bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy
Authors: Mainini Francesco , Eccles Michael R.
Published: June 2020

RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.
Computational Study of the Coupled Mechanism of Thermophoretic Transportation and Mixed Convection Flow around the Surface of a Sphere
Authors: Abbas Amir , Ashraf Muhammad , Chu Yu-Ming , Zia Saqib , Khan Ilyas , Nisar Kottakkaran Sooppy
Published: June 2020

The main goal of the current work was to study the coupled mechanism of thermophoretic transportation and mixed convection flow around the surface of the sphere. To analyze the characteristics of heat and fluid flow in the presence of thermophoretic transportation, a mathematical model in terms of non-linear coupled partial differential equations obeying the laws of conservation was formulated. Moreover, the mathematical model of the proposed phenomena was approximated by implementing the finite difference scheme and boundary value problem of fourth order code BVP4C built-in scheme. The novelty point of this paper is that the primitive variable formulation is introduced to transform the system of partial differential equations into a primitive form to make the line of the algorithm smooth. Secondly, the term thermophoretic transportation in the mass equation is introduced in the mass equation and thus the effect of thermophoretic transportation can be calculated at different positions of the sphere. Basically, in this study, some favorite positions around the sphere were located, where the velocity field, temperature distribution, mass concentration, skin friction, and rate of heat transfer can be calculated simultaneously without any separation in flow around the surface of the sphere.
Phenylacetonitrile (C6H5CH2CN) Ionic Liquid Blends as Alternative Electrolytes for Safe and High-Performance Supercapacitors
Authors: Ivol Flavien , Porcher Marina , Ghosh Arunabh , Jacquemin Johan , Ghamouss Fouad
Published: June 2020

The increasing need in the development of storage devices is calling for the formulation of alternative electrolytes, electrochemically stable and safe over a wide range of conditions. To achieve this goal, electrolyte chemistry must be explored to propose alternative solvents and salts to the current acetonitrile (ACN) and tetraethylammonium tetrafluoroborate (Et4NBF4) benchmarks, respectively. Herein, phenylacetonitrile (Ph-ACN) has been proposed as a novel alternative solvent to ACN in supercapacitors. To establish the main advantages and drawbacks of such a substitution, Ph-ACN + Et4NBF4 blends were formulated and characterized prior to being compared with the benchmark electrolyte and another alternative electrolyte based on adiponitrile (ADN). While promising results were obtained, the low Et4NBF4 solubility in Ph-ACN seems to be the main limiting factor. To solve such an issue, an ionic liquid (IL), namely 1-ethyl-3-methylimidazolium bis [(trifluoromethyl)sulfonyl] imide (EmimTFSI), was proposed to replace Et4NBF4. Unsurprisingly, the Ph-ACN + EmimTFSI blend was found to be fully miscible over the whole range of composition giving thus the flexibility to optimize the electrolyte formulation over a large range of IL concentrations up to 4.0 M. The electrolyte containing 2.7 M of EmimTFSI in Ph-ACN was identified as the optimized blend thanks to its interesting transport properties. Furthermore, this blend possesses also the prerequisites of a safe electrolyte, with an operating liquid range from at least −60 °C to +130 °C, and operating window of 3.0 V and more importantly, a flash point of 125 °C. Finally, excellent electrochemical performances were observed by using this electrolyte in a symmetric supercapacitor configuration, showing another advantage of mixing an ionic liquid with Ph-ACN. We also supported key structural descriptors by density functional theory (DFT) and COnductor-like Screening Model for Real Solvents (COSMO-RS) calculations, which can be associated to physical and electrochemical properties of the resultant electrolytes.
Laser-Inscribed Diamond Waveguide Resonantly Coupled to Diamond Microsphere
Authors: Yavuz Nurperi , Bayer Mustafa Mert , Ҫirkinoğlu Hüseyin Ozan , Serpengüzel Ali , Le Phu Thien , Giakoumaki Argyro , Bharadwaj Vibhav , Ramponi Roberta , Eaton Shane M.
Published: June 2020

An all-diamond photonic circuit was implemented by integrating a diamond microsphere with a femtosecond-laser-written bulk diamond waveguide. The near surface waveguide was fabricated by exploiting the Type II fabrication method to achieve stress-induced waveguiding. Transverse electrically and transverse magnetically polarized light from a tunable laser operating in the near-infrared region was injected into the diamond waveguide, which when coupled to the diamond microsphere showed whispering-gallery modes with a spacing of 0.33 nm and high-quality factors of 105. By carefully engineering these high-quality factor resonances, and further exploiting the properties of existing nitrogen-vacancy centers in diamond microspheres and diamond waveguides in such configurations, it should be possible to realize filtering, sensing and nonlinear optical applications in integrated diamond photonics.
Nanomaterials for Wound Dressings: An Up-to-Date Overview
Authors: Stoica Alexandra Elena , Chircov Cristina , Grumezescu Alexandru Mihai
Published: June 2020

