Application of a novel hybrid MIL-53(Al)@rice husk for the adsorption of glyphosate in water: Characteristics and mechanism of the process.

The development of new materials that have a high capacity to remove pollutants in water-based media is becoming increasingly important because of the serious contamination of water and the negative impact on biodiversity and public health. The presence of glyphosate in water, the most widely used herbicide worldwide, has triggered alerts owing to the collateral effects it may cause on human health. The main objective of the present study was to investigate the potential of the hybrid material MIL-53(Al)@RH for the adsorption of glyphosate in aqueous solution. The material was obtained following the methodology of MIL-53(Al) synthesis in the presence of hydrolyzed rice husk assisted by microwave. Batch adsorption experiments were carried out to evaluate the adsorbent dosage, pH0 solution effect, contact time, adsorbate concentration, and temperature effect. The results demonstrated that a maximum adsorption capacity of 296.95 mg g-1, at pH0 4 with a ratio of 0.04 g MIL-53(Al)@RH/50 mL of solution, was achieved in 30 min. The Avrami and pseudo-second order models appropriately described the adsorption kinetics and the equilibrium by Langmuir and Sips models. The enthalpy changes (ΔH°) determined propose an endothermic reaction governed by chemisorption, corroborating the kinetic and equilibrium settings. Hydrogen bonds, π*-π interactions, and complexation between the metal centers of MIL-53(Al) and the anionic groups of glyphosate were postulated to be involved as adsorption mechanisms. Finally, for practical application, MIL-53(Al)@RH was packed in a column for a fixed-bed test which revealed that the hybrid can remove glyphosate with an adsorption capacity of 76.304 mg L-1, utilizing 90% of the bed.

Development of an inexpensive and rapidly preparable enzymatic pencil graphite biosensor for monitoring of glyphosate in waters.

Glyphosate (GLY) is the most widely used non-selective broad-spectrum herbicide worldwide under well-reported side effects on the environment and human health. That's why it's necessary to control its presence in the environment. This work describes the development of an affordable, simple, and accurate electrochemical biosensor using a pencil graphite electrode as support, a horseradish peroxidase enzyme immobilized on a polysulfone membrane doped with multi-walled carbon nanotubes. The developed electrochemical sensor was used in the determination of GLY in river and drinking water samples. Cyclic voltammetry and amperometry were used as electrochemical detection techniques for the characterization and analytical application of the developed biosensor. The working mechanism of the biosensor is based on the inhibition of the peroxidase enzyme by GLY. Under optimal experimental conditions, the biosensor showed a linear response in the concentration range of 0.1 to 10 mg L-1. The limits of detection and quantification are 0.025 ± 0.002 and 0.084 ± 0.007 mg L-1, respectively, which covers the maximum residual limit established by the EPA for drinking water (0.7 mg L-1). The proposed biosensor demonstrated high reproducibility, excellent analytical performance, repeatability, and accuracy. The sensor proved to be selective against other pesticides, organic acids, and inorganic salts. Application on real samples showed recovery rates ranging between 98.18 ± 0.11 % and 97.32 ± 0.23 %. The analytical features of the proposed biosensor make it an effective and useful tool for the detection of GLY for environmental analysis.

Inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by hydroxylated xanthones.

Xanthones are oxygen-containing heterocyclic compounds that exhibit a wide range of biological and pharmacological properties. Some natural and synthetic derivatives have been identified for their antidiabetic profile, mainly as α-glucosidase inhibitors. However, studies concerning the inhibition of both carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase are scarce. Thus, in order to identify some of these dual-target antidiabetic agents, a series of new synthetic xanthones were evaluated together with their commercial parents mangiferin (4), α-mangostin (5) and γ-mangostin (6). The results showed that xanthones exhibited a systematic stronger inhibition against α-glucosidase rather than for α-amylase. Derivatives 2c, 3a and 3b, bearing one catechol moiety, were the most active inhibitors of α-amylase, while xanthones 2c, 3b and 3c were the most active against α-glucosidase activity, with IC50 values lower than 10 µM. These findings suggest that the substitution pattern of the xanthone scaffold modulated the inhibitory activity of these compounds, and some structure-activity relationships could be established for both assays. In addition, the type of inhibition was also studied, and the results indicate a competitive type of inhibition for α-amylase activity by xanthones 2c, 3b, 3c and γ-mangostin (6). On the other hand, non-competitive inhibition mechanisms can be ascribed for all xanthones 1-6 against α-glucosidase. The present work can open a promising area of research based on the design of novel xanthone derivatives, based on natural ones, for targeting key enzymes involved in glucose metabolism and therefore in the management of type 2 diabetes mellitus.

A combined experimental and computational study to discover novel tyrosinase inhibitors.

Depigmenting properties of tyrosinase inhibitors (TAi) boosted the search for new compounds applicable in cosmetics. Kojic acid, a 3-hydroxy-4-pyrone, is the most studied tyrosinase inhibitor but undesirable side effects, like dermatitis, and unspecified mechanism led to its exclusion in several countries. To discover safer and more efficient TA, we evaluated tyrosinase inhibitory effect of twelve 3-hydroxy-4-pyridinones (3,4-HPO) in vitro and considering the two reaction steps of inhibition in mushroom tyrosinase enzyme. In parallel we performed molecular docking studies in human and mushroom enzymes. Ligands I6 and I11 were the most effective compounds considering their inhibitory activity in both reaction steps. Our studies revealed that I6 has a non-competitive and mixed type of inhibition for monophenolase and diphenolase activity, while ligand I11 showed a mixed and competitive inhibition type for each reaction step. Molecular Docking results indicated that ligands tend to bind the enzyme by coordinating directly with the binuclear cooper centre and highlighted the relevance of voluminous and non-polar substituents at R2 to avoid the binding of the ligands to the enzyme. The work clarifies the type of inhibition established for kojic acid and points out the differences found for the set of 3,4-HPO chelators studied as prospective tyrosinase inhibitors.

Minimizing the Silver Free Ion Content in Starch Coated Silver Nanoparticle Suspensions with Exchange Cationic Resins.

This work describes the optimization of a methodology for the reduction of silver ions from silver nanoparticle suspensions obtained from low-yield laboratory procedures. The laboratory synthesis of silver nanoparticles following a bottom-up approach starting from silver nitrate, originates silver ions that were not reduced to their fundamental state for nanoparticles creation at the end of the process. However, it is well known that silver ions can easily influence chemical assays due to their chemical reactivity properties and can limit biological assays since they interfere with several biological processes, namely intracellular ones, leading to the death of living cells or organisms. As such, the presence of silver ions is highly undesirable when conducting biological assays to evaluate the influence of silver nanoparticles. We report the development of an easy, low-cost, and rapid methodology that is based on cation exchange resins to minimize the silver ion content in a raw suspension of silver nanoparticles while preserving the integrity of the nanomaterials. This procedure preserves the physical-chemical properties of the nanoparticles, thus allowing the purified nanoparticulate systems to be biologically tested. Different types of cationic resins were tested, and the developed methodology was optimized by changing several parameters. A reduction from 92% to 10% of free silver/total silver ratio was achieved when using the Bio-Rad 50W-X8 100-200 mesh resin and a contact time of 15 min. Filtration by vacuum was used to separate the used resin from the nanoparticles suspension, allowing it to be further reused, as well as the purified AgNPs suspension.

HPLC-potentiometric method for determination of biogenic amines in alcoholic beverages: A reliable approach for food quality control.

Determination of ten biogenic amines in alcoholic beverages by HPLC coupled to a potentiometric detector for food quality control is herein presented. Biogenic amines were separated by ion-pair chromatography on a C18 column using a gradient mobile phase of acetic acid, acetonitrile, and butane-sulfonic acid. Detection was accomplished by a miniaturized amine-selective electrode. The method was validated following ICH and Eurachem guidelines. Linear regression models provided R2 values from 0.9870 ± 0.0019 to 0.9991 ± 0.0014 for tyramine and cadaverine, respectively. Detection and quantification limits depend on the molecular weight of BAs, ranging from 9.3 to 60.5 and from 31.1 to 202.3 µg L-1 for methylamine and spermine, respectively. Repeatability and intermediate precision showed RSD values lower than 5.8 and 8.3%, respectively. Accuracy of assays yielded recovery values from 86.4 to 109.9%. The biogenic amines content in red wine, white wine, and beer samples were 7.54, 5.24, and 4.58 mg L-1, respectively.

Influence of Brewing Process on the Profile of Biogenic Amines in Craft Beers.

The evaluation of the biogenic amines (BAs) profile of different types of craft beers is herein presented. A previously developed and validated analytical method based on ion-pair chromatography coupled with potentiometric detection was used to determine the presence of 10 BAs. Good analytical features were obtained for all amines regarding linearity (R2 values from 0.9873 ± 0.0015 to 0.9973 ± 0.0015), intra- and inter-day precision (RSD lower than 6.9% and 9.7% for beer samples, respectively), and accuracy (recovery between 83.2-108.9%). Detection and quantification limits range from 9.3 to 60.5 and from 31.1 to 202.3 µg L-1, respectively. The validated method was applied to the analysis of four ale beers and one lager craft beer. Ethylamine, spermidine, spermine, and tyramine were detected in all analyzed samples while methylamine and phenylethylamine were not detected. Overall, pale ale beers had a significantly higher total content of BAs than those found in wheat pale and dark samples. A general least square regression model showed a good correlation between the total content of BAs and the brewing process, especially for Plato degree, mashing, and fermentation temperatures. Knowledge about the type of ingredients and manufacturing processes that contribute to higher concentrations of these compounds is crucial to ensuring consumer safety.

Optimization and Validation of an In Vitro Standardized Glycogen Phosphorylase Activity Assay.

Glycogen phosphorylase (GP) is a key enzyme in the glycogenolysis pathway and a potential therapeutic target in the management of type 2 diabetes. It catalyzes a reversible reaction: the release of the terminal glucosyl residue from glycogen as glucose 1-phosphate; or the transfer of glucose from glucose 1-phosphate to glycogen. A colorimetric method to follow in vitro the activity of GP with usefulness in structure-activity relationship studies and high-throughput screening capability is herein described. The obtained results allowed the choice of the optimal concentration of enzyme of 0.38 U/mL, 0.25 mM glucose 1-phosphate, 0.25 mg/mL glycogen, and temperature of 37 °C. Three known GP inhibitors, CP-91149, a synthetic inhibitor, caffeine, an alkaloid, and ellagic acid, a polyphenol, were used to validate the method, CP-91149 being the most active inhibitor. The effect of glucose on the IC50 value of CP-91149 was also investigated, which decreased when the concentration of glucose increased. The assay parameters for a high-throughput screening method for discovery of new potential GP inhibitors were optimized and standardized, which is desirable for the reproducibility and comparison of results in the literature. The optimized method can be applied to the study of a panel of synthetic and/or natural compounds, such as polyphenols.

Challenges in the design of electrochemical sensor for glyphosate-based on new materials and biological recognition.

Glyphosate (GLY) is the main ingredient in the weed killer Roundup and the most widely used pesticide in the world. Studies of the harmful effects of GLY on human health began to become more wide-ranging after 2015. GLY is listed by the International Agency for Research on Cancer (IARC) as a carcinogenic hazard to humans. Moreover, GLY has the property to complex with transition metals and are stable for long periods, being considered a high-risk element for different matrices, such as environmental (soil and water) and food (usually genetically modified crops). Since that, it was noticed an increment in the development of new analytical methods for its determination in different matrices like food, environmental and biological fluids. Noteworthy, the application of electrochemical techniques for downstream detection sparked interest due to the ability to minimize or eliminate the use of polluting chemicals, using simple and affordable equipment. This work aims to review the contribution of the electroanalytical methods for the determination of GLY in different food and environmental matrices. Parameters such as the electrochemical transduction techniques based on the electrical measurement signals, receptor materials for electrodes preparation, and the detection mechanisms are described in this review. The literature review shows that the electrochemical sensors are powerful detection system that can be improved by their design and by their portability to fulfil the needs of the GLY determination in laboratory benches, or even in situ analysis.

