NanoLC/ESI+ HRMS3 Quantitation of DNA Adducts Induced by 1,3-Butadiene

Human exposure to 1,3-butadiene (BD) present in automobile exhaust, cigarette smoke, and forest fires is of great concern because of its potent carcinogenicity. The adverse health effects of BD are mediated by its epoxide metabolites such as 3,4-epoxy-1-butene (EB), which covalently modify genomic DNA to form promutagenic nucleobase adducts. Because of their direct role in cancer, BD-DNA adducts can be used as mechanism-based biomarkers of BD exposure. In the present work, a mass spectrometry-based methodology was developed for accurate, sensitive, and precise quantification of EB-induced N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-GII) DNA adducts in vivo. In our approach, EB-GII adducts are selectively released from DNA backbone by neutral thermal hydrolysis, followed by ultrafiltration, offline HPLC purification, and isotope dilution nanoLC/ESI⁺-HRMS³ analysis on an Orbitrap Velos mass spectrometer. Following method validation, EB-GII lesions were quantified in human fibrosarcoma (HT1080) cells treated with micromolar concentrations of EB and in liver tissues of rats exposed to sub-ppm concentrations of BD (0.5–1.5 ppm). EB-GII concentrations increased linearly from 1.15?±?0.23 to 10.11?±?0.45 adducts per 10⁶ nucleotides in HT1080 cells treated with 0.5–10 μM DEB. EB-GII concentrations in DNA of laboratory rats exposed to 0.5, 1.0, and 1.5 ppm BD were 0.17?±?0.05, 0.33?±?0.08, and 0.50?±?0.04 adducts per 10⁶ nucleotides, respectively. We also used the new method to determine the in vivo half-life of EB-GII adducts in rat liver DNA (2.20?±?0.12 d) and to detect EB-GII in human blood DNA. To our knowledge, this is the first application of nanoLC/ESI⁺-HRMS³ Orbitrap methodology to quantitative analysis of DNA adducts in vivo.

Antiferromagnetic interactions in Er-doped SnO<Subscript>2</Subscript> DMS nanoparticles

Diluted magnetic semiconductor (DMS) nanoparticles of Sn_1−x Er _x O₂ (x = 0.0, 0.02, 0.04, and 0.1) were prepared by sol–gel method. The X-ray diffraction patterns showed SnO₂ rutile structure for all samples with no impurity peaks. The decrease in crystallite size with Er concentration was confirmed from TEM measurements (from 12 to 4 nm). The UV–Visible absorption spectra of Er-doped SnO₂ nanoparticles showed blue shift in band gap compared to undoped SnO₂. The electron spin resonance analysis of Er-doped SnO₂ nanoparticles indicate Er³⁺ in a rutile lattice and also decrease in intensity with Er concentration above x = 0.02. Temperature-dependent magnetization studies and the inverse susceptibility curves indicated increased antiferromagnetic interaction with Er concentration.     

Intrinsic magnetism in Fe doped SnO2 nanoparticles

Iron doped semiconducting nanoparticles Sn_1−xFe_xO₂ with x=0, 0.001, 0.002, 0.003, 0.004, 0.01 and 0.03 were prepared by a sol-gel method. The X-ray diffraction, Transmission Electron Microscopy measurements confirm the rutile structure with no impurity phase. The three characteristic lines of electron spin resonance (ESR) are observed in the doped samples for all compositions, which is a clear evidence for rhombic Fe³⁺ in rutile phase. The line width of ESR increases with increase in Fe concentration due to induced disorder. The spin-pumping effect is observed at temperatures below 250 K for the samples with x=0.01 and 0.03. However, based on the Curie-Weiss susceptibility, iron is in paramagnetic state and is subject to weak antiferromagnetic interaction. Blue shift in the optical band gap is observed with increase in the Fe content.     

Optical and ESR studies on Fe doped ZnS nanocrystals

Zn_1 − xFe_xS (x=0.0, 0.1, 0.2, 0.4 and 0.6) nanocrystals have been obtained by chemical co-precipitation from homogeneous solutions of zinc and iron salt compounds, with S²⁻ as precipitating anion formed by decomposition of thiophenol. The TEM micrographs show a spherical shape for ZnS nanocrystals and their average size is around 7 nm. The optical absorption spectra indicate a blue shift of the absorption edge with increasing Fe-content. The luminescence of nanoparticles excite at about 370 nm with an emission peak at around 490 nm. At room temperature, ESR signal characteristic of Fe³⁺ was observed in samples of all concentrations.     

