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Analytical Chemistry Jul 2023Ion-selective electrode (ISE) potentiometry is reliable only if on-site calibration using a standard solution is performed before ion measurements. The complex device...
Ion-selective electrode (ISE) potentiometry is reliable only if on-site calibration using a standard solution is performed before ion measurements. The complex device and operation required for calibration hinder the implementation of ISEs in decentralized sensing. Reported herein is a new type of ISE that is calibrated by a built-in component of the sensor without requiring any fluid handling processes. The indicator and reference electrodes are connected by a thin ionic conductor such as an aqueous phase containing the measuring ions in a capillary tube. This connection establishes a baseline electromotive force (EMF) that incorporates phase boundary potentials across multiple interfaces of the electrochemical cell and serves as a one-point calibration. Unlike conventional ISEs that rely on one EMF reading for each measurement, the proposed sensor utilizes a sample-induced EMF change relative to the baseline for each ion measurement. The variability in relative EMF is found to be <2.0 mV for multiple full potentiometric sensors consisting of plasticizer-based K ISEs and hydrogel-based Ag/AgCl reference electrodes. This value is significantly smaller than the variability of absolute EMF readouts in similar sensors without the self-calibration design. Moreover, when the ion-conducting calibration bridge has a low concentration of primary ions, low ion mobility, and/or a small contact area with the indicator and reference phases, it does not compromise the Nernstian response slope toward the analyte ions in the sample and therefore does not need to be removed for sample testing. The accuracy of the single-use self-calibrated K sensor in testing undiluted human blood samples is validated using a commercial blood gas analyzer as the reference method. Although this study focuses on disposable sensors consisting of tubes, the fluidics-free self-calibration strategy may be adapted to other sensor configurations such as planar sensors.
PubMed: 37439818
DOI: 10.1021/acs.analchem.3c02135 -
Bioorganic Chemistry Nov 20235-Fluorouracil (5-FU) is one of the most widely applied chemotherapeutic agents with a broad spectrum of activity. However, despite this versatile activity, its use...
5-Fluorouracil (5-FU) is one of the most widely applied chemotherapeutic agents with a broad spectrum of activity. However, despite this versatile activity, its use poses many limitations. Herein, novel derivatives of 5-FU and dichloroacetic acid have been designed and synthesized as a new type of codrugs, also known as mutual prodrugs, to overcome the drawbacks of 5-FU and enhance its therapeutic efficiency. The stability of the obtained compounds has been tested at various pH values using different analytical techniques, namely HPLC and potentiometry. The antiproliferative activity of the new 5-FU derivatives was assessed in vitro on SK-MEL-28 and WM793 human melanoma cell lines in 2D culture as well as on A549 human lung carcinoma, MDA-MB-231 breast adenocarcinoma, LL24 normal lung tissue, and HMF normal breast tissue as a multicellular 3D spheroid model cultured in standard (static) conditions and with the use of microfluidic systems, which to a great extent resembles the in vivo environment. In all cases, new mutual prodrugs showed a higher cytotoxic activity toward cancer models and lower to normal cell models than the parent 5-FU itself.
Topics: Humans; Fluorouracil; Prodrugs; Antineoplastic Agents; Acetates; Cell Line; Hydrocarbons, Chlorinated
PubMed: 37639758
DOI: 10.1016/j.bioorg.2023.106784 -
Materials (Basel, Switzerland) Aug 2023Ion-selective electrodes are a popular analytical tool useful in the analysis of cations and anions in environmental, industrial and clinical samples. This paper... (Review)
Review
Ion-selective electrodes are a popular analytical tool useful in the analysis of cations and anions in environmental, industrial and clinical samples. This paper presents an overview of new materials used for the preparation of anion-sensitive ion-selective electrodes during the last five years. Design variants of anion-sensitive electrodes, their advantages and disadvantages as well as research methods used to assess their parameters and analytical usefulness are presented. The work is divided into chapters according to the type of ion to which the electrode is selective. Characteristics of new ionophores used as the electroactive component of ion-sensitive membranes and other materials used to achieve improvement of sensor performance (e.g., nanomaterials, composite and hybrid materials) are presented. Analytical parameters of the electrodes presented in the paper are collected in tables, which allows for easy comparison of different variants of electrodes sensitive to the same ion.