As wound healing continues to be a challenge for the medical field, wound management has become an essential factor for healthcare systems. Nanotechnology is a domain that could provide different new approaches concerning regenerative medicine. It is worth mentioning the importance of nanoparticles, which, when embedded in biomaterials, can induce specific properties that make them of interest in applications as materials for wound dressings. In the last years, nano research has taken steps to develop molecular engineering strategies for different self-assembling biocompatible nanoparticles. It is well-known that nanomaterials can improve burn treatment and also the delayed wound healing process. In this review, the first-line of bioactive nanomaterials-based dressing categories frequently applied in clinical practice, including semi-permeable films, semipermeable foam dressings, hydrogel dressings, hydrocolloid dressings, alginate dressings, non-adherent contact layer dressings, and multilayer dressings will be discussed. Additionally, this review will highlight the lack of high-quality evidence and the necessity for future advanced trials because current wound healing therapies generally fail to provide an excellent clinical outcome, either structurally or functionally. The use of nanomaterials in wound management represents a unique tool that can be specifically designed to closely reflect the underlying physiological processes in tissue repair.
Modulation of Macrophage Polarization by Phospholipids on the Surface of Titanium
Authors: Quan Hongxuan , Kim Yongjoon , Wu Lele , Park Hee-Chul , Yang Hyeong-Cheol
Published: June 2020

Macrophage polarization has become increasingly important for the improvement of the biocompatibility of biomaterials. In this study, we coated Ti discs with phospholipids (phosphatidylserine/phosphatidylcholine [4:1 mole/mole]) by evaporating the solvent under vacuum, and observed the polarization of RAW 264.7 cells cultured on the discs. The coated discs were hydrated before cell culture was added. The shape of the hydrated phospholipids varied with the concentration of loaded phospholipids: a perforated layer (0.1 mM), tubules and spheres (1 mM), and spheres (10 mM). RAW 264.7 cells exhibited different morphologies, depending on the concentration of phospholipids. On the coated discs, the gene expression and protein release of TGF-β1, VEGF, Arg-1, and TNF-α were downregulated, especially with 10 mM phospholipids. The stimulation of mRNA expression and the protein release of those genes by IL-4 and LPS were also disturbed on the phospholipid-coated discs. In conclusion, the polarization of RAW 264.7 cells was prevented by hydrated phospholipids on Ti discs.
The Nature of Triel Bonds, a Case of B and Al Centres Bonded with Electron Rich Sites
Authors: Grabowski Sławomir J.
Published: June 2020

The second-order Møller–Plesset perturbation theory calculations with the aug-cc-pVTZ basis set were performed on complexes of triel species: BCl3, BH3, AlCl3, and AlH3 acting as Lewis acids through the B or Al centre with Lewis base units: NCH, N2, NH3, and Cl− anion. These complexes are linked by triel bonds: B/Al⋅⋅⋅N or B/Al⋅⋅⋅Cl. The Quantum Theory of ´Atoms in Molecules´ approach, Natural Bond Orbital method, and the decomposition of energy of interaction were applied to characterise the latter links. The majority of complexes are connected through strong interactions possessing features of covalent bonds and characterised by short intermolecular distances, often below 2 Å. The BCl3⋅⋅⋅N2 complex is linked by a weak interaction corresponding to the B⋅⋅⋅N distance of ~3 Å. For the BCl3⋅⋅⋅NCH complex, two configurations corresponding to local energetic minima are observed, one characterised by a short B⋅⋅⋅N distance and a strong interaction and another one characterised by a longer B⋅⋅⋅N distance and a weak triel bond. The tetrahedral triel structure is observed for complexes linked by strong triel bonds, while, for complexes connected by weak interactions, the structure is close to the trigonal pyramid, particularly observed for the BCl3⋅⋅⋅N2 complex.
The Lisbon Supramolecular Green Story: Mechanochemistry towards New Forms of Pharmaceuticals
Authors: Ferreira da Silva João Luís , Minas da Piedade M. Fátima , André Vânia , Domingos Sofia , Martins Inês C. B. , Duarte M. Teresa
Published: June 2020

This short review presents and highlights the work performed by the Lisbon Group on the mechanochemical synthesis of active pharmaceutical ingredients (APIs) multicomponent compounds. Here, we show some of our most relevant contributions on the synthesis of supramolecular derivatives of well-known commercial used drugs and the corresponding improvement on their physicochemical properties. The study reflects, not only our pursuit of using crystal engineering principles for the search of supramolecular entities, but also our aim to correlate them with the desired properties. The work also covers our results on polymorphic screening and describes our proposed alternatives to induce and maintain specific polymorphic forms, and our approach to avoid polymorphism using APIs as ionic liquids. We want to stress that all the work was performed using mechanochemistry, a green advantageous synthetic technique.
Potential of Flavonoid-Inspired Phytomedicines against COVID-19
Authors: Ngwa Wilfred , Kumar Rajiv , Thompson Daryl , Lyerly William , Moore Roscoe , Reid Terry-Elinor , Lowe Henry , Toyang Ngeh
Published: June 2020

Flavonoids are widely used as phytomedicines. Here, we report on flavonoid phytomedicines with potential for development into prophylactics or therapeutics against coronavirus disease 2019 (COVID-19). These flavonoid-based phytomedicines include: caflanone, Equivir, hesperetin, myricetin, and Linebacker. Our in silico studies show that these flavonoid-based molecules can bind with high affinity to the spike protein, helicase, and protease sites on the ACE2 receptor used by the severe acute respiratory syndrome coronavirus 2 to infect cells and cause COVID-19. Meanwhile, in vitro studies show potential of caflanone to inhibit virus entry factors including, ABL-2, cathepsin L, cytokines (IL-1β, IL-6, IL-8, Mip-1α, TNF-α), and PI4Kiiiβ as well as AXL-2, which facilitates mother-to-fetus transmission of coronavirus. The potential for the use of smart drug delivery technologies like nanoparticle drones loaded with these phytomedicines to overcome bioavailability limitations and improve therapeutic efficacy are discussed.
Synthesis and Characterization of New Series of 1,3-5-Triazine Hydrazone Derivatives with Promising Antiproliferative Activity
Authors: H. Al Rasheed Hessa , M. Malebari Azizah , A. Dahlous Kholood , El-Faham Ayman
Published: June 2020

