New organoruthenium metallates containing ferrocenecarboxalidine thiosemicarbazones and their nucleic acid/albumin binding and in vitro cytotoxicity

A string of four new hetero binuclear Ru(III) complexes of ferrocenecarboxaldehyde-4(N)-substituted thiosemicarbazones were synthesized and characterized by various spectral (infrared, ultraviolet–visible, Electron Paramagnetic Resonance (EPR) and High Resolution Mass Spectrometry (HR-MS) techniques. The binding abilities of the ligands/complexes with nucleic acid (calf thymus DNA, CT-DNA) and bovine serum albumin (BSA) were analyzed by absorption and emission titration methods. The complexes exhibited better DNA binding affinity than their parent ligands. The interaction with CT-DNA was found to be intercalative and with BSA static quenching mechanism was observed. All the synthesized Ru(III) complexes were subjected to study their in vitro cytotoxicity against MCF-7 (human breast cancer) and HT-29 (human colon cancer) cell lines. Among the four complexes, complex 3 [RuCp (FF-etsc)PPh₃]Cl exhibited the highest cytotoxicity in MCF-7 cells and complex 4 [RuCp (FF-ptsc)PPh₃]Cl was the most active on HT-29 cells.     

Are antibiotic screening approaches sufficiently adequate? A proficiency test

A proficiency test including the screening analysis of antibiotics in beef using cryogenicly minced materials was organized by RIKILT in 2009. The test included blank beef samples and beef samples spiked with either flumequine or a combination of lincomycin and spectinomycin around the maximum residue limits [1]. The suitability of the materials was demonstrated with a homogeneity and a stability study. This study showed that cryogenically minced spiked muscle material is suited for proficiency tests aiming at the screening and the confirmatory analysis.Of the 26 participants, 23 carried out their in-house screening approach involving microbial, biochemical or instrumental methods, or a combination of these to cover the broad range of antibiotic groups. The false negative rate was 73% for microbial methods, 50% for biochemical and 22% for instrumental methods. These results indicate that substantial effort is needed to improve screening approaches and that more regular proficiency tests are needed to reveal the shortcomings in the currently applied screening methods.     

Analysis of dihydroindole‐type alkaloids in Strychnos nux‐vomica unprocessed and processed seeds by high‐performance liquid chromatography coupled with diode array detection and mass spectrometry

The ripened seeds of Strychnos nux‐vomica L. have been extensively used as herbal medicines in Asian countries. Dihydroindole‐type alkaloids are not only the active constituents but also the toxicants in Strychnos. However, the simultaneous determination of these alkaloids in both crude and processed Semen Strychni is still lacking. The present study represents the first quantitation and relative quantitation assay of 12 dihydroindole‐type alkaloids in Strychnos nux‐vomica unprocessed and sand‐processed seeds using high‐performance liquid chromatography coupled with diode array detection and mass spectrometry. The relative concentration of ten alkaloids was calculated by semi‐quantification using the internal standard and their amounts in unprocessed and detoxified Semen Strychni were compared. We report here for the first time the significant increase of the two alkaloids, 19‐N‐methyl‐strychnine, and 2,3‐dimethoxy‐19‐N‐methyl‐strychnine, during the processing of Semen Strychni. Our study provides new insight into the true complexity of seed processing procedure and valuable information for assessing the efficacy and safety for clinical applications of Semen Strychni‐containing drugs.     

伊马替尼衍生物的合成及其抗肿瘤活性

以4-硝基-2-氨基甲苯为起始原料,经加成、缩合、环化和还原反应制得中间体N-(2-甲基-5-氨基苯基)-4-(3-吡啶基)嘧啶-2-胺(4),再与取代酰氯反应,合成了7个新型伊马替尼衍生物（5a~5g）,其结构经¹H NMR, ¹³C NMR和HR-MS 表征。采用四甲基偶氮唑盐(MTT)法考察了5对人肝癌细胞(HepG₂)、子宫颈癌细胞（Hela）、肺癌细胞（H460）和乳腺癌细胞（MCF-7）体外抑制活性。结果显示：5e体外抑制活性最优,其IC₅₀分别为10.90±1.00 μmol·L^-1; 8.51±0.90 μmol·L^-1; 13.15±1.11 μmol·L^-1; 14.75±0.78 μmol·L^-1。     

