Synthesis, in vitro antitumor evaluation and structure activity relationship of heptacoordinated amino-bis(Phenolato) Ti(IV) complexes stabilized by 2,6-dipicolinic acid.

Eighteen novel Ti(IV) complexes stabilized by different chelating amino-bis(phenolato) (ONNO, ONON, ONOO) ligands and 2,6-dipicolinic acid as a second chelator were synthesized with isolated yields ranging from 79 to 93%. Complexes were characterized by 1H and 13C-NMR spectroscopy, as well as by HRMS and X-Ray diffraction analysis. The good to excellent aqueous stability of these Ti(IV) complexes can be modulated by the substitutions on the 2-position of the phenolato ligands. Most of the synthesized Ti(IV) complexes demonstrated potent inhibitory activity against Hela S3 and Hep G2 tumor cells. Among them, the naphthalenyl based Salan type 2j, 2-picolylamine based [ONON] type 2n and N-(2-hydroxyethyl) based [ONOO] type 2p demonstrated up to 40 folds enhanced cytotoxicity compared to cisplatin together with a significantly reduced activity against healthy AML12 cells. The three Ti(IV) complexes exhibited fast cellular uptake by Hela S3 cells and induced almost exclusively apoptosis. 2j could trigger higher level of ROS generation than 2p and 2n.

Ionic γ-FeO(OH) Nanocrystal Stabilized by Small Isopolymolybdate Clusters as Reactive Core for Water Oxidation.

At near neutral to basic pH, hydrolysis-induced aggregation to insoluble bulk iron-oxide is often regarded as the pitfalls of molecular iron clusters. Iron-oxide nanocrystals are encouragingly active over the molecular clusters and/or bulk oxides albeit, stabilizing such nanostructures in aqueous pH and under turnover condition remain a perdurable challenge. Herein, an Anderson-type [Mo7 O24 ]6- isopolyanion, a small (dimension ca. 0.85 nm) isolable polyoxometalate (POM) possessing only {31} atoms, has been introduced for the first time as a covalent linker to stabilize an infinitely stable and aqueous-soluble γ-FeO(OH) nanocore. During the hydrothermal isolation of the material, a partial dissociation of the parent [Mo7 O24 ]6- may lead to the in situ generation of few analogous [Mox Oy ]n- clusters, proved by Raman study, which can also participate in stabilizing the γ-FeO(OH) nanocore, Mox Oy @FeO(OH). However, due to high ionic charge on {Mo=O} terminals of the [Mox Oy ]n- , they are covalently linked via MoVI -µ2 O-FeIII bridging to γ-FeO(OH) core in Mox Oy @FeO(OH), established by numerous spectroscopic and microscopic evidence. Such bonding mode is more likely as precedent from the coordination motif documented in the transition metal clusters stabilized by this POM. The γ-FeO(OH) nanocore of Mox Oy @FeO(OH) behaves as potent active center for electrochemical water oxidation with a overpotential, 263 mV @ 10 mA cm-2 , lower than that observed for bare γ-FeO(OH). Despite of some molybdenum dissolution from the POM ligands to the electrolyte, residual anionic POM fragments covalently bound to the OER active γ-FeO(OH) core of the Mox Oy @FeO(OH) makes the surface predominantly ionic that results in an ordered electrical double layer to promote a better charge transport across the electrode-electrolyte junction, less likely in bulk γ-FeO(OH).

Biomimic Heterostructured Graphene Oxide Membranes via Supramolecular-Mediated Intercalation Assembly for Efficient Water Transport.

Two-dimensional (2D) lamellar membranes have attracted increasing attention for efficient water purification. However, the low water-permeability, structural failure in aqua and high production cost have significantly restricted their practical large-scale applications. Inspired by the structures of glomerular filtration barrier (GFB) and nacre, a high-performance biomimic membrane via supramolecular-mediated intercalation assembly is reported, where rod-shaped cyclodextrin (CD) functionalized attapulgite (ATP-CD) is intercalated into CD-modified graphene oxide (GO-CD) lamellar channels, followed by locking adjacent ATP-CD and GO-CD through tannic acid (TA) and CD supramolecular networks. The formed GFB-like heterostructure endows the membrane with excellent water transport capability and the bionic "brick and mortar" nacre configuration boosts its anti-swelling stability simultaneously. The heterostructured GO membranes (≈100 nm) fabricated in this way exhibit a good water permeability of 55.6 L m-2  h-1  bar-1 (≈20-fold higher than GO membrane) maintaining excellent dye rejection of >99% during 480 h immersion. Given the low-cost materials (ATP, CD, and TA) and the modification generality, this economic strategy can hopefully achieve large-scale membrane fabrication and afford high applicability, which promotes the practical engineering applications of such 2D material membranes.

Degradation of Sub-Micrometer Sensitive Polymer Layers of Acoustic Sensors Exposed to Chlorpyrifos Water-Solution.

The detection of organophosphates, a wide class of pesticides, in water-solution has a huge impact in environmental monitoring. Acoustic transducers are used to design passive wireless sensors for the direct detection of pesticides in water-solution by using tailored polymers as sensitive layers. We demonstrate by combining analytical chemistry tools that organophosphate molecules strongly alter polymer layers widely used in acoustic sensors in the presence of water. This chemical degradation can limit the use of these polymers in detection of organophosphates in water-solution.

Development and Validation of a Reversed-Phase HPLC Method with UV Detection for the Determination of L-Dopa in Vicia faba L. Broad Beans.

L-Dopa (LD), a substance used medically in the treatment of Parkinson's disease, is found in several natural products, such as Vicia faba L., also known as broad beans. Due to its low chemical stability, LD analysis in plant matrices requires an appropriate optimization of the chosen analytical method to obtain reliable results. This work proposes an HPLC-UV method, validated according to EURACHEM guidelines as regards linearity, limits of detection and quantification, precision, accuracy, and matrix effect. The LD extraction was studied by evaluating its aqueous stability over 3 months. The best chromatographic conditions were found by systematically testing several C18 stationary phases and acidic mobile phases. In addition, the assessment of the best storage treatment of Vicia faba L. broad beans able to preserve a high LD content was performed. The best LD determination conditions include sun-drying storage, extraction in HCl 0.1 M, chromatographic separation with a Discovery C18 column, 250 × 4.6 mm, 5 µm particle size, and 99% formic acid 0.2% v/v and 1% methanol as the mobile phase. The optimized method proposed here overcomes the problems linked to LD stability and separation, thus contributing to the improvement of its analytical determination.

Racemisation in Chemistry and Biology.

The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.

Understanding the Aqueous Stability and Filtration Capability of MoS2 Membranes.

Membranes made of layer-stacked two-dimensional molybdenum disulfide (MoS2) nanosheets have recently shown great promise for water filtration. At present, the reported water fluxes vary significantly, while the accountable structure and properties of MoS2 nanochannels are largely unknown. This paper aims to mechanistically relate the performance of MoS2 membranes to the size of their nanochannels in different hydration states. We discovered that fully hydrated MoS2 membranes retained a 1.2 nm interlayer spacing (or 0.9 nm free spacing), leading to high water permeability and moderate-to-high ionic and molecular rejection. In comparison, completely dry MoS2 membranes had a 0.62 nm interlayer spacing (or 0.3 nm free spacing) due to irreversible nanosheet restacking and were almost impermeable to water. Furthermore, we revealed that the interlayer spacing of MoS2 membranes in aqueous solution is maintained by comparable van der Waals and hydration forces, thereby ensuring the aqueous stability of MoS2 membranes without the need of cross-linking. In addition, we attributed the high water flux (30-250 L m-2 h-1 bar-1) of MoS2 membranes to the low hydraulic resistance of smooth, rigid MoS2 nanochannels. We also concluded that compaction of MoS2 membranes with a high pressure helps create a more neatly stacked nanostructure with minimum voids or looseness, leading to stable water flux and separation performance. Besides, this paper systematically compares MoS2 membranes with the widely studied graphene oxide membranes to highlight the uniqueness and advantages of MoS2 membranes for water-filtration applications.