A new series of s-triazine hydrazone derivatives was prepared based on the reaction of 6-hydrazino-2,4-disubstituted-s-triazine with p-substituted benzaldehyde derivatives using a straightforward synthetic pathway. The antiproliferative activity of all synthesized compounds was evaluated against two human cancer cell lines; breast cancer MCF-7 and colon carcinoma HCT-116 using MTT assay. Among all, 11 compounds have shown strong to moderate antiproliferative activity with IC50 values in the range 1.01–18.20 µM in MCF-7 and 0.97–19.51 µM in HCT-116. The best results were obtained with 4,4’-(6-(2-(pyridin-2-ylmethylene)hydrazinyl)-1,3,5-triazine-2,4-diyl) dimorpholine 11 (IC50 = 1.0 µM and 0.98 µM in MCF-7 and HCT-116 cell lines, respectively). The substituents on the s-triazine core as well as the substituent at the benzylidene moiety have a great effect on the antiproliferative activity. Whereas compounds containing dimorpholino-s-triazine derivatives 8a–e showed more potent antiproliferative in MCF-7 compared to their analogs 7a–f (compounds containing two-piperidine rings), compounds containing one piperidine and one morpholine ring 9a–f showed better IC50 values in the range 10.4–22.2 µM. On the other hand, compounds containing two-piperidine rings 7a–f showed more potent antiproliferative in HCT-116 (IC50 values in the range 8.8–19.5 µM) than their analogs 8a–e and 9a–f.
One-Pot Multicomponent Synthesis and Bioevaluation of Tetrahydroquinoline Derivatives as Potential Antioxidants, α-Amylase Enzyme Inhibitors, Anti-Cancerous and Anti-Inflammatory Agents
Authors: Farooq Samra , Mazhar Aqsa , Ghouri Areej , Ihsan-Ul-Haq  , Ullah Naseem
Published: June 2020

Mankind has always suffered from multiple diseases. Therefore, there has been a rigorous need in the field of medicinal chemistry for the design and discovery of new and potent molecular entities. In this work, thirteen tetrahydroquinoline derivatives were synthesized and evaluated biologically for their antioxidant, α-amylase enzyme inhibitory, anti-proliferative and anti-inflammatory activities. SF8 showed the lowest IC50 of 29.19 ± 0.25 µg/mL by scavenging DPPH free radicals. SF5 showed significant antioxidant activity in total antioxidant capacity (TAC) and total reducing power (TRP) assays. SF5 and SF9 showed the maximum inhibition of α-amylase enzyme i.e., 97.47% and 89.93%, respectively, at 200 µg/mL concentration. Five compounds were shortlisted to determine their anti-proliferative potential against Hep-2C cells. The study was conducted for 24, 48 and 72 h. SF8 showed significant results, having an IC50 value of 11.9 ± 1.04 µM at 72 h when compared with standard cisplatin (IC50 value of 14.6 ± 1.01 µM). An in vitro nitric oxide (NO) assay was performed to select compounds for in vivo anti-inflammatory activity evaluation. SF13 scavenged the NO level to a maximum of 85% at 50 µM concentration, followed by SF1 and SF2. Based on the NO scavenging assay results, in vivo anti-inflammatory studies were also performed and the results showed significant activity compared to the standard, acetylsalicylic acid (ASA).
Synthesis and Antibacterial Analysis of Analogues of the Marine Alkaloid Pseudoceratidine
Authors: Barker David , Lee Stephanie , Varnava Kyriakos G. , Sparrow Kevin , van Rensburg Michelle , Deed Rebecca C. , Cadelis Melissa M. , Li Steven A. , Copp Brent R. , Sarojini Vijayalekshmi , Pilkington Lisa I.
Published: June 2020

In an effort to gain more understanding on the structure activity relationship of pseudoceratidine 1, a di-bromo pyrrole spermidine alkaloid derived from the marine sponge Pseudoceratina purpurea that has been shown to exhibit potent biofouling, anti-fungal, antibacterial, and anti-malarial activities, a large series of 65 compounds that incorporated several aspects of structural variation has been synthesised through an efficient, divergent method that allowed for a number of analogues to be generated from common precursors. Subsequently, all analogues were assessed for their antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Overall, several compounds exhibited comparable or better activity than that of pseudoceratidine 1, and it was found that this class of compounds is generally more effective against Gram-positive than Gram-negative bacteria. Furthermore, altering several structural features allowed for the establishment of a comprehensive structure activity relationship (SAR), where it was concluded that several structural features are critical for potent anti-bacterial activity, including di-halogenation (preferable bromine, but chlorine is also effective) on the pyrrole ring, two pyrrolic units in the structure and with one or more secondary amines in the chain adjoining these units, with longer chains giving rise to better activities.
Conjugation of Doxorubicin to siRNA Through Disulfide-based Self-immolative Linkers
Authors: Gauthier Florian , Bertrand Jean-Rémi , Vasseur Jean-Jacques , Dupouy Christelle , Debart Françoise
Published: June 2020

