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Inorganic Chemistry Dec 2023We report here the improved synthesis of the tripodal picolinate chelator , with an overall yield of 41% over five steps, in comparison to the previously reported 6%...
We report here the improved synthesis of the tripodal picolinate chelator , with an overall yield of 41% over five steps, in comparison to the previously reported 6% yield. was investigated for its coordination chemistry with Ga(III) and radiolabeling properties with gallium-68 (Ga). The obtained crystal structure for [Ga()] shows that the three picolinate arms coordinate to the Ga(III) ion, fully occupying the octahedral coordination geometry. This is supported by H NMR which shows that the three arms are symmetrical when coordinated to Ga(III). Assessment of the thermodynamic stability through potentiometry gives log = 21.32, with a single species being produced across the range of pH 3.5-7.5. achieved >99% radiochemical conversion with Ga under mild conditions ([] = 6.6 μM, pH 7.4, 37 °C) with a molar activity of 3.1 GBq μmol. The resulting complex, [Ga][Ga()], showed improved stability over the previously reported [Ga][Ga()(HO)] in a serum challenge, with 32% of [Ga][Ga()] remaining intact after 30 min of incubation with fetal bovine serum.
PubMed: 37793007
DOI: 10.1021/acs.inorgchem.3c02459 -
Sensors (Basel, Switzerland) Sep 2023For the first time, a prototype of a portable device for the potentiometric determination of antioxidant capacity based on a new measurement principle is proposed. A...
For the first time, a prototype of a portable device for the potentiometric determination of antioxidant capacity based on a new measurement principle is proposed. A feature of the approach is the use of an electrochemical microcell with separated spaces and two identical electrodes with immobilized reagents. An antioxidant solution is introduced into one half-cell, and the antioxidants interact with the reagents. The other half-cell contains only reagents. The potential difference between the electrodes is due to the change in the ratio of the oxidized and reduced form of the reagents, which occurs as a result of the reaction with the antioxidants in one of the half-cells and is related to their concentration. The range of linearity of the microcell with immobilized reagents is 40-4000 μM-eq, and the limit of detection is 20 μM-eq. The device was successfully tested in the analysis of standard antioxidant solutions. The recoveries were (92-113)%, and the relative standard deviation did not exceed 15%. A good correlation was found between the data obtained by the approach and the potentiometric method in a macrocell for fruit juice analysis. Pearson's coefficient for the obtained experimental data was 0.9955. The proposed portable device is promising and can be used in field conditions.
Topics: Antioxidants; Potentiometry; Electrodes
PubMed: 37765901
DOI: 10.3390/s23187845 -
Biosensors & Bioelectronics Dec 2023We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold...
We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. The platform comprises a disposable chip hosting an array of 32 extended gate electrodes, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. Although employing only off-the-shelf electronic components, our platform achieves sensitivities comparable to fully customized nanofabricated potentiometric sensors. In particular, it reaches a detection limit of 0.2 fM for the pure molecular assay when sensing horseradish peroxidase-linked secondary antibody (∼0.4 nM reached by standard microplate methods). Furthermore, with the gold nanoparticle bioconjugation format, we demonstrate ca. 5-fold amplification of the potentiometric response compared to a pure molecular assay, at the detection limit of 13.3 fM. Finally, we elaborate on the mechanism of this amplification and propose that nanoparticle-mediated disruption of the diffusion barrier layer is the main contributor to the potentiometric signal enhancement. These results show the great potential of our portable, sensitive, and cost-efficient biosensor for multidimensional diagnostics in the clinical and laboratory settings, including e.g., serological tests or pathogen screening.
Topics: Gold; Metal Nanoparticles; Biosensing Techniques; Potentiometry; Immunoassay; Electrodes
PubMed: 37757510
DOI: 10.1016/j.bios.2023.115701 -
Journal of Inorganic Biochemistry Dec 2023Nalidixic acid (NAL) is a broad-spectrum antimicrobial widely used for urinary tract infections. As demonstrated, complexation of NAL with Zn, Mn and Cu was often used...