Pyrazoles as novel protein tyrosine phosphatase 1B (PTP1B) inhibitors: An in vitro and in silico study.

Type 2 diabetes mellitus (DM) is a complex chronic disorder and a major global health problem. Insulin resistance is the primary detectable abnormality and the main characteristic feature in individuals with type 2 DM. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathway, which dephosphorylates insulin receptor and insulin receptor substrates, suppressing the insulin signaling cascade. Therefore, the inhibition of PTP1B has become a potential strategy in the management of type 2 DM. In this study, a library of 22 pyrazoles was evaluated here for the first time against human PTP1B activity, using a microanalysis screening system. The results showed that 5-(2-hydroxyphenyl)-3-{2-[3-(4-nitrophenyl)-1,2,3,4-tetrahydronaphthyl]}-1-phenylpyrazole 20 and 3-(2-hydroxyphenyl)-5-{2-[3-(4-methoxyphenyl)]naphthyl}pyrazole 22 excelled as the most potent inhibitors of PTP1B, through noncompetitive inhibition mechanism. These findings suggest that the presence of additional benzene rings as functional groups in the pyrazole moiety increases the ability of pyrazoles to inhibit PTP1B. The most active compounds showed selectivity over the homologous T-cell protein tyrosine phosphatase (TCPTP). Molecular docking analyses were performed and revealed a particular contact signature involving residues like TYR46, ASP48, PHE182, TYR46, ALA217 and ILE219. This study represents a significant beginning for the design of novel PTP1B inhibitors.

Nanostructured pencil graphite electrodes for application as high power biocathodes in miniaturized biofuel cells and bio-batteries.

This work describes a simple method for the fabrication of an enzymatic electrode with high sensitivity to oxygen and good performance when applied as biocathode. Pencil graphite electrodes (PGE) were chosen as disposable transducers given their availability and good electrochemical response. After electrochemical characterization regarding hardness and surface pre-treatment suited modification with carbon-based nanostructures, namely with reduced graphene, MWCNT and carbon black for optimal performance was proceeded. The bioelectrode was finally assembled through immobilization of bilirubin oxidase (BOx) lashed on the modified surface of MWCNT via π-π stacking and amide bond functionalization. The high sensitivity towards dissolved oxygen of 648 ± 51 µA mM-1 cm-2, and a LOD of 1.7 µM, was achieved for the PGE with surface previously modified with reduced graphene (rGO), almost the double registered for direct anchorage on the bare PGE surface. Polarization curves resulted in an open circuit potential (OCP) of 1.68 V (vs Zn electrode) and generated a maximum current density of about 650 µA cm-2 in O2 saturated solution.

Correction: A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives.

Correction for 'A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives' by Sónia Rocha, et al., Food Funct., 2019, DOI: 10.1039/c9fo01298b.

The dipeptidyl peptidase-4 inhibitory effect of flavonoids is hindered in protein rich environments.

Dipeptidyl peptidase-4 (DPP-4) inhibitors present a unique approach for the management of type 2 diabetes (T2D). In the present study, the inhibition of DPP-4 was evaluated for a large panel of flavonoids, important components of the human diet, using in vitro and ex vivo models. The activity of the isolated enzyme was assayed in vitro. Subsequently, the most active flavonoids were tested ex vivo in human whole blood and plasma. In this study, contrary to the in vitro fluorometric tests, flavonoids did not show inhibitory activity against DPP-4. Due to the discrepancy in the results between the in vitro and ex vivo approaches, plasma protein binding values were determined, presenting values from 43.9 to 100.0%. This work provides a new insight into the inhibitory activity for DPP-4, based on the flavonoid scaffold. Additionally, the obtained results showed that the inhibitory effect of flavonoids against DPP-4 was hindered in protein rich environments, like that occurring in blood, and indicated the need for experimental refinement in drug discovery for blood targets.