Co-delivery systems of siRNA and chemotherapeutic drugs have been developed as an attractive strategy to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. In these typical systems, siRNAs are usually associated to drugs within a carrier but without covalent interactions with the risk of a premature release and degradation of the drugs inside the cells. To address this issue, we propose a covalent approach to co-deliver a siRNA-drug conjugate with a redox-responsive self-immolative linker prone to intracellular glutathione-mediated disulfide cleavage. Herein, we report the use of two disulfide bonds connected by a pentane spacer or a p-xylene spacer as self-immolative linker between the primary amine of the anticancer drug doxorubicin (Dox) and the 2′-position of one or two ribonucleotides in RNA. Five Dox-RNA conjugates were successfully synthesized using two successive thiol-disulfide exchange reactions. The Dox-RNA conjugates were annealed with their complementary strands and the duplexes were shown to form an A-helix sufficiently stable under physiological conditions. The enzymatic stability of Dox-siRNAs in human serum was enhanced compared to the unmodified siRNA, especially when two Dox are attached to siRNA. The release of native Dox and RNA from the bioconjugate was demonstrated under reducing conditions suggesting efficient linker disintegration. These results demonstrate the feasibility of making siRNA-drug conjugates via disulfide-based self-immolative linkers for potential therapeutic applications.
Valorization of Lignin via Oxidative Depolymerization with Hydrogen Peroxide: Towards Carboxyl-Rich Oligomeric Lignin Fragments
Authors: Junghans Ulrike , Bernhardt Justin J. , Wollnik Ronja , Triebert Dominik , Unkelbach Gerd , Pufky-Heinrich Daniela
Published: June 2020

The extraction and characterization of defined and carboxyl-rich oligomeric lignin fragments with narrow molecular weight distribution is presented herein. With regard to the well-known pulp bleaching process, oxidative lignin depolymerization was investigated using hydrogen peroxide in an aqueous alkaline solution (i.e., at T = 318 K, t = 1 h) and subsequent selective fractionation with a 10/90 (v/v) acetone/water mixture. While the weight average molecular weight (MW) of lignin in comparison to the starting material was reduced by 82% after oxidation (T = 318 K, t = 1 h, clignin = 40 g L−1, cH2O2 = 80 g L−1, cNaOH = 2 mol L−1) and subsequent solvent fractionation (T = 298 K, t = 18 h, ccleavage product = 20 g L−1), the carboxyl group (–COOH) content increased from 1.29 mmol g−1 up to 2.66 mmol g−1. Finally, the successful scale-up of this whole process to 3 L scale led to gram amounts (14% yield) of oligomeric lignin fragments with a MW of 1607 g mol−1, a number average molecular weight (MN) of 646 g mol−1, a narrow polydispersity index of 3.0, and a high –COOH content of 2.96 mmol g−1. Application of these oligomeric lignin fragments in epoxy resins or as adsorbents is conceivable without further functionalization.
Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Proteomics of Drug-Metabolizing Enzymes and Transporters
Authors: Li Jiapeng , Zhu Hao-Jie
Published: June 2020

Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful tool for identifying and quantifying proteins in biological samples, outperforming conventional antibody-based methods in many aspects. LC-MS/MS-based proteomics studies have revealed the protein abundances of many drug-metabolizing enzymes and transporters (DMETs) in tissues relevant to drug metabolism and disposition. Previous studies have consistently demonstrated marked interindividual variability in DMET protein expression, suggesting that varied DMET function is an important contributing factor for interindividual variability in pharmacokinetics (PK) and pharmacodynamics (PD) of medications. Moreover, differential DMET expression profiles were observed across different species and in vitro models. Therefore, caution must be exercised when extrapolating animal and in vitro DMET proteomics findings to humans. In recent years, DMET proteomics has been increasingly utilized for the development of physiologically based pharmacokinetic models, and DMET proteins have also been proposed as biomarkers for prediction of the PK and PD of the corresponding substrate drugs. In sum, despite the existence of many challenges in the analytical technology and data analysis methods of LC-MS/MS-based proteomics, DMET proteomics holds great potential to advance our understanding of PK behavior at the individual level and to optimize treatment regimens via the DMET protein biomarker-guided precision pharmacotherapy.
Ammonium Recovery and Biogas Upgrading in a Tubular Micro-Pilot Microbial Electrolysis Cell (MEC)
Authors: Cristiani Lorenzo , Zeppilli Marco , Porcu Cristina , Majone Mauro
Published: June 2020

