| 1. |
- Bäck, Marcus, et al.
(författare)
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Tyrosine Side-Chain Functionalities at Distinct Positions Determine the Chirooptical Properties and Supramolecular Structures of Pentameric Oligothiophenes
- 2020
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 9:11, s. 1100-1108
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Tidskriftsartikel (refereegranskat)abstract
- Control over the photophysical properties and molecular organization of pi-conjugated oligothiophenes is essential to their use in organic electronics. Herein we synthesized and characterized a variety of anionic pentameric oligothiophenes with different substitution patterns of L- or D-tyrosine at distinct positions along the thiophene backbone. Spectroscopic, microscopic, and theoretical studies of L- or D-tyrosine substituted pentameric oligothiophene conjugates revealed the formation of optically active pi-stacked self-assembled aggregates under acid conditions. The distinct photophysical characteristics, as well as the supramolecular structures of the assemblies, were highly influenced by the positioning of the L- or D-tyrosine moieties along the thiophene backbone. Overall, the obtained results clearly demonstrate how fundamental changes in the position of the enantiomeric side-chain functionalities greatly affect the optical properties as well as the architecture of the self-assembled supramolecular structures.
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| 2. |
- Chien, Yu-Chuan, 1990-, et al.
(författare)
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Poly(Ethylene Glycol-block-2-Ethyl-2-Oxazoline) as Cathode Binder in Lithium-Sulfur Batteries
- 2021
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Ingår i: ChemistryOpen. - : John Wiley & Sons. - 2191-1363. ; 10:10, s. 960-965
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Tidskriftsartikel (refereegranskat)abstract
- Functional binders constitute a strategy to overcome several challenges that lithium-sulfur (Li-S) batteries are facing due to soluble reaction intermediates in the positive electrode. Poly (ethylene oxide) (PEO) and poly (vinylpyrrolidone) (PVP) are in this context a previously well-explored binder mixture. Their ether and amide groups possess affinity to the dissolved sulfur species, which enhances the sulfur utilization and mitigates the parasitic redox shuttle. However, the immiscibility of PEO and PVP is a concern for electrode stability. Copolymers comprising ether and amide groups are thus promising candidates to improve the stability the system. Here, a series of poly (ethylene glycol-block-2-ethyl-2-oxazoline) with various block lengths is synthesized and explored as binders in S/C composite electrodes in Li-S cells. While the electrochemical analyses show that although the sulfur utilization and capacity retention of the tested electrodes are similar, the integrity of the as-cast electrodes can play a key role for power capability.
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| 3. |
- Engen, Karin, et al.
(författare)
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Synthesis, Evaluation and Proposed Binding Pose of Substituted Spiro-Oxindole Dihydroquinazolinones as IRAP Inhibitors
- 2020
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 9:3, s. 325-337
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Tidskriftsartikel (refereegranskat)abstract
- Insulin‐regulated aminopeptidase (IRAP) is a new potential macromolecular target for drugs aimed for treatment of cognitive disorders. Inhibition of IRAP by angiotensin IV (Ang IV) improves the memory and learning in rats. The majority of the known IRAP inhibitors are peptidic in character and suffer from poor pharmacokinetic properties. Herein, we present a series of small non‐peptide IRAP inhibitors derived from a spiro‐oxindole dihydroquinazolinone screening hit (pIC50 5.8). The compounds were synthesized either by a simple microwave (MW)‐promoted three‐component reaction, or by a two‐step one‐pot procedure. For decoration of the oxindole ring system, rapid MW‐assisted Suzuki‐Miyaura cross‐couplings (1 min) were performed. A small improvement of potency (pIC50 6.6 for the most potent compound) and an increased solubility could be achieved. As deduced from computational modelling and MD simulations it is proposed that the S‐configuration of the spiro‐oxindole dihydroquinazolinones accounts for the inhibition of IRAP.
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| 4. |
- Jha, Vibhu, et al.