Thermal and aqueous stability improvement of graphene oxide enhanced diphenylalanine nanocomposites.

Nanocomposites of diphenylalanine (FF) and carbon based materials provide an opportunity to overcome drawbacks associated with using FF micro- and nanostructures in nanobiotechnology applications, in particular their poor structural stability in liquid solutions. In this study, FF/graphene oxide (GO) composites were found to self-assemble into layered micro- and nanostructures, which exhibited improved thermal and aqueous stability. Dependent on the FF/GO ratio, the solubility of these structures was reduced to 35.65% after 30 min as compared to 92.4% for pure FF samples. Such functional nanocomposites may extend the use of FF structures to e.g. biosensing, electrochemical, electromechanical or electronic applications.

Aqueous stability of leuprolide acetate: effect of temperature, dissolved oxygen, pH and complexation with ß-cyclodextrin.

In the present research, the aqueous stability of leuprolide acetate (LA) in phosphate buffered saline (PBS) medium was studied (pH = 2.0-7.4). For this purpose, the effect of temperature, dissolved oxygen and pH on the stability of LA during 35 days was investigated. Results showed that the aqueous stability of LA was higher at low temperatures. Degassing of the PBS medium partially increased the stability of LA at 4 °C, while did not change at 37 °C. The degradation of LA was accelerated at lower pH values. In addition, complexes of LA with different portions of ß-cyclodextrin (ß-CD) were prepared through freeze-drying procedure and characterized by Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) analyses. Studying their aqueous stability at various pH values (2.0-7.4) showed LA/ß-CD complexes exhibited higher stability when compared with LA at all pH values. The stability of complexes was also improved by increasing the portion of LA/ß-CD up to 1/10.

Preformulation studies of novel 5'-O-carbonates of lamivudine with biological activity: solubility and stability assays.

As a part of preformulation studies, the aim of this work was to examine the solubility and stability of a series of 5'-O-carbonates of lamivudine with proven antihuman immunodeficiency virus activity. Solubility studies were carried out using pure solvents (water, ethanol and polyethylene glycol 400 [PEG 400]), as well as cosolvents in binary mixture systems (water-ethanol and water-PEG 400). These ionizable compounds showed that their aqueous solubility is decreasing as the carbon length of the substituent moiety increases, but being enhanced as the pH was reduced from 7.4 to 1.2. Thus, 3TC-Metha an active compound of the series, with an intrinsic solubility at 25 °C of 17 mg/mL, was about 70 times more soluble than 3TC-Octa (0.24 mg/mL), and at pHs of 1.2, 5.8 and 7.4 had intrinsic solubilities of 36.48, 19.20 and 15.40 mg/mL, respectively. In addition, the solubility was enhanced significantly by using ethanol and PEG 400 as cosolvents. A stability study was conducted in buffer solutions at pH 1.2, 5.8, 7.4 and 13.0 and in human plasma at 37 °C. Stability-indicating high-performance liquid chromatography procedure was found to be selective, sensitive and accurate for these compounds and good recovery, linearity and precision were also observed.

Size-structure-property relationship of wood particles in aqueous and dry insulative foams.

