Mixing of endogenous CO2 and meteoric H2O causes extremely efficient carbonate dissolution.

Karst corrosion of carbonate rocks by water with dissolved gases proceeds in most cases along two major scenarios: (i) meteoric water absorbs CO2 from soil and atmosphere, or (ii) ascending water of deep circulation carries with it dissolved endogenous gases, mainly CO2 and H2S. We have observed a peculiar variant where meteoric water absorbs ascending endogenous gases at a natural gas vent on a travertine mound in Slovakia. Carbonate dissolution's extreme effectiveness is demonstrated by mineralization of rainwater ponded at a gas vent, rising to 3.2 g/L of dissolved solids shortly after the rainfall. One liter of water ponded at the vent and mixing with the venting gas, dissolved up to 800 mg of calcium at a rate exceeding 5.8 mg/L·min. Limestone tablets placed at the vent show signs of significant corrosion, at rates up to 126 mm/ka. The rate is comparable to those in coastal karst, where freshwater is mixing with seawater and to those in sulfuric acid speleogenesis (SAS), both the highest hitherto known rates of karst corrosion in carbonates. The geomorphic effects of the process described are depressions on the surface of travertine near the vents of endogenous CO2. This type of corrosion seems to be universal and probably occurs everywhere where endogenous CO2 is exhaled to the surface from carbonate rocks.

Expanding the library of sumanene molecular receptors for caesium-selective potentiometric sensors.

This paper reports the synthesis and characterization of eight sumanene molecular receptors for the selective recognition of caesium cations (Cs+). The sumanene derivatives differed in the number (from one to nine), type (electron donating or electron withdrawing) and method of the attachment (functionalization of sumanene at the benzylic or aromatic carbons) of substituents in the sumanene skeleton. The ultimate goal of this work was to investigate the prospective use of various sumanene derivatives in the design of Cs+-selective potentiometric sensors, thus, expanding the library of sumanene receptors for such applications. Spectroscopic fluorescence titration with caesium hexafluorophosphate revealed that the formation of sandwich complexes is highly favourable, but the steric hindrance of bulky substituents can disrupt this preference. In the case of triaryl-substituted sumanene derivatives, theoretical calculations show that, indeed, sandwich complexes are energetically more advantageous by 2.3 times than 1 : 1 complexes. Furthermore, such functionalization significantly increases receptor solubility in the polymeric membrane of the potentiometric sensors, which was quantitatively evaluated with the COSMO model.

Development of 5-fluorouracil-dichloroacetate mutual prodrugs as anticancer agents.

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.

Dual mode of voltammetric studies on Cu(II) complexes of His2 peptides: phosphate and peptide sequence recognition.

Copper(II) complexes of peptides with a histidine residue at the second position (His2 peptides) provide a unique profile of electrochemical behavior, offering signals of both Cu(II) reduction and Cu(II) oxidation. Furthermore, their structures with vacant positions in the equatorial coordination plane could facilitate interactions with other biomolecules. In this work, we designed a library of His2 peptides based on the sequence of Aß5-9 (RHDSG), an amyloid beta peptide derivative. The changes in the Aß5-9 sequence highly affect the Cu(II) oxidation signals, altered further by anionic species. As a result, Cu(II) complexes of Arg1 peptides without Asp residues were chosen as the most promising peptide-based molecular receptors for phosphates. The voltammetric data on Cu(II) oxidation for binary Cu(II)-His2 peptide complexes and ternary Cu(II)-His2 peptide/phosphate systems were also tested for His2 peptide recognition. We achieved a highly promising identification of subtle modifications in the peptide sequence. Thus, we introduce voltammetric measurement as a potential novel tool for peptide sequence recognition.

Analysis of the Flammability and the Mechanical and Electrostatic Discharge Properties of Selected Personal Protective Equipment Used in Oxygen-Enriched Atmosphere in a State of Epidemic Emergency.

