Molecules

20 pages, 3001 KiB

Open AccessReview

Synergistic Approach of Ultrafast Spectroscopy and Molecular Simulations in the Characterization of Intramolecular Charge Transfer in Push-Pull Molecules

by Barbara Patrizi, Concetta Cozza, Adriana Pietropaolo, Paolo Foggi and Mario Siciliani de Cumis

Molecules 2020, 25(2), 430; https://doi.org/10.3390/molecules25020430 - 20 Jan 2020

Cited by 27 | Viewed by 7878

Abstract

The comprehensive characterization of Intramolecular Charge Transfer (ICT) stemming in push-pull molecules with a delocalized π-system of electrons is noteworthy for a bespoke design of organic materials, spanning widespread applications from photovoltaics to nanomedicine imaging devices. Photo-induced ICT is characterized by structural reorganizations, [...] Read more.

The comprehensive characterization of Intramolecular Charge Transfer (ICT) stemming in push-pull molecules with a delocalized π-system of electrons is noteworthy for a bespoke design of organic materials, spanning widespread applications from photovoltaics to nanomedicine imaging devices. Photo-induced ICT is characterized by structural reorganizations, which allows the molecule to adapt to the new electronic density distribution. Herein, we discuss recent photophysical advances combined with recent progresses in the computational chemistry of photoactive molecular ensembles. We focus the discussion on femtosecond Transient Absorption Spectroscopy (TAS) enabling us to follow the transition from a Locally Excited (LE) state to the ICT and to understand how the environment polarity influences radiative and non-radiative decay mechanisms. In many cases, the charge transfer transition is accompanied by structural rearrangements, such as the twisting or molecule planarization. The possibility of an accurate prediction of the charge-transfer occurring in complex molecules and molecular materials represents an enormous advantage in guiding new molecular and materials design. We briefly report on recent advances in ultrafast multidimensional spectroscopy, in particular, Two-Dimensional Electronic Spectroscopy (2DES), in unraveling the ICT nature of push-pull molecular systems. A theoretical description at the atomistic level of photo-induced molecular transitions can predict with reasonable accuracy the properties of photoactive molecules. In this framework, the review includes a discussion on the advances from simulation and modeling, which have provided, over the years, significant information on photoexcitation, emission, charge-transport, and decay pathways. Density Functional Theory (DFT) coupled with the Time-Dependent (TD) framework can describe electronic properties and dynamics for a limited system size. More recently, Machine Learning (ML) or deep learning approaches, as well as free-energy simulations containing excited state potentials, can speed up the calculations with transferable accuracy to more complex molecules with extended system size. A perspective on combining ultrafast spectroscopy with molecular simulations is foreseen for optimizing the design of photoactive compounds with tunable properties. Full article

(This article belongs to the Special Issue Computational Spectroscopy 2020)

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13 pages, 734 KiB

Open AccessReview

Pharmacological Overview of the BGP-15 Chemical Agent as a New Drug Candidate for the Treatment of Symptoms of Metabolic Syndrome

by Ágota Pető, Dóra Kósa, Pálma Fehér, Zoltán Ujhelyi, Dávid Sinka, Miklós Vecsernyés, Zoltán Szilvássy, Béla Juhász, Zoltán Csanádi, László Vígh and Ildikó Bácskay

Molecules 2020, 25(2), 429; https://doi.org/10.3390/molecules25020429 - 20 Jan 2020

Cited by 27 | Viewed by 6357

Abstract

BGP-15 is a new insulin sensitizer drug candidate, which was developed by Hungarian researchers. In recent years, numerous research groups have studied its beneficial effects. It is effective in the treatment of insulin resistance and it has protective effects in Duchenne muscular dystrophy, [...] Read more.

BGP-15 is a new insulin sensitizer drug candidate, which was developed by Hungarian researchers. In recent years, numerous research groups have studied its beneficial effects. It is effective in the treatment of insulin resistance and it has protective effects in Duchenne muscular dystrophy, diastolic dysfunction, tachycardia, heart failure, and atrial fibrillation, and it can alleviate cardiotoxicity. BGP-15 exhibits chemoprotective properties in different cytostatic therapies, and has also proven to be photoprotective. It can additionally have advantageous effects in mitochondrial-stress-related diseases. Although the precise mechanism of the effect is still unknown to us, we know that the molecule is a PARP inhibitor, chaperone co-inducer, reduces ROS production, and is able to remodel the organization of cholesterol-rich membrane domains. In the following review, our aim was to summarize the investigated molecular mechanisms and pharmacological effects of this potential API. The main objective was to present the wide pharmacological potentials of this chemical agent. Full article

(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes-II)

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15 pages, 2570 KiB

Open AccessFeature PaperReview

Solid State NMR: A Powerful Tool for the Characterization of Borophosphate Glasses

by Grégory Tricot, Lazzat Alpysbay and Bertrand Doumert

Molecules 2020, 25(2), 428; https://doi.org/10.3390/molecules25020428 - 20 Jan 2020

Cited by 25 | Viewed by 5208

Abstract

This review will show how solid state nuclear magnetic resonance (NMR) has contributed to a better understanding of the borophosphate glass structure. Over the last fifteen years, 1D and 2D magic angle spinning (MAS)-NMR has been used to produce key information about both [...] Read more.

This review will show how solid state nuclear magnetic resonance (NMR) has contributed to a better understanding of the borophosphate glass structure. Over the last fifteen years, 1D and 2D magic angle spinning (MAS)-NMR has been used to produce key information about both local and medium range organization in this type of glass. After a brief presentation on borophosphate glasses, the paper will focus on the description of the local order of phosphate and borate species obtained by 1D ³¹P-and ¹¹B-MAS-NMR experiments, with a special emphasis on the improvements obtained at high magnetic fields on the borate speciation description. The last part of this review will show how correlation NMR provided new insights into the intermediate length scale order. Special attention will be paid to the quantitative data retrieved from ¹¹B/³¹P REDOR-based NMR sequences and to the qualitative connectivity schemes observed on the 2D ¹¹B/³¹P maps edited with the heteronuclear multiple quantum coherence (HMQC) NMR techniques. Full article

(This article belongs to the Special Issue Solid-State NMR Spectroscopy in Materials Chemistry)

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112 pages, 580 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Molecules in 2019

by Molecules Editorial Office

Molecules 2020, 25(2), 427; https://doi.org/10.3390/molecules25020427 - 20 Jan 2020

Cited by 2 | Viewed by 9587

Abstract

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...] Full article

15 pages, 3367 KiB

Open AccessArticle

Thymoquinone Enhances Paclitaxel Anti-Breast Cancer Activity via Inhibiting Tumor-Associated Stem Cells Despite Apparent Mathematical Antagonism

by Hanan A. Bashmail, Aliaa A. Alamoudi, Abdulwahab Noorwali, Gehan A. Hegazy, Ghada M. Ajabnoor and Ahmed M. Al-Abd

Molecules 2020, 25(2), 426; https://doi.org/10.3390/molecules25020426 - 20 Jan 2020

Cited by 34 | Viewed by 6746

Abstract

Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC₅₀ values of 64.93 [...] Read more.