A study towards drug discovery for the management of type 2 diabetes mellitus through inhibition of the carbohydrate-hydrolyzing enzymes α-amylase and α-glucosidase by chalcone derivatives.

The inhibition of carbohydrate-hydrolyzing enzymes, α-amylase and α-glucosidase, is one of the major therapeutic strategies for the treatment of type 2 diabetes mellitus. Chalcones have been recognized for their multiple biological activities, including antidiabetic properties, through unclear mechanisms. In the present work, a panel of chalcones bearing hydroxy, methoxy, methyl, nitro, chloro, fluoro and bromo substituents were evaluated against α-amylase and α-glucosidase activities, most of them for the first time. The results showed that the substitution patterns and the type of substituents of chalcones influence their inhibitory activity. The presence of hydroxy groups at C-2'- and C-4' of the A ring and at C-3 and C-4 of the B ring favors the intended effect. Chalcones holding nitro groups and chloro substituents, together with a hydroxy group in the chalcone scaffold, showed strong inhibition of the α-glucosidase activity. The present study provides related scaffolds that may serve as the basis for the design and synthesis of new structures in order to obtain the ideal antidiabetic chalcone.

Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure-activity relationship.

α-Amylase has been considered an important therapeutic target for the management of type 2 diabetes mellitus (T2DM), decreasing postprandial hyperglycaemia (PPHG). In the present work, a panel of 40 structurally related flavonoids was tested, concerning their ability to inhibit α-amylase activity, using a microanalysis screening system, an inhibitory kinetic analysis and molecular docking calculations. From the obtained results, it was possible to observe that the flavone with a -Cl ion at 3-position of C-ring, an -OH group at 3'- and 4'- positions of B-ring and at 5- and 7- positions of A-ring and the C2 = C3 double bond, was the most active tested flavonoid, through competitive inhibition. In conclusion, some of the tested flavonoids have shown promising inhibition of α-amylase and may be considered as possible alternatives to the modulation of T2DM.

Biosensing based on pencil graphite electrodes.

Pencil leads have been increasingly used as electrode material in electrochemical applications. Commonly denominated as pencil graphite electrodes (PGE), they represent a viable alternative to other standard electrodes due to their comparable electrical properties but mainly for their low cost and availability, enabling disposable applications. In order to achieve the best analytical performance literature evidences the type of lead (hardness level) and electrode surface pre-treatment are critical to the envisaged application. The present review describes the use of PGE in biosensing analysis, more specifically those sensors comprising immobilized enzymes but also briefly referring nucleic acids and other biological entities. It lays an emphasis in the immobilization process of the biological entities while focusing in the analytical performance of each biosensor, mainly sensitivity, linear range and limit of detection as comparative criteria. This review also addresses the main characteristics and properties of PGEs as transducer material in the electrochemical field.

Potentiometric perchlorate determination at nanomolar concentrations in vegetables.

In this work, an expeditious method based on the multi-commutated flow-analysis concept with potentiometric detection is proposed to perform determinations of the emergent contaminant perchlorate in vegetable matrices down to nanomolar concentration. To accomplish the task, a tubular shaped potentiometric sensor selective to perchlorate ion was constructed with a PVC membrane containing 12mmol/kg of the polyamine bisnaphthalimidopropyl-4,4'-diaminodiphenylmethane and 2-nitrophenyl phenyl ether 68% (w/w) as plasticizer casted on a conductive epoxy resin. Under optimal flow conditions, the sensor responded linearly in the concentration range of 6.3×10-7-1.0×10-3mol/L perchlorate. In order to extend the determinations to lower concentrations (4.6(±1.3)×10-10mol/L perchlorate), a column packed with 70mg of sodium 2,5,8,11,14-pentaoxa-1-silacyclotetradecane-polymer was coupled to the flow-system thus enabling prior pre-concentration of the perchlorate. The proposed procedure provides a simpler alternative for the determination of perchlorate in foods, nowadays only allowed by sophisticated and expensive equipment and laborious methods.