Numerous fires occurring in hospitals during the COVID-19 pandemic highlighted the dangers of the existence of an oxygen-enriched atmosphere. At oxygen concentrations higher than 21%, fires spread faster and more vigorously; thus, the safety of healthcare workers and patients is significantly reduced. Personal protective equipment (PPE) made mainly from plastics is combustible and directly affects their safety. The aim of this study was to assess its fire safety in an oxygen-enriched atmosphere. The thermodynamic properties, fire, and burning behavior of the selected PPE were studied, as well as its mechanical and electrostatic discharge properties. Cotton and disposable aprons were classified as combustible according to their LOI values of 17.17% and 17.39%, respectively. Conall Health A (23.37%) and B/C (23.51%) aprons and the Prion Guard suit (24.51%) were classified as self-extinguishing. The cone calorimeter test revealed that the cotton apron ignites the fastest (at 10 s), while for the polypropylene PPE, flaming combustion starts between 42 and 60 s. The highest peak heat release rates were observed for the disposable apron (62.70 kW/m2), Prion Guard suit (61.57 kW/m2), and the cotton apron (62.81 kW/m2). The mean CO yields were the lowest for these PPEs. Although the Conall Health A and B/C aprons exhibited lower pHRR values, their toxic CO yield values were the highest. The most durable fabrics of the highest maximum tensile strength were the cotton apron (592.1 N) and the Prion Guard suit (274.5 N), which also exhibited the lowest electrification capability. Both fabrics showed the best abrasion resistance of 40,000 and 38,000 cycles, respectively. The abrasion values of other fabrics were significantly lower. The research revealed that the usage of PPE made from polypropylene in an oxygen-enriched atmosphere may pose a fire risk.

Tuning the sumanene receptor structure towards the development of potentiometric sensors.

Herein, we report for the first time the application of a sumanene derivative in potentiometric recognition of caesium cations. The structure of the sumanene receptor was carefully tuned to obtain its compatibility with polyvinyl chloride plasticized membranes of potentiometric sensors. The developed ion-selective electrodes based on membranes doped with octyloxybenzene sumanene exhibited a near theoretical sensitivity towards caesium cations, with a detection limit of 4 µM Cs+.

Tuning Receptor Properties of Metal-Amyloid Beta Complexes. Studies on the Interaction between Ni(II)-Aß5-9 and Phosphates/Nucleotides.

Amyloid-beta (Aß) peptides, potentially relevant in the pathology of Alzheimer's disease, possess distinctive coordination properties, enabling an effective binding of transition-metal ions, with a preference for Cu(II). In this work, we found that a N-truncated Aß analogue bearing a His-2 motif, Aß5-9, forms a stable Ni(II) high-spin octahedral complex at a physiological pH of 7.4 with labile coordination sites and facilitates ternary interactions with phosphates and nucleotides. As the pH increased above 9, a spin transition from a high-spin to a low-spin square-planar Ni(II) complex was observed. Employing electrochemical techniques, we showed that interactions between the binary Ni(II)-Aß5-9 complex and phosphate species result in significant changes in the Ni(II) oxidation signal. Thus, the Ni(II)-Aß5-9 complex could potentially serve as a receptor in electrochemical biosensors for phosphate species. The obtained results could also be important for nickel toxicology.

Intermediate Cu(II)-Thiolate Species in the Reduction of Cu(II)GHK by Glutathione: A Handy Chelate for Biological Cu(II) Reduction.

Gly-His-Lys (GHK) is a tripeptide present in the human bloodstream that exhibits a number of biological functions. Its activity is attributed to the copper-complexed form, Cu(II)GHK. Little is known, however, about the molecular aspects of the mechanism of its action. Here, we examined the reaction of Cu(II)GHK with reduced glutathione (GSH), which is the strongest reductant naturally occurring in human plasma. Spectroscopic techniques (UV-vis, CD, EPR, and NMR) and cyclic voltammetry helped unravel the reaction mechanism. The impact of temperature, GSH concentration, oxygen access, and the presence of ternary ligands on the reaction were explored. The transient GSH-Cu(II)GHK complex was found to be an important reaction intermediate. The kinetic and redox properties of this complex, including tuning of the reduction rate by ternary ligands, suggest that it may provide a missing link in copper trafficking as a precursor of Cu(I) ions, for example, for their acquisition by the CTR1 cellular copper transporter.