PubMed: 37687472
DOI: 10.3390/ma16175779 -
Journal of Experimental & Clinical... Sep 2023Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis....
BACKGROUND
Malignant ascites commonly occurs in advanced or recurrent stages of epithelial ovarian cancer during peritoneal carcinomatosis and is correlated with poor prognosis. Due to its complex composition of cellular and acellular components malignant ascites creates a unique tumor microenvironment, which mediates immunosuppression and promotes progression of disease. However, the immunosuppressive mechanisms remain poorly understood.
METHODS
In the present study, we explored the antitumor activity of healthy donor NK and T cells directed against ovarian cancer cells in presence of malignant ascites derived from patients with advanced or recurrent peritoneal carcinomatosis. A wide range of methods was used to study the effect of ascites on NK and T cells (FACS, ELISA, EliSpot, qPCR, Live-cell and confocal microscopy, Western blot and electrolyte flux assays). The ascites components were assessed using quantitative analysis (nephelometry, potentiometry and clinical chemistry) and separation methods (dialysis, ultracentrifugal filtration and lipid depletion).
RESULTS
Ascites rapidly inhibited NK cell degranulation, tumor lysis, cytokine secretion and calcium signaling. Similarly, target independent NK and T cell activation was impaired in ascites environment. We identified imbalanced electrolytes in ascites as crucial factors causing extensive immunosuppression of NK and T cells. Specifically, high sodium, low chloride and low potassium content significantly suppressed NK-mediated cytotoxicity. Electrolyte imbalance led to changes in transcription and protein expression of electrolyte channels and impaired NK and T cell activation. Selected inhibitors of sodium electrolyte channels restored intracellular calcium flux, conjugation, degranulation and transcript expression of signaling molecules. The levels of ascites-mediated immunosuppression and sodium/chloride/potassium imbalance correlated with poor patient outcome and selected molecular alterations were confirmed in immune cells from ovarian cancer patients.
CONCLUSION
Our data suggest a novel electrolyte-based mechanism of immunosuppression in malignant ascites of patients with peritoneal carcinomatosis. We show for the first time that the immunosuppression of NK cytotoxicity in coculture assays is correlated to patient poor survival. Therapeutic application of sodium channel inhibitors may provide new means for restoring immune cell activity in ascites or similar electrolyte imbalanced environments.
Topics: Humans; Female; Peritoneal Neoplasms; Ascites; Chlorides; T-Lymphocytes; Ovarian Neoplasms; Potassium; Tumor Microenvironment
PubMed: 37684704
DOI: 10.1186/s13046-023-02798-8 -
Biomolecules Jan 2024Because of their capacity to bind metals, metal chelators are primarily employed for therapeutic purposes, but they can also find applications as colorimetric reagents...
Because of their capacity to bind metals, metal chelators are primarily employed for therapeutic purposes, but they can also find applications as colorimetric reagents and cleaning solutions as well as in soil remediation, electroplating, waste treatment, and so on. For instance, iron-chelation therapy, which is used to treat iron-overload disorders, involves removing excess iron from the blood through the use of particular molecules, like deferoxamine, that have the ability to chelate the metal. The creation of bioinspired and biodegradable chelating agents is a crucial objective that draws inspiration from natural products. In this context, starting from bioavailable molecules such as maltol and pyrogallol, new molecules have been synthetized and characterized by potentiometry, infrared spectroscopy and cyclic voltammetry. Finally, the ability of these to bind iron has been investigated, and the stability constants of ferric complexes are measured using spectrophotometry. These compounds offer intriguing scaffolds for an innovative class of versatile, multipurpose chelating agents.
Topics: Iron Chelating Agents; Iron; Chelation Therapy; Biological Products; Colorimetry; Ligands
PubMed: 38254692
DOI: 10.3390/biom14010092 -
Journal of Inorganic Biochemistry Sep 2023Two silver(I) complexes with biologically relevant heterocyclic ligands, pyrrole and furan-2- carboxylic acid, were synthesized and their composition was confirmed using...