Thymoquinone (TQ) has shown substantial evidence for its anticancer effects. Using human breast cancer cells, we evaluated the chemomodulatory effect of TQ on paclitaxel (PTX). TQ showed weak cytotoxic properties against MCF-7 and T47D breast cancer cells with IC₅₀ values of 64.93 ± 14 µM and 165 ± 2 µM, respectively. Combining TQ with PTX showed apparent antagonism, increasing the IC₅₀ values of PTX from 0.2 ± 0.07 µM to 0.7 ± 0.01 µM and from 0.1 ± 0.01 µM to 0.15 ± 0.02 µM in MCF-7 and T47D cells, respectively. Combination index analysis showed antagonism in both cell lines with CI values of 4.6 and 1.6, respectively. However, resistance fractions to PTX within MCF-7 and T47D cells (42.3 ± 1.4% and 41.9 ± 1.1%, respectively) were completely depleted by combination with TQ. TQ minimally affected the cell cycle, with moderate accumulation of cells in the S-phase. However, a significant increase in Pre-G phase cells was observed due to PTX alone and PTX combination with TQ. To dissect this increase in the Pre-G phase, apoptosis, necrosis, and autophagy were assessed by flowcytometry. TQ significantly increased the percent of apoptotic/necrotic cell death in T47D cells after combination with paclitaxel. On the other hand, TQ significantly induced autophagy in MCF-7 cells. Furthermore, TQ was found to significantly decrease breast cancer-associated stem cell clone (CD44+/CD24-cell) in both MCF-7 and T47D cells. This was mirrored by the downregulation of TWIST-1 gene and overexpression of SNAIL-1 and SNAIL-2 genes. TQ therefore possesses potential chemomodulatory effects to PTX when studied in breast cancer cells via enhancing PTX induced cell death including autophagy. In addition, TQ depletes breast cancer-associated stem cells and sensitizes breast cancer cells to PTX killing effects. Full article

(This article belongs to the Special Issue Polyphenols in Crops, Medicinal and Wild Edible Plants: From Their Metabolism to Their Benefits for Human Health)

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15 pages, 1173 KiB

Open AccessArticle

Characterization of Eucalyptus nitens Lignins Obtained by Biorefinery Methods Based on Ionic Liquids

by Lucía Penín, Heiko Lange, Valentín Santos, Claudia Crestini and Juan Carlos Parajó

Molecules 2020, 25(2), 425; https://doi.org/10.3390/molecules25020425 - 20 Jan 2020

Cited by 10 | Viewed by 3903

Abstract

Eucalyptus nitens wood samples were subjected to consecutive stages of hydrothermal processing for hemicellulose solubilization and delignification with an ionic liquid, i.e., either 1-butyl-3-methylimidazolium hydrogen sulfate or triethylammonium hydrogen sulfate. Delignification experiments were carried out a 170 °C for 10–50 min. The solid [...] Read more.

Eucalyptus nitens wood samples were subjected to consecutive stages of hydrothermal processing for hemicellulose solubilization and delignification with an ionic liquid, i.e., either 1-butyl-3-methylimidazolium hydrogen sulfate or triethylammonium hydrogen sulfate. Delignification experiments were carried out a 170 °C for 10–50 min. The solid phases from treatments, i.e., cellulose-enriched solids, were recovered by centrifugation, and lignin was separated from the ionic liquid by water precipitation. The best delignification conditions were identified on the basis of the results determined for delignification percentage, lignin recovery yield, and cellulose recovery in solid phase. The lignins obtained under selected conditions were characterized in deep by ³¹P-NMR, ¹³C-NMR, HSQC, and gel permeation chromatography. The major structural features of the lignins were discussed in comparison with the results determined for a model Ionosolv lignin. Full article

(This article belongs to the Special Issue Lignin—Chemistry and Materials: Past, Present and Future)

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14 pages, 1932 KiB

Open AccessArticle

Mapping the Photochemistry of European Mid-Latitudes Rivers: An Assessment of Their Ability to Photodegrade Contaminants

by Luca Carena and Davide Vione

Molecules 2020, 25(2), 424; https://doi.org/10.3390/molecules25020424 - 20 Jan 2020

Cited by 8 | Viewed by 3623

Abstract

The abiotic photochemical reactions that take place naturally in sunlit surface waters can degrade many contaminants that pose concern to water bodies for their potentially toxic and long-term effects. This works aims at assessing the ability of European rivers to photoproduce reactive transient [...] Read more.

The abiotic photochemical reactions that take place naturally in sunlit surface waters can degrade many contaminants that pose concern to water bodies for their potentially toxic and long-term effects. This works aims at assessing the ability of European rivers to photoproduce reactive transient intermediates, such as HO^• radicals and the excited triplet states of chromophoric dissolved organic matter (³CDOM*), involved in pollutant degradation. A photochemical mapping of the steady-state concentrations of these transients was carried out by means of a suitable modeling tool, in the latitude belt between 40 and 50°N. Such a map allowed for the prediction of the photochemical lifetimes of the phenylurea herbicide isoproturon (mostly undergoing photodegradation upon reaction with HO^• and especially ³CDOM*) across different European countries. For some rivers, a more extensive dataset was available spanning the years 1990–2002, which allowed for the computation of the steady-state concentration of the carbonate radicals (CO₃^•⁻). With these data, it was possible to assess the time trends of the photochemical half-lives of further contaminants (atrazine, ibuprofen, carbamazepine, and clofibric acid). The calculated lifetimes were in the range of days to weeks, which might or might not allow for efficient depollution depending on the river-water flow velocity. Full article

(This article belongs to the Special Issue Photochemical Processes in Sunlit Surface and Atmospheric Waters)

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23 pages, 1728 KiB

Open AccessReview

Photochemistry of the Cloud Aqueous Phase: A Review

by Angelica Bianco, Monica Passananti, Marcello Brigante and Gilles Mailhot

Molecules 2020, 25(2), 423; https://doi.org/10.3390/molecules25020423 - 20 Jan 2020

Cited by 43 | Viewed by 6188

Abstract

This review paper describes briefly the cloud aqueous phase composition and deeply its reactivity in the dark and mainly under solar radiation. The role of the main oxidants (hydrogen peroxide, nitrate radical, and hydroxyl radical) is presented with a focus on the hydroxyl [...] Read more.

