Effect of substituent structure on pyrimidine electrophilic substitution

In an investigation into the electrophilic nitrosation reactions of a series of 4,6-disubstituted pyrimidine derivatives, a subtle interplay between the electronic nature of the C-4 and C-6 substituents and reactivity was found where these were chloro-, mono- or disubstituted amino groups. Effects such as the presence of an aryl group or two alkyl groups on the amino moiety impede the progress of the reaction despite the presence of a second activating group.     

Hydrolytically stable linkers for silicone carbohydrates derived from hydrodiisopropylsilanes

Two strategies were developed for the attachment of sugars to siloxanes using bifunctional silicon linkers: the substrate could be functionalized with a silyl hydride before coupling to a vinyl-terminated siloxane through platinum catalyzed hydrosilylation; alternatively, unprotected glucose could be directly silylated by a silicone terminated with a chlorosilyl group. Optimal steric bulk was found with difunctional diisopropylsilanes, which exhibit excellent reactivity for preparation of sugarsilane derivatives, and also permit efficient grafting to silicones via hydrosilylation. The resulting product alkoxysilane-silicone exhibits greater stability to hydrolysis than the silicone itself.     

Determination of Se in biological samples by axial view inductively coupled plasma optical emission spectrometry after digestion with aqua regia and on-line chemical vapor generation

A simple and fast method for the determination of Se in biological samples, including food, by axial view inductively coupled plasma optical emission spectrometry using on-line chemical vapor generation (CVG–ICP OES) is proposed. The concentrations of HCl and NaBH₄, used in the chemical vapor generation were optimized by factorial analysis. Six certified materials (non-fat milk powder, lobster hepatopancreas, human hair, whole egg powder, oyster tissue, and lyophilised pig kidney) were treated with 10 mL of aqua regia in a microwave system under reflux for 15 min followed by additional 15 min in an ultrasonic bath. The solutions were transferred to a 100 mL volumetric flask and the final volume was made up with water. The Se was determined directly in these solutions by CVG–ICP OES, using the analytical line at 196.026 nm. Calibration against aqueous standards in 10% v/v aqua regia in the concentration range of 0.5–10.0 µg L^− 1 Se(IV) was used for the analysis. The quantification limit, considering a 0.5 g sample weight in a final volume of 100 mL^− 1 was 0.10 µg g^− 1. The obtained concentration values were in agreement with the total certified concentrations, according to the t-test for a 95% confidence level.     

Follicle development and luteal cell morphology altered by phosphodiesterase-5 inhibitor

Vardenafil citrate is a potent vasodilator used in the treatment of patients with erectile dysfunction. Its mechanism of action is based on the selective inhibition of phosphodiesterase-5 (PDE5), specific to guanosine 3′,5′-cyclic monophosphate (cGMP). Recently, chronic treatment with Vardenafil has been successfully used in cases of pulmonary hypertension and, despite being used in high doses for long periods, little is known about its effects on other systems. In the present study, female mice were treated daily with 5 mg/kg Vardenafil for 4 weeks, after which the ovaries were collected for morphological analyses and sera were collected for biochemical assays. This study found that treatment with Vardenafil decreased HDL serum levels and the number of antral follicles as well as induced lesser lipid content in luteal cells, suggesting that high levels of cGMP may affect follicle development.     

Long cycles in abc-permutations

An abc-permutation is a permutation σ _abc ∈S _n obtained by exchanging an initial block of length a and a final block of length c of {1,…,n}, where n=a+b+c. In this note we compute the limit of the probability that a random abc-permutation is a long cycle. This resolves Arnold’s open problem (Arnold in Arnold’s problems, 2004, p. 144).      

Nanodiamond Particles: Properties and Perspectives for Bioapplications

Nanodiamonds (NDs) are members of the diverse structural family of nanocarbons that includes many varieties based on synthesis conditions, post-synthesis processes, and modifications. First studied in detail beginning in the 1960s in Russia, NDs have now gained world-wide attention due to their inexpensive large-scale synthesis based on the detonation of carbon-containing explosives, small primary particle size (～ 4 to 5 nm) with narrow size distribution, facile surface functionalization including bio-conjugation, as well as high biocompatibility. It is anticipated that the attractive properties of NDs will be exploited for the development of therapeutic agents for diagnostic probes, delivery vehicles, gene therapy, anti-viral and anti-bacterial treatments, tissue scaffolds, and novel medical devