Glutathione In Aqueous Solution Research Articles

On Polymeric Gold(I) Complexes with Glutathione in Aqueous Solutions

On Polymeric Gold(I) Complexes with Glutathione in Aqueous Solutions

Substitution of Cl– by OH– in the Phenanthroline Gold(III) Complex and Its Redox Interaction with Glutathione in Aqueous Solution

Substitution of Cl– by OH– in the Phenanthroline Gold(III) Complex and Its Redox Interaction with Glutathione in Aqueous Solution

Voltammetric studies of glutathione transfer across arrays of liquid-liquid microinterfaces for sensing applications.

The simple and facilitated transfer of tripeptide glutathione across the water/2-nitrophenyl octhyl ether interface was studied via cyclic voltammetry at interface between two immiscible electrolyte solutions (ITIES). The micro-perforated membrane prepared with a laser with a femtosecond pulse was used for mechanical stabilization of the interface. The method of cyclic voltammetry was used to study the passive and facilitated interfacial transfer of glutathione and its complex with the crown ether dibenzo-18-crown-6 (DB18C6).The glutathione mass transfer mechanism was established and substantiated, the diffusion coefficients, thermodynamic characteristics of interphase transfer and the constant of complexation of the glutathione by DB18C6 were determined. Square wave voltammetry based on facilitated transfer was used for more accurate and sensitive determination of glutathione low detection limit (0.8μM) with wide linear dynamic range (from 3.0 to 80μM) was reached. The influence of various potentially interfering ions on the voltammetric determination of glutathione has also been investigated. The method developed was applied to determine glutathione in aqueous solutions and malt extract.

Red-emission carbon dots as fluorescent "on-off-on" probe for highly sensitive and selective detection of Cu2+ and glutathione.

A highly sensitive and selective fluorescent "on-off-on" strategy is established for the synchronous detection of Cu2+ and glutathione in aqueous solution. Red carbon dots (R-CDs) were prepared by using precursors of 4,5-difluoro-1,2-phenylenediamine and citric acid via a one-step hydrothermal strategy. R-CDs show a relatively long fluorescence lifetime of 3.47ns under 455nm excitation and high absolute fluorescent quantum yield of 20.1% with an excitation wavelength of 550nm. R-CDs exhibit a marked pH-responsive fluorescence property with no significant perturbation from pH 4 to pH 13 even after five cycles. R-CDs with higher concentration of 750μg·mL-1 exhibit no significant cytotoxicity and good biocompatibility on HeLa cells and A549 cells after incubation for 48h. The fluorescence of R-CDs at 619nm (excited at 550nm) is quenched statically by Cu2+ and recovered by glutathione subsequently, resulting in a fluorescent "on-off-on" assay for the synchronous detection of Cu2+ and glutathione. Under optimal conditions, the linear response covers the Cu2+ concentration range of 1 to 50μM and the glutathione concentration range of 1 to 70μM. Detection limits of Cu2+ and glutathione are 0.16 and 0.41μM, respectively. This fluorescent probe is applied to the determination of Cu2+ and glutathione in authentic samples with satisfying results. Such an assay broadens the potential application of CDs in environmental areas and clinical therapy fields.

On the redox interaction of HAuCl4 with thiomalate, as well as with cysteine and glutathione in aqueous solutions

The process of AuCl4− reduction by thiomalate (mercaptosuccinate, TM*,–OOCCH2CH(SH)COO−) at CAu = (2–10) × 10−4 M and CTM/CAu < 2 in aqueous solution was studied. Most of the experiments were performed at I = 0.2 M (NaCl), pH 2.00, t = 25 °C, and τ < 20 min. At CTM < CAu, a fast process (τ < 3 s) occurs at the initial stage, AuCl4− + 2TM* = AuTM* + TMox, where AuTM* is a polymer complex of gold(I) (AumTMm*), TMox is a partially oxidized thiomalate. Further slower reduction of AuCl4− proceeds both due to TM from AuTM* and further oxidation of TMox. The change in the concentration of some forms during the process is calculated. In addition to AuCl4−, AuTM* and TMox, the solution contains other gold(I) complexes. A common feature of the process is a much slower change in the concentration of AuTM* compared to the concentrations of other forms. The ratio between products depends on CTM/CAu, with an increase in CTM, the fraction of AuTM* increases. The rate of the process is strongly influenced by the concentration of chloride; with increasing CCl, the rate increases. With increasing pH, the process slows down greatly. An increase in temperature leads to an acceleration of the process, but the ratio of products changes little. To further clarify the features of the process, the reduction of AuCl4− using AuTM* was also studied. The use of cysteine and glutathione instead of TM* did not show significant differences in the nature of the process and the resulting products.

On the Complexation of Gold(I) with Glutathione in Aqueous Solutions

Some processes of interaction between $${\text{AuCl}}_{2}^{ - }$$ and glutathione with the formation of polymeric $$\left( {-{\text{AuGSH}}_{i}-} \right)_{n}^{n(i - 2) + }$$ and monomeric $${\text{Au}} ({\text{GS}})_2{\text{H}}_{i}^{i - 5}$$ gold(I) complexes in aqueous solutions at ionic strength of I = 0.2 mol·L−1 (NaCl) have been studied at 25 °C. The precipitate formed in the acidic region corresponds to the ordinary polymer $$\left( {-{\text{AuGSH}}_{2}-} \right)_{n}$$. The dependence of its solubility upon pH has been investigated. The substitution equilibria, $${\text{Au}}({\text{GS}})_{2}^{5 - } + {\text{S}}_{2} {\text{O}}_{3}^{2 - } \rightleftharpoons {\text{Au}}({\text{GS}}){\text{S}}_{2} {\text{O}}_{3}^{4 - } + {\text{GS}}^{3 - }$$, log10 β1 = − 4.5 ± 0.3, and $${\text{Au}}({\text{GS}})_{2}^{5 - } + 2{\text{S}}_{2} {\text{O}}_{3}^{2 - } \rightleftharpoons {\text{Au}}({\text{S}}_{2} {\text{O}}_{3} )_{2}^{3 - } + 2{\text{GS}}^{3 - }$$, log10 β2 = − 8.5 ± 0.2, have been studied and the effective protonation constants of the complexes have been determined. It is shown that under the action of $${\text{AuCl}}_{4}^{ - }$$ GSH is oxidized to sulfinic and sulfonic acids. The potential of using highly stable gold(I) complexes with glutathione as ligands, for metal ions having an affinity with respect to the amine nitrogen atom, has been established.

Colorimetric chemosensor based on a carminic acid and Pb2+ complex for selective detection of cysteine over homocysteine and glutathione in aqueous solution

We have developed a colorimetric chemosensor for the selective and sensitive detection of Cys based on the complex (CA-2Pb2+) between a commercially available natural organic dye, carminic acid (CA) and Pb2+ in pure aqueous solution at physiological pH. The addition of Cys to the CA-2Pb2+ solution resulted in a distinct color change from purple to red together with a remarkable absorption spectral change by the restoration of CA through a displacement mechanism with formation of the Cys-Pb2+ complex, whereas other amino acids and glutathione induce no or minimal spectral and color changes. Moreover, the other amino acids and GSH do not affect the detection ability of CA-2Pb2+ for Cys. The reversibility even through several cycles was established for practical applications. The results indicate that CA-2Pb2+ may be useful as a potential colorimetric and naked-eye chemosensor for Cys over Hcy and GSH in aqueous solution.

Identification of novel reaction products of methylene-bis-phenylisocyanate (“MDI”) with oxidized glutathione in aqueous solution and also during incubation of MDI with a murine hepatic S9 fraction

Methylene diphenyl diisocyanate (MDI) is an important industrial chemical and asthmagenic respiratory sensitizer, however its metabolism remains unclear. In this study we used LC-MS and LC-MS/MS to identify novel reaction products of MDI with oxidized glutathione (GSSG), including an 837m/z [M+H]+ ion corresponding to GSSG bound (via one of its N-termini) to partially hydrolyzed MDI, and an 863m/z [M+H]+ ion corresponding to GSSG cross-linked by MDI (via its two γ-glutamine N-termini). Further studies with heavy isotope labeled and native reduced glutathione (GSH) identified an [M+H]+ ion corresponding to previously described mono(GSH)-MDI, and evidence for “oligomeric” GSH-MDI conjugates. This study also investigated transformational changes in MDI after incubation with an S9 fraction prepared from murine liver. LC-MS analyses of the S9 reaction products revealed the formation of [M+H]+ ions with m/z's and retention times identical to the newly described GSSG-MDI (837 and 863) conjugates and the previously described mono(GSH)-MDI conjugate. Together the data identify novel biological transformations of MDI, which could have implications for exposure-related health effects, and may help target future in vivo studies of metabolism.

An ESIPT-based fluorescent probe for highly selective detection of glutathione in aqueous solution and living cells

In this paper, highly sensitive and selective fluorescent probe 1 for GSH is designed and synthesized based on modulation of the excited-state intramolecular proton transfer (ESIPT) process of 2-(2′-hydroxy-3′-ethoxyphenyl)benzothiazole. Upon introducing GSH in neutral solution containing CTAB micelles, dinitrophenyl, the protecting group of the probe, is removed via the nucleophilic substitution, thereby retrieving the ESIPT process of 2-(2′-hydroxy-3′-ethoxyphenyl)benzothiazole, which results in a fluorescence enhancement at 485 nm. Additionally, the fluorescence intensity of the probe is linearly proportional to GSH concentration ranging from 0 to 100 μM and the obtained detection limit is as low as 0.81 μM. The enhanced selectivity toward GSH over Cys and Hcy is also attributed to one more carboxyl group in GSH. Importantly, the probe is successfully utilized for monitoring GSH in living HeLa cells.

Ab Initio MD Simulations of the Brønsted Acidity of Glutathione in Aqueous Solutions: Predicting pKa Shifts of the Cysteine Residue.

The tripeptide glutathione (GSH) is one of the most abundant peptides and the major repository for nonprotein sulfur in both animal and plant cells. It plays a critical role in intracellular oxidative stress management by the reversible formation of glutathione disulfide with the thiol-disulfide pair acting as a redox buffer. The state of charge of the ionizable groups of GSH can influence the redox couple, and hence the pKa value of the cysteine residue of GSH is critical to its functioning. Here we report ab initio Car-Parrinello molecular dynamics simulations of glutathione solvated by 200 water molecules, all of which are considered in the simulation. We show that the free-energy landscape for the protonation-deprotonation reaction of the cysteine residue of GSH computed using metadynamics sampling provides accurate estimates of the pKa and correctly predicts the shift in the dissociation constant values as compared with the isolated cysteine amino acid.

A sensitive turn-on fluorescent probe for intracellular imaging of glutathione using single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots.

A sensitive turn-on fluorescent sensor based on single-layer MnO2 nanosheet-quenched fluorescent carbon quantum dots has been developed for rapid and selective sensing of glutathione in aqueous solutions, as well as in living cells.

Thermodynamic Data for the Modeling of Lanthanoid(III) Sequestration by Reduced Glutathione in Aqueous Solution

This contribution reports the results of an investigation on the speciation of various lanthanoid(III) cations (Ln3+), namely, La3+, Nd3+, Sm3+, Eu3+, Gd3+, Dy3+, and Yb3+, in the presence of reduced glutathione (or simply glutathione, GSH), in NaCl(aq) at I = 0.15 mol·dm–3 and T = 298.15 K. GSH forms in all cases the same four species, namely, Ln(GSH)H3, Ln(GSH)H2, Ln(GSH)H, and Ln(GSH)OH, whose stability depends on the type of lanthanoid, although it is also possible to consider an average stability for a generic lanthanoid, at least for the protonated species. Measurements at different temperatures and ionic strengths for the La3+/GSH and Gd3+/GSH systems have also been performed, to evaluate their effect on the speciation of both GSH and the Ln3+ cations. The dependence of the determined stability constants on I and T has been modeled by an extended Debye–Huckel type and by the van’t Hoff equations. In this last case, the formation enthalpy changes of La3+/GSH species have also been determined. The st...

Kinetics and Mechanism of the Interaction of Di-μ-hydroxobis(1,10-phenanthroline)dipalladium(II) Perchlorate with Thioglycolic Acid and Glutathione in Aqueous Solution

The kinetics of interaction between di-μ-hydroxobis(1,10-phenanthroline)dipalladium(II) perchlorate and thioglycolic acid and with glutathione has been studied spectrophotometrically in aqueous medium as a function of the complex concentration as well as the ligand concentrations, pH, and temperature at constant ionic strength. The observed pseudo-first-order rate constants k obs (s−1) obeyed the equation k obs = k 1[Nu] (Nu = nucleophile). At pH = 6.5, the interaction with thioglycolic acid shows two distinct consecutive steps and both steps are dependent on the concentration of thioglycolic acid. The rate constants for the process are: k 1 ≈ 10−5 s−1 and k 2 ≈ 10−3 dm3 · mol−1 · s−1. The association equilibrium constant (K E) for the outer sphere complex formation has been evaluated together with the rate constants for the two subsequent steps. The other bio-active ligand, glutathione, showed a single step reaction depending on [ligand] with a second-order anation rate constant: the 102 (k 2) values are (61.72, 79.20, 109.24 and 154.33) dm3 · mol−1 · s−1 at 20, 25, 30 and 35 °C, respectively. On the basis of the kinetic observations and evaluated activation parameters, plausible associative mechanisms are proposed for both interaction processes.

On the Chemical Repair of DNA Radicals by Glutathione: Hydrogen vs Electron Transfer

The chemical repair of radical-damaged DNA by glutathione in aqueous solution has been studied using density functional theory. Two main mechanisms were investigated: the single electron transfer (SET) and the hydrogen transfer (HT). Glutathione was found to repair radical damaged DNA by HT from the thiol group with rate constants that are close to the diffusion-limited regime, which means that the process is fast enough for repairing the damage before replication and therefore for preventing permanent DNA damage. The SET mechanism was found to be of minor importance for the activity of glutathione. In addition while SET can be essential for other compounds when repairing radical cation species, repairing the C'-centered guanosyl radicals via SET is not a viable mechanism, due to the very low electron affinity of these species. The importance of considering pH-related physiological conditions and using complex enough models, including the ribose moiety and the H bonding between base pairs, to study this kind of systems is discussed.

Intracellular Glutathione Detection Using MnO2-Nanosheet-Modified Upconversion Nanoparticles

We report a novel design, based on a combination of lanthanide-doped upconversion nanoparticles and manganese dioxide nanosheets, for rapid, selective detection of glutathione in aqueous solutions and living cells. In this approach, manganese dioxide (MnO(2)) nanosheets formed on the surface of nanoparticles serve as an efficient quencher for upconverted luminescence. The luminescence can be turned on by introducing glutathione that reduces MnO(2) into Mn(2+). The ability to monitor the glutathione concentration intracellularly may enable rational design of a convenient platform for targeted drug and gene delivery.

Modeling the acid–base properties of glutathione in different ionic media, with particular reference to natural waters and biological fluids

The acid-base properties of γ-L-glutamyl-L-cysteinyl-glycine (glutathione, GSH) were determined by potentiometry (ISE-H(+), glass electrode) in pure NaI((aq)) and in NaCl((aq))/MgCl(2(aq)), and NaCl((aq))/CaCl(2(aq)) mixtures, at T = 298.15 K and different ionic strengths (up to I(c) ~ 5.0 mol L(-1)). In addition, the activity coefficients of glutathione were also determined by the distribution method at the same temperature in various ionic media (LiCl((aq)), NaCl((aq)), KCl((aq)), CsCl((aq)), MgCl(2(aq)), CaCl(2(aq)), NaI((aq))). The results obtained were also used to calculate the Specific ion Interaction Theory (SIT) and Pitzer coefficients for the dependence on medium and ionic strength of glutathione species, as well as the formation constants of weak Mg(j)H( i )(GSH)((i+2j-3)) and Ca(j)H(i)(GSH)((i+2j-3)) complexes. Direct calorimetric titrations were also carried out in pure NaCl((aq)) and in NaCl((aq))/CaCl(2(aq)) mixtures at different ionic strengths (0.25 ≤ I (c )/mol L(-1) ≤ 5.0) in order to determine the enthalpy changes for the protonation and complex formation equilibria in these media at T = 298.15 K. Results obtained are useful for the definition of glutathione speciation in any aqueous media containing the main cations of natural waters and biological fluids, such as Na(+), K(+), Mg(2+), and Ca(2+). Finally, this kind of systematic studies, where a series of ionic media (e.g., all alkali metal chlorides) is taken into account in the determination of various thermodynamic parameters, is useful for the definition of some trends in the thermodynamic behavior of glutathione in aqueous solution.