Three size-fractionated samples of pine beetle-killed wood particles were used to prepare lightweight insulative foams. The foams were produced by foam-forming an aqueous slurry containing wood particles (125-1000 µm), a polymer binder, and surfactant, followed by oven drying. The effect of wood particle size on the aqueous foam stability, structure, and performance of insulative foams was investigated. While all aqueous foams were highly stable, aqueous foam stability increased with decreasing particle size. For dry foams, the cell size distribution was similar for all particle sizes as it was primarily controlled by the surfactant; differences occurred within the cell wall structure. A size-structure-property relationship was identified using x-ray micro-computed tomography where smaller particles produced lighter cell wall frameworks, leading to lower densities and decreased thermal conductivity and compressive strength. Larger particles produced denser cell wall frameworks that were more resistant to deformation, although all dry foams had sufficient mechanical properties for use as insulation panels. Thermal conductivity for all wood particle size-fractionated samples was <0.047 W m-1 K-1 making the foams similar to expanded polystyrene/polyurethane and supporting their use as thermal insulation in buildings.

Identifying Stable Electrocatalysts Initialized by Data Mining: Sb2 WO6 for Oxygen Reduction.

Data mining from computational materials database has become a popular strategy to identify unexplored catalysts. Herein, the opportunities and challenges of this strategy are analyzed by investigating a discrepancy between data mining and experiments in identifying low-cost metal oxide (MO) electrocatalysts. Based on a search engine capable of identifying stable MOs at the pH and potentials of interest, a series of MO electrocatalysts is identified as potential candidates for various reactions. Sb2 WO6 attracted the attention among the identified stable MOs in acid. Based on the aqueous stability diagram, Sb2 WO6 is stable under oxygen reduction reaction (ORR) in acidic media but rather unstable under high-pH ORR conditions. However, this contradicts to the subsequent experimental observation in alkaline ORR conditions. Based on the post-catalysis characterizations, surface state analysis, and an advanced pH-field coupled microkinetic modeling, it is found that the Sb2 WO6 surface will undergo electrochemical passivation under ORR potentials and form a stable and 4e-ORR active surface. The results presented here suggest that though data mining is promising for exploring electrocatalysts, a refined strategy needs to be further developed by considering the electrochemistry-induced surface stability and activity.

Synthesis, pH-dependent, and plasma stability of meropenem prodrugs for potential use against drug-resistant tuberculosis.

Meropenem, a broad-spectrum parenteral ß-lactam antibiotic, in combination with clavulanate has recently shown efficacy in patients with extensively drug-resistant tuberculosis. As a result of meropenem's short half-life and lack of oral bioavailability, the development of an oral therapy is warranted for TB treatment in underserved countries where chronic parenteral therapy is impractical. To improve the oral absorption of meropenem, several alkyloxycarbonyloxyalkyl ester prodrugs with increased lipophilicity were synthesized and their stability in physiological aqueous solutions and guinea pig as well as human plasma was evaluated. The stability of prodrugs in aqueous solution at pH 6.0 and 7.4 was significantly dependent on the ester promoiety with the major degradation product identified as the parent compound meropenem. However, in simulated gastrointestinal fluid (pH 1.2) the major degradation product identified was ring-opened meropenem with the promoiety still intact, suggesting the gastrointestinal environment may reduce the absorption of meropenem prodrugs in vivo unless administered as an enteric-coated formulation. Additionally, the stability of the most aqueous stable prodrugs in guinea pig or human plasma was short, implying a rapid release of parent meropenem.

Organic ligands regulate the environmental impacts of metal-organic frameworks on nitrogen-fixing bacterium Azotobacter vinelandii.

