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Molecules (Basel, Switzerland) May 2024Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides...
Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH), tau(385-390) (Ac-KTDHGA-NH) and tau(404-409) (Ac-SPRHLS-NH). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions, but in the case of copper(II) and nickel(II), the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ions, but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relatively low thermodynamic stability with these peptides. The copper(II)-catalyzed oxidation of the peptides was also studied. In the presence of HO, the fragmentation of peptides was detected in all cases. In the simultaneous presence of HO and ascorbic acid, the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.
Topics: Nickel; Copper; Zinc; tau Proteins; Coordination Complexes; Peptide Fragments; Oxidation-Reduction; Histidine; Hydrogen-Ion Concentration; Hydrogen Peroxide; Thermodynamics
PubMed: 38792033
DOI: 10.3390/molecules29102171 -
Scientific Reports Oct 2023The main limitation to the use of antimicrobial peptides (AMPs) as regular drugs, against antibiotic and antifungal resistance, mainly relates to their rapid degradation...
The main limitation to the use of antimicrobial peptides (AMPs) as regular drugs, against antibiotic and antifungal resistance, mainly relates to their rapid degradation by proteolytic enzymes. The introduction of suitable structural changes in the peptide chain can make the peptide less susceptible to the action of proteases, thus overcoming this problem. To improve the plasma stability of calcitermin, a metal-chelating AMP present in the human respiratory tract and investigated in the present study, C- and/or N- terminal modifications have been introduced in the native sequence. Evaluation of peptide stability has been performed to determine the half-life times in human plasma of both native calcitermin and its derivatives. However, the protection of the peptide termini can also affect its metal coordination behaviour. Thus, the characterization of Zn and Cu complexes has been performed by means of several techniques, including potentiometry, high-resolution mass spectrometry, UV-Vis, circular dichroism and EPR. On the basis of the obtained results, it was possible to compare the biological activity of the studied systems, taking into account both the metal-binding ability and the peptide stability to search for a link among them. A significant result of this study is that the N-terminal protection increases the calcitermin half-life over seven times and the formation of metal complexes confers resistance towards degradation almost doubling its half-life.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Chelating Agents; Circular Dichroism; Copper; Mass Spectrometry; Peptides
PubMed: 37880318
DOI: 10.1038/s41598-023-45437-0 -
Analytical Methods : Advancing Methods... Jan 2024Gallic acid and its metal complexes are good antioxidants that could be used to increase the body's immune system against degenerative and viral diseases. Therefore,...
Gallic acid and its metal complexes are good antioxidants that could be used to increase the body's immune system against degenerative and viral diseases. Therefore, such complexes could be used as a good alternative to supplementary medicines and may have potential significance in clinical trials. Differential pulse voltammetry, UV/VIS spectroscopy, and potentiometry were used to analyse the complexation of gallic acid with calcium in this study. The metal : ligand ratio was determined using Job's continuous variation method and was found to be 2 : 1. The stability constant of calcium gallate was determined with potentiometric titration with a calcium electrode, which amounted to ° = 4.83 × 10 (log ° = 6.7). The combination of the results obtained in this study gives a deeper insight into the complexation of gallic acid with calcium and determines the stability constant of calcium gallate.
PubMed: 38126741
DOI: 10.1039/d3ay01586f -
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 -
ACS Sensors Nov 2023The high-temperature potentiometry operated by nonisothermal heating is a promising way to break through the traditional potentiometric responses of ion-selective...