This review paper describes briefly the cloud aqueous phase composition and deeply its reactivity in the dark and mainly under solar radiation. The role of the main oxidants (hydrogen peroxide, nitrate radical, and hydroxyl radical) is presented with a focus on the hydroxyl radical, which drives the oxidation capacity during the day. Its sources in the aqueous phase, mainly through photochemical mechanisms with H₂O₂, iron complexes, or nitrate/nitrite ions, are presented in detail. The formation rate of hydroxyl radical and its steady state concentration evaluated by different authors are listed and compared. Finally, a paragraph is also dedicated to the sinks and the reactivity of the HO^• radical with the main compounds found in the cloud aqueous phase. This review presents an assessment of the reactivity in the cloud aqueous phase and shows the significant potential impact that this medium can have on the chemistry of the atmosphere and more generally on the climate. Full article

(This article belongs to the Special Issue Photochemical Processes in Sunlit Surface and Atmospheric Waters)

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14 pages, 14877 KiB

Open AccessArticle

Study on Structure Activity Relationship of Natural Flavonoids against Thrombin by Molecular Docking Virtual Screening Combined with Activity Evaluation In Vitro

by Xiaoyan Wang, Zhen Yang, Feifei Su, Jin Li, Evans Owusu Boadi, Yan-xu Chang and Hui Wang

Molecules 2020, 25(2), 422; https://doi.org/10.3390/molecules25020422 - 20 Jan 2020

Cited by 25 | Viewed by 6913

Abstract

Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well [...] Read more.

Thrombin, a key enzyme of the serine protease superfamily, plays an integral role in the blood coagulation cascade and thrombotic diseases. In view of this, it is worthwhile to establish a method to screen thrombin inhibitors (such as natural flavonoid-type inhibitors) as well as investigate their structure activity relationships. Virtual screening using molecular docking technique was used to screen 103 flavonoids. Out of this number, 42 target compounds were selected, and their inhibitory effects on thrombin assayed by chromogenic substrate method. The results indicated that the carbon-carbon double bond group at the C2, C3 sites and the carbonyl group at the C4 sites of flavones were essential for thrombin inhibition, whereas the methoxy and O-glycosyl groups reduced thrombin inhibition. Noteworthy, introduction of OH groups at different positions on flavonoids either decreased or increased anti-thrombin potential. Myricetin exhibited the highest inhibitory potential against thrombin with an IC₅₀ value of 56 μM. Purposively, the established molecular docking virtual screening method is not limited to exploring flavonoid structure activity relationships to anti-thrombin activity but also usefully discovering other natural active constituents. Full article

(This article belongs to the Special Issue Flavonoids: From Structure to Health Issues II)

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11 pages, 1880 KiB

Open AccessFeature PaperCommunication

Cyclopentadienone Iron Tricarbonyl Complexes-Catalyzed Hydrogen Transfer in Water

by Daouda Ndiaye, Sébastien Coufourier, Mbaye Diagne Mbaye, Sylvain Gaillard and Jean-Luc Renaud

Molecules 2020, 25(2), 421; https://doi.org/10.3390/molecules25020421 - 20 Jan 2020

Cited by 11 | Viewed by 3823

Abstract

The development of efficient and low-cost catalytic systems is important for the replacement of robust noble metal complexes. The synthesis and application of a stable, phosphine-free, water-soluble cyclopentadienone iron tricarbonyl complex in the reduction of polarized double bonds in pure water is reported. [...] Read more.

The development of efficient and low-cost catalytic systems is important for the replacement of robust noble metal complexes. The synthesis and application of a stable, phosphine-free, water-soluble cyclopentadienone iron tricarbonyl complex in the reduction of polarized double bonds in pure water is reported. In the presence of cationic bifunctional iron complexes, a variety of alcohols and amines were prepared in good yields under mild reaction conditions. Full article

(This article belongs to the Special Issue Recent Advances in Iron Catalysis)

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15 pages, 879 KiB

Open AccessArticle

Understanding Olive Oil Stability Using Filtration and High Hydrostatic Pressure

by Lorenzo Guerrini, Bruno Zanoni, Carlotta Breschi, Giulia Angeloni, Piernicola Masella, Luca Calamai and Alessandro Parenti

Molecules 2020, 25(2), 420; https://doi.org/10.3390/molecules25020420 - 20 Jan 2020

Cited by 25 | Viewed by 4110

Abstract

Veiled extra virgin olive oil (VEVOO) is very attractive on the global market. A study was performed to highlight the role of different amounts of water and microorganisms on the evolution of VEVOO quality during storage, using the selective effects of the application [...] Read more.

Veiled extra virgin olive oil (VEVOO) is very attractive on the global market. A study was performed to highlight the role of different amounts of water and microorganisms on the evolution of VEVOO quality during storage, using the selective effects of the application of individual or combined filtration and high hydrostatic pressure (HHP) treatments. Four oil processing trials were carried out in four replicates, resulting in a full factorial design with two independent fixed factors: filtration and HPP treatments. The turbidity of all the olive oil samples was characterized. Furthermore, all the olive oil samples were analysed for legal parameters, volatile organic compounds and phenolic compounds during the storage tests. The microbial contamination in the presence of a high level of water activity (>0.6 Aw) was related to the formation of volatile aroma compounds, which were responsible for the “fusty” sensory defect. Furthermore, high water activity values were related to an increase in the hydrolytic degradation rate of the phenolic compounds. The oil turbidity has to be planned and controlled, starting from adjustment of the water content and application of good manufacturing practices. Full article

(This article belongs to the Special Issue Green Extraction of Natural Products)

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22 pages, 1456 KiB

Open AccessEditor’s ChoiceArticle

Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones

by Xue Yan, Ying-De Tang, Cheng-Shi Jiang, Xigong Liu and Hua Zhang

Molecules 2020, 25(2), 419; https://doi.org/10.3390/molecules25020419 - 20 Jan 2020

Cited by 14 | Viewed by 4560

Abstract

The oxidative, dearomative cross-dehydrogenative coupling of indoles with various C-H nucleophiles is developed. This process features a broad substrate scope with respect to both indoles and nucleophiles, affording structurally diverse 2,2-disubstituted indolin-3-ones in high yields (up to 99%). The oxidative dimerization and trimerization [...] Read more.

The oxidative, dearomative cross-dehydrogenative coupling of indoles with various C-H nucleophiles is developed. This process features a broad substrate scope with respect to both indoles and nucleophiles, affording structurally diverse 2,2-disubstituted indolin-3-ones in high yields (up to 99%). The oxidative dimerization and trimerization of indoles has also been demonstrated under the same conditions. Full article

(This article belongs to the Special Issue Advances in Cross-Coupling Reactions)

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14 pages, 1667 KiB

Open AccessArticle

Analgesic, Anti-Inflammatory, Cytotoxic Activity Screening and UPLC-PDA-ESI-MS Metabolites Determination of Bioactive Fractions of Kleinia pendula

by Mohammad Alfaifi, Abdulrhman Alsayari, Narasimman Gurusamy, Justin Louis, Serag Eldin Elbehairi, Kumar Venkatesan, Sivakumar Annadurai, Yahya I. Asiri, Ali Shati, Kamel Saleh, Helmi Alboushnak, Heba Handoussa, Abdullatif Bin Muhsinah and Amira Abdel Motaal

Molecules 2020, 25(2), 418; https://doi.org/10.3390/molecules25020418 - 20 Jan 2020

Cited by 9 | Viewed by 4301

Abstract

Kleinia pendula (Forssk.) DC. is a prostrate or pendent dark green succulent herb found in the southwestern mountain regions of Saudi Arabia. The literature survey of the plant reveals a lack of phytochemical and pharmacological studies, although traditional uses have been noted. The [...] Read more.

