT cleavage promotion with varied OCVs using a molecular dynamics (MD) simulation. The production and purification via the CBD-INT-SRA-cecB2 fusion protein resulted in a cecB2 yield of 58.7 mg/L with antimicrobial activity. Full article

(This article belongs to the Special Issue Bioactive Peptides—From Therapy to Nutrition)

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26 pages, 414 KiB

Open AccessReview

Potential Use of Marine Seaweeds as Prebiotics: A Review

by Aroa Lopez-Santamarina, Jose Manuel Miranda, Alicia del Carmen Mondragon, Alexandre Lamas, Alejandra Cardelle-Cobas, Carlos Manuel Franco and Alberto Cepeda

Molecules 2020, 25(4), 1004; https://doi.org/10.3390/molecules25041004 - 24 Feb 2020

Cited by 112 | Viewed by 8125

Abstract

Human gut microbiota plays an important role in several metabolic processes and human diseases. Various dietary factors, including complex carbohydrates, such as polysaccharides, provide abundant nutrients and substrates for microbial metabolism in the gut, affecting the members and their functionality. Nowadays, the main [...] Read more.

Human gut microbiota plays an important role in several metabolic processes and human diseases. Various dietary factors, including complex carbohydrates, such as polysaccharides, provide abundant nutrients and substrates for microbial metabolism in the gut, affecting the members and their functionality. Nowadays, the main sources of complex carbohydrates destined for human consumption are terrestrial plants. However, fresh water is an increasingly scarce commodity and world agricultural productivity is in a persistent decline, thus demanding the exploration of other sources of complex carbohydrates. As an interesting option, marine seaweeds show rapid growth and do not require arable land, fresh water or fertilizers. The present review offers an objective perspective of the current knowledge surrounding the impacts of seaweeds and their derived polysaccharides on the human microbiome and the profound need for more in-depth investigations into this topic. Animal experiments and in vitro colonic-simulating trials investigating the effects of seaweed ingestion on human gut microbiota are discussed. Full article

(This article belongs to the Special Issue Analytical Technology in Nutrition Analysis)

16 pages, 3365 KiB

Open AccessReview

Perceptions and Misconceptions in Molecular Recognition: Key Factors in Self-Assembling Multivalent (SAMul) Ligands/Polyanions Selectivity

by Domenico Marson, Erik Laurini, Suzana Aulic, Maurizio Fermeglia and Sabrina Pricl

Molecules 2020, 25(4), 1003; https://doi.org/10.3390/molecules25041003 - 24 Feb 2020

Cited by 1 | Viewed by 2701

Abstract

Biology is dominated by polyanions (cell membranes, nucleic acids, and polysaccharides just to name a few), and achieving selective recognition between biological polyanions and synthetic systems currently constitutes a major challenge in many biomedical applications, nanovectors-assisted gene delivery being a prime example. This [...] Read more.

Biology is dominated by polyanions (cell membranes, nucleic acids, and polysaccharides just to name a few), and achieving selective recognition between biological polyanions and synthetic systems currently constitutes a major challenge in many biomedical applications, nanovectors-assisted gene delivery being a prime example. This review work summarizes some of our recent efforts in this field; in particular, by using a combined experimental/computation approach, we investigated in detail some critical aspects in self-assembled nanomicelles and two major polyanions—DNA and heparin. Full article

(This article belongs to the Special Issue Dendrimers in Biomedicine)

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14 pages, 2476 KiB

Open AccessArticle

Novel Chaperones RrGroEL and RrGroES for Activity and Stability Enhancement of Nitrilase in Escherichia coli and Rhodococcus ruber

by Chunmeng Xu, Lingjun Tang, Youxiang Liang, Song Jiao, Huimin Yu and Hui Luo

Molecules 2020, 25(4), 1002; https://doi.org/10.3390/molecules25041002 - 24 Feb 2020

Cited by 12 | Viewed by 4063

Abstract

For large-scale bioproduction, thermal stability is a crucial property for most industrial enzymes. A new method to improve both the thermal stability and activity of enzymes is of great significance. In this work, the novel chaperones RrGroEL and RrGroES from Rhodococcus [...] Read more.

For large-scale bioproduction, thermal stability is a crucial property for most industrial enzymes. A new method to improve both the thermal stability and activity of enzymes is of great significance. In this work, the novel chaperones RrGroEL and RrGroES from Rhodococcus ruber, a nontypical actinomycete with high organic solvent tolerance, were evaluated and applied for thermal stability and activity enhancement of a model enzyme, nitrilase. Two expression strategies, namely, fusion expression and co-expression, were compared in two different hosts, E. coli and R. ruber. In the E. coli host, fusion expression of nitrilase with either RrGroES or RrGroEL significantly enhanced nitrilase thermal stability (4.8-fold and 10.6-fold, respectively) but at the expense of enzyme activity (32–47% reduction). The co-expression strategy was applied in R. ruber via either a plasmid-only or genome-plus-plasmid method. Through integration of the nitrilase gene into the R. ruber genome at the site of nitrile hydratase (NHase) gene via CRISPR/Cas9 technology and overexpression of RrGroES or RrGroEL with a plasmid, the engineered strains R. ruber TH3 dNHase::RrNit (pNV18.1-Pami-RrNit-Pami-RrGroES) and TH3 dNHase::RrNit (pNV18.1-Pami-RrNit-Pami-RrGroEL) were constructed and showed remarkably enhanced nitrilase activity and thermal stability. In particular, the RrGroEL and nitrilase co-expressing mutant showed the best performance, with nitrilase activity and thermal stability 1.3- and 8.4-fold greater than that of the control TH3 (pNV18.1-Pami-RrNit), respectively. These findings are of great value for production of diverse chemicals using free bacterial cells as biocatalysts. Full article

(This article belongs to the Special Issue Nitrilases and Nitrile Hydratases)

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10 pages, 2622 KiB

Open AccessArticle

The Effect of Mg, Fe(II), and Al Doping on CH₄: Adsorption and Diffusion on the Surface of Na-Kaolinite (001) by Molecular Simulations

by Kai Wang, Bin Zhang and Tianhe Kang

Molecules 2020, 25(4), 1001; https://doi.org/10.3390/molecules25041001 - 24 Feb 2020

Cited by 10 | Viewed by 2593

Abstract

Because kaolinite includes a large range of defect elements, the effects of Mg, Fe(II), and Al doping on the CH₄ adsorption and diffusion on the surface of Na-kaolinite (001) were investigated by molecular simulations. The simulation results illustrate that ion doping can [...] Read more.

Because kaolinite includes a large range of defect elements, the effects of Mg, Fe(II), and Al doping on the CH₄ adsorption and diffusion on the surface of Na-kaolinite (001) were investigated by molecular simulations. The simulation results illustrate that ion doping can significantly reduce the amount of CH₄ adsorbed by kaolinite, but the type of doped ions has little effect on the amount of adsorption. The specific surface area of kaolinite and the interaction energy between CH₄ and the kaolinite’s surface are two key factors that can determine CH₄ adsorption capacity. The first peak value of the radial distribution functions (RDFs) between CH₄ and the pure kaolinite is larger than that between Mg-, Fe(II)-, and Al-doped kaolinite, which indicates that ion doping can reduce the strength of the interactions between CH₄ and the kaolinite’s surface. Besides hydrogen and oxygen atoms, interlayer sodium ions are also strong adsorption sites for CH₄ and lead to a weakened interaction between CH₄ and the kaolinite’s surface, as well as a decrease in CH₄ adsorption. Contrary to the adsorption results, ion doping facilitates the diffusion of CH₄, which is beneficial for actual shale gas extraction. Full article

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

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9 pages, 2494 KiB

Open AccessArticle

Recognition of V³⁺/V⁴⁺/V⁵⁺ Multielectron Reactions in Na₃V(PO₄)₂: A Potential High Energy Density Cathode for Sodium-Ion Batteries

by Rui Liu, Ziteng Liang, Yuxuan Xiang, Weimin Zhao, Haodong Liu, Yan Chen, Ke An and Yong Yang