(författare)
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Binding Modes of Xanthine-Derived Selective Allosteric Site Inhibitors of MTHFD2
- 2023
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Ingår i: Chemistryopen. - 2191-1363. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Methylenetetrahydrofolate dehydrogenase (MTHFD2) is a mitochondrial enzyme involved in 1 C metabolism that is upregulated in various cancer cells, but absent in normal proliferating cells. Xanthine derivatives are the first selective inhibitors of MTHFD2 which bind to its allosteric site. Xanthine derivatives (including the co-crystallized inhibitors) were herein interrogated by molecular/induced-fit docking, MM-GBSA binding free energy calculations and molecular dynamics simulations in both MTHFD2 and MTHFD1 (a close homolog expressed in healthy cells). The gained insights from our in silico protocol allowed us to study binding mode, key protein-ligand interactions and dynamic movement of the allosteric inhibitors, correlating with their experimental binding affinities, biological activities and selectivity for MTHFD2. The reported conformational changes with MTHFD2 upon binding of xanthine derivatives were furthermore evaluated and confirmed by RMSF analyses of the MD simulation trajectories. The results reported herein are expected to benefit in the rational design of selective MTHFD2 allosteric inhibitors.
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| 5. |
- Liu, Ya, 1991, et al.
(författare)
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A Novel Graphene Quantum Dot-Based mRNA Delivery Platform
- 2021
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 10:7, s. 666-671
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Tidskriftsartikel (refereegranskat)abstract
- During the last decades, there has been growing interest in using therapeutic messager RNA (mRNA) together with drug delivery systems. Naked, unformulated mRNA is, however, unable to cross the cell membrane and is susceptible to degradation. Here we use graphene quantum dots (GQDs) functionalized with polyethyleneimine (PEI) as a novel mRNA delivery system. Our results show that these modified GQDs can be used to deliver intact and functional mRNA to Huh-7 hepatocarcinoma cells at low doses and, that the GQDs are not toxic, although cellular toxicity is a problem for these first-generation modified particles. Functionalized GQDs represent a potentially interesting delivery system that is easy to manufacture, stable and effective.
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| 6. |
- Manojveer, Seetharaman, et al.
(författare)
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Ligand-Promoted [Pd]-Catalyzed α-Alkylation of Ketones through a Borrowing-Hydrogen Approach
- 2023
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- A new class of palladium complexes bearing bidentate 2-hydroxypyridine based ligands have been prepared and fully characterized. The applications of these new complexes towards ketone alkylation reactions with alcohols through a metal-ligand cooperative borrowing-hydrogen (BH) process were demonstrated.
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| 7. |
- Neranon, Kitjanit, 1985-, et al.
(författare)
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Design, Synthesis and Self-Assembly of Functional Amphiphilic Metallodendrimers
- 2020
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Ingår i: ChemistryOpen. - : John Wiley & Sons. - 2191-1363. ; 9:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- A new family of alkynylated, amphiphilic dendrimers consisting of amidoamine linkers connected to 5,5 '-functionalized 2,2 '-bipyridine cores has been developed and evaluated in the formation of metallodendrimers of different generations and in self-assembly protocols. A convergent synthetic strategy was applied to provide dumbbell-shaped amphiphilic dendrimers, where the 2,2 '-bipyridine cores could be coordinated to Fe-II centers to afford corresponding metallodendrimers. The ability of the metallic- and non-metallic dendritic structures to self-assemble into functional supramolecular aggregates were furthermore evaluated in aqueous solution. Spherical aggregates with sizes of a few hundred nanometers were generally produced, where controlled disassembly of the metallodendrimers through decomplexation could be achieved.
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| 8. |
- Nermark, Fiona M., et al.
(författare)
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Desulfurization of Morupule Coal with Subcritical Aqueous Ethanol Extraction
- 2022
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Coal combustion greatly contributes to global emissions of toxic gases into the atmosphere, with sulfur emissions as one of the prominent pollutants in addition to carbon dioxide. Nevertheless, Botswana utilizes Morupule's sub-bituminous coal with average sulfur and ash contents, as determined in this study being 1.9 and 24.4 % by weight with an average calorific value of 22 MJ Kg−1 to generate electricity. We report an optimized extraction method for reducing total sulfur in Morupule coal from 1.9±0.2 to 0.43±0.02 wt.% at optimum conditions of ethanol/water (90/10, v/v %) at 129 °C (105 bars) in 10 minutes. A Box–Behnken experimental design was employed to select the optimal conditions of temperature (100–180 °C), water proportion in ethanol (10–90, v/v %) and extraction time (10–30 minutes), thus reducing the total sulfur under these mild conditions compared to conventional extraction. The optimized conditions were however not efficient in removing ash.
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| 9. |
- Perez, Oswaldo, et al.