Kleinia pendula (Forssk.) DC. is a prostrate or pendent dark green succulent herb found in the southwestern mountain regions of Saudi Arabia. The literature survey of the plant reveals a lack of phytochemical and pharmacological studies, although traditional uses have been noted. The objective of the present work was to assess the in vivo analgesic and anti-inflammatory activities, as well as, the in vitro cytotoxic potential of the fractions of Kleinia pendula, and correlate these activities to the plant metabolites. The methanolic extract of Kleinia pendula was subjected to fractionation with n-hexane, ethyl acetate, chloroform, n-butanol, and water. The fractions were screened for their analgesic and anti-inflammatory activities, as well as cytotoxic activity against breast, liver, and colon cancer cell lines. The n-hexane and chloroform fractions of Kleinia pendula showed significant cytotoxic activity against all three cancer cell lines tested. The ethyl acetate and chloroform fractions showed significant analgesic and anti-inflammatory activities. The metabolites in these three active fractions were determined using UPLC-PDA-ESI-MS. Thus, the analgesic and anti-inflammatory activities of the plant were attributed to its phenolic acids (caffeoylquinic acid derivatives, protocatechuic, and chlorogenic acids). While fatty acids and triterpenoids such as (tormentic acid) in the hexane fraction are responsible for the cytotoxic activity; thus, these fractions of Kleinia pendula may be a novel source for the development of new plant-based analgesic, anti-inflammatory, and anticancer drugs. Full article

(This article belongs to the Section Natural Products Chemistry)

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11 pages, 2997 KiB

Open AccessArticle

Allosteric Cannabinoid Receptor 1 (CB1) Ligands Reduce Ocular Pain and Inflammation

by Dinesh Thapa, Elizabeth A. Cairns, Anna-Maria Szczesniak, Pushkar M. Kulkarni, Alex J. Straiker, Ganesh A. Thakur and Melanie E. M. Kelly

Molecules 2020, 25(2), 417; https://doi.org/10.3390/molecules25020417 - 20 Jan 2020

Cited by 29 | Viewed by 7030

Abstract

Cannabinoid receptor 1 (CB1) activation has been reported to reduce transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced inflammatory responses and is anti-nociceptive and anti-inflammatory in corneal injury. We examined whether allosteric ligands, can modulate CB1 signaling to reduce pain and [...] Read more.

Cannabinoid receptor 1 (CB1) activation has been reported to reduce transient receptor potential cation channel subfamily V member 1 (TRPV1)-induced inflammatory responses and is anti-nociceptive and anti-inflammatory in corneal injury. We examined whether allosteric ligands, can modulate CB1 signaling to reduce pain and inflammation in corneal hyperalgesia. Corneal hyperalgesia was generated by chemical cauterization of cornea in wildtype and CB2 knockout (CB2^−/−) mice. The novel racemic CB1 allosteric ligand GAT211 and its enantiomers GAT228 and GAT229 were examined alone or in combination with the orthosteric CB1 agonist Δ⁸-tetrahydrocannabinol (Δ⁸-THC). Pain responses were assessed following capsaicin (1 µM) stimulation of injured corneas at 6 h post-cauterization. Corneal neutrophil infiltration was also analyzed. GAT228, but not GAT229 or GAT211, reduced pain scores in response to capsaicin stimulation. Combination treatments of 0.5% GAT229 or 1% GAT211 with subthreshold Δ⁸-THC (0.4%) significantly reduced pain scores following capsaicin stimulation. The anti-nociceptive effects of both GAT229 and GAT228 were blocked with CB1 antagonist AM251, but remained unaffected in CB2^−/− mice. Two percent GAT228, or the combination of 0.2% Δ⁸-THC with 0.5% GAT229 also significantly reduced corneal inflammation. CB1 allosteric ligands could offer a novel approach for treating corneal pain and inflammation. Full article

(This article belongs to the Special Issue Cannabinergic Ligands: Chemistry, Pharmacology and Therapeutic Potential)

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15 pages, 1441 KiB

Open AccessArticle

Nature of the Interaction of Pyridines with OCS. A Theoretical Investigation

by Sumitra Bhattarai, Dipankar Sutradhar, Asit K. Chandra and Therese Zeegers-Huyskens

Molecules 2020, 25(2), 416; https://doi.org/10.3390/molecules25020416 - 19 Jan 2020

Cited by 8 | Viewed by 3240

Abstract

Ab initio calculations were carried out to investigate the interaction between para-substituted pyridines (X-C₅H₄N, X=NH₂, CH₃, H, CN, NO₂) and OCS. Three stable structures of pyridine.OCS complexes were detected at the MP2=full/aug-cc-pVDZ [...] Read more.

Ab initio calculations were carried out to investigate the interaction between para-substituted pyridines (X-C₅H₄N, X=NH₂, CH₃, H, CN, NO₂) and OCS. Three stable structures of pyridine.OCS complexes were detected at the MP2=full/aug-cc-pVDZ level. The A structure is characterized by N…S chalcogen bonds and has binding energies between −9.58 and −12.24 kJ/mol. The B structure is bonded by N…C tetrel bond and has binding energies between −10.78 and −11.81 kJ/mol. The C structure is characterized by π-interaction and has binding energies between −10.76 and −13.33 kJ/mol. The properties of the systems were analyzed by AIM, NBO, and SAPT calculations. The role of the electrostatic potential of the pyridines on the properties of the systems is outlined. The frequency shift of relevant vibrational modes is analyzed. Full article

(This article belongs to the Special Issue Spectroscopic Aspects of Noncovalent Interactions)

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17 pages, 1466 KiB

Open AccessArticle

Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Mycobacterium tuberculosis Phosphoserine Phosphatase

by Elise Pierson, Marie Haufroid, Tannu Priya Gosain, Pankaj Chopra, Ramandeep Singh and Johan Wouters

Molecules 2020, 25(2), 415; https://doi.org/10.3390/molecules25020415 - 19 Jan 2020

Cited by 10 | Viewed by 3859

Abstract

Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of [...] Read more.

Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen’s serine pathway, it appears to be involved in immune evasion mechanisms. In this work, a malachite green-based phosphatase assay has been used to screen 122 compounds from an internal chemolibrary. Trisubstituted harmine derivatives were found among the best hits that inhibited SerB2 activity. Synthesis of an original compound helped to discuss a brief structure activity relationship evaluation. Kinetics experiments showed that the most potent derivatives inhibit the phosphatase in a parabolic competitive fashion with apparent inhibition constants (

K_{i}

) values in the micromolar range. Their interaction modes with the enzyme were investigated through induced fit docking experiments, leading to results consistent with the experimental data. Cellular assays showed that the selected compounds also inhibited M. tuberculosis growth in vitro. Those promising results may provide a basis for the development of new antimycobacterial agents targeting SerB2. Full article

(This article belongs to the Special Issue Recent Advances in Antitubercular Drug Discovery)

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82 pages, 37510 KiB

Open AccessReview

The Pictet-Spengler Reaction Updates Its Habits

by Andrea Calcaterra, Laura Mangiardi, Giuliano Delle Monache, Deborah Quaglio, Silvia Balducci, Simone Berardozzi, Antonia Iazzetti, Roberta Franzini, Bruno Botta and Francesca Ghirga

Molecules 2020, 25(2), 414; https://doi.org/10.3390/molecules25020414 - 19 Jan 2020

Cited by 59 | Viewed by 12462

Abstract

The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did [...] Read more.

The Pictet-Spengler reaction (P-S) is one of the most direct, efficient, and variable synthetic method for the construction of privileged pharmacophores such as tetrahydro-isoquinolines (THIQs), tetrahydro-β-carbolines (THBCs), and polyheterocyclic frameworks. In the lustro (five-year period) following its centenary birthday, the P-S reaction did not exit the stage but it came up again on limelight with new features. This review focuses on the interesting results achieved in this period (2011–2015), analyzing the versatility of this reaction. Classic P-S was reported in the total synthesis of complex alkaloids, in combination with chiral catalysts as well as for the generation of libraries of compounds in medicinal chemistry. The P-S has been used also in tandem reactions, with the sequences including ring closing metathesis, isomerization, Michael addition, and Gold- or Brønsted acid-catalyzed N-acyliminium cyclization. Moreover, the combination of P-S reaction with Ugi multicomponent reaction has been exploited for the construction of highly complex polycyclic architectures in few steps and high yields. The P-S reaction has also been successfully employed in solid-phase synthesis, affording products with different structures, including peptidomimetics, synthetic heterocycles, and natural compounds. Finally, the enzymatic version of P-S has been reported for biosynthesis, biotransformations, and bioconjugations. Full article

(This article belongs to the Special Issue Total Synthesis of Natural Products: A Themed Issue Dedicated to Professor Dr. Dieter Schinzer for His 65th Birthday)

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18 pages, 2887 KiB

Open AccessFeature PaperArticle

Multifunctional Hydroxyapatite Coated with Arthemisia absinthium Composites

by Mariana Stefania Raita, Simona Liliana Iconaru, Andreea Groza, Carmen Cimpeanu, Gabriel Predoi, Liliana Ghegoiu, Monica Luminita Badea, Mariana Carmen Chifiriuc, Luminita Marutescu, Roxana Trusca, Ciprian Florin Furnaris, Claudiu Stefan Turculet, Dorin Valter Enache and Daniela Predoi

Molecules 2020, 25(2), 413; https://doi.org/10.3390/molecules25020413 - 19 Jan 2020

Cited by 18 | Viewed by 4551

Abstract

There is significant research showing that essential oils extracted from the plants have antibacterial effects. The purpose of this study was to develop a biocomposite based on hydroxyapatite coated with Artemisia absinthium essential oil and to highlight its antibacterial activity. Therefore, present studies [...] Read more.

There is significant research showing that essential oils extracted from the plants have antibacterial effects. The purpose of this study was to develop a biocomposite based on hydroxyapatite coated with Artemisia absinthium essential oil and to highlight its antibacterial activity. Therefore, present studies are aimed at developing new materials combining hydroxyapatite with Artemisia absinthium essential oil, in order to avoid postoperative infections. The purpose of this work is to highlight the antimicrobial properties of the Artemisia absinthium essential oil-hydroxyapatite composites obtained by a simple method and at low costs. The structural properties and antimicrobial efficiency of the Artemisia absinthium essential oil-hydroxyapatite composite have been studied. The samples based on Artemisia absinthium essential oil analyzed in this study showed that wormwood essential oil presented the highest efficacy against the fungal strain of C. parapsilosis. It has been shown that wormwood essential oil has a strong antimicrobial effect against the microbial strains tested in this study. Furthermore, the antimicrobial properties of the biocomposites based on hydroxyapatite and essential oil are due to the presence of the essential oil in the samples. Full article

(This article belongs to the Special Issue Natural Product Pharmacology and Medicinal Chemistry)

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16 pages, 1558 KiB

Open AccessArticle

Changes in Cuticle Components and Morphology of ‘Satsuma’ Mandarin (Citrus unshiu) during Ambient Storage and Their Potential Role on Penicillium digitatum Infection

by Shenghua Ding, Jing Zhang, Lvzhu Yang, Xinyu Wang, Fuhua Fu, Rongrong Wang, Qun Zhang and Yang Shan

Molecules 2020, 25(2), 412; https://doi.org/10.3390/molecules25020412 - 19 Jan 2020

Cited by 36 | Viewed by 4165

Abstract

To elucidate the role of fruit cuticle in fungal infection, changes in cuticle composition and morphology of ‘Satsuma’ mandarin during ambient (at 25 °C) storage and their role in Penicillium digitatum infection were investigated. Results showed that the epicuticular wax yield increased from [...] Read more.

To elucidate the role of fruit cuticle in fungal infection, changes in cuticle composition and morphology of ‘Satsuma’ mandarin during ambient (at 25 °C) storage and their role in Penicillium digitatum infection were investigated. Results showed that the epicuticular wax yield increased from 1.11 μg cm⁻² to 4.21 μg cm⁻² during storage for 20 days and then decreased to 1.35 μg cm⁻² as storage time prolonged to 40 days. Intracuticular wax content of fruits stored for 20 days showed a peak value that was 1.7-fold higher than that of fruits stored for 40 days. The contents of cutin monomers of fruits showed a decreased trend during storage, while their proportions in the cutin stayed stable. Acids were identified as the most abundant components in epicuticular wax independently of the storage time, followed by alkanes and terpenoids. Terpenoids were found as the predominant components in intracuticular wax during the whole storage, followed by alkanes and acids. The flattened platelets crystals of fruits at harvest changed into small granule-like wax ones after 10 days of storage then gradually distributed across the surface of the fruits as stored for 40 days. Results of in vitro tests showed that mycelial growth of Penicillium digitatum could be promoted by epicuticular wax and conidial germination could be inhibited by cutin at different storage stages. These results shed new light on the chemical basis for cuticle involvement in fungal infection. Full article

(This article belongs to the Section Natural Products Chemistry)

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8 pages, 428 KiB

Open AccessArticle

Constituents from the Seeds of Sophora Alopecuroides L.

by Zi-Jian Rong, Gao-Sheng Hu, Shi-Yi Lin, Ting Yan, Na Li, Yue Zhao, Jing-Ming Jia and An-Hua Wang

Molecules 2020, 25(2), 411; https://doi.org/10.3390/molecules25020411 - 19 Jan 2020

Cited by 12 | Viewed by 3028

Abstract

Three new isoflavone glucosides, kudonol A−C (1–3), two new ester derivatives of phenylpropanoid, kudolignan A and B (4–5) and five known compounds, (−)-maackiain (6), neoliquiritin (7), methyl 4-coumarate (8), [...] Read more.