Correction: Copper(II) complex of N-truncated amyloid-ß peptide bearing a His-2 motif as a potential receptor for phosphate anions.

Correction for 'Copper(ii) complex of N-truncated amyloid-ß peptide bearing a His-2 motif as a potential receptor for phosphate anions' by Aleksandra Tobolska et al., Dalton Trans., 2021, DOI: 10.1039/d0dt03898a.

Copper(ii) complex of N-truncated amyloid-ß peptide bearing a His-2 motif as a potential receptor for phosphate anions.

Electrochemical and spectroscopic studies demonstrated that the N-truncated amyloid ß peptide Aß5-9 (Arg-His-Asp-Ser-Gly-NH2) possessing histidine at position 2 (His-2) formed ternary complexes with copper(ii) and phosphate anions or phosphate groups of biomolecules. The recognition ability of Cu(ii)-Aß5-9 toward phosphate species provided a new perspective on designing phosphate-selective molecular receptors.

Aß5-x Peptides: N-Terminal Truncation Yields Tunable Cu(II) Complexes.

The Aß5-x peptides (x = 38, 40, 42) are minor Aß species in normal brains but elevated upon the application of inhibitors of Aß processing enzymes. They are interesting from the point of view of coordination chemistry for the presence of an Arg-His metal binding sequence at their N-terminus capable of forming a 3-nitrogen (3N) three-coordinate chelate system. Similar sequences in other bioactive peptides were shown to bind Cu(II) ions in biological systems. Therefore, we investigated Cu(II) complex formation and reactivity of a series of truncated Aß5-x peptide models comprising the metal binding site: Aß5-9, Aß5-12, Aß5-12Y10F, and Aß5-16. Using CD and UV-vis spectroscopies and potentiometry, we found that all peptides coordinated the Cu(II) ion with substantial affinities higher than 3 × 1012 M-1 at pH 7.4 for Aß5-9 and Aß5-12. This affinity was elevated 3-fold in Aß5-16 by the formation of the internal macrochelate with the fourth coordination site occupied by the imidazole nitrogen of the His13 or His14 residue. A much higher boost of affinity could be achieved in Aß5-9 and Aß5-12 by adding appropriate amounts of the external imidazole ligand. The 3N Cu-Aß5-x complexes could be irreversibly reduced to Cu(I) at about -0.6 V vs Ag/AgCl and oxidized to Cu(III) at about 1.2 V vs Ag/AgCl. The internal or external imidazole coordination to the 3N core resulted in a slight destabilization of the Cu(I) state and stabilization of the Cu(III) state. Taken together these results indicate that Aß5-x peptides, which bind Cu(II) ions much more strongly than Aß1-x peptides and only slightly weaker than Aß4-x peptides could interfere with Cu(II) handling by these peptides, adding to copper dyshomeostasis in Alzheimer brains.

Differential Sensing of Saccharides Based on an Array of Fluorinated Benzosiloxaborole Receptors.

Fluorinated benzosiloxaboroles-silicon congeners of benzoxaboroles, were synthesized and tested as molecular receptors for mono- and disaccharides. The receptors differed in the Lewis acidity of the boron center as well as in the number of potential binding sites. The calculated stability constants indicated different binding affinity of benzosiloxaborole derivatives towards selected saccharides, enabling their classification using a receptor array-based sensing. Unique fluorescence fingerprints were created on the basis of competitive interactions of the studied receptors with both Alizarin Red S (ARS) and tested saccharide molecules. Detailed chemometric analysis of the obtained fluorescence data (based on partial least squares-discriminant analysis and hierarchical clustering analysis) provided the differential sensing of common saccharides, in particular the differentiation between glucose and fructose. In addition, DFT calculations were carried out to shed light on the binding mechanism under different pH conditions.

Critical Evaluation of Laboratory Potentiometric Electronic Tongues for Pharmaceutical Analysis-An Overview.

Electronic tongue systems equipped with cross-sensitive potentiometric sensors have been applied to pharmaceutical analysis, due to the possibility of various applications and developing new formulations. Many studies already proved the complementarity between the electronic tongue and classical analysis such as dissolution tests indicated by Pharmacopeias. However, as a new approach to study pharmaceuticals, electronic tongues lack strict testing protocols and specification limits; therefore, their results can be improperly interpreted and inconsistent with the reference studies. Therefore, all aspects of the development, measurement conditions, data analysis, and interpretation of electronic tongue results were discussed in this overview. The critical evaluation of the effectiveness and reliability of constructed devices may be helpful for a better understanding of electronic tongue systems development and for providing strict testing protocols.

Dopamine/2-Phenylethylamine Sensitivity of Ion-Selective Electrodes Based on Bifunctional-Symmetrical Boron Receptors.

Piperazine-based compounds bearing two phenylboronic acid or two benzoxaborole groups (PBPA and PBBB) were applied as dopamine receptors in polymeric membranes (PVC/DOS) of ion-selective electrodes. The potentiometric sensitivity and selectivity of the sensors towards dopamine were evaluated and compared with the results obtained for 2-phenylethylamine. Since the developed electrodes displayed strong interference from 2-phenylethylamine, single-molecule geometry optimizations were performed using the density functional theory (DFT) method in order to investigate the origin of dopamine/2-phenylethylamine selectivity. The results indicated that phenylboronic acid and benzoxaborole receptors bind dopamine mainly through the dative B⁻N bond (like 2-phenylethylamine) and the potentiometric selectivity is mainly governed by the higher lipophilicity of 2-phenylethylamine.

Dissolution studies of metamizole sodium and pseudoephedrine sulphate dosage forms - comparison and correlation of electronic tongue results with reference studies.

This work reports a critical evaluation of the results of the release of active substances (APIs) from novel pharmaceutical formulations provided by an electronic tongue system (ET). Detailed dissolution studies of modified-release granules used in pharmacotherapy containing metamizole sodium and pseudoephedrine sulphate were carried out. The impact of the dissolution-modifying excipients (carmellose sodium and hypromellose) on the dissolution process as well as on the outcomes of the sensor array of ion-selective electrodes was investigated. The obtained dissolution profiles were compared and correlated with those registered during the reference studies performed according to the pharmacopoeial method. It was pointed out that the proper evaluation of the efficiency of the release modification requires the examination of dosage forms as well as physical mixtures of API and excipient. Moreover, the results obtained using potentiometric ET were complementary to the classical methodology. Their partial inconsistency, remarked during several experiments, should be interpreted with caution owing to simultaneous sensing of APIs and excipients by the sensors and their various performances (i.e. selectivity and sensitivity) towards these components.

Influence of dissolution-modifying excipients in various pharmaceutical formulations on electronic tongue results.

The overall performance of a potentiometric electronic tongue (ET) as well as the sensitivity and selectivity pattern of particular ion-selective electrodes forming the array towards exemplary APIs (metamizole sodium, pseudoephedrine sulphate) and excipients (hypromellose, carmellose, Eudragit E) was determined. Simultaneous sensing of both API and the encapsulating excipient in their physical mixture was noticed using potentiometric sensors. Usually, such altering of chemical image is treated as an evidence of taste masking/modified release effect (linked with chemical entrapment of API in polymer matrix), while the observed "mixture effect" can also take place which may complicate the interpretation of ET results. Moreover, the influence of the same excipients on chemical images of various APIs was compared and related to sensor array performance. The presented considerations should be taken into account in the case of ET assessment of drug dissolution profiles and detection of modified release effect, especially when novel drug delivery systems are considered.

Redox Activity of Copper(II) Complexes with NSFRY Pentapeptide and Its Analogues.