Studies on the structures and interactions of glutathione in aqueous solution by molecular dynamics simulations and NMR spectroscopy

All-atom molecular simulations and temperature-dependent NMR have been used to investigate the conformations and hydrogen bonds of glutathione (GSH) in aqueous solution. The simulations start from three different initial conformations. The properties are characterized by intramolecular distances, radius of gyration, root-mean-square deviation, and solvent-accessible surface. GSH is highly flexible in aqueous solutions in the simulations. Moreover, conformations can covert between “extended” and “folded” states. Interestingly, the two different hydrogen atoms in cysteine (H N2) and glycin (H N3) show different capabilities in forming N H⋯OW hydrogen bonds. The temperature-dependent NMR results of the different amide hydrogen atoms also show agreements with the MD simulations. Competing formation of GSH hydrogen-bonding interactions in aqueous solutions leads to hydrogen-bonding networks and the distribution of conformations. These changes will affect the activity of GSH under physiological conditions.

Multi-wall carbon nanotubes as a sensor and ferrocene dicarboxylic acid as a mediator for voltammetric determination of glutathione in hemolysed erythrocyte

A sensitive and selective electrochemical method was developed for determination of glutathione (GSH) in hemolysed erythrocyte using a ferrocene dicarboxylic acid modified carbon nanotubes paste electrode (FDCCNTPE). Cyclic voltammetry (CV), double potential-step chronoamperometry and differential pulse voltammetric (DPV) were used to investigate the suitability of ferrocene dicarboxylic acid at the surface of a multi-wall carbon nanotubes paste electrode as a mediator for the electrocatalytic oxidation of glutathione in aqueous solutions with various pH. The results showed that FDCCNTPE had high electrocatalytic activity for the electrooxidation of glutathione. Under optimum conditions (pH 7.00), oxidation of GSH occurs at a potential about 230 mV less positive than that at the unmodified carbon nanotubes paste electrode. The catalytic reaction rate constant, kh was calculated (1.98 × 104 M−1 s−1) using chronoamperometry. The electrocatalytic oxidation peak current of GSH showed two linear dynamic ranges with a detection limit of 0.2 μmol L−1 GSH. The linear calibration ranges were obtained between 0.5–24 μmol L−1 and 24–122 μmol L−1 GSH using the DPV method. Finally, the proposed method was also examined as a selective, simple and precise electrochemical sensor for the determination of GSH in real samples such as hemolysed erythrocyte.

Colorimetric Detection of Thiols Using a Chromene Molecule

A new thiol-containing colorimetric probe has been developed by using a chromene derivative, 7-nitro-2,3-dihydro-1H-cyclopenta[b]chromen-1-one (1). The molecule exhibited high selectivity and sensitivity for detecting thiol species as cysteine, homocysteine, and glutathione in aqueous solution through a rapid visual color change from colorless to yellow.

Development of a Heat-Induced Surface-Enhanced Raman Scattering Sensing Method for Rapid Detection of Glutathione in Aqueous Solutions

In this paper, a direct and simple detection method based on surface-enhanced Raman scattering (SERS) named "heat-induced SERS sensing method" is proposed for rapid determination of glutathione in aqueous solutions. It was found that highly enhanced SERS spectra of glutathione can be obtained if the silver colloids adsorbed with the analyte were heated up before the SERS measurement. Besides, it was revealed that silver particles with a size of approximately 60 nm are suitable for this study and that the SERS intensity is also influenced by the dropped sample volume, drying temperature, buffer concentration, and pH of the solution. It is noted that the thiol group of glutathione has a particularly strong interaction with a silver surface compared with other small biological molecules without a thiol group, validating this method to detect glutathione selectively. Under the optimal conditions, the detection of glutathione can be finished within 5 min, and the detection limit of ca. 50 nM can be reached, which is much better than the reported detection limit of glutathione (approximately 1 microM) by SERS. The enhancement factor of the proposed heat-induced SERS sensing method for the detection of glutathione is about 7.5 x 10(6). The proposed method holds a specific selectivity toward glutathione, facilitating its rapid detection in practical applications.