Elucidating the Anomalous Binding Enhancement of Isoquinoline Boronic Acid for Sialic Acid Under Acidic Conditions: Expanding Biorecognition Beyond Vicinal Diols

A zwitterionic heterocyclic boronic acid based on 4-isoquinolineboronic acid (IQBA) exhibits the highest reported binding affinity for sialic acid or N-acetylneuraminic acid (Neu5Ac, K=5390±190 m ⁻¹) through the formation of a cyclic boronate ester complex under acidic conditions (pH 3). This anomalous pH-dependent binding enhancement does not occur with common neutral saccharides (e.g., glucose, fructose, sorbitiol), because it is mediated via selective complexation to a α-hydroxycarboxylate moiety forming a stable ion pair and ternary complex with Neu5Ac in phosphate buffer. IQBA expands biorecognition beyond classical vicinal diols under neutral or alkaline buffer conditions, which enables the direct analysis of Neu5Ac by native fluorescence with sub-micromolar detection limits.     

Thermodynamic study of transthyretin association (wild‐type and senile forms) with heparan sulfate proteoglycan: pH effect and implication of the reactive histidine residue

The tetramer destabilization of transthyretin into monomers and its fibrillation are phenomena leading to amyloid deposition. Heparan sulfate proteoglycan (HSPG) has been found in all amyloid deposits. A chromatographic approach was developed to compare binding parameters between wild‐type transthyretin (wtTTR) and an amyloidogenic transthyretin (sTTR). Results showed a greater affinity of sTTR for HSPG at pH 7.4 compared with wtTTR owing to the monomeric form of sTTR. Analysis of the thermodynamic parameters showed that van der Waals interactions were involved at the complex interface for both transthyretin forms. For sTTR, results from the plot representing the number of protons exchanged vs pH showed that the binding mechanism was pH‐dependent with a critical value at a pH 6.5. This observation was due to the protonation of a histidine residue as an imidazolium cation, which was not accessible when TTR was in its tetrameric structure. At pH >6.5, dehydration at the binding interface and several contacts between nonpolar groups of sTTR and HSPG were also coupled to binding for an optimal hydrogen‐bond network. At pH <6.5, the protonation of the His residue from sTTR monomer when pH decreased broke the hydrogen‐bond network, leading to its destabilization and thus producing slight conformational changes in the sTTR monomer structure. Copyright © 2014 John Wiley & Sons, Ltd.     

Cu-Doped ZnO Nanoparticles for Non-Enzymatic Glucose Sensing

Copper-doped zinc oxide nanoparticles (NPs) Cu_xZn_1−xO (x = 0, 0.01, 0.02, 0.03, and 0.04) were synthesized via a sol-gel process and used as an active electrode material to fabricate a non-enzymatic electrochemical sensor for the detection of glucose. Their structure, composition, and chemical properties were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared (FTIR) and Raman spectroscopies, and zeta potential measurements. The electrochemical characterization of the sensors was studied using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). Cu doping was shown to improve the electrocatalytic activity for the oxidation of glucose, which resulted from the accelerated electron transfer and greatly improved electrochemical conductivity. The experimental conditions for the detection of glucose were optimized: a linear dependence between the glucose concentration and current intensity was established in the range from 1 nM to 100 μM with a limit of detection of 0.7 nM. The proposed sensor exhibited high selectivity for glucose in the presence of various interfering species. The developed sensor was also successfully tested for the detection of glucose in human serum samples.     

Modular Synthetic Approach to Carboranyl‒Biomolecules Conjugates

The development of novel, tumor-selective and boron-rich compounds as potential agents for use in boron neutron capture therapy (BNCT) represents a very important field in cancer treatment by radiation therapy. Here, we report the design and synthesis of two promising compounds that combine meta-carborane, a water-soluble monosaccharide and a linking unit, namely glycine or ethylenediamine, for facile coupling with various tumor-selective biomolecules bearing a free amino or carboxylic acid group. In this work, coupling experiments with two selected biomolecules, a coumarin derivative and folic acid, were included. The task of every component in this approach was carefully chosen: the carborane moiety supplies ten boron atoms, which is a tenfold increase in boron content compared to the l-boronophenylalanine (l-BPA) presently used in BNCT; the sugar moiety compensates for the hydrophobic character of the carborane; the linking unit, depending on the chosen biomolecule, acts as the connection between the tumor-selective component and the boron-rich moiety; and the respective tumor-selective biomolecule provides the necessary selectivity. This approach makes it possible to develop a modular and feasible strategy for the synthesis of readily obtainable boron-rich agents with optimized properties for potential applications in BNCT.     