Here, a 12-liter tubular microbial electrolysis cell (MEC) was developed as a post treatment unit for simultaneous biogas upgrading and ammonium recovery from the liquid effluent of an anaerobic digestion process. The MEC configuration adopted a cation exchange membrane to separate the inner anodic chamber and the external cathodic chamber, which were filled with graphite granules. The cathodic chamber performed the CO2 removal through the bioelectromethanogenesis reaction and alkalinity generation while the anodic oxidation of a synthetic fermentate partially sustained the energy demand of the process. Three different nitrogen load rates (73, 365, and 2229 mg N/Ld) were applied to the inner anodic chamber to test the performances of the whole process in terms of COD (Chemical Oxygen Demand) removal, CO2 removal, and nitrogen recovery. By maintaining the organic load rate at 2.55 g COD/Ld and the anodic chamber polarization at +0.2 V vs. SHE (Standard Hydrogen Electrode), the increase of the nitrogen load rate promoted the ammonium migration and recovery, i.e., the percentage of current counterbalanced by the ammonium migration increased from 1% to 100% by increasing the nitrogen load rate by 30-fold. The CO2 removal slightly increased during the three periods, and permitted the removal of 65% of the influent CO2, which corresponded to an average removal of 2.2 g CO2/Ld. During the operation with the higher nitrogen load rate, the MEC energy consumption, which was simultaneously used for the different operations, was lower than the selected benchmark technologies, i.e., 0.47 kW/N·m3 for CO2 removal and 0.88 kW·h/kg COD for COD oxidation were consumed by the MEC while the ammonium nitrogen recovery consumed 2.3 kW·h/kg N.
Ethanol Determination in Post-Mortem Samples: Correlation between Blood and Vitreous Humor Concentration
Authors: Savini Fabio , Tartaglia Angela , Coccia Ludovica , Palestini Danilo , D’Ovidio Cristian , de Grazia Ugo , Merone Giuseppe Maria , Bassotti Elisa , Locatelli Marcello
Published: June 2020

Ethanol (ethylic alcohol) represents the most commonly used drug worldwide and is often involved in clinical and forensic toxicology. Based on several reports, excessive alcohol consumption is the main contributing factor in traffic accidents, drownings, suicides, and other crimes. For these reasons, it becomes essential to analyze the alcohol concentration during autopsy. Although blood is usually used for alcohol analysis in post-mortem cases, it could suffer alterations, putrefaction, and microbial contaminations. As an alternative to whole blood, vitreous humor has been successfully used in medico-legal studies. In this work, post-mortem specimens were analyzed for ethanol determination. The analysis of blood and vitreous humor were carried-out using gas chromatography-flame ionized detector (GC-FID) with a total run time of 6 min. The method was validated in terms of limit of detection, limit of quantification, dynamic range, sensibility, recovery, precision and trueness. A linear regression analysis indicated a coefficient of determination (R2) of 0.9981. The study confirmed no statistically differences between alcohol concentration in blood and vitreous humor, leading vitreous humor as an excellent matrix that could be used as an alternative to whole blood in toxicological analysis in cases where blood is not available.
Activation of Peracetic Acid with Lanthanum Cobaltite Perovskite for Sulfamethoxazole Degradation under a Neutral pH: The Contribution of Organic Radicals
Authors: Zhou Xuefei , Wu Haowei , Zhang Longlong , Liang Bowen , Sun Xiaoqi , Chen Jiabin
Published: June 2020

Advanced oxidation processes (AOPs) are effective ways to degrade refractory organic contaminants, relying on the generation of inorganic radicals (e.g., •OH and SO4•−). Herein, a novel AOP with organic radicals (R-O•) was reported to degrade contaminants. Lanthanum cobaltite perovskite (LaCoO3) was used to activate peracetic acid (PAA) for organic radical generation to degrade sulfamethoxazole (SMX). The results show that LaCoO3 exhibited an excellent performance on PAA activation and SMX degradation at neutral pH, with low cobalt leaching. Meanwhile, LaCoO3 also showed an excellent reusability during PAA activation. In-depth investigation confirmed CH3C(O)O• and CH3C(O)OO• as the key reactive species for SMX degradation in LaCoO3/PAA system. The presence of Cl− (1–100 mM) slightly inhibited the degradation of SMX in the LaCoO3/PAA system, whereas the addition of HCO3− (0.1–1 mM) and humic aid (1–10 mg/L) could significantly inhibit SMX degradation. This work highlights the generation of organic radicals via the heterogeneous activation of PAA and thus provides a promising way to destruct contaminants in wastewater treatment.
Investigation on Adsorption and Decomposition Properties of CL-20/FOX-7 Molecules on MgH2(110) Surface by First-Principles
Authors: Yang Zhang , Fengqi Zhao , Siyu Xu , Fusheng Yang , Ergang Yao , Xiaobing Ren , Zhen Wu , Zaoxiao Zhang
Published: June 2020

Metal hydrides are regarded as promising hydrogen-supplying fuel for energetic materials while CL-20 (Hexanitrohexaazaisowurtzitane) and FOX-7 (1,1-Diamino-2,2-dinitroethylene) are typical principal components commonly used in energetic materials. Hence, it is interesting to explore the interactions between them for development of new energetic systems. In this paper, the adsorption and decomposition of CL-20 or FOX-7 molecules on the MgH2 (110) crystal surface were investigated by employing the First-Principles. In total, 18 adsorption configurations for CL-20/MgH2 (110) and 12 adsorption configurations for FOX-7/MgH2 (110) were considered. The geometric parameters for the configurations, adsorption energies, charge transfer, density of states, and decomposition mechanism were obtained and analyzed. In most of the configurations, chemical adsorption will occur. Moreover, the orientation of the nitro-group in CL-20 or FOX-7 with regard to the MgH2 (110) surface plays an important role on whether and how the energetic molecule decomposes. The adsorption and decomposition of CL-20 or FOX-7 on MgH2 could be attributed to the strong charge transfer between Mg atoms in the first layer of MgH2 (110) surface and oxygen as well as nitrogen atoms in the nitro-group of CL-20 or FOX-7 molecules.
Pharmacological Evaluation of Artemisia cina Crude CO2 Subcritical Extract after the Removal of Santonin by Means of High Speed Countercurrent Chromatography
Authors: Sakipova Zuriyadda , Giorno Thais Biondino Sardella , Bekezhanova Tolkyn , Siu Hai Wong Nikki , Shukirbekova Alma , Fernandes Patricia Dias , Boylan Fabio
Published: June 2020

Artemisia species are highly important due to their economic significance as medicines, fodder and food. Artemisia cina is an endemic species to Kazakhstan. In folk medicine, water extract of A. cina was used in the treatment of bronchial asthma while the alcohol extract has larvicidal and antituberculosis activity. The most common and most extensively studied compound from this species is the terpenoid santonin. The toxicity of this compound occurs at the doses of 60 mg for children and 200 mg for adults causing among other issues xanthopsia, leading to blindness. Having this in mind, the main idea of this work was to remove santonin from the crude extract and to check if the santonin-free extract would still be of any pharmacological importance. A CO2 subcritical extract was chromatographed using high-speed countercurrent chromatography (HSCCC) for the removal of santonin. The santonin-free CO2 subcritical extract (SFCO2E) as well as the isolated compound pectolinarigenin, a flavonoid, were assessed for their pharmacological actions. From the results obtained we can safely suggest that HSCCC is an efficient methodology to completely remove santonin from the CO2 subcritical extract. It was also possible to observe promising antinociceptive and anti–inflammatory activities for both SFCO2E and pectolinarigenin at concentrations that can justify the production of a phytomedicine with this endemic plant from Kazakhstan.
Untargeted Characterization of Chestnut (Castanea sativa Mill.) Shell Polyphenol Extract: A Valued Bioresource for Prostate Cancer Cell Growth Inhibition
Authors: Cacciola Nunzio Antonio , Cerrato Andrea , Capriotti Anna Laura , Cavaliere Chiara , D’Apolito Maria , Montone Carmela Maria , Piovesana Susy , Squillaci Giuseppe , Peluso Gianfranco , Laganà Aldo
Published: June 2020

Chestnut seeds are used for fresh consumption and for the industrial preparation of derivatives, such as chestnut flour. During industrial processing, large amounts of by-products are generally produced, such as leaves, flowers, shells and burs. In the present study, chestnut shells were extracted by boiling water in order to obtain polyphenol-rich extracts. Moreover, for the removal or non-phenolic compounds, a separation by preparative reverse phase chromatography in ten fractions was carried out. The richest fractions in terms of phenolic content were characterized by means of untargeted high-resolution mass spectrometric analysis together with a dedicated and customized data processing workflow. A total of 243 flavonoids, phenolic acids, proanthocyanidins and ellagitannins were tentatively identified in the five richest fractions. Due its high phenolic content (450.03 µg GAE per mg of fraction), one tumor cell line (DU 145) and one normal prostate epithelial cell line (PNT2) were exposed to increasing concentration of fraction 3 dry extract for 24, 48 and 72 h. Moreover, for DU 145 cell lines, increase of apoptotic cells and perturbation of cell cycle was demonstrated for the same extract. Those outcomes suggest that chestnut industrial by-products could be potentially employed as a source of bioresources.
Screening of Phosphodiesterase-5 Inhibitors and Their Analogs in Dietary Supplements by Liquid Chromatography–Hybrid Ion Trap–Time of Flight Mass Spectrometry
Authors: Kim Unyong , Cho Hyun-Deok , Kang Myung Hee , Suh Joon Hyuk , Eom Han Young , Kim Junghyun , Seo Sumin , Kim Gunwoo , Koo Hye Ryoung , Ha Nary , Song Un Tak , Han Sang Beom
Published: June 2020

An accurate and reliable method based on ion trap–time of flight mass spectrometry (IT–TOF MS) was developed for screening phosphodiesterase-5 inhibitors, including sildenafil, vardenafil, and tadalafil, and their analogs in dietary supplements. Various parameters affecting liquid chromatographic separation and IT–TOF detection were investigated, and the optimal conditions were determined. The separation was achieved on a reversed-phase column under gradient elution using acetonitrile and water containing 0.2% acetic acid at a flow rate of 0.2 mL/min. The chromatographic eluents were directly ionized in the IT–TOF system equipped with an electrospray ion source operating in the positive ion mode. The proposed screening method was validated by assessing its linearity, precision, and accuracy. Sequential tandem MS was conducted to obtain structural information of the references, and the fragmentation mechanism of each reference was proposed for providing spectral insight for newly synthesized analogs. Structural information, including accurate masses of both parent and fragment ions, was incorporated into the MSn spectral library. The developed method was successfully applied for screening adulterated dietary supplement samples.
Excited-State Proton Transfer in 8-Azapurines I: A Kinetic Analysis of 8-Azaxanthine Fluorescence
Authors: Wierzchowski Jacek , Smyk Bogdan
Published: June 2020

A super-continuum white laser with a half-pulse width of ~75 ps was used to observe the kinetics of a postulated excited-state proton transfer in 8-azaxanthine and its 8-methyl derivative. Both compounds exhibited dual emissions in weakly acidified alcoholic media, but only one band was present in aqueous solutions, exhibiting an abnormal Stokes shift (>12,000 cm−1). It was shown that long-wavelength emissions were delayed relative to the excitation pulse within alcoholic media. The rise time was calculated to be 0.4–0.5 ns in both methanol and deuterated methanol. This is equal to the main component of the fluorescence decay in the short-wavelength band (340 nm). Time-resolved emission spectra (TRES) indicated a two-state photo-transformation model in both compounds. Global analysis of the time dependence revealed three exponential components in each compound, one of which had an identical rise-time, with the second attributed to a long-wavelength band decay (6.4 ns for aza-xanthine and 8.3 ns for its 8-methyl derivative). The origin of the third, intermediate decay time (1.41 ns for aza-xanthine and 0.87 ns for 8-methyl-azaxanthine) is uncertain, but decay-associated spectra (DAS) containing both bands suggest the participation of a contact ion pair. These results confirm the model of phototautomerism proposed earlier, but the question of the anomalous isotope effect remains unsolved.
How ‘Protein-Docking’ Translates into the New Emerging Field of Docking Small Molecules to Nucleic Acids?
Authors: Tessaro Francesca , Scapozza Leonardo
Published: June 2020

