Layer-by-layer sensor architecture of polymers and nanoparticles for electrochemical detection of uric acid in human urine samples

Excessive uric acid levels in the human body (hyperuricemia) are the main causes of kidney stones and diabetes. In this study, a layer-by-layer arrangement of polymers and nanocomposites is used as a new electrode sensing material for rapid and direct electrochemical determination of uric acid (UA). The electrode surface architecture was constructed by the incorporation of poly (amidoamine) dendrimer with 0.5 generation (poly (amidoamine) [PAMAM] [D-G0.5]) of multiwalled carbon nanotube-silver nanoparticles (MWCNT-AgNP) and a poly (neutral-red) (poly [NR]) polymer. The PAMAM (D-G0.5)/MWCNT-AgNP/poly (NR)-coated electrode has a good electrocatalytic activity for the determination of UA using cyclic voltammetry and showed remarkable enhancement in current response at a low-oxidation potential (0.3 V). Under optimal conditions, the developed electrochemical sensor showed an excellent and wide linear range for the determination of UA (i.e. 0.016 μM–2500 μM), and the limit of detection was found to be 0.005 μM. The modified sensor system demonstrated excellent sensitivity and selectivity toward the detection of UA in the presence of interfering substances, which are commonly found in urine and human fluid samples. Furthermore, the developed sensor has represented both reproducibility and excellent stability for the UA determination in real samples (human urine).     

Chemical Conversion of Hardly Ionizable Rhenium Aryl Chlorocomplexes with p-Substituted Anilines

Fast and selective analytical methods help to ensure the chemical identity and desired purity of the prepared complexes before their medical application, and play an indispensable role in clinical practice. Mass spectrometry, despite some limitations, is an integral part of these methods. In the context of mass spectrometry, specific problems arise with the low ionization efficiency of particular analytes. Chemical derivatization was used as one of the most effective methods to improve the analyte’s response and separation characteristics. The Schotten–Baumann reaction was successfully adapted for the derivatization of ESI hardly ionizable Re(VII) bis(catechol) oxochlorocomplex. Various alkyl and halogen p-substituted anilines as possible derivatization agents were tested. Unlike the starting complex, the reaction products were easily ionizable in electrospray, providing structurally characteristic molecular and fragment anions. DFT computer modeling, which proposed significant conformation changes of prepared complexes within their deprotonation, proved to have a close link to MS spectra. High-resolution MS and MS/MS measurements complemented with collision-induced dissociation experiments for detailed specification of prepared complexes’ fragmentation pathways were used. The specified fragmentation schemes were analogous for all studied derivatives, with an exception for [Re(O)(Cat)₂PIPA].     

Investigating the Disordered and Membrane-Active Peptide A-Cage-C Using Conformational Ensembles

The driving forces and conformational pathways leading to amphitropic protein-membrane binding and in some cases also to protein misfolding and aggregation is the subject of intensive research. In this study, a chimeric polypeptide, A-Cage-C, derived from α-Lactalbumin is investigated with the aim of elucidating conformational changes promoting interaction with bilayers. From previous studies, it is known that A-Cage-C causes membrane leakages associated with the sporadic formation of amorphous aggregates on solid-supported bilayers. Here we express and purify double-labelled A-Cage-C and prepare partially deuterated bicelles as a membrane mimicking system. We investigate A-Cage-C in the presence and absence of these bicelles at non-binding (pH 7.0) and binding (pH 4.5) conditions. Using in silico analyses, NMR, conformational clustering, and Molecular Dynamics, we provide tentative insights into the conformations of bound and unbound A-Cage-C. The conformation of each state is dynamic and samples a large amount of overlapping conformational space. We identify one of the clusters as likely representing the binding conformation and conclude tentatively that the unfolding around the central W23 segment and its reorientation may be necessary for full intercalation at binding conditions (pH 4.5). We also see evidence for an overall elongation of A-Cage-C in the presence of model bilayers.     