The high-temperature potentiometry operated by nonisothermal heating is a promising way to break through the traditional potentiometric responses of ion-selective electrodes (ISEs) at room temperature. Herein, a locally heated strategy through near-infrared region (NIR) laser irradiation upon the photothermal mesoporous carbon material placed between the ion-selective membrane and the glassy carbon substrate is introduced to obtain the high-temperature potentiometric performance of a solid-contact Ca-ISE for detection of Ca in seawater. Based on the light-to-heat conversion of the mesoporous carbon-based solid contact, the temperature of the solid-contact Ca-ISE upon continuous NIR laser irradiation can be increased from room temperature to 60-70 °C, and the slope of the electrode is promoted up to about 30% according to the thermodynamic steady-state potentiometric response. The pulsed potentiometric response of the solid-contact Ca-ISE upon a pulsed NIR laser irradiation of 5 s also shows a linear change as a function of Ca activities, and the improved slope from 27.1 ± 0.6 to 38.1 ± 0.9 mV/dec can be obtained under dual control of the temperature of the electrode and the transient current induced by the pulsed NIR laser irradiation. As compared to the traditional potentiometric measurement under zero-current conditions at room temperature, the NIR laser-modulated high-temperature potentiometric response provides an alternative way for measurement of the solid-contact ISEs.
Topics: Ion-Selective Electrodes; Potentiometry; Temperature; Carbon; Seawater; Infrared Rays
PubMed: 37773015
DOI: 10.1021/acssensors.3c01533 -
Analytica Chimica Acta Dec 2023Uranium is a toxic, heavy metal that can pose elevated health risks if leached into the environment. Uranium mobility is dependent on many factors, including speciation,...
Uranium is a toxic, heavy metal that can pose elevated health risks if leached into the environment. Uranium mobility is dependent on many factors, including speciation, solution pH, ligands in solution, and presence of surfaces. Surface adsorption is one phenomenon that inhibits uranium mobility in the environment and is studied as a naturally occurring phenomenon as well an intentional tool for environmental remediation. This work presents and validates a potentiometric, electrochemical technique for sensing uranium adsorption on and desorption from an electrochemically active surface solely through changes of the electrode potential. This novel electrochemical technique presents a new lens to study adsorption that complements external techniques (e.g., spectroscopy). Indication of adsorption and desorption via the electrochemical technique are gravimetrically validated using an electrochemical quartz crystal microbalance. This work contributes a unique, complementary technique that corroborates the adsorption of uranium on an electrode surface.
PubMed: 37996162
DOI: 10.1016/j.aca.2023.342003 -
Turkish Journal of Chemistry 2023An AISI 304 stainless steel laminar electrode without oxidative treatment was investigated for the potentiometric titration of hydrochloric acid with sodium hydroxide....
An AISI 304 stainless steel laminar electrode without oxidative treatment was investigated for the potentiometric titration of hydrochloric acid with sodium hydroxide. The proposed electrode was obtained from metalworking cuttings. Scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence spectroscopy and X-ray diffraction were used to study the surface morphology and chemical composition of the electrode. The electrode showed a sensitivity of 59.18 ± 0.37 mV/pH, which was reproducible under intermediate conditions. Potentiometric titration showed a curve with deviations from pH 9.5 with respect to the glass electrode. However, this did not affect the quantification as the jumps of the curves coincided. The endpoint was 9.25 mL for both electrodes and the hydrochloric acid concentration was 0.0845 mol/L, with a deviation of 0.0004 mol/L from the standard concentration of 0.0841 mol/L. The nonartificially oxidised electrode did not show any crystalline oxide phases, whereas after oxidation it showed semicrystalline phases of iron and chromium oxides and increased the crystallinity of the steel. Despite the low content of surface oxides, stainless steel electrodes can give a Nernstian response to pH, depending on the surface characteristics of the material. This leads to the need to calibrate any electrode prior to oxidative treatment to rule out a Nernstian response without surface modification.
PubMed: 38174066
DOI: 10.55730/1300-0527.3580 -
Molecules (Basel, Switzerland) May 2024Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their...
Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties, putting them on a new path in medicine. Their conformational rigidity improves proteolytic stability and leads to rapid penetration into tissues via any possible route of administration. Moreover, elimination of renal metabolism is of great importance, for example, for people with a history of liver diseases. In addition, each ring can function independently, making bicyclic peptides extremely versatile molecules for further optimization. In this paper, we compared the potentiometric and spectroscopic properties studied by UV-vis, MCD, and EPR of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH) (BCL). In particular, we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL1 (Ac-PKKHPc(CFWKTC)PKKH-NH) that contains the unbinding cycle and N- and C-terminal linear parts with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position, i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH) and in the C-terminal position, i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH), respectively; and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH). Potentiometric results have shown that the bicyclic structure promotes the involvement of the side chain imidazole donors in Cu(II) binding. On the other hand, the results obtained for the mono-cyclic analogues lead to the conclusion that the coordination of the histidine moiety as an anchoring group is promoted by its location in the peptide sequence further from the nonbinding cycle, strongly influencing the involvement of the amide donors in Cu(II) coordination.
Topics: Copper; Peptides, Cyclic; Coordination Complexes; Ligands; Ions; Potentiometry
PubMed: 38792059
DOI: 10.3390/molecules29102197 -
Journal of Pharmaceutical and... Sep 2023We describe a new high-throughput automated pK workflow using potentiometry starting with 10 mM DMSO stock (solution pH-metric). Two approaches using either neat DMSO...
We describe a new high-throughput automated pK workflow using potentiometry starting with 10 mM DMSO stock (solution pH-metric). Two approaches using either neat DMSO stock solution or removal of DMSO were evaluated with different sample amounts and cosolvent schemes. These were validated against traditional potentiometric measurements for optimal conditions. Further, we detail how high throughput solution pH-metric experiments are performed in tandem with established UV-metric measurements to capitalize on the advantages of both approaches. This new workflow maintains the sample and time savings required for measuring a large number of samples in a drug discovery setting, while avoiding "missing pKs" due to lack of sufficient UV chromophores. The combination of the two assays is key to tackle the challenges of low solubility, overlapping pKs, and preliminary assignment of pKs for Structure-Activity Relationship (SAR) understanding.
Topics: Dimethyl Sulfoxide; Workflow; Solubility; Drug Discovery; Hydrogen-Ion Concentration
PubMed: 37343451
DOI: 10.1016/j.jpba.2023.115530 -
ACS Sensors Oct 2023Citalopram (CTLP) is one of the most common antidepressants prescribed worldwide. It has a narrow therapeutic window and can cause severe toxicity and mortality if the...
Toward Personalized Treatment of Depression: An Affordable Citalopram Test based on a Solid-Contact Potentiometric Electrode for at-Home Monitoring of the Antidepressant Dosage.
Citalopram (CTLP) is one of the most common antidepressants prescribed worldwide. It has a narrow therapeutic window and can cause severe toxicity and mortality if the dosage exceeds the safe level. Reports indicated that at-home monitoring of citalopram dosage considerably benefits the patients, yet there are no devices capable of such measurement of citalopram in biofluids. This work presents an affordable citalopram test for at-home and point-of-care monitoring of citalopram levels in urine, ensuring a safe and effective drug compliance. Our platform consists of a citalopram-selective yarn-based electrode (CTLP-SYE) that uses polymeric sensing membranes to provide valuable information about drug concentration in urine. CTLP-SYE is noninvasive and has a response time of fewer than 10 s. The fabricated electrode showed near-Nernstian behavior with a 52.3 mV/decade slope in citalopram hydrobromide solutions ranging from 0.5 μM to 1.0 mM, with a detection limit of 0.2 μM. Results also indicated that neither interfering ions nor pH affects electrode performance. We showed that CTLP-SYE could accurately and reproducibly measure citalopram in human urine (RSD 2.0 to 3.2%, error <12%) at clinically relevant concentrations. This work paves the way for the personalized treatment of depression and accessible companion diagnostics to improve treatment efficacy and safety.
Topics: Humans; Citalopram; Depression; Precision Medicine; Antidepressive Agents; Electrodes
PubMed: 37734027
DOI: 10.1021/acssensors.3c01545