The influence of cation-π interactions on the electrochemical properties of copper(II) complexes with synthesized pentapeptide C-terminal fragment of Atrial Natriuretic Factor (ANF) hormone was studied in this work. Molecular modeling performed for Cu(II)-NSFRY-NH2 complex indicated that the cation-π interactions between Tyr and Cu(II), and also between Phe-Arg led to specific conformation defined as peptide box, in which the metal cation is isolated from the solvent by peptide ligand. Voltammetry experiments enabled to compare the redox properties and stability of copper(II) complexes with NSFRY-NH2 and its analogues (namely: NSFRA-NH2, NSFRF-NH2, NSAAY-NH2, NSAAA-NH2, AAAAA-NH2) as well as to evaluate the contribution of individual amino acid residues to these properties. The obtained results led to the conclusion, that cation-π interactions play a crucial role in the effective stabilization of copper(II) complexes with the fragments of ANF peptide hormone and therefore could control the redox processes in other metalloproteins.

Influence of Experimental Conditions on Electronic Tongue Results-Case of Valsartan Minitablets Dissolution.

A potentiometric electronic tongue was applied to study the release of valsartan from pharmaceutical formulations, i.e., minitablets uncoated and coated with Eudragit E. Special attention was paid to evaluate the influence of medium temperature and composition, as well as to compare the performances of the sensor arrays working in various hydrodynamic conditions. The drug dissolution profiles registered with the ion-sensitive electrodes were compared with standard dissolution tests performed with USP Apparatus 2 (paddle). Moreover, the signal changes of all sensors were processed by principal component analysis to visualize the release modifications, related to the presence of the coating agent. Finally, the importance and influence of the experimental conditions on the results obtained using potentiometric sensor arrays were discussed.

Copper Exchange and Redox Activity of a Prototypical 8-Hydroxyquinoline: Implications for Therapeutic Chelation.

The N-truncated ß-amyloid (Aß) isoform Aß4-x is known to bind Cu(2+) via a redox-silent ATCUN motif with a conditional Kd = 30 fM at pH 7.4. This study characterizes the Cu(2+) interactions and redox activity of Aßx-16 (x = 1, 4) and 2-[(dimethylamino)-methyl-8-hydroxyquinoline, a terdentate 8-hydroxyquinoline (8HQ) with a conditional Kd(CuL) = 35 pM at pH 7.4. Metal transfer between Cu(Aß1-16), CuL, CuL2, and ternary CuL(NIm(Aß)) was rapid, while the corresponding equilibrium between L and Aß4-16 occurred slowly via a metastable CuL(NIm(Aß)) intermediate. Both CuL and CuL2 were redox-silent in the presence of ascorbate, but a CuL(NIm) complex can generate reactive oxygen species. Because the NIm(Aß) ligand will be readily exchangeable with NIm ligands of ubiquitous protein His side chains in vivo, this class of 8HQ ligand could transfer Cu(2+) from inert Cu(Aß4-x) to redox-active CuL(NIm). These findings have implications for the use of terdentate 8HQs as therapeutic chelators to treat neurodegenerative disease.

Independent comparison study of six different electronic tongues applied for pharmaceutical analysis.

Electronic tongue technology based on arrays of cross-sensitive chemical sensors and chemometric data processing has attracted a lot of researchers' attention through the last years. Several so far reported applications dealing with pharmaceutical related tasks employed different e-tongue systems to address different objectives. In this situation, it is hard to judge on the benefits and drawbacks of particular e-tongue implementations for R&D in pharmaceutics. The objective of this study was to compare the performance of six different e-tongues applied to the same set of pharmaceutical samples. For this purpose, two commercially available systems (from Insent and AlphaMOS) and four laboratory prototype systems (two potentiometric systems from Warsaw operating in flow and static modes, one potentiometric system from St. Petersburg, one voltammetric system from Barcelona) were employed. The sample set addressed in the study comprised nine different formulations based on caffeine citrate, lactose monohydrate, maltodextrine, saccharin sodium and citric acid in various combinations. To provide for the fair and unbiased comparison, samples were evaluated under blind conditions and data processing from all the systems was performed in a uniform way. Different mathematical methods were applied to judge on similarity of the e-tongues response from the samples. These were principal component analysis (PCA), RV' matrix correlation coefficients and Tuckers congruency coefficients.