Molecules 2020, 25(4), 1000; https://doi.org/10.3390/molecules25041000 - 24 Feb 2020

Cited by 11 | Viewed by 4698

Abstract

Na₃V(PO₄)₂ was reported recently as a novel cathode material with high theoretical energy density for Sodium-ion batteries (SIBs). However, whether V³⁺/V⁴⁺/V⁵⁺ multielectron reactions can be realized during the charging process is still an [...] Read more.

Na₃V(PO₄)₂ was reported recently as a novel cathode material with high theoretical energy density for Sodium-ion batteries (SIBs). However, whether V³⁺/V⁴⁺/V⁵⁺ multielectron reactions can be realized during the charging process is still an open question. In this work, Na₃V(PO₄)₂ is synthesized by using a solid-state method. Its atomic composition and crystal structure are verified by X-ray diffraction (XRD) and neutron diffraction (ND) joint refinement. The electrochemical performance of Na₃V(PO₄)₂ is evaluated in two different voltage windows, namely 2.5–3.8 and 2.5–4.3 V. ⁵¹V solid-state NMR (ssNMR) results disclose the presence of V⁵⁺ in Na_2−xV(PO₄)₂ when charging Na₃V(PO₄)₂ to 4.3 V, confirming Na₃V(PO₄)₂ is a potential high energy density cathode through realization of V³⁺/V⁴⁺/V⁵⁺ multielectron reactions. Full article

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

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11 pages, 6079 KiB

Open AccessArticle

The Effect of Thermomechanical Pretreatment on the Structure and Properties of Lignin-Rich Plant Biomass

by Ekaterina M. Podgorbunskikh, Aleksey L. Bychkov, Elena I. Ryabchikova and Oleg I. Lomovsky

Molecules 2020, 25(4), 995; https://doi.org/10.3390/molecules25040995 - 23 Feb 2020

Cited by 18 | Viewed by 5901

Abstract

The cooperative thermomechanical properties of plant-derived polymers have been studied insufficiently, although this feedstock has a very high potential. In the present paper, we analyzed the changes in the structure and physicochemical properties of lignin-rich biomass induced by thermomechanical pretreatment. Low-temperature treatment allows [...] Read more.

The cooperative thermomechanical properties of plant-derived polymers have been studied insufficiently, although this feedstock has a very high potential. In the present paper, we analyzed the changes in the structure and physicochemical properties of lignin-rich biomass induced by thermomechanical pretreatment. Low-temperature treatment allows one to retain the original supramolecular structure of the cell walls, while an appreciably high disintegration degree is reached. This increases the reactivity of the material in the subsequent heterogeneous reactions. Mechanical pretreatment at medium temperatures (10 °C), when almost all cell wall polymers except for low-molecular-weight lignin are in the glassy state, enhances the mobility of cell wall polymers and causes sufficient cellulose disordering, while the specific surface area is not significantly increased. High-temperature pretreatment of reed biomass is accompanied by pore formation and lignin release from the cell wall structure, which opens up new prospects for using this biomass as a matrix to produce core–shell-structured sorbents of heavy metals. The energy consumed by mechanochemical equipment for the activation of reed biomass was determined. Full article

(This article belongs to the Special Issue Advances in Conversion of Biomass and Waste to Chemicals and Fuels)

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11 pages, 3030 KiB

Open AccessArticle

Inhibitory Effects of Eriodictyol-7-O-β-d-glucuronide and 5,7-Dihydroxy-4-chromene Isolated from Chrysanthemum zawadskii var. latilobum in FcεRI-Mediated Human Basophilic KU812F Cell Activation

by Mina Lee and Sun-Yup Shim

Molecules 2020, 25(4), 994; https://doi.org/10.3390/molecules25040994 - 23 Feb 2020

Cited by 6 | Viewed by 3002

Abstract

Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from [...] Read more.