(författare)
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Crystal Modifications of a Cyclic Guanosine Phosphorothioate Analogue, a Drug Candidate for Retinal Neurodegenerations
- 2023
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Ingår i: ChemistryOpen. - : John Wiley and Sons Inc. - 2191-1363. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active pharmaceutical ingredient (API) for the treatment of inherited retinal degenerations (IRDs), its neutral form (cGMPSA-H) and salts of sodium (-Na), calcium (-Ca), ammonium (-NH4), triethylammonium (-TEA), tris(hydroxymethyl)aminomethane (-Tris), benethamine (-Bnet), and benzathine (-BZ) were prepared. Their solid-state properties were studied with differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, and dynamic vapor sorption, and their solubilities were measured in deionized H2O as well as aqueous HCl and NaOH buffers. A total of 21 crystal modifications of cGMPSA were found and characterized by X-ray powder diffraction. Despite their crystalline character, no API forms featured any observable melting points during thermal analyses and instead underwent exothermic decomposition at ≥163 °C. Both the vapor sorption behavior and solubility were found to differ significantly across the API forms. cGMPSA-BZ featured the lowest aqueous solubility and hygroscopicity, with 50 μg/mL and 5 % mass gain at maximum relative humidity. The synthesis and crystallization of some crystal modifications were upscaled to >10 g. Single crystal X-ray diffraction was performed which resulted in the first crystal structure determination and absolute configuration of a cyclic guanosine monophosphorothioate, confirming the RP- conformation at the phosphorus atom.
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| 10. |
- Perez, Oswaldo, et al.
(författare)
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Crystal Modifications of a Cyclic Guanosine Phosphorothioate Analogue, a Drug Candidate for Retinal Neurodegenerations
- 2023
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 12:12
-
Tidskriftsartikel (refereegranskat)abstract
- In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active pharmaceutical ingredient (API) for the treatment of inherited retinal degenerations (IRDs), its neutral form (cGMPSA-H) and salts of sodium (-Na), calcium (-Ca), ammonium (-NH4), triethylammonium (-TEA), tris(hydroxymethyl)aminomethane (-Tris), benethamine (-Bnet), and benzathine (-BZ) were prepared. Their solid-state properties were studied with differential scanning calorimetry, thermogravimetric analysis, hot-stage microscopy, and dynamic vapor sorption, and their solubilities were measured in deionized H2O as well as aqueous HCl and NaOH buffers. A total of 21 crystal modifications of cGMPSA were found and characterized by X-ray powder diffraction. Despite their crystalline character, no API forms featured any observable melting points during thermal analyses and instead underwent exothermic decomposition at ≥163 °C. Both the vapor sorption behavior and solubility were found to differ significantly across the API forms. cGMPSA-BZ featured the lowest aqueous solubility and hygroscopicity, with 50 μg/mL and 5 % mass gain at maximum relative humidity. The synthesis and crystallization of some crystal modifications were upscaled to >10 g. Single crystal X-ray diffraction was performed which resulted in the first crystal structure determination and absolute configuration of a cyclic guanosine monophosphorothioate, confirming the RP- conformation at the phosphorus atom.
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| 11. |
- Prejanò, Mario, et al.
(författare)
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Computational Study of Mechanism and Enantioselectivity of Imine Reductase from Amycolatopsis orientalis
- 2022
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Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Imine reductases (IREDs) are NADPH-dependent enzymes (NADPH=nicotinamide adenine dinucleotide phosphate) that catalyze the reduction of imines to amines. They exhibit high enantioselectivity for a broad range of substrates, making them of interest for biocatalytic applications. In this work, we have employed density functional theory (DFT) calculations to elucidate the reaction mechanism and the origins of enantioselectivity of IRED from Amycolatopsis orientalis. Two substrates are considered, namely 1-methyl-3,4-dihydroisoquinoline and 2-propyl-piperideine. A model of the active site is built on the basis of the available crystal structure. For both substrates, different binding modes are first evaluated, followed by calculation of the hydride transfer transition states from each complex. We have also investigated the effect of mutations of certain important active site residues (Tyr179Ala and Asn241Ala) on the enantioselectivity. The calculated energies are consistent with the experimental observations and the analysis of transition states geometries provides insights into the origins of enantioselectivity of this enzyme.
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| 12. |
- Salian, Girish D., et al.
