Sodium hydrogen bis­(phenoxy­acetate)

In the title compound, Na⁺·H⁺·2C₈H₇O₃⁻, the anion contains a short Speakman-type hydrogen bond [O⃛O = 2.413 (2) Å]. The anions and the Na atoms lie across twofold axes.     

Precise Quantification of Molybdate In Vitro by the FRET-Based Nanosensor ‘MolyProbe’

Molybdenum (Mo) is an essential trace element in all kingdoms of life. Mo is bioavailable as the oxyanion molybdate and gains biological activity in eukaryotes when bound to molybdopterin, forming the molybdenum cofactor. The imbalance of molybdate homeostasis results in growth deficiencies or toxic symptoms within plants, fungi and animals. Recently, fluorescence resonance energy transfer (FRET) methods have emerged, monitoring cellular and subcellular molybdate distribution dynamics using a genetically encoded molybdate-specific FRET nanosensor, named MolyProbe. Here, we show that the MolyProbe system is a fast and reliable in vitro assay for quantitative molybdate determination. We added a Strep-TagII affinity tag to the MolyProbe protein for quick and easy purification. This MolyProbe is highly stable, resistant to freezing and can be stored for several weeks at 4 °C. Furthermore, the molybdate sensitivity of the assay peaked at low nM levels. Additionally, The MolyProbe was applied in vitro for quantitative molybdate determination in cell extracts of the plant Arabidopsis thaliana, the fungus Neurospora crassa and the yeast Saccharomyces cerevisiae. Our results show the functionality of the Arabidopsis thaliana molybdate transporter MOT1.1 and indicate that FRET-based molybdate detection is an excellent tool for measuring bioavailable Mo.     

Evolution of Artificial Arginine Analogues—Fluorescent Guanidiniocarbonyl-Indoles as Efficient Oxo-Anion Binders

In this article, we present fluorescent guanidiniocarbonyl-indoles as versatile oxo-anion binders. Herein, the guanidiniocarbonyl-indole (GCI) and methoxy-guanidiniocarbonyl-indole (MGCI) were investigated as ethylamides and compared with the well-known guanidiniocarbonyl-pyrrole (GCP) concerning their photophysical properties as well as their binding behavior towards oxo-anions. Hence, a variety of anionic species, such as carboxylates, phosphonates and sulfonates, have been studied regarding their binding properties with GCP, GCI and MGCI using UV-Vis titrations, in combination with the determination of the complex stoichiometry using the Job method. The emission properties were studied in relation to the pH value using fluorescence spectroscopy as well as the determination of the photoluminescence quantum yields (PLQY). Density functional theory (DFT) calculations were undertaken to obtain a better understanding of the ground-lying electronic properties of the investigated oxo-anion binders. Additionally, X-ray diffraction of GCP and GCI was conducted. We found that GCI and MGCI efficiently bind carboxylates, phosphonates and sulfonates in buffered aqueous solution and in a similar range as GCP (K_ass ≈ 1000–18,000 M⁻¹, in bis-tris buffer, pH = 6); thus, they could be regarded as promising emissive oxo-anion binders. They also exhibit a visible fluorescence with a sufficient PLQY. Additionally, the excitation and emission wavelength of MGCI was successfully shifted closer to the visible region of the electromagnetic spectrum by introducing a methoxy-group into the core structure, which makes them interesting for biological applications.     

Bioactive Components and Anticancer Activities of Spray-Dried New Zealand Tamarillo Powder

Tamarillo fruit contains many phytochemicals that have beneficial therapeutic and nutritional properties. Spray-drying is widely used to preserve fruit puree in powder form. However, to obtain high-quality fruit powder, the optimisation of spray-drying conditions is necessary, as a high drying temperature can damage sensitive bioactive compounds. This study investigated the effects of spray-drying on the microstructure, polyphenolics, total flavonoids, total carotenoids, antioxidant activity, and anticancer capacity of tamarillo powder. Response surface methodology (RSM) was used to optimise the spray-drying process to produce tamarillo powder. The independent variables were inlet drying temperature (120–160 °C), flow rate (1–5 g/mL), and maltodextrin concentration (0–10%). These variables influenced the microstructural attributes, bioactive components, and cytotoxicity of the spray-dried tamarillo powder. The increase in polyphenols and antioxidant activities were favoured under high-temperature spray drying conditions and a low carrier concentration. The optimised spray-drying conditions for producing tamarillo powder with high antioxidant and anticancer activities, high yield, and stable bioactive compounds were found to be at 146.8 °C inlet temperature, and a flow rate of 1.76 g/mL.     