Vortex-assisted liquid-liquid micro-extraction and high-performance liquid chromatography for a higher sensitivity methyl methacrylate determination in biological matrices.

A vortex-assisted liquid-liquid micro-extraction coupled with high-performance liquid chromatography, with UV-vis, is proposed to pre-concentrate methyl methacrylate and to improve separation in biological matrices. The use of 1-octanol as extracting phase, its volume, the need for a dispersant agent, the agitation conditions and the cooling time before phase separation were evaluated. In optimum conditions, enrichment factors of 20 (±0.5) and enrichment recovery of 99% were obtained. The straightforward association of this extraction process with the HPLC method, previously regulated by the International Organization for Standardization, afforded a detection limit of 122 ng/mL and a quantification limit of 370 ng/mL. The within-batch precision, relative standard deviation, was 3% for a sample with 1.49 µg/mL and 4% for a sample with 13.4 µg/mL. The results showed a between batch-precision of 21% for experiments performed on five different days, for a sample with a concentration of 1.10 µg/mL in methyl methacrylate.

Fully automated analytical procedure for propofol determination by sequential injection technique with spectrophotometric and fluorimetric detections.

In this work, an application of an enzymatic reaction for the determination of the highly hydrophobic drug propofol in emulsion dosage form is presented. Emulsions represent a complex and therefore challenging matrix for analysis. Ethanol was used for breakage of a lipid emulsion, which enabled optical detection. A fully automated method based on Sequential Injection Analysis was developed, allowing propofol determination without the requirement of tedious sample pre-treatment. The method was based on spectrophotometric detection after the enzymatic oxidation catalysed by horseradish peroxidase and subsequent coupling with 4-aminoantipyrine leading to a coloured product with an absorbance maximum at 485 nm. This procedure was compared with a simple fluorimetric method, which was based on the direct selective fluorescence emission of propofol in ethanol at 347 nm. Both methods provide comparable validation parameters with linear working ranges of 0.005-0.100 mg mL(-1) and 0.004-0.243 mg mL(-1) for the spectrophotometric and fluorimetric methods, respectively. The detection and quantitation limits achieved with the spectrophotometric method were 0.0016 and 0.0053 mg mL(-1), respectively. The fluorimetric method provided the detection limit of 0.0013 mg mL(-1) and limit of quantitation of 0.0043 mg mL(-1). The RSD did not exceed 5% and 2% (n=10), correspondingly. A sample throughput of approx. 14 h(-1) for the spectrophotometric and 68 h(-1) for the fluorimetric detection was achieved. Both methods proved to be suitable for the determination of propofol in pharmaceutical formulation with average recovery values of 98.1 and 98.5%.

A SO2-selective electrode based on a Zn-porphyrin for wine analysis.

This work describes the assessment of a SO2-selective electrode based on the use of the neutral carrier 5,10,15,20-tetraphenyl(porphyrinate)zinc(II) in a PVC membrane plasticized with 2-nitrophenyl phenyl ether. After being conditioned in 2 mol L(-1) diethylamine solution for 24 h, the electrode exhibited selective anionic response toward the analyte in a concentration interval of more than four decades, with an slope of -59.5 mV dec(-1), a practical detection limit of 3.7×10(-6) mol L(-1) and a low limit of linear range of 7.2×10(-6) mol L(-1). The response mechanism is based on the displacement of the diethylamine:metalloporphyrin complex equilibrium within membrane bulk, inducing a variation in the cationic-sites to ionophore ratio. In turn, free hydroxyl ions are complexed by the displaced ionophore in a ratio 1:1 and translated as single negative charge nernstian response. Finally, the selectivity of the electrode is evaluated in view of its application to wine analysis. Results had high accuracy and precision when compared with a reference method.