Doping induced magnetism in Co-ZnS nanoparticles

Zn_1−xCo_xS nanoparticles with x=0, 0.1, 0.2, and 0.3 were synthesized by the co-precipitation method using thiophenol as capping agent. The effect of Co doping on the structural, optical and magnetic properties are investigated. The X-ray diffraction patterns show single phase with cubic structure and the images of Transmission Electron Microscopy indicate an average particle size of 39 nm. Significant blue shift in the optical absorbing band edge was observed with increasing Co doping. In the Co doped samples, room-temperature (RT) magnetic hysteresis is observed and the magnetization reduces with increasing Co content. However, these samples show paramagnetic resonance instead of ferromagnetic resonance at both 300 and 80 K, suggesting that the origin of RT magnetization in these Zn_1−xCo_xS nanoparticles involves with the frustration of antiferromagnetic interactions.     

A Validated Chiral LC Method for the Enantiomeric Separation of Nateglinide and the Quantitative Determination of Its l-Enantiomer

A simple and accurate chiral liquid chromatographic method was developed for the enantiomeric purity determination of d-nateglinide and quantitative determination of l-nateglinide in bulk drug samples. Good resolution (R _s  > 6.0) between d-enantiomer and l-enantiomer of nateglinide were achieved with Chiralpak AD-H (250 × 4.6 mm, 5 μm particle size) column using hexane and ethanol (90:10 v/v) as mobile phase at 25 °C temperature. Flow rate was kept as 1.0 mL min^?1 and elution was monitored at 210 nm. The effects of the mobile phase composition, the flow rate and the temperature on the chromatographic separation were investigated. Developed method is capable to detect (LOD) and quantitate (LOQ) l-nateglinide to the levels of 0.3 and 1.0 μg mL^?1 respectively, for 10 μL injection volume. The percentage RSD of the peak area of six replicate injections of l-nateglinide at LOQ concentration was 5.2. The percentage recoveries of l-nateglinide from d-nateglinide ranged from 97.9 to 99.7. The test solution and mobile phase was found to be stable up to 24 h after preparation. The developed method was validated with respect to LOD, LOQ, precision, linearity, accuracy, robustness and ruggedness.     

MnO octahedral nanocrystals and MnO@C core-shell composites: synthesis, characterization, and electrocatalytic properties

We present a simple and facile synthesis of MnO octahedral nanocrystals and MnO@C core-shell composite nanoparticles. The synthesis is accomplished by a single-step direct pyrolysis of cetyltrimethylammonium permanganate in specially made Let-lock union cells. The products are characterized by HRSEM, HRTEM, Raman spectroscopy, and cyclic voltammetry (CV). The product consists mainly of octahedral MnO nanocrystals and MnO coated with carbon (MnO@C). The core-shell particles are observed only when the core size is smaller than 150 nm. The shape of the nanocrystals can be controlled by varying parameters such as reaction temperature and duration. As the temperature increases from 600 to 800 degrees C, the octahedral MnO crystals observed are without any carbon shell. The effect of time and temperature on the octahedral MnO nanocrystal formation is described. The electrocatalytic activities of the products are studied for oxygen reduction reaction in aqueous basic medium and are compared with bulk MnO. The MnO nanocrystals and core-shell composites exhibit higher activity than that of bulk MnO.     

Amperometric hydrogen peroxide and cholesterol biosensors designed by using hierarchical curtailed silver flowers functionalized graphene and enzymes deposits

Novel flower-like silver particles with triangular plates as building block along with functionalized graphene (straggled sheets) and enzymes horseradish peroxidase (HRP) or cholesterol oxidase (ChOx), were obtained on graphite electrode by galvanostatic electrodeposition method. The morphology of the electrodeposits has been characterized using scanning electron microscopy and energy-dispersive analysis of X-ray. The resulting biosensors named Nf/(HRP-f-graphene-Ag)/Gr and Nf/(ChOx-f-graphene-Ag)/Gr were evaluated for electrochemical activity using cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry. Optimization of the interdependent experimental parameters such as pH and temperature were achieved and maintained constant throughout the experiments. An activation energy of 2.5 kJ mol^?1 was obtained for Nf/(HRP-f-graphene-Ag)/Gr electrode while Nf/(ChOx-f-graphene-Ag)/Gr showed an activation energy of 2.06 and 3.12 kJ mol^?1. Furthermore, the former electrode demonstrated a good linear range of 25 μM to 19.35 mM with rapid response time of 3 s and detection limit of 5 μM for hydrogen peroxide. Similarly, the Nf/(ChOx-f-graphene-Ag)/Gr electrode revealed a linear range of 0.1–4.5 mM with rapid response time of 3 s and an excellent detection limit of 0.514 mM for cholesterol. Besides this, the Nf/(HRP-f-graphene-Ag)/Gr and Nf/(ChOx-f-graphene-Ag)/Gr electrodes displayed a Michaelis–Menten constant of 0.26 and 0.57 mM, respectively, suggesting high affinity and enzymatic activity. The enhanced performance of biosensors towards detection of substrate and rejection of interferents, provided an evidence for its high anti-interference ability. Additionally the biosensors exhibit long term storage stability and reproducibility with antifouling properties.