Chrysanthemum zawadskii var. latilobum (CZL) has been used in Eastern medicine for the treatment of various diseases, such as pneumonia, bronchitis, cough, the common cold, pharyngitis, bladder-related disorders, gastroenteric disorders, and hypertension. In the present study, we isolated two strong antiallergic compounds from CZL, namely, eriodictyol-7-O-β-d-glucuronide (EDG) and 5,7-dihydroxy-4-chromene (DC), and investigated their antiallergic effects in FcεRI-mediated human basophilic KU812F cells. EDG and DC downregulated the protein and messenger RNA (mRNA) expression of FcεRI on the cell surface. Moreover, Western blotting analysis showed that EDG and DC inhibited the expression of protein tyrosine kinases such as Syk and Lyn, and extracellular-regulated kinases (ERK) 1/2. These results suggested that EDG and DC, antiallergic constituents of CZL, are potential therapeutic candidates for protection against and for the treatment of allergic disorders. Full article

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14 pages, 1916 KiB

Open AccessArticle

Interplay between Polymorphism and Isostructurality in the 2-Fur- and 2-Thenaldehyde Semi- and Thiosemicarbazones

by Marcin Swiatkowski, Agata Trzesowska-Kruszynska, Agnieszka Danielewicz, Paulina Sobczak and Rafal Kruszynski

Molecules 2020, 25(4), 993; https://doi.org/10.3390/molecules25040993 - 23 Feb 2020

Cited by 2 | Viewed by 2666

Abstract

The four compounds, namely: 5-nitro-2-furaldehyde thiosemicarbazone (1); 5-nitro-2-thiophene thiosemicarbazone (2); 5-nitro-2-furaldehyde semicarbazone (3); and 5-nitro-2-thiophene semicarbazone (4) were synthesized and crystallized. The three new crystal structures of 1, 2, and 4 were determined [...] Read more.

The four compounds, namely: 5-nitro-2-furaldehyde thiosemicarbazone (1); 5-nitro-2-thiophene thiosemicarbazone (2); 5-nitro-2-furaldehyde semicarbazone (3); and 5-nitro-2-thiophene semicarbazone (4) were synthesized and crystallized. The three new crystal structures of 1, 2, and 4 were determined and compared to three already known crystal structures of 3. Additionally, two new polymorphic forms of 1 solvate were synthesized and studied. The influence of the exchange of 2-thiophene to 2-furaldehyde as well as thiosemicarbazone and semicarbazone on the self-assembly of supramolecular nets was elucidated and discussed in terms of the formed synthons and assemblies accompanied by Full Interaction Maps analysis. Changes in the strength of IR oscillators caused by the molecular and crystal packing effects are described and explained in terms of changes of electron density. Full article

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13 pages, 1924 KiB

Open AccessArticle

Vitamin C Enhances the Antibacterial Activity of Honey against Planktonic and Biofilm-Embedded Bacteria

by Juraj Majtan, Martin Sojka, Helena Palenikova, Marcela Bucekova and Viktor Majtan

Molecules 2020, 25(4), 992; https://doi.org/10.3390/molecules25040992 - 23 Feb 2020

Cited by 35 | Viewed by 8081

Abstract

Multifactorial antibacterial action is an important feature of honey; however, its bactericidal efficacy against biofilm-embedded bacteria is limited. The aim of this study was to investigate the impact of vitamin C (Vit C) on the antibacterial activity of natural honeys against planktonic as [...] Read more.