Three new isoflavone glucosides, kudonol A−C (1–3), two new ester derivatives of phenylpropanoid, kudolignan A and B (4–5) and five known compounds, (−)-maackiain (6), neoliquiritin (7), methyl 4-coumarate (8), methyl ferulate (9) and (+)-wikstromol (10), were isolated from an extract of dried seeds of the traditional Chinese medicinal plant Sophora alopecuroides L. Their structures were established by NMR and HRESIMS data analyses. The monosaccharide part’s configuration of isoflavone glucosides was confirmed by acid hydrolysis and analyzed by a JAsco OR-4090 chiral detector, comparing it to standard substance D-glucose. The cytotoxicity effects against HeLa, Hep3B, MCF-7 and H1299 cells were tested by CCK-8 assay. Full article

(This article belongs to the Section Natural Products Chemistry)

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14 pages, 3556 KiB

Open AccessFeature PaperArticle

Cross-Linked Cyclodextrins Bimetallic Nanocatalysts: Applications in Microwave-Assisted Reductive Aminations

by Emanuela Calcio Gaudino, Elisa Acciardo, Silvia Tabasso, Maela Manzoli, Giancarlo Cravotto and Rajender S. Varma

Molecules 2020, 25(2), 410; https://doi.org/10.3390/molecules25020410 - 19 Jan 2020

Cited by 10 | Viewed by 3524

Abstract

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H [...] Read more.

The optimization of sustainable protocols for reductive amination has been a lingering challenge in green synthesis. In this context, a comparative study of different metal-loaded cross-linked cyclodextrins (CDs) were examined for the microwave (MW)-assisted reductive amination of aldehydes and ketones using either H₂ or formic acid as a hydrogen source. The Pd/Cu heterogeneous nanocatalyst based on Pd (II) and Cu (I) salts embedded in a β-CD network was the most efficient in terms of yield and selectivity attained. In addition, the polymeric cross-linking avoided metal leaching, thus enhancing the process sustainability; good yields were realized using benzylamine under H₂. These interesting findings were then applied to the MW-assisted one-pot synthesis of secondary amines via a tandem reductive amination of benzaldehyde with nitroaromatics under H₂ pressure. The formation of a Cu_xPd_y alloy under reaction conditions was discerned, and a synergic effect due to the cooperation between Cu and Pd has been hypothesized. During the reaction, the system worked as a bifunctional nanocatalyst wherein the Pd sites facilitate the reduction of nitro compounds, while the Cu species promote the subsequent imine hydrogenation affording structurally diverse secondary amines with high yields. Full article

(This article belongs to the Special Issue Nanocatalysis)

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14 pages, 1462 KiB

Open AccessFeature PaperArticle

Antioxidant and Compositional HPLC Analysis of Three Common Bamboo Leaves

by Ning-Hui Ma, Jing Guo, Si-Han Xu Chen, Xiu-Rong Yuan, Tong Zhang and Yue Ding

Molecules 2020, 25(2), 409; https://doi.org/10.3390/molecules25020409 - 18 Jan 2020

Cited by 26 | Viewed by 4570

Abstract

Bamboo leaves of Phyllostachys nigra (PN), Lophatherum gracile (LG), and Pleioblastus amarus (PA) are three common herbs in China. In this work, a new high performance liquid chromatography (HPLC) method for the simultaneous determination of seven compounds in bamboo leaves has been developed; [...] Read more.

Bamboo leaves of Phyllostachys nigra (PN), Lophatherum gracile (LG), and Pleioblastus amarus (PA) are three common herbs in China. In this work, a new high performance liquid chromatography (HPLC) method for the simultaneous determination of seven compounds in bamboo leaves has been developed; and PN, LG, and PA leaves were analyzed. PN showed four times as much chlorogenic acid (CA) than the other two, and contained the most isoorientin (iso-ORI) and isovitexin (iso-VIT) as well. The PA presented the most orientin (ORI) and LG covered a majority of cynaroside (CYN). We measured the antioxidant activity by scavenging the stable 2,2-diphenyl-1-pyridinohydrazinyl (DPPH) free radicals, and found that Luteolin (inhibitory concentration (IC)₅₀ = 0.42 µM, LUT) and CYN (IC₅₀ = 0.43 µM) showed 2–3 times higher antioxidant activity than iso-ORI (IC₅₀ = 0.81 µM), ORI (IC₅₀ = 0.84 µM), and other related antioxidant standards such as trolox (IC₅₀ = 0.97 µM) and ascorbic acid (IC₅₀ = 0.93 µM, VC). Among extracts, PN and PA showed considerable antioxidant activity, which was related well with the contents of CA, iso-ORI, and iso-VIT (p < 0.05). This study firstly provides evidence for functional antioxidant compounds of bamboo leaves based on statistical analysis of the HPLC analysis and DPPH assay, and it lays a foundation for its further development or utilization. Full article

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14 pages, 1084 KiB

Open AccessEditor’s ChoiceArticle

Characterization of Volatile and Flavonoid Composition of Different Cuts of Dried Onion (Allium cepa L.) by HS-SPME-GC-MS, HS-SPME-GC×GC-TOF and HPLC-DAD

by Lorenzo Cecchi, Francesca Ieri, Pamela Vignolini, Nadia Mulinacci and Annalisa Romani

Molecules 2020, 25(2), 408; https://doi.org/10.3390/molecules25020408 - 18 Jan 2020

Cited by 45 | Viewed by 6851

Abstract

Onion is widely used worldwide in various forms for both food and medicinal applications, thanks to its high content of phytonutrients, such as flavonoids and volatile sulfur compounds. Fresh onion is very perishable and drying is widely applied for extending shelf-life, thus obtaining [...] Read more.

Onion is widely used worldwide in various forms for both food and medicinal applications, thanks to its high content of phytonutrients, such as flavonoids and volatile sulfur compounds. Fresh onion is very perishable and drying is widely applied for extending shelf-life, thus obtaining a very easy-to-use functional food ingredient. The flavonoid and volatile fractions of different onion cuts (flakes, rings) prepared through different drying cycles in a static oven, were characterized by high-performance liquid chromatography with a diode-array detector HPLC-DAD, Head Space-Solid Phase Micro Extraction followed by Gas Chromatography coupled with Mass Spectrometry (HS-SPME-GC-MS) and Head-Space Solid Phase Micro Extraction followed by comprehensive two-dimensional Gas-Chromatography (HS-SPME-GC×GC-TOF). Onion flakes showed a significantly higher flavonoid content (3.56 mg g⁻¹) than onion rings (2.04 mg g⁻¹). Onion flakes showed greater amount of volatile organic compounds (VOCs) (127.26 mg g⁻¹) than onion rings (42.79 mg g⁻¹), with different relative amounts of di- and trisulfides—disulfides largely predominate the volatile fraction (amounts over 60% on the total volatile content), followed by trisulfides and dipropyl disulfide and dipropyl trisulfide were the most abundant VOCs. HS-SPME-GC×GC-TOF allowed for the detection of the presence of allylthiol, diethanol sulfide, 4,6-diethyl1,2,3,5-tetrathiolane, not detected by HS-SPME-GC-MS, and provided a fast and direct visualization and comparison of different samples. These results highlight different nutraceutical properties of dried onion samples processed otherwise, only differing in shape and size, thus pointing out potentially different uses as functional ingredients. Full article