(författare)
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Investigation of Water-Soluble Binders for LiNi0.5Mn1.5O4-Based Full Cells
- 2022
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Ingår i: ChemistryOpen. - : John Wiley & Sons. - 2191-1363. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Two water-soluble binders of carboxymethyl cellulose (CMC) and sodium alginate (SA) have been studied in comparison with N-methylpyrrolidone-soluble poly(vinylidene difluoride-co-hexafluoropropylene) (PVdF-HFP) to understand their effect on the electrochemical performance of a high-voltage lithium nickel manganese oxide (LNMO) cathode. The electrochemical performance has been investigated in full cells using a Li4Ti5O12 (LTO) anode. At room temperature, LNMO cathodes prepared with aqueous binders provided a similar electrochemical performance as those prepared with PVdF-HFP. However, at 55 degrees C, the full cells containing LNMO with the aqueous binders showed higher cycling stability. The results are supported by intermittent current interruption resistance measurements, wherein the electrodes with SA showed lower resistance. The surface layer formed on the electrodes after cycling has been characterized by X-ray photoelectron spectroscopy. The amount of transition metal dissolutions was comparable for all three cells. However, the amount of hydrogen fluoride (HF) content in the electrolyte cycled at 55 degrees C is lower in the cell with the SA binder. These results suggest that use of water-soluble binders could provide a practical and more sustainable alternative to PVdF-based binders for the fabrication of LNMO electrodes.
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| 13. |
- Sheng, Xiang, et al.
(författare)
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Computational Study of the Fries Rearrangement Catalyzed by Acyltransferase from Pseudomonas protegens
- 2024
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Ingår i: ChemistryOpen. - 2191-1363.
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Tidskriftsartikel (refereegranskat)abstract
- The acyltransferase from Pseudomonas protegens (PpATase) catalyzes in nature the reversible transformation of monoacetylphloroglucinol to diacetylphloroglucinol and phloroglucinol. Interestingly, this enzyme has been shown to catalyze the promiscuous transformation of 3-hydroxyphenyl acetate to 2′,4′-dihydroxyacetophenone, representing a biological version of the Fries rearrangement. In the present study, we report a mechanistic investigation of this activity of PpATase using quantum chemical calculations. A detailed mechanism is proposed, and the energy profile for the reaction is presented. The calculations show that the acylation of the enzyme is highly exothermic, while the acetyl transfer back to the substrate is only slightly exothermic. The deprotonation of the C6−H of the substrate is rate-limiting, and a remote aspartate residue (Asp137) is proposed to be the general base group in this step. Analysis of the binding energies of various acetyl acceptors shows that PpATase can promote both intramolecular and intermolecular Fries rearrangement towards diverse compounds.
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| 14. |
- Szego, Anthony E., et al.
(författare)
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Precapture of CO2 and Hydrogenation into Methanol on Heterogenized Ruthenium and Amine-Rich Catalytic Systems
- 2023
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Ingår i: ChemistryOpen. - 2191-1363. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- A heterogenized alternative to the homogeneous precapture of CO2 with amines and subsequent hydrogenation to MeOH was developed using aminated silica and a Ru-MACHOTM catalyst. Commercial mesoporous silica was modified with three different amino-silane monomers and used as support for the Ru catalyst. These composites were studied by TEM and solid-state NMR spectroscopy before and after the catalytic reaction. These catalytic reactions were conducted at 155 degrees C at a H-2 and CO2 pressures of 75 and 2 bar, respectively, with the heterogeneous system (gas-solid) being probed with gas-phase infrared spectroscopy used to quantify the resulting products. High turnover number (TON) values were observed for the samples aminated with secondary amines.
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| 15. |
- Yu, Mingjia, et al.
(författare)
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Elucidating the Binding Mode between Heparin and Inflammatory Cytokines by Molecular Modeling
- 2021
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Ingår i: ChemistryOpen. - : John Wiley & Sons. - 2191-1363. ; 10:10, s. 966-975
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) interacts with a broad spectrum of inflammatory cytokines, thereby modulating their biological activities. It is believed that there is a structural-functional correlation between each protein and sugar sequences in the HS polysaccharides, however, the information in this regard is limited. In this study, we compared the binding of four inflammatory cytokines (CCL8, IL-1beta, IL-2 and IL-6) to immobilized heparin by an SPR analysis. To define the molecular base of the binding, we used a heparin pentasaccharide as representative structure to dock into the 3D-molecular structure of the cytokines. The results show a discrepancy in KD values obtained by SPR analysis and theoretical calculation, pointing to the importance to apply more than one method when describing affinity between proteins and HS. By cluster analysis of the complex formed between the pentasaccharide and cytokines, we have identified several groups in heparin forming strong hydrogen bonds with all four cytokines, which is a significant finding. This molecular and conformational information should be valuable for rational design of HS/heparin-mimetics to interfere cytokine-HS interactions.
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