Two silver(I) complexes with biologically relevant heterocyclic ligands, pyrrole and furan-2- carboxylic acid, were synthesized and their composition was confirmed using elemental, spectral, thermal and structural analyses. The {[Ag(Py2c)]} (AgPy2c, Py2c = pyrrole-2-carboxylate) and {[Ag(Fu2c)]} (AgFu2c, Fu2c = furan-2-carboxylate) solubility and stability in biological test stock solution were confirmed by H NMR spectroscopy. The X-ray analysis has enabled us to determine typical argentophilic interactions and bridging carboxylate coordination mode of both ligands. Potentiometric data analysis by BSTAC program resulted in the determination of the stability constant of only one species, i.e., the ML (M = Ag, L = Fu2c), log β = 0.59 ± 0.04. Antimicrobial and anticancer tests were performed against selected microorganisms and cell lines with new silver(I) complexes and compared with AgSD (silver(I) sulfadiazine) and cisplatin. From their microbial toxicity point of view, selectivity was determined against lactobacilli (AgPy2c is 8× more effective against S. aureus and E. coli and AgFu2c is 8× more effective against E. coli and 4× against S. aureus). AgFu2c significant anticancer activity was determined against Jurkat cell lines (IC = 8.00 μM) and was similar to cisPt (IC = 6.3 μM) similarly to its selectivity (SI (AgFu2c) = 7.3, SI (cisPt) = 6.4, SI = selectivity index). In addition, cell cycle arrest was observed already in the Sub-G0 phase during a flow cytometry experiment. To evaluate the AgPy2c and AgFu2c bioavailability we also discuss their Lipinski's Rule of Five.
Topics: Silver; Coordination Complexes; Ligands; Escherichia coli; Staphylococcus aureus; Anti-Infective Agents; Furans; Microbial Sensitivity Tests; Anti-Bacterial Agents
PubMed: 37271621
DOI: 10.1016/j.jinorgbio.2023.112266 -
Organic & Biomolecular Chemistry Jul 2023The synthesis, acid-base behaviour and anion recognition of neurotransmitters (dopamine, tyramine and serotonin) in aqueous solution of different aza-scorpiand ligands...
The synthesis, acid-base behaviour and anion recognition of neurotransmitters (dopamine, tyramine and serotonin) in aqueous solution of different aza-scorpiand ligands functionalized with hydroxyphenyl and phenyl moieties (L1-L3 and L4, respectively) have been studied by potentiometry, NMR, UV-Vis and fluorescence spectroscopy and isothermal titration calorimetry (ITC). The analysis of the potentiometric results shows the selective recognition of serotonin at physiological pH ( = 8.64 × 10) by L1. This selectivity has an entropic origin probably coming from a fine pre-organization of the interacting partners. Thus, the complementarity of the receptor and the substrate allows the reciprocal formation of hydrogen bonds, π-π and cation-π interactions, stabilizing the receptors and slowing the rate of oxidative degradation, and satisfactory results are obtained at acidic and neutral pH values. NMR and molecular dynamics studies reveal the rotation blockage in the neurotransmitter side chain once complexed with L1.
Topics: Ligands; Serotonin; Water; Anions; Oxidation-Reduction
PubMed: 37335019
DOI: 10.1039/d3ob00562c -
Journal of Biological Inorganic... Sep 2023A series of novel Ga(III)-pyridine carboxylates ([Ga(Pic)]·HO (GaPic; HPic = picolinic acid), HO[Ga(Dpic)]·HO (GaDpic; HDpic = dipicolinic acid),...