(This article belongs to the Special Issue Analysis of Volatile and Odor Compounds in Food)

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14 pages, 2349 KiB

Open AccessArticle

Design, Synthesis, and In Vitro Evaluation of the Photoactivatable Prodrug of the PARP Inhibitor Talazoparib

by Jiaguo Li, Dian Xiao, Lianqi Liu, Fei Xie, Wei Li, Wei Sun, Xiaohong Yang and Xinbo Zhou

Molecules 2020, 25(2), 407; https://doi.org/10.3390/molecules25020407 - 18 Jan 2020

Cited by 4 | Viewed by 5335

Abstract

In this article, we report the design, synthesis, photodynamic properties, and in vitro evaluation of photoactivatable prodrug for the poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor Talazoparib. In order to yield a photoactivatable, inactive prodrug, photoactivatable protecting groups (PPGs) were employed to mask the [...] Read more.

In this article, we report the design, synthesis, photodynamic properties, and in vitro evaluation of photoactivatable prodrug for the poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor Talazoparib. In order to yield a photoactivatable, inactive prodrug, photoactivatable protecting groups (PPGs) were employed to mask the key pharmacophore of Talazoparib. Our study confirmed the good stability and photolytic effect of prodrugs. A PARP-1 enzyme inhibition assay and PARylation experiment showed that the inhibitory activity of the prodrug was reduced 380 times and more than 658 times, respectively, which proved that the prodrug’s expected activity was lost after PPG protection. In BRCA1- and BRCA2-deficient cell lines, the inhibitory activity of the compound was significantly restored after ultraviolet (UV) irradiation. The results indicate that the photoactivatable prodrug strategy is an interesting approach for studying PARP inhibitors. Meanwhile, the described photoactivatable prodrug also provided a new biological tool for the mechanism research of PARP. Full article

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

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22 pages, 11087 KiB

Open AccessArticle

Profiling the Structural Determinants of Aryl Benzamide Derivatives as Negative Allosteric Modulators of mGluR5 by In Silico Study

by Yujing Zhao, Jiabin Chen, Qilei Liu and Yan Li

Molecules 2020, 25(2), 406; https://doi.org/10.3390/molecules25020406 - 18 Jan 2020

Cited by 10 | Viewed by 3281

Abstract

Glutamate plays a crucial role in the treatment of depression by interacting with the metabotropic glutamate receptor subtype 5 (mGluR5), whose negative allosteric modulators (NAMs) are thus promising antidepressants. At present, to explore the structural features of 106 newly synthesized aryl benzamide series [...] Read more.

Glutamate plays a crucial role in the treatment of depression by interacting with the metabotropic glutamate receptor subtype 5 (mGluR5), whose negative allosteric modulators (NAMs) are thus promising antidepressants. At present, to explore the structural features of 106 newly synthesized aryl benzamide series molecules as mGluR5 NAMs, a set of ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses were firstly carried out applying comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. In addition, receptor-based analysis, namely molecular docking and molecular dynamics (MD) simulations, were performed to further elucidate the binding modes of mGluR5 NAMs. As a result, the optimal CoMSIA model obtained shows that cross-validated correlation coefficient Q² = 0.70, non-cross-validated correlation coefficient R²_ncv = 0.89, predicted correlation coefficient R²_pre = 0.87. Moreover, we found that aryl benzamide series molecules bind as mGluR5 NAMs at Site 1, which consists of amino acids Pro655, Tyr659, Ile625, Ile651, Ile944, Ser658, Ser654, Ser969, Ser965, Ala970, Ala973, Trp945, Phe948, Pro903, Asn907, Val966, Leu904, and Met962. This site is the same as that of other types of NAMs; mGluR5 NAMs are stabilized in the “linear” and “arc” configurations mainly through the H-bonds interactions, π–π stacking interaction with Trp945, and hydrophobic contacts. We hope that the models and information obtained will help understand the interaction mechanism of NAMs and design and optimize NAMs as new types of antidepressants. Full article

(This article belongs to the Special Issue Recent Advances in Computational Drug Discovery: From In Silico Screening to Multiscale De Novo Drug Design)

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14 pages, 3158 KiB

Open AccessArticle

The Synthesis of α-Aminophosphonates via Enantioselective Organocatalytic Reaction of 1-(N-Acylamino)alkylphosphonium Salts with Dimethyl Phosphite

by Alicja Walęcka-Kurczyk, Krzysztof Walczak, Anna Kuźnik, Sebastian Stecko and Agnieszka Październiok-Holewa

Molecules 2020, 25(2), 405; https://doi.org/10.3390/molecules25020405 - 18 Jan 2020

Cited by 12 | Viewed by 4480

Abstract

α-Aminophosphonic acids are phosphorus analogues of α-amino acids. Compounds of this type find numerous applications in medicine and crop protection due to their unique biological activities. A crucial factor in these activities is the configuration of the stereoisomers. Only a few methods of [...] Read more.

α-Aminophosphonic acids are phosphorus analogues of α-amino acids. Compounds of this type find numerous applications in medicine and crop protection due to their unique biological activities. A crucial factor in these activities is the configuration of the stereoisomers. Only a few methods of stereoselective transformation of α-amino acids into their phosphorus analogues are known so far and all of them are based on asymmetric induction, thus involving the use of a chiral substrate. In contrast, we have focused our efforts on the development of an effective method for this type of transformation using a racemic mixture of starting N-protected α-amino acids and a chiral catalyst. Herein, a simple and efficient stereoselective organocatalytic α-amidoalkylation of dimethyl phosphite by 1-(N-acylamino)alkyltriphenylphosphonium salts to enantiomerically enriched α-aminophosphonates is reported. Using 5 mol% of chiral quinine- or hydroquinine-derived quaternary ammonium salts provides final products in very good yields up to 98% and with up to 92% ee. The starting phosphonium salts were easily obtained from α-amino acid derivatives by decarboxylative methoxylation and subsequent substitution with triphenylphosphonium tetrafluoroborate. The appropriate self-disproportionation of enantiomers (SDE) test for selected α-aminophosphonate derivatives via achiral flash chromatography was performed to confirm the reliability of the enantioselectivity results that were obtained. Full article

(This article belongs to the Special Issue Recent Developments in the Synthesis and Utilization of Organophosphorus Compounds)

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17 pages, 4222 KiB

Open AccessArticle

Synthesis of Novel Structural Hybrids between Aza-Heterocycles and Azelaic Acid Moiety with a Specific Activity on Osteosarcoma Cells

by Gabriele Micheletti, Natalia Calonghi, Giovanna Farruggia, Elena Strocchi, Vincenzo Palmacci, Dario Telese, Silvia Bordoni, Giulia Frisco and Carla Boga

Molecules 2020, 25(2), 404; https://doi.org/10.3390/molecules25020404 - 18 Jan 2020

Cited by 15 | Viewed by 3805

Abstract

Nine compounds bearing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups bound to an azelayl moiety through an amide bond were synthesized. The structural analogy with some histone deacetylase inhibitors inspired their syntheses, seeking new selective histone deacetylase inhibitors (HDACi). The azelayl moiety recalls part [...] Read more.