Nalidixic acid (NAL) is a broad-spectrum antimicrobial widely used for urinary tract infections. As demonstrated, complexation of NAL with Zn, Mn and Cu was often used to get new formulations with an enhanced efficiency and potency. Therefore, the elucidation of behavior of NAL in solution and of its interaction with metal cations are crucial to better understand the influence of complexation on NAL efficiency and to find the optimal conditions to propose novel formulations. As a preliminary study, spectrophotometric titrations were carried out on NAL to determine the values of the protonation constants and to define its acid-base behavior. Then, the interaction with the three metal cations Zn, Mn and Cu was investigated by potentiometric and spectrophotometric titrations, varying the conditions of temperature, ionic strength and metal-ligand ratio, thus allowing to get the most robust speciation model and to determine the formation constants with Zn, Mn, and Cu under different conditions, the sequestering ability of NAL towards metal cations, the formation enthalpic and entropic changes. A simulation under serum conditions was reported to show the relevance of the investigated species. Finally, LD-MS (laser desorption ionization mass spectrometry) and MS/MS analyses highlighted for all systems the formation of the complex species between Zn, Mn and Cu with NAL. MS/MS investigations assigned the sites of coordination of the ligand with the metal cation. More precisely, deprotonated NAL coordinates the metal cation via the oxygens of the carboxylate and the carbonyl groups.
Topics: Nalidixic Acid; Tandem Mass Spectrometry; Ligands; Metals; Cations; Water
PubMed: 37734219
DOI: 10.1016/j.jinorgbio.2023.112366 -
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 -
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 -
Antioxidants (Basel, Switzerland) Aug 2023This work presents a new method using kinetic potentiometry to study the thermodynamic and kinetic parameters of the reactions of antioxidants with peroxyl radicals. The...
This work presents a new method using kinetic potentiometry to study the thermodynamic and kinetic parameters of the reactions of antioxidants with peroxyl radicals. The rate constants of the reaction of antioxidants with radicals have been determined, and the groups of "fast" and "slow" antioxidants have been conventionally distinguished. Fast antioxidants include ascorbic, uric, gallic, chlorogenic, caffeic acids, glutathione, L-cysteine, and catechol with constant values from (1.05-9.25) × 10 M·s; "slow" antioxidants are α-tocopherol (in aqueous media), ionol, 2,6-ditretbutylphenol, and compounds of the azoloazine series, modified with polyphenolic fragments, with constant values from (4.00-8.50) × 10 M·s. It is shown that the value of the rate constant is directly related to the type of kinetic dependence of the potential recorded when an antioxidant is introduced into the solution of the radical initiator. It is shown that the method with the determination of the induction period is difficult in the study of "slow" antioxidants. It has been established that the area above the curve of the kinetic dependence Exp(∆E) is directly related to the amount of inhibited peroxyl radicals and can be used to assess the inhibitory properties of an antioxidant from a thermodynamic point of view. "Fixed time method" and "Initial rate method" were used. Positive correlations between the described method have been established. The utility of the parameter of the area above the curve of the kinetic dependence Exp(∆E) in the study of objects of complex composition is shown.
PubMed: 37627605
DOI: 10.3390/antiox12081608 -
Chemical Science Aug 2023Although metal-organic framework (MOF) photocatalysts have become ubiquitous, basic aspects of their photoredox mechanisms remain elusive. Nanosizing MOFs enables...
Although metal-organic framework (MOF) photocatalysts have become ubiquitous, basic aspects of their photoredox mechanisms remain elusive. Nanosizing MOFs enables solution-state techniques to probe size-dependent properties and molecular reactivity, but few MOFs have been prepared as nanoparticles (nanoMOFs) with sufficiently small sizes. Here, we report a rapid reflux-based synthesis of the photoredox-active MOF TiO(OH)(terephthalate) (MIL-125) to achieve diameters below 30 nm in less than 2 hours. Whereas MOFs generally require analysis by solid-state techniques, sub-30 nm diameters ensure colloidal stability for weeks and minimal light scattering, permitting analysis by solution-state methods. Optical absorption and photoluminescence spectra of free-standing colloids provide direct evidence that the photoredox chemistry of MIL-125 involves Ti trapping and charge accumulation onto the Ti-oxo clusters. Solution-state potentiometry collected during the photochemical process also allows simultaneous measurement of MOF Fermi-level energies . Finally, by leveraging the solution-processability of these nanoparticles, we demonstrate facile preparation of mixed-matrix membranes with high MOF loadings that retain the reversible photochromism. Taken together, these results demonstrate the feasibility of a rapid nanoMOF synthesis and fabrication of a photoactive membrane, and the fundamental insights they offer into heterogeneous photoredox chemistry.
PubMed: 37621428
DOI: 10.1039/d3sc02257a -
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