Amphiphobic fluoroalkyl chains are exploited for creating robust and diverse self-assembled biomimetic catalysts in aqueous solution. Long terminal perfluoroalkyl chains (CnF2n+1 with n = 6, 8, and 10) yoked with a short perhydroalkyl chains (CmH2m with m = 2 and 3) were used to synthesize several 1,4,7-triazacyclononane (TACN) derivatives, CnF2n+1-CmH2m-TACN. In the presence of an equimolar amount of Zn2+ ions that coordinate the TACN moiety and drive the self-assembly into micelle-like aggregates, the critical aggregation concentration of polyfluorinated CnF2n+1-CmH2mTACN·Zn2+ was lowered by ~1 order of magnitude compared to the traditional perhyroalkyl counterpart with identical carbon number of alkyl chain. When 2’-hydroxypropyl-4-nitrophenyl phosphate was used as the model phosphate substrate, polyfluorinated CnF2n+1CmH2m-TACN·Zn2+ assemblies showed higher affinity and catalytic activity, compared to its perhyroalkyl chain-based counterpart. Coarse-grained molecular dynamic simulations have been introduced to explore the supramolecular assembly of polyfluoroalkyl chains in the presence of Zn2+ ions and to better understand their enhanced catalytic activity.
Monthly Archives: October 2023
9‐Azahomocubane
Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e.g., a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9-azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9-azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1-azahomocubane.
Cross‐Binding of Adenosine by Aptamers Selected Using Theophylline
The newly selected DNA aptamer for theophylline can also bind adenosine, whereas the classical RNA aptamer cannot. Theophylline and adenosine are related molecules in regulating sleep, suggesting that nucleic acids also have the chemical basis for a similar function.
Abstract
We recently reported that some adenosine binding aptamers can also bind caffeine and theophylline with around 20-fold lower affinities. This discovery led to the current work to examine the cross-binding of adenosine to theophylline aptamers. For the DNA aptamer for theophylline, cross-binding to adenosine was observed, and the affinity was 18 to 38-fold lower for adenosine based on assays using isothermal titration calorimetry and ThT fluorescence spectroscopy. The binding complexes were characterized using NMR spectroscopy, and both adenosine and theophylline showed an overall similar binding structure to the DNA theophylline aptamer, although small differences were also observed. In contrast, the RNA aptamer did not show binding to adenosine, although both aptamers have very similar relative selectivity for various methylxanthines including caffeine. After a negative selection, a few new aptamers with completely different primary sequences for theophylline were obtained and they did not show binding to adenosine. Thus, there are many ways for aptamers to bind theophylline and some can have cross-binding to adenosine. In biology, theophylline, caffeine, and adenosine can bind to the same protein receptors to regulate sleep, and their binding to the same DNA motifs may suggest an early role of nucleic acids in similar regulatory functions.
Covalent Targeting of Glutamate Cysteine Ligase to Inhibit Glutathione Synthesis
We have discovered a covalent inhibitor of glutamate-cysteine ligase (GCL) that targets an allosteric C114 in the regulatory subunit GCLM to inhibit GCL activity, lower GSH levels, and impair cell viability in ARID1A-negative cancer cells.
Abstract
Dysregulated oxidative stress plays a major role in cancer pathogenesis and some types of cancer cells are particularly vulnerable to inhibition of their cellular antioxidant capacity. Glutamate-cysteine ligase (GCL) is the first and rate-limiting step in the synthesis of the major cellular antioxidant glutathione (GSH). Developing a GCL inhibitor may be an attractive therapeutic strategy for certain cancer types that are particularly sensitive to oxidative stress. In this study, we reveal a cysteine-reactive ligand, EN25, that covalently targets an allosteric cysteine C114 on GCLM, the modifier subunit of GCL, and leads to inhibition of GCL activity. This interaction also leads to reduced cellular GSH levels and impaired cell viability in ARID1A-deficient cancer cells, which are particularly vulnerable to glutathione depletion, but not in ARID1A-positive cancer cells. Our studies uncover a novel potential ligandable site within GCLM that can be targeted to inhibit GSH synthesis in vulnerable cancer cell types.
Deriving Novel Quaternary Ammonium Compound Disinfectant Scaffolds from a Natural Product: Mechanistic Insights of the Quaternization of Ianthelliformisamine C
In the search for polypharmacological quaternary ammonium compound disinfectants, we sought to investigate the quaternization of the ianthelliformisamine C scaffold. We synthesized a small library of quaternary ammonium compounds, finding that the tetramethyl derivative had the best activity. We investigated the mechanism of action of the natural product and methylated derivative, finding that both permeabilized the membrane.
Abstract
In the search for novel quaternary ammonium compound (QAC) disinfectants that can evade bacterial resistance, we turned to natural products as a source of inspiration. Herein we used natural product ianthelliformisamine C as a scaffold to design a small library of QACs. We first synthesized ianthelliformisamine C via an amide coupling that allowed for facile purification without the need for protecting groups. We then alkylated and quaternized the internal amines to yield four novel QACs, but all but one demonstrated no antibacterial activity against the tested strains. Using a combination of membrane depolarization and permeabilization assays, we were able to demonstrate that ianthelliformisamine C and the active QAC analog enact cell death via membrane permeabilization, contrary to prior reports on ianthelliformisamine C's mechanism of action.