Multifactorial antibacterial action is an important feature of honey; however, its bactericidal efficacy against biofilm-embedded bacteria is limited. The aim of this study was to investigate the impact of vitamin C (Vit C) on the antibacterial activity of natural honeys against planktonic as well as biofilm-embedded bacterial pathogens. The antibacterial activity of four honey samples supplemented with Vit C was expressed as the minimum inhibitory concentration (MIC). At sub-MICs, Vit C significantly increased the antibacterial activity of the tested honeys against Pseudomonas aeruginosa in planktonic cultures. However, after supplementation, honeydew honey, the most active honey, was ineffective against Staphylococcus aureus. On the other hand, when 100% honeydew honey was supplemented with Vit C (100 mg/g of honey) in a multispecies wound biofilm model, complete eradication of almost all bacterial isolates, including S. aureus, was observed. Furthermore, a mixture of honey and Vit C was partially effective against Enterococcus faecalis, whereas honey alone exhibited no antibacterial activity against this bacterium. Vit C counteracted hydrogen peroxide in honey solution and, thus, eliminated the major antibacterial compound present in honey. It is likely that a combination of honey with Vit C may trigger the intracellular production of reactive oxygen species in bacterial cells, but the exact cellular mechanisms warrant further investigations. Full article

(This article belongs to the Special Issue Antibiofilm Efficacy of Natural and Natural-Based Products)

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22 pages, 2340 KiB

Open AccessReview

Isothiazolinone Biocides: Chemistry, Biological, and Toxicity Profiles

by Vânia Silva, Cátia Silva, Pedro Soares, E. Manuela Garrido, Fernanda Borges and Jorge Garrido

Molecules 2020, 25(4), 991; https://doi.org/10.3390/molecules25040991 - 23 Feb 2020

Cited by 115 | Viewed by 19526

Abstract

The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness [...] Read more.

The importance of isothiazole and of compounds containing the isothiazole nucleus has been growing over the last few years. Isothiazolinones are used in cosmetic and as chemical additives for occupational and industrial usage due to their bacteriostatic and fungiostatic activity. Despite their effectiveness as biocides, isothiazolinones are strong sensitizers, producing skin irritations and allergies and may pose ecotoxicological hazards. Therefore, their use is restricted by EU legislation. Considering the relevance and importance of isothiazolinone biocides, the present review describes the state-of-the-art knowledge regarding their synthesis, antibacterial components, toxicity (including structure–activity–toxicity relationships) outlines, and (photo)chemical stability. Due to the increasing prevalence and impact of isothiazolinones in consumer’s health, analytical methods for the identification and determination of this type of biocides were also discussed. Full article

(This article belongs to the Special Issue Microbiocides Chemistry)

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9 pages, 2308 KiB

Open AccessArticle

Asymmetric Transfer Hydrogenation of Arylketones Catalyzed by Enantiopure Ruthenium(II)/Pybox Complexes Containing Achiral Phosphonite and Phosphinite Ligands

by Miguel Claros, Eire de Julián, Josefina Díez, Elena Lastra and M. Pilar Gamasa

Molecules 2020, 25(4), 990; https://doi.org/10.3390/molecules25040990 - 23 Feb 2020

Cited by 3 | Viewed by 3030

Abstract

A family of complexes of the formula trans-[RuCl₂(L)(R-pybox)] (R-pybox = (S,S)-ⁱPr-pybox, (R,R)-Ph-pybox, L = monodentate phosphonite, PPh(OR)₂, and phosphinite, L = PPh₂(OR), ligands) were screened in [...] Read more.

A family of complexes of the formula trans-[RuCl₂(L)(R-pybox)] (R-pybox = (S,S)-ⁱPr-pybox, (R,R)-Ph-pybox, L = monodentate phosphonite, PPh(OR)₂, and phosphinite, L = PPh₂(OR), ligands) were screened in the catalytic asymmetric transfer hydrogenation of acetophenone, observing a strong influence of the nature of both the R-pybox substituents and the L ligand in the process. The best results were obtained with complex trans-[RuCl₂{PPh₂(OEt)}{(R,R)-Ph-pybox}] (2c), which provided high conversion and enantioselectivity (up to 96% enantiomeric excess, e.e.) for the reduction of a variety of aromatic ketones, affording the (S)-benzylalcohols. Full article

(This article belongs to the Special Issue Development of Asymmetric Synthesis)