Nine compounds bearing pyridinyl (or piperidinyl, benzimidazolyl, benzotriazolyl) groups bound to an azelayl moiety through an amide bond were synthesized. The structural analogy with some histone deacetylase inhibitors inspired their syntheses, seeking new selective histone deacetylase inhibitors (HDACi). The azelayl moiety recalls part of 9-hydroxystearic acid, a cellular lipid showing antiproliferative activity toward cancer cells with HDAC as a molecular target. Azelayl derivatives bound to a benzothiazolyl moiety further proved to be active as HDACi. The novel compounds were tested on a panel of both normal and tumor cell lines. Non-specific induction of cytotoxicity was observed in the normal cell line, while three of them induced a biological effect only on the osteosarcoma (U2OS) cell line. One of them induced a change in nuclear shape and size. Cell-cycle alterations are associated with post-transcriptional modification of both H2/H3 and H4 histones. In line with recent studies, revealing unexpected HDAC7 function in osteoclasts, molecular docking studies on the active molecules predicted their proneness to interact with HDAC7. By reducing side effects associated with the action of the first-generation inhibitors, the herein reported compounds, thus, sound promising as selective HDACi. Full article

(This article belongs to the Special Issue Design and Synthesis of Organic Molecules as Antineoplastic Agents)

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16 pages, 4084 KiB

Open AccessArticle

Soft-Templating of Sulfur and Iron Dual-Doped Mesoporous Carbons: Lead Adsorption in Mixtures

by Dipendu Saha, Connelly P. Richards, Robert G. Haines, Nicholas D. D’Alessandro, Madeleine J. Kienbaum and Christian A. Griffaton

Molecules 2020, 25(2), 403; https://doi.org/10.3390/molecules25020403 - 18 Jan 2020

Cited by 11 | Viewed by 2453

Abstract

Lead pollution in drinking water is one of the most common problems worldwide. In this research, sulfur and iron dual-doped mesoporous carbons are synthesized by soft-templating with sulfur content 4.4–6.1 atom% and iron content 7.8–9 atom%. Sulfur functionalities of the carbons are expected [...] Read more.

Lead pollution in drinking water is one of the most common problems worldwide. In this research, sulfur and iron dual-doped mesoporous carbons are synthesized by soft-templating with sulfur content 4.4–6.1 atom% and iron content 7.8–9 atom%. Sulfur functionalities of the carbons are expected to enhance the affinity of the carbon toward lead whereas iron content is expected to separate the carbon from water owing to its magnetic properties. All the carbons were characterized by pore textural properties, x-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive x-ray (EDX). In order to study the Pb(II) removal efficiently of this carbon in competitive mode and to mimic the real-world use, one additional heavy-metal, including Cr(III), and four other commonly occurring metals—Na(I), K(I), Ca(II) and Fe (III)—are added with lead prior to adsorption experiments. It was observed that Pb(II) adsorption capacity of this carbon was not influenced by the presence of other metals. A highly elevated concentration of Na(I), K(I), Ca(II) and Fe(III) in the eluting solution compared to the initial dose suggested possible leaching of those metals from other salts as impurities, water source or even from the carbon itself, although the XPS analysis of the carbon confirmed negligible adsorption of those metals in carbon. From the equilibrium and kinetic data of adsorption, few parameters have been calculated, including distribution coefficient, diffusive time constant and pseudosecond order rate constant. The overall results suggest that these iron and sulfur dual-doped mesoporous carbons can serve as potential adsorbents for removal of lead from drinking water in the presence of other competing metals. Full article

(This article belongs to the Special Issue Porous Carbon Materials and Their Applications)

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13 pages, 2219 KiB

Open AccessArticle

Homochiral Supramolecular Thin Film from Self-Assembly of Achiral Triarylamine Molecules by Circularly Polarized Light

by Changjun Park, Jinhee Lee, Taehyoung Kim, Jaechang Lim, Jeyoung Park, Woo Youn Kim and Sang Youl Kim

Molecules 2020, 25(2), 402; https://doi.org/10.3390/molecules25020402 - 18 Jan 2020

Cited by 12 | Viewed by 4602

Abstract

Here, we report the formation of homochiral supramolecular thin film from achiral molecules, by using circularly polarized light (CPL) only as a chiral source, on the condition that irradiation of CPL does not induce a photochemical change of the achiral molecules. Thin films [...] Read more.

Here, we report the formation of homochiral supramolecular thin film from achiral molecules, by using circularly polarized light (CPL) only as a chiral source, on the condition that irradiation of CPL does not induce a photochemical change of the achiral molecules. Thin films of self-assembled structures consisting of chiral supramolecular fibrils was obtained from the triarylamine derivatives through evaporation of the self-assembled triarylamine solution. The homochiral supramolecular helices with the desired handedness was achieved by irradiation of circularly polarized visible light during the self-assembly process, and the chiral stability of supramolecular self-assembled product was achieved by photopolymerization of the diacetylene moieties at side chains of the building blocks, with irradiation of circularly polarized ultraviolet light. This work provides a novel methodology for the generation of homochiral supramolecular thin film from the corresponding achiral molecules. Full article

(This article belongs to the Special Issue Helical Chirality in Chemistry, Materials Science and Biology)

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56 pages, 14468 KiB

Open AccessReview

Chiral Thioureas—Preparation and Significance in Asymmetric Synthesis and Medicinal Chemistry

by Franz Steppeler, Dominika Iwan, Elżbieta Wojaczyńska and Jacek Wojaczyński

Molecules 2020, 25(2), 401; https://doi.org/10.3390/molecules25020401 - 18 Jan 2020

Cited by 56 | Viewed by 12106

Abstract

For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as [...] Read more.

For almost 20 years, thioureas have been experiencing a renaissance of interest with the emerged development of asymmetric organocatalysts. Due to their relatively high acidity and strong hydrogen bond donor capability, they differ significantly from ureas and offer, appropriately modified, great potential as organocatalysts, chelators, drug candidates, etc. The review focuses on the family of chiral thioureas, presenting an overview of the current state of knowledge on their synthesis and selected applications in stereoselective synthesis and drug development. Full article

(This article belongs to the Special Issue Stereochemistry in Action)

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