Dually Responsive Poly(N-vinylcaprolactam)-b-poly(dimethylsiloxane)-b-poly(N-vinylcaprolactam) Polymersomes for Controlled Delivery

Limited tissue selectivity and targeting of anticancer therapeutics in systemic administration can produce harmful side effects in the body. Various polymer nano-vehicles have been developed to encapsulate therapeutics and prevent premature drug release. Dually responsive polymeric vesicles (polymersomes) assembled from temperature-/pH-sensitive block copolymers are particularly interesting for the delivery of encapsulated therapeutics to targeted tumors and inflamed tissues. We have previously demonstrated that temperature-responsive poly(N-vinylcaprolactam) (PVCL)-b-poly(dimethylsiloxane) (PDMS)-b-PVCL polymersomes exhibit high loading efficiency of anticancer therapeutics in physiological conditions. However, the in-vivo toxicity of these polymersomes as biocompatible materials has not yet been explored. Nevertheless, developing an advanced therapeutic nanocarrier must provide the knowledge of possible risks from the material’s toxicity to support its future clinical research in humans. Herein, we studied pH-induced degradation of PVCL₁₀-b-PDMS₆₅-b-PVCL₁₀ vesicles in-situ and their dually (pH- and temperature-) responsive release of the anticancer drug, doxorubicin, using NMR, DLS, TEM, and absorbance spectroscopy. The toxic potential of the polymersomes was evaluated in-vivo by intravenous injection (40 mg kg⁻¹ single dose) of PVCL₁₀-PDMS₆₅-PVCL₁₀ vesicles to mice. The sub-acute toxicity study (14 days) included gravimetric, histological, and hematological analyses and provided evidence for good biocompatibility and non-toxicity of the biomaterial. These results show the potential of these vesicles to be used in clinical research.     

“Click handle”-modified 2′-deoxy-2′-fluoroarabino nucleic acid as a synthetic genetic polymer capable of post-polymerization functionalization

The functions of natural nucleic acids such as DNA and RNA have transcended genetic information carriers and now encompass affinity reagents, molecular catalysts, nanostructures, data storage, and many others. However, the vulnerability of natural nucleic acids to nuclease degradation and the lack of chemical functionality have imposed a significant constraint on their ever-expanding applications. Herein, we report the synthesis and polymerase recognition of a 5-(octa-1,7-diynyl)uracil 2′-deoxy-2′-fluoroarabinonucleic acid (FANA) triphosphate. The DNA-templated, polymerase-mediated primer extension using this “click handle”-modified FANA (cmFANA) triphosphate and other FANA nucleotide triphosphates consisting of canonical nucleobases efficiently generated full-length products. The resulting cmFANA polymers exhibited excellent nuclease resistance and the ability to undergo efficient click conjugation with azide-functionalized molecules, thereby becoming a promising platform for serving as a programmable and evolvable synthetic genetic polymer capable of post-polymerization functionalization.

Polymerase-mediated incorporation of a “click handle”-modified fluoroarabinonucleic acid (cmFANA) triphosphate produces a new class of nuclease-resistant, evolvable genetic polymers that can be functionalized with azide-containing molecules.     

Piezo1 Mechano-Activation Is Augmented by Resveratrol and Differs between Colorectal Cancer Cells of Primary and Metastatic Origin