A series of novel Ga(III)-pyridine carboxylates ([Ga(Pic)]·HO (GaPic; HPic = picolinic acid), HO[Ga(Dpic)]·HO (GaDpic; HDpic = dipicolinic acid), [Ga(Chel)(HO)(OH)]·4HO (GaChel; HChel = chelidamic acid) and [Ga(Cldpic)(HO)(OH)] (GaCldpic; HCldpic = 4-chlorodipicolinic acid)) have been synthesized by simple one-step procedure. Vibrational spectroscopy (mid-IR), elemental analysis, thermogravimetric analysis and X-ray diffraction confirmed complexes molecular structure, inter and intramolecular interactions and their influence to spectral and thermal properties. Moreover, complex species speciation was described in Ga(III)-HPic and Ga(III)-HDpic systems by potentiometry and H NMR spectroscopy and mononuclear complex species were determined; [Ga(Pic)] (logβ = 16.23(6)), [Ga(Pic)] (logβ = 20.86(2)), [Ga(Dpic)] (logβ = 15.42(9)) and [Ga(Dpic)(OH)] (logβ = 11.08(4)). To confirm the complexes stability in 1% DMSO (primary solvent for biological testing), timescale H NMR spectra were measured (immediately after dissolution up to 96 h). Antimicrobial activity evaluated by IC (0.05 mM) is significant for GaDpic and GaCldpic against difficult to treat and multi-resistant P. aeruginosa. On the other hand, the GaPic complex is most effective against Jurkat, MDA-MB-231 and A2058 cancer cell lines and significantly also decreases the HepG2 cancer cells viability at 75 and 100 μM concentrations in a relatively short time (up to 48 h). In addition, fluorescence measurements have been used to elucidate bovine serum albumin binding activity between ligands, Ga(III) complexes and bovine serum albumin.
Topics: Humans; Serum Albumin, Bovine; Pyridines; Neoplasms; Molecular Structure; Cell Line; Coordination Complexes; Ligands
PubMed: 37498326
DOI: 10.1007/s00775-023-02012-2 -
Membranes Nov 2023Recently, there has been rapid development of electrochemical sensors, and there have been numerous reports in the literature that describe new constructions with... (Review)
Review
Recently, there has been rapid development of electrochemical sensors, and there have been numerous reports in the literature that describe new constructions with improved performance parameters. Undoubtedly, this is due to the fact that those sensors are characterized by very good analytical parameters, and at the same time, they are cheap and easy to use, which distinguishes them from other analytical tools. One of the trends observed in their development is the search for new functional materials. This review focuses on potentiometric sensors designed with the use of various metal oxides. Metal oxides, because of their remarkable properties including high electrical capacity and mixed ion-electron conductivity, have found applications as both sensing layers (e.g., of screen-printing pH sensors) or solid-contact layers and paste components in solid-contact and paste-ion-selective electrodes. All the mentioned applications of metal oxides are described in the scope of the paper. This paper presents a survey on the use of metal oxides in the field of the potentiometry method as both single-component layers and as a component of hybrid materials. Metal oxides are allowed to obtain potentiometric sensors of all-solid-state construction characterized by remarkable analytical parameters. These new types of sensors exhibit properties that are competitive with those of the commonly used conventional electrodes. Different construction solutions and various metal oxides were compared in the scope of this review based on their analytical parameters.
PubMed: 37999362
DOI: 10.3390/membranes13110876 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2023Modern potentiometric sensors based on polymeric membrane ion-selective electrodes (ISEs) have achieved new breakthroughs in sensitivity, selectivity, and stability and...
Modern potentiometric sensors based on polymeric membrane ion-selective electrodes (ISEs) have achieved new breakthroughs in sensitivity, selectivity, and stability and have extended applications in environmental surveillance, medical diagnostics, and industrial analysis. Moreover, nonclassical potentiometry shows promise for many applications and opens up new opportunities for potentiometric biosensing. Here, we aim to provide a concept to summarize advances over the past decade in the development of potentiometric biosensors with polymeric membrane ISEs. This Concept article articulates sensing mechanisms based on non-equilibrium measurement techniques. In particular, we emphasize new trends in potentiometric biosensing based on attractive dynamic approaches. Representative examples are selected to illustrate key applications under zero-current conditions and stimulus-controlled modes. More importantly, fruitful information obtained from non-equilibrium measurements with dynamic responses can be useful for artificial intelligence (AI). The combination of ISEs with advanced AI techniques for effective data processing is also discussed. We hope that this Concept will illustrate the great possibilities offered by non-equilibrium measurement techniques and AI in potentiometric biosensing and encourage further innovations in this exciting field.
PubMed: 37733874
DOI: 10.1002/chem.202302647