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19 pages, 3849 KiB

Open AccessArticle

Therapeutic Effects of Cold-Pressed Perilla Oil Mainly Consisting of Linolenic acid, Oleic Acid and Linoleic Acid on UV-Induced Photoaging in NHDF Cells and SKH-1 Hairless Mice

by Hyeon Jun Choi, Bo Ram Song, Ji Eun Kim, Su Ji Bae, Yun Ju Choi, Su Jin Lee, Jeong Eun Gong, Hee Seob Lee, Chung Yeoul Lee, Bae-Hwan Kim and Dae Youn Hwang

Molecules 2020, 25(4), 989; https://doi.org/10.3390/molecules25040989 - 22 Feb 2020

Cited by 21 | Viewed by 5120

Abstract

Positive physiological benefits of several plant oils on the UV-induced photoaging have been reported in some cell lines and model mice, but perilla oil collected from the seeds of Perilla frutescens L. has not been investigated in this context. To study the therapeutic [...] Read more.

Positive physiological benefits of several plant oils on the UV-induced photoaging have been reported in some cell lines and model mice, but perilla oil collected from the seeds of Perilla frutescens L. has not been investigated in this context. To study the therapeutic effects of cold-pressed perilla oil (CPO) on UV-induced photoaging in vitro and in vivo, UV-induced cellular damage and cutaneous photoaging were assessed in normal human dermal fibroblasts (NHDFs) and HR-1 hairless mice. CPO contained five major fatty acids including linolenic acid (64.11%), oleic acid (16.34%), linoleic acid (11.87%), palmitic acid (5.06%), and stearic acid (2.48%). UV-induced reductions in NHDF cell viability, ROS production, SOD activity, and G2/M cell cycle arrest were remarkably improved in UV + CPO treated NHDF cells as compared with UV + Vehicle treated controls. Also, UV-induced increases in MMP-1 protein and galactosidase levels were remarkably suppressed by CPO. In UV-radiated hairless mice, topical application of CPO inhibited an increase in wrinkle formation, transepidermal water loss (TEWL), erythema value, hydration and melanin index on dorsal skin of UVB-irradiated hairless mice. CPO was observed to similarly suppress UV-induced increases in epidermal thickness, mast cell numbers, and galactosidase and MMP-3 mRNA levels. These results suggest CPO has therapeutic potential in terms of protecting against skin photoaging by regulating skin morphology, histopathology and oxidative status. Full article

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18 pages, 4048 KiB

Open AccessFeature PaperArticle

Laser-Plasma Spectroscopy of Hydroxyl with Applications

by Christian G. Parigger, Christopher M. Helstern, Benjamin S. Jordan, David M. Surmick and Robert Splinter

Molecules 2020, 25(4), 988; https://doi.org/10.3390/molecules25040988 - 22 Feb 2020

Cited by 10 | Viewed by 4662

Abstract

This article discusses laser-induced laboratory-air plasma measurements and analysis of hydroxyl (OH) ultraviolet spectra. The computations of the OH spectra utilize line strength data that were developed previously and that are now communicated for the first time. The line strengths have been utilized [...] Read more.

This article discusses laser-induced laboratory-air plasma measurements and analysis of hydroxyl (OH) ultraviolet spectra. The computations of the OH spectra utilize line strength data that were developed previously and that are now communicated for the first time. The line strengths have been utilized extensively in interpretation of recorded molecular emission spectra and have been well-tested in laser-induced fluorescence applications for the purpose of temperature inferences from recorded data. Moreover, new experiments with Q-switched laser pulses illustrate occurrence of molecular recombination spectra for time delays of the order of several dozen of microseconds after plasma initiation. The OH signals occur due to the natural humidity in laboratory air. Centrifugal stretching of the Franck-Condon factors and r-centroids are included in the process of determining the line strengths that are communicated as a Supplementary File. Laser spectroscopy applications of detailed OH computations include laser-induced plasma and combustion analyses, to name but two applications. This work also includes literature references that address various diagnosis applications. Full article

(This article belongs to the Special Issue Practical Applications of Molecular Spectroscopy)

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