Optical probes for detection and quantification of neutrophils’ oxidative burst. A review

Neutrophils, also known as polymorphonuclear leukocytes (PMN), are the most common type of white blood cells, comprising about 50-70% of all white blood cells. In the event of inflammatory processes, neutrophils display increased mobility, tissue influx ability, prolonged life span, and an increased phagocytic capacity, constituting the initial participants in the cellular defense of the organism. One of the most important defense systems of neutrophils corresponds to their ability to mediate a strong oxidative burst through the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). While oxidative burst is important for the elimination of invading microorganisms, the overproduction of ROS and RNS or the impairment of endogenous antioxidant defenses may result to detrimental effects to the host. The nature and the extent of ROS and RNS production by neutrophils in response to different stimuli is, consequently, a matter of extensive research, with scientific reports showing an enormous variability on the detection methodologies employed. This review attempts to provide a critical assessment of the most common approaches to identify and quantify reactive species formed during the neutrophils’ oxidative burst. The detection mechanisms and performance, as well as advantages and limitations of the different methodologies, are scrutinized, focusing on the use of fluorimetric, chemiluminometric and colorimetric probes.     

A Three‐Dimensional Origami Paper‐Based Device for Potentiometric Biosensing

Current paper‐based potentiometric ion‐sensing platforms are planar devices used for clinically relevant ions. These devices, however, have not been designed for the potentiometric biosensing of proteins or small molecule analytes. A three‐dimensional origami paper‐based device, in which a solid‐contact ion‐selective electrode is integrated with an all‐solid‐state reference electrode, is described for the first time. The device is made by impregnation of paper with appropriate bioreceptors and reporting reagents on different zones. By folding and unfolding the paper structures, versatile potentiometric bioassays can be performed. A USB‐controlled miniaturized electrochemical detector can be used for simple and in situ measurements. Using butyrylcholinesterase as a model enzyme, the device has been successfully applied to the detection of enzyme activities and organophosphate pesticides involved in the enzymatic system as inhibitors. The proposed 3D origami paper device allows the potentiometric biosensing of proteins and small molecules in a simple, portable, and cost‐effective way.     

Preparation of Highly Stable and Photoluminescent Cadmium-Free InP/GaP/ZnS Core/Shell Quantum Dots and Application to Quantitative Immunoassay

Indium phosphide (InP) quantum dots (QDs) are ideal substitutes for widely used cadmium-based QDs and have great application prospects in biological fields due to their environmentally benign properties and human safety. However, the synthesis of InP core/shell QDs with biocompatibility, high quantum yield (QY), uniform particle size, and high stability is still a challenging subject. Herein, high quality (QY up to 72%) thick shell InP/GaP/ZnS core/shell QDs (12.8 ± 1.4 nm) are synthesized using multiple injections of shell precursor and extension of shell growth time, with GaP serving as the intermediate layer and 1-octanethiol acting as the new S source. The thick shell InP/GaP/ZnS core/shell QDs still keep high QY and photostability after transfer into water. InP/GaP/ZnS core/shell QDs as fluorescence labels to establish QD-based fluorescence-linked immunosorbent assay (QD-FLISA) for quantitative detection of C-reactive protein (CRP), and a calibration curve is established between fluorescence intensity and CRP concentrations (range: 1–800 ng mL⁻¹, correlation coefficient: R² = 0.9992). The limit of detection is 2.9 ng mL⁻¹, which increases twofold compared to previously reported cadmium-free QD-based immunoassays. Thus, InP/GaP/ZnS core/shell QDs as a great promise fluorescence labeling material, provide a new route for cadmium-free sensitive and specific immunoassays in biomedical fields.     

The selective introduction of organometallic markers into estrogens. A-ring propargylation of β-estradiol

Introduction of the propargyl dicobalt hexacarbonyl moiety onto the estradiol A ring as a potential probe in receptor studies requires protection of the ring phenolic group, and the regio-selectivity of the attack (2- versus 4-position) depends on the bulkiness of the organometallic carbenium ion.