Multidimensional De Novo Design Reveals 5‐HT2B Receptor‐Selective Ligands

We report a multi‐objective de novo design study driven by synthetic tractability and aimed at the prioritization of computer‐generated 5‐HT_2B receptor ligands with accurately predicted target‐binding affinities. Relying on quantitative bioactivity models we designed and synthesized structurally novel, selective, nanomolar, and ligand‐efficient 5‐HT_2B modulators with sustained cell‐based effects. Our results suggest that seamless amalgamation of computational activity prediction and molecular design with microfluidics‐assisted synthesis enables the swift generation of small molecules with the desired polypharmacology.     

PAH metabolism in the earthworm Eisenia fetida – identification of phase II metabolites of phenanthrene and pyrene

Polycyclic aromatic hydrocarbons (PAHs) are soil contaminants. Because of their high lipophilicity, PAHs are associated with the organic matter in the soil. Transformation of PAHs generates polar metabolites and the interaction with organic matter in the soil changes. The polar PAH metabolites are persistent, highly water-soluble and potentially leachable from the soil; the understanding of transformation of PAHs to polar metabolites in the responsible organisms is of great importance. Here, we present a study of transformation of the PAHs pyrene and phenanthrene, by the common earthworm Eisenia fetida. The study showed that E. fetida in hydroponic culture was able to transform PAHs to conjugated phase II metabolites. We detected phenanthrene and pyrene metabolites with single- and multiple-phase II-conjugated groups. Sulphate conjugates were excreted to experiment water, and glucuronide and glucoside conjugates and metabolites with several hydroxylations and multiple conjugations were detected in worm tissue. The results demonstrate that earthworms are able to transform PAHs to water-soluble phase II metabolites, which can be excreted to the surrounding environment.     

Enhanced UV photosensing properties of ZnO nanowires prepared by electrodeposition and atomic layer deposition

A new process enabling the synthesis of zinc oxide (ZnO) and Al-doped ZnO nanowires (NWs) for photosensing applications is reported. By combining atomic layer deposition (ALD) for the seed layer preparation and electrodeposition for the NW growth, high-quality ZnO nanomaterials were prepared and tested as ultraviolet (UV) sensors. The obtained NWs are grown as arrays perpendicular to the substrate surface and present diameters between 70 and 130 nm depending on the Al doping, as seen from scanning electron microscopy (SEM) studies. Their hexagonal microstructure has been determined using X-ray diffraction and Raman spectroscopy. An excellent performance in UV sensing has been observed for the ZnO NWs with low Al doping, and a maximal photoresponse current of 11.1 mA has been measured. In addition, initial studies on the stability have shown that the NW photoresponse currents are stable, even after ten UV on/off cycles.     

Formulation of Cannabidiol in Colloidal Lipid Carriers

In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C.     

Controlled pinewood fractionation with supercritical ethanol: A prerequisite toward pinewood conversion into chemicals and biofuels

The objective of this work was to investigate the ability of supercritical (SC) ethanol conditions to attack preferentially the lignin fraction against the carbohydrate fraction and their effects on the product distribution among gases, light products, bio-oils, and chars. In this study, the conversion of each pinewood component was determined by the analysis of solid residues to quantify cellulose, hemicellulose, lignin, and char contents. It is shown that, by tuning the temperature, hemicellulose and lignin are already transformed in subcritical ethanol conditions, lignin being more reactive than hemicellulose. In contrast, native wood cellulose is recalcitrant to liquefaction in SC ethanol near the critical point (T_c = 241 °C and P_c = 61 bar), but 20% of native wood cellulose is converted in SC ethanol at 280 °C. Besides, the severity of the conditions, in terms of temperature and treatment time, does not significantly influence the yields of gases, light products, and bio-oils but strongly enhances char formation. Interestingly, the increase in SC ethanol density does not change the conversion of biomass components but has a marked effect on bio-oil yield and prevents char formation. The optimum fractionation conditions to convert the lignin component, while keeping unattacked the cellulose fraction with a minimum formation of char, are dense SC ethanol, at 250 °C for 1 h, in batch conditions. However, although lignin is more reactive than hemicellulose under these conditions, these fractions are converted, in a parallel way, to around 50% and 60%, respectively.