The Conversion of UDP‐Glc to UDP‐Man: In Silico and Biochemical Exploration To Improve the Catalytic Efficiency of CDP‐Tyvelose C2‐Epimerases
Promiscuous CDP-tyvelose 2-epimerase (TyvE) converts NDP-glucose to NDP-mannose. We present the sequence fingerprints that are indicative of this conversion in TyvE-like enzymes. Eleven TyvE-like enzymes were identified, and the top two wild-type candidates and a quadruple mutant were characterized. The improved catalytic efficiency of these enzymes might help the design of new nucleotide production pathways starting from a cheap sugar substrates like sucrose.
Abstract
A promiscuous CDP-tyvelose 2-epimerase (TyvE) from Thermodesulfatator atlanticus (TaTyvE) belonging to the nucleotide sugar active short-chain dehydrogenase/reductase superfamily (NS-SDRs) was recently discovered. TaTyvE performs the slow conversion of NDP-glucose (NDP-Glc) to NDP-mannose (NDP-Man). Here, we present the sequence fingerprints that are indicative of the conversion of UDP-Glc to UDP-Man in TyvE-like enzymes based on the heptagonal box motifs. Our data-mining approach led to the identification of 11 additional TyvE-like enzymes for the conversion of UDP-Glc to UDP-Man. We characterized the top two wild-type candidates, which show a 15- and 20-fold improved catalytic efficiency, respectively, on UDP-Glc compared to TaTyvE. In addition, we present a quadruple variant of one of the identified enzymes with a 70-fold improved catalytic efficiency on UDP-Glc compared to TaTyvE. These findings could help the design of new nucleotide production pathways starting from a cheap sugar substrate like glucose or sucrose.
New Insights into the Behaviour of Commercial Silicon Electrode Materials via Empirical Fitting of Galvanostatic Charge‐Discharge Curves
The fast fading of silicon electrodes is a known issue preventing commercialization. Using empirical equations and electrochemical impedance spectroscopy, we isolate the lithiation phases of silicon and show that the capacity fade of commercial silicon electrodes is reversible and related to the iR drop of the cell.
Abstract
Silicon (Si) materials for use in Lithium ion batteries (LIBs) are of continued interest to battery manufacturers. With an increasing number of commercially available Si materials, evaluating their performance becomes a challenge. Here, we use an empirical fitting function presented earlier to aid in the analysis of galvanostatic charge-discharge data of commercial Si half-cells with relatively high loading. We find that the fitting procedure is capable of detecting dynamic changes in the cell, such as reversible capacity fade of the Si electrode. This fading is found to be due to the highly lithiated Li2Si Li3.5Si phase and that the behaviour is strongly dependent on the potential of this phase. EIS reveals that the Si electrode is responsible for the reversible behaviour due to progressive loss of Li+ leading to increasing resistance. SEM/EDX and XPS characterization are also employed to determine the origin of the irreversible resistance growth on the Si electrodes.
Metal Carbide Additives in Graphite‐Silicon Composites for Lithium‐Ion Batteries
Graphite-silicon composites for batteries: Molybdenum and Chromium Carbides are used as additives to stabilize graphite/silicon composites. Spark plasma sintering technology is used to sinter the electrode powders. The presence of molybdenum or chromium carbides promotes the performance of C/Si electrodes in lithium cells, improving the cycling stability compared to pristine graphite/silicon compounds.
Abstract
The pathway for improving lithium-ion batteries′ energy density strongly depends on finding materials with enhanced performance. Although great efforts have been done, on the anode-side, graphite is still the best choice. In the last decade, silicon elements are attracting growing attention as anode since their use can theoretically increase specific capacity of the negative electrode side. However, as the electrochemical mechanism involves the alligation of a large amount of Li, the silicon electrode experiences huge volume changes (more than 300 % of its initial volume), leading to fractures and pulverizations of the electrode. Herein, we propose for the first time using Molybdenum and Chromium Carbides as additive to stabilize graphite/silicon composites. Spark plasma sintering technology is used to sinter the electrode powders. We demonstrated that the presence of molybdenum or chromium carbides promotes the performance of C/Si electrodes, improving the cycling stability compared to pristine graphite/silicon electrodes.
Unravelling the Secrets of α‐Pyrones from Aspergillus Fungi: A Comprehensive Review of Their Natural Sources, Biosynthesis, and Biological Activities
Aspergillus, one of the most product-rich and genetically robust genera, contains a diverse range of species with potential economic and ecological implications. Chemically, Aspergillus is one of the essential sources of polyketides, alkaloids, diphenyl ethers, diketopiperazines, and other miscellaneous compounds, displaying a variety of pharmacological activities. The α-pyrones are unsaturated six-membered lactones. Although α-pyrone has a small structure, it is responsible for the structural diversity of several natural and synthetic compounds and multiple biological activities. In this review, we have summarized approximately 178 α-pyrone containing metabolites derivatives identified/reported from terrestrial, marine, endophytic, and filamentous Aspergillus species, including their sources, biological properties, and biosynthetic pathways until mid-2023, for the first time. This review is the first to compile and analyze the available data on α-pyrone metabolites from Aspergillus, which could facilitate further research and innovation in this field. Additionally, it offers a valuable source of scaffolds for future bioactive drug development, as some of these metabolites have shown potent antimicrobial, anti-inflammatory, and anticancer effects. Therefore, this review has significant implications for the advancement of natural product chemistry, pharmacology, biotechnology, and medicine.
[ASAP] Controlling Platinum Active Sites on Silver Nanoparticles for Hydrogen Evolution Reaction
Chemistry of Materials
DOI: 10.1021/acs.chemmater.3c01765