Prebiotic Route to Thymine from Formamide—A Combined Experimental–Theoretical Study

Synthesis of RNA nucleobases from formamide is one of the recurring topics of prebiotic chemistry research. Earlier reports suggest that thymine, the substitute for uracil in DNA, may also be synthesized from formamide in the presence of catalysts enabling conversion of formamide to formaldehyde. In the current paper, we show that to a lesser extent conversion of uracil to thymine may occur even in the absence of catalysts. This is enabled by the presence of formic acid in the reaction mixture that forms as the hydrolysis product of formamide. Under the reaction conditions of our study, the disproportionation of formic acid may produce formaldehyde that hydroxymethylates uracil in the first step of the conversion process. The experiments are supplemented by quantum chemical modeling of the reaction pathway, supporting the plausibility of the mechanism suggested by Saladino and coworkers.     

Effects of accelerated carbonation on properties of ceramic-based geopolymers

Journal of Thermal Analysis and Calorimetry - Geopolymers are considered as environmentally friendly binders with a high potential not only to lower the prices of binders, but mainly to decrease...     

Selected Thoughts on Hydrophobicity in Drug Design

The fundamental aim of drug design in research and development is to invent molecules with selective affinity towards desired disease-associated targets. At the atomic loci of binding surfaces, systematic structural variations can define affinities between drug candidates and biomolecules, and thereby guide the optimization of safety, efficacy and pharmacologic properties. Hydrophobic interaction between biomolecules and drugs is integral to binding affinity and specificity. Examples of antiviral drug discovery are discussed.     

Hydrazones of 4-(Trifluoromethyl)benzohydrazide as New Inhibitors of Acetyl- and Butyrylcholinesterase

Based on the broad spectrum of biological activity of hydrazide–hydrazones, trifluoromethyl compounds, and clinical usage of cholinesterase inhibitors, we investigated hydrazones obtained from 4-(trifluoromethyl)benzohydrazide and various benzaldehydes or aliphatic ketones as potential inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). They were evaluated using Ellman’s spectrophotometric method. The hydrazide–hydrazones produced a dual inhibition of both cholinesterase enzymes with IC₅₀ values of 46.8–137.7 µM and 19.1–881.1 µM for AChE and BuChE, respectively. The majority of the compounds were stronger inhibitors of AChE; four of them (2-bromobenzaldehyde, 3-(trifluoromethyl)benzaldehyde, cyclohexanone, and camphor-based 2o, 2p, 3c, and 3d, respectively) produced a balanced inhibition of the enzymes and only 2-chloro/trifluoromethyl benzylidene derivatives 2d and 2q were found to be more potent inhibitors of BuChE. 4-(Trifluoromethyl)-N’-[4-(trifluoromethyl)benzylidene]benzohydrazide 2l produced the strongest inhibition of AChE via mixed-type inhibition determined experimentally. Structure–activity relationships were identified. The compounds fit physicochemical space for targeting central nervous systems with no apparent cytotoxicity for eukaryotic cell line together. The study provides new insights into this CF₃-hydrazide–hydrazone scaffold.     

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column–ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power—a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.     

Timing performance of ZnO:Ga nanopowder composite scintillators

The implementation of nanocrystal‐based composite scintillators as a new generation of ultrafast particle detectors is explored using ZnO:Ga nanopowder. Samples are characterized with a spectral‐time resolved photon counting system and pulsed X‐rays, followed by coincidence time resolution (CTR) measurements under 511 keV gamma excitation. Results are comparable to CTR values obtained using bulk inorganic scintillators. Bringing the ZnO:Ga nanocrystal's timing performance to radiation detectors could pave the research path towards sub‐20 ps time resolution as shown in this contribution. However, an efficiency boost when placing nanopowders in a transparent host constitutes the main challenge in order to benefit from sub‐nanosecond recombination times. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)