In this review, we retraced the ‘40-year evolution’ of molecular docking algorithms. Over the course of the years, their development allowed to progress from the so-called ‘rigid-docking’ searching methods to the more sophisticated ‘semi-flexible’ and ‘flexible docking’ algorithms. Together with the advancement of computing architecture and power, molecular docking’s applications also exponentially increased, from a single-ligand binding calculation to large screening and polypharmacology profiles. Recently targeting nucleic acids with small molecules has emerged as a valuable therapeutic strategy especially for cancer treatment, along with bacterial and viral infections. For example, therapeutic intervention at the mRNA level allows to overcome the problematic of undruggable proteins without modifying the genome. Despite the promising therapeutic potential of nucleic acids, molecular docking programs have been optimized mostly for proteins. Here, we have analyzed literature data on nucleic acid to benchmark some of the widely used docking programs. Finally, the comparison between proteins and nucleic acid targets docking highlighted similarity and differences, which are intrinsically related to their chemical and structural nature.
Recent Trends in Controlling the Enzymatic Browning of Fruit and Vegetable Products
Authors: Moon Kyoung Mi , Kwon Eun-Bin , Lee Bonggi , Kim Choon Young
Published: June 2020

Enzymatic browning because of polyphenol oxidases (PPOs) contributes to the color quality of fruit and vegetable (FV) products. Physical and chemical methods have been developed to inhibit the activity of PPOs, and several synthetic chemical compounds are commonly being used as PPO inhibitors in FV products. Recently, there has been an emphasis on consumer-oriented innovations in the food industry. Consumers tend to urge the use of natural and environment-friendly PPO inhibitors. The purpose of this review is to summarize the mechanisms underlying the anti-browning action of chemical PPO inhibitors and current trends in the research on these inhibitors. Based on their mechanisms of action, chemical inhibitors can be categorized as antioxidants, reducing agents, chelating agents, acidulants, and/or mixed-type PPO inhibitors. Here, we focused on the food ingredients, dietary components, food by-products, and waste associated with anti-browning activity.
Design, Synthesis, and Biological Evaluation of 8-Mercapto-3,7-Dihydro-1H-Purine-2,6-Diones as Potent Inhibitors of SIRT1, SIRT2, SIRT3, and SIRT5
Authors: Han Haozhen , Li Chunpu , Li Man , Yang Lisheng , Zhao Sen , Wang Zhifei , Liu Hong , Liu Dongxiang
Published: June 2020

Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases. They regulate many physiological processes and play important roles in inflammation, diabetes, cancers, and neurodegeneration diseases. Sirtuin inhibitors have potential applications in the treatment of neurodegenerative diseases and various cancers. Herein, we identified new sirtuin inhibitors based on the scaffold of 8-mercapto-3,7-dihydro-1H-purine-2,6-dione. To elucidate the inhibitory mechanism, the binding modes of the inhibitors in SIRT3 were established by molecular docking, showing that the inhibitors occupy the acetyl lysine binding site and interact with SIRT3, mainly through hydrophobic interactions. The interactions were validated by site-directed mutagenesis of SIRT3 and structure–activity relationship analysis of the inhibitors. Consistently, enzyme kinetic assays and microscale thermophoresis showed that these compounds are competitive inhibitors to the acetyl substrate, and mix-type inhibitors to NAD+. Furthermore, we demonstrated that the compounds are potent SIRT1/2/3/5 pan-inhibitors. This study provides novel hits for developing more potent sirtuin inhibitors.
Evaluation of Two Fully Automated Setups for Mycotoxin Analysis Based on Online Extraction-Liquid Chromatography–Tandem Mass Spectrometry
Authors: Vasconcelos Soares Maciel Edvaldo , Mejía-Carmona Karen , Lanças Fernando Mauro
Published: June 2020

Mycotoxins are secondary metabolites of fungi species widely known for their potentially toxic effects on human health. Considering their frequent presence in crops and their processed food, monitoring them on food-based matrices is now an important topic. Within such a context, the sample preparation step is usually mandatory before the chromatographic analysis, due to the complexity of matrices such as nuts, cereals, beverages, and others. For these reasons, we herein present the evaluation of two greener setups, based on the automation and miniaturization of the sample preparation step for mycotoxin analysis in different beverages. Firstly, we describe an analytical method based on a multidimensional assembly, coupling a lab-made microextraction column (508 µm i.d. × 100 mm) to a UPLC–MS/MS for the analysis of ochratoxin A in beverages. This configuration used a synthesized sorbent phase containing C18-functionalized graphene–silica particles, which exhibited excellent extraction performance, as well as being reusable and cheaper than commercially available extractive phases. Sequentially, a second setup, based on a multidimensional capillary LC coupled to MS/MS, was assessed for the same purpose. In this case, a graphene oxide-based capillary extraction column (254 µm i.d. × 200 mm) was used as the first dimension, while a C18 analytical capillary column performed the mycotoxin separation in beverages. Although this second one has similarities with the first, we focused mainly on the benefits related to the link between a miniaturized/automated sample preparation device with a capillary LC–MS/MS system, which made our analysis greener. Additionally, the chromatographic efficiency could even be enhanced.
Positional Isomerism in the N^N Ligand: How Much Difference Does a Methyl Group Make in [Cu(P^P)(N^N)]+ Complexes?
Authors: Brunner Fabian , Prescimone Alessandro , Constable Edwin C. , Housecroft Catherine E.
Published: June 2020