Metal-organic frameworks (MOFs) are rapidly developed materials with fantastic properties and wide applications. The increasing studies highlighted the potential threats of MOF materials to the environment. Comparing to the limited species of metal elements, the organic ligands have much higher diversity, but the influence of organic ligands on the environmental impacts of MOFs has not been revealed. Herein, we synthesized three Cu-MOFs with different organic ligands, namely Cu-BDC (1,4-terephthalic acid), Cu-IM (imidazole) and Cu-TATB (2,4,6-tris(4-carboxyphenyl)- 1,3,5-triazine), and evaluated their environmental toxicity to the nitrogen-fixing bacterium Azotobacter vinelandii. Cu-BDC inhibited the bacterial growth at lower concentrations than Cu-IM and Cu-TATB. The transcriptomes suggested the changes of membrane components by Cu-MOFs, consistent with the membrane leakage and cell wall damages. Cu-MOFs inhibited the nitrogen fixation activity through energy metabolism disturbance according to Gene Ontology functional annotation of ATP binding, Ca2+Mg2+-ATPase activity and ATP content. Only Cu-IM lowered the nitrogen fixation related nif genes, and affected the ribosome, purine metabolism and oxidative phosphorylation pathways. Otherwise, Cu-BDC and Cu-TATB mainly affected the flagellar assemblies and bacterial chemotaxis pathways. Our results collectively indicated that organic ligands regulated the environmental toxicity of MOFs through different metabolism pathways.

Synthesis and X-ray structure analysis of cytotoxic heptacoordinated Salan hafnium(IV) complexes stabilized with 2,6-dipicolinic acid.

Four novel Salan Hf(IV) complexes stabilized by 2,6-dipicolinic acid (Dipic) were synthesized and characterized by 1H, 13C NMR and X-ray diffraction spectroscopy. These Hf(IV)bis-chelates could be obtained in good to excellent yields (88%-91%) and demonstrated rather good stability in aqueous media and on silica gel. [L2Hf(IV)Dipic4-H,Cl] containing steric bulk L2 were stable in about 10% H2O (H2O/THF (v/v)), however, [L1Hf(IV)Dipic4-H,Cl] with non-steric L1 could slowly dissociate and release nontoxic L1. [L1-2Hf(IV)Dipic4-Cl] showed excellent anti-tumoral activity in the range of cisplatin (Hela S3: IC50 = 3.5 ± 0.4 µM, Hep G2: IC50 = 11.2 ± 2.1 µM). In addition, the cellular uptake and apoptosis investigation of [L1Hf(IV)Dipic4-Cl] suggested a fast cellular uptake process against Hela S3 cells with an almost exclusive induced apoptosis cell death path.

Electronegativity-Induced Charge Balancing to Boost Stability and Activity of Amorphous Electrocatalysts.

Amorphization is an efficient strategy to activate intrinsically inert catalysts. However, the low crystallinity of amorphous catalysts often causes high solubility and poor electrochemical stability in aqueous solution. Here, a different mechanism is developed to simultaneously stabilize and activate the water-soluble amorphous MoSx Oy via a charge-balancing strategy, which is induced by different electronegativity between the co-dopants Rh (2.28) and Sn (1.96). The electron-rich Sn prefers to stabilize the unstable apical O sites in MoSx Oy through charge transfer, which can prevent the H from attacking. Meanwhile, the Rh, as the charge regulator, shifts the main active sites on the basal plane from inert Sn to active apical Rh sites. As a result, the amorphous RhSn-MoSx Oy exhibits drastic enhancement in electrochemical stability (η10 increases only by 12 mV) after 1000 cycles and a distinct activity (η10 : 26 mV and Tafel: 30.8 mV dec-1 ) for the hydrogen evolution reaction in acidic solution. This work paves a route for turning impracticably water-soluble catalysts into treasure and inspires new ideas to design high-performance amorphous electrocatalysts.

Investigation on chlorogenic acid stability in aqueous solution after microwave treatment.

Recently, several health benefits associated with the consumption of foods rich in chlorogenic acid (5-CQA) have been reported. However, an important issue is its low stability during extraction and food processing, resulting in isomerization to neochlorogenic and cryptochlorogenic acids and the formation of further degradation products. This work describes the evaluation of 5-CQA reactivity in commercial waters after microwave treatment. An optimized HPLC-UV method was used to monitor 5-CQA conversion to its main isomers, while LC-HRMS/MS was performed for the elucidation of transformation products. Results revealed different degrees of isomerization in 5-CQA depending on the water sample, and the formation of oxidation derivatives of CQA isomers. This study highlights the importance of analytical monitoring of food compounds, during microwave treatment for example. In the case of 5-CQA, understanding of the degradation process would allow better preservation of bioactive constituent in foods and beverages and health promoting effects.