Cancer cells must survive aberrant fluid shear stress (FSS) in the circulation to metastasize. Herein, we investigate the role that FSS has on colorectal cancer cell apoptosis, proliferation, membrane damage, calcium influx, and therapeutic sensitization. We tested this using SW480 (primary tumor) and SW620 cells (lymph node metastasis) derived from the same patient. The cells were exposed to either shear pulses, modeling millisecond intervals of high FSS seen in regions of turbulent flow, or sustained shear to model average magnitudes experienced by circulating tumor cells. SW480 cells were significantly more sensitive to FSS-induced death than their metastatic counterparts. Shear pulses caused significant cell membrane damage, while constant shear decreased cell proliferation and increased the expression of CD133. To investigate the role of mechanosensitive ion channels, we treated cells with the Piezo1 agonist Yoda1, which increased intracellular calcium. Pretreatment with resveratrol further increased the calcium influx via the lipid-raft colocalization of Piezo1. However, minimal changes in apoptosis were observed due to calcium saturation, as predicted via a computational model of apoptosis. Furthermore, SW480 cells had increased levels of Piezo1, calcium influx, and TRAIL-mediated apoptosis compared to SW620 cells, highlighting differences in the mechano-activation of metastatic cells, which may be a necessary element for successful dissemination in vivo.     

Optimization of thin film solid phase microextraction and data deconvolution methods for accurate characterization of organic compounds in produced water

The continued rise in the extraction of unconventional oil and gas across the globe poses many questions about how to manage these relatively new waste‐streams. Produced water, the primary waste by‐product, contains a diverse number of anthropogenic additives together with the numerous hydrocarbons extracted from the well. Due to potential environmental hazards, it is critical to characterize the chemical composition of this type of waste before proper disposal or remediation/reuse. In this work, a thin film solid phase microextraction approach was developed and optimized to characterize produced water. The thin film device consisted of hydrophilic‐lipophilic balance particles embedded in polydimethylsiloxane and immobilized on a carbon mesh surface. These devices were chosen to provide broad extraction coverage and high reusability. Various parameters were evaluated to ensure reproducible results while minimizing analyte loss. This optimized protocol, consisting of a 15 min extraction followed by a short (3 s) rinsing step, enabled the reproducible analysis of produced water without any sample pretreatment. Extraction efficiency was suitable for both produced water additives and hydrocarbons. The developed approach was able to tentatively identify a total of 201 compounds from produced water samples, by using one‐dimensional gas chromatography hyphenated to mass spectrometry and data deconvolution.     

Biocompatible Lipid‐Coated Persistent Luminescent Nanoparticles for In Vivo Imaging of Dendritic Cell Migration

Dendritic cell (DC)‐based vaccines for immunotherapy have already achieved promising results in the last decade. To further improve current treatment protocols and enhance the therapeutic outcome, noninvasive in vivo tracking of DCs remains of crucial importance. Persistent luminescent nanoparticles (PLNPs) are inorganic materials which show an afterglow for hours after the optical excitation has ceased. If the afterglow is in the near‐infrared, the emission of injected particles can be tracked in vivo. However, stability and toxicity issues limit the use of bare PLNPs for biological applications. Therefore, appropriate surface functionalization is needed to improve their biocompatibility. In this study, it is demonstrated that near‐infrared light emitting LiGa₅O₈:Cr³⁺ nanoparticles can be functionalized with a biocompatible lipid coating which provides them with outstanding stability in biological media. In vitro experiments show efficient uptake, absence of cytotoxicity even at very high particle concentrations, and no adverse effects on the maturation potential of DCs. DCs labeled with lipid‐coated LiGa₅O₈:Cr³⁺ nanoparticles injected in mice can be imaged over days, confirming efficient in vivo migration to the popliteal lymph node. Together the results show that lipid coated LiGa₅O₈:Cr³⁺ nanoparticles possess excellent possibilities for further use in research and development of DC based vaccines.     

Economical,Green, and Safe Route Towards Substituted Lactones by Anodic Generation of Oxycarbonyl Radicals

A new electrochemical methodology has been developed for the generation of oxycarbonyl radicals under mild and green conditions from readily available hemioxalate salts. Mono‐ and multi‐functionalised γ‐butyrolactones were synthesised through exo‐cyclisation of these oxycarbonyl radicals with an alkene, followed by the sp³–sp³ capture of the newly formed carbon‐centred radical. The synthesis of functionalised valerolactone derivatives was also achieved, demonstrating the versatility of the newly developed methodology. This represents a viable synthetic route towards pharmaceutically important fragments and further demonstrates the practicality of electrosynthesis as a green and economical method to activate small organic molecules.