The synthesis and structural characterization of 5,6′-dimethyl-2,2′-bipyridine (5,6′-Me2bpy) are reported, along with the preparations and characterizations of [Cu(POP)(5,6′-Me2bpy)][PF6] and [Cu(xantphos)(5,6′-Me2bpy)][PF6] (POP = bis(2-(diphenylphosphanyl)phenyl)ether, xantphos = 4,5-bis(diphenylphosphanyl)-9,9-dimethyl-9H-xanthene). Single-crystal X-ray structure determinations of [Cu(POP)(5,6′-Me2bpy)][PF6] and [Cu(xantphos)(5,6′-Me2bpy)][PF6] confirmed distorted tetrahedral copper(I) coordination environments with the 5-methylpyridine ring of 5,6′-Me2bpy directed towards the (C6H4)2O unit of POP or the xanthene unit of xantphos. In the xantphos case, this preference may be attributed to C–H…π interactions involving both the 6-CH unit and the 5-methyl substituent in the 5-methylpyridine ring and the arene rings of the xanthene unit. 1H NMR spectroscopic data indicate that this ligand orientation is also preferred in solution. In solution and the solid state, [Cu(POP)(5,6′-Me2bpy)][PF6] and [Cu(xantphos)(5,6′-Me2bpy)][PF6] are yellow emitters, and, for powdered samples, photoluminescence quantum yields (PLQYs) are 12 and 11%, respectively, and excited-state lifetimes are 5 and 6 μs, respectively. These values are lower than PLQY and τ values for [Cu(POP)(6,6′-Me2bpy)][PF6] and [Cu(xantphos)(6,6′-Me2bpy)][PF6], and the investigation points to the 6,6′-dimethyl substitution pattern in the bpy ligand being critical for enhancement of the PLQY.
Assembling Polyiodides and Iodobismuthates Using a Template Effect of a Cyclic Diammonium Cation and Formation of a Low-Gap Hybrid Iodobismuthate with High Thermal Stability
Authors: Shestimerova Tatiana A. , Mironov Andrei V. , Bykov Mikhail A. , Grigorieva Anastasia V. , Wei Zheng , Dikarev Evgeny V. , Shevelkov Andrei V.
Published: June 2020

Exploiting a template effect of 1,4-diazacycloheptane (also known as homopiperazine, Hpipe), four new hybrid iodides, (HpipeH2)2Bi2I10·2H2O, (HpipeH2)I(I3), (HpipeH2)3I6·H2O, and (HpipeH2)3(H3O)I7, were prepared and their crystal structures were solved using single crystal X-ray diffraction data. All four solid-state crystal structures feature the HpipeH22+ cation alternating with Bi2I104–, I3–, or I– anions and solvent water or H3O+ cation. HpipeH22+ assembles anionic and neutral building blocks into polymer structures by forming four strong (N)H···I and (N)H···O hydrogen bonds per cation, with the H···I distances ranging from 2.44 to 2.93 Å and H···O distances of 1.88–1.89 Å. These hydrogen bonds strongly affect the properties of compounds; in particular, in the case of (HpipeH2)2Bi2I10·2H2O, they ensure narrowing of the band gap down to 1.8 eV and provide high thermal stability up to 240 °C, remarkable for a hydrated molecular solid.
Influence of Concentration on Release and Permeation Process of Model Peptide Substance-Corticotropin-From Semisolid Formulations
Authors: Siemiradzka Wioletta , Dolińska Barbara , Ryszka Florian
Published: June 2020

The transdermal route of administration of drug substances allows clinicians to obtain a therapeutic effect bypassing the gastrointestinal tract, where the active substance could be inactivated. The hormonal substance used in the study-corticotropin (ACTH)-shows systemic effects. Therefore, the study of the effect of the type of ointment base and drug concentration on the release rate and also permeation rate in in vivo simulated conditions may be a valuable source of information for clinical trials to effectively optimize corticotropin treatment. This goal was achieved by preparation ointment formulation selecting the appropriate ointment base and determining the effect of ACTH concentration on the release and permeation studies of the ACTH. Semi-solid preparations containing ACTH were prepared using Unguator CITO e/s. The release study of ACTH was tested using a modified USP apparatus 2 with Enhancer cells. The permeation study was conducted with vertical Franz cells. Rheograms of hydrogels were made with the use of a universal rotational rheometer. The dependence of the amount of released and permeated hormone on the ointment concentration was found. Based on the test of ACTH release from semi-solid formulations and evaluation of rheological parameters, it was found that glycerol ointment is the most favourable base for ACTH. The ACTH release and permeation process depends on both viscosity and ACTH concentration. The higher the hormone concentration, the higher the amount of released ACTH but it reduces the amount of ACTH penetrating through porcine skin.