Enhanced Ultrasensitive Photoelectrochemical Probe for Phosphate Detection in Water Based on a Zirconium-Porphyrin Framework.

Excessive phosphate poses a serious ecological and human health risk, and thereby, monitoring its trace concentration is of great significance to environmental protection and human health. In this work, a zirconium-porphyrin framework (PCN-222) with excellent stability and unique luminescence properties was designed to modify the surface of the indium tin oxide electrode, which was first used as a photoelectrochemical (PEC) probe for phosphate detection. The PCN-222-modified PEC probe demonstrated an excellent selectivity and stability and indicated a linear response to phosphate in the range of 0-106 nM with a limit of detection (LOD) as low as 1.964 nM. To the best of our knowledge, this is the phosphate probe with the lowest LOD, and this is also the first signal-on PEC probe toward phosphate based on PCN-222. More importantly, the PEC probe can be validated for the good applicability of trace phosphate detection in real water samples, indicating a good application prospect. Finally, a series of electrochemical and spectroscopic studies have proved that phosphate can bind to the indium tin oxide (ITO)/PCN-222 electrode, which shortens the distance of the space charge region while reducing the bandwidth and thus facilitates the transfer of photogenerated electrons across the energy band barrier to reduce O2 in the electrolyte, producing an enhanced cathodic photocurrent signal. The proposed strategy of the highly sensitive PEC probe provides a promising platform for more effective label-free phosphate monitoring in the environment and organisms.

Facile synthesis of [ONON] type titanium(IV)bis-chelated complexes in alcoholic solvents and evaluation of anti-tumor activity.

Novel anti-tumoral diamino-bis-(phenolato) [ONON] type titanium(IV) complexes stabilized by 2,6-dipicolinic acid were synthesis via an efficient protocol using n-propanol as solvent and H2O for isolation. In total 20 [ONON] type and 2 Salan Ti(IV)bis-chelated complexes were synthesized with yields ranging from 68% to 96%. All reactions could reach to completion in 1.5 min at 80 °C either using Ti(OiPr)4 or TiCl4 as starting materials. Most [ONON] type Ti(IV) complexes exhibit selectively enhanced inhibition activity against Hep G2 cells in comparison with Salan Ti(IV) complexes. Among which, the inhibitory activity of 2 t (IC50: 0.15 ±â€¯0.1 µM) against Hep G2 cells is about 80 times enhanced than that of cisplatin (IC50: 12.4 ±â€¯1.2 µM). The [ONON] type Ti(IV) complexes slowly released nontoxic phenolato ligands in presence of large amount of aqueous media, and a fast cellular uptake process was proposed for these Ti(IV) complexes based on metal uptake analysis. Decagram scale synthesis indicates this facile synthetic methodology can be applied to large scale synthesis.

Arresting Aqueous Swelling of Layered Graphene-Oxide Membranes with H3O+ and OH- Ions.

Over the past decade, graphene oxide (GO) has emerged as a promising membrane material with superior separation performance and intriguing mechanical/chemical stability. However, its practical implementation remains very challenging primarily because of its undesirable swelling in an aqueous environment. Here, we demonstrated that dissociation of water molecules into H3O+ and OH- ions inside the interlayer gallery of a layered GO membrane can strongly affect its stability and performance. We reveal that H3O+ and OH- ions form clusters inside the GO laminates that impede the permeance of water and salt ions through the membrane. Dynamics of those clusters is sensitive to an external ac electric field, which can be used to tailor the membrane performance. The presence of H3O+ and OH- ions also leads to increased stability of the hydrogen bond (H-bond) network among the water molecules and the GO layers, which further reduces water permeance through the membrane, while crucially imparting stability to the layered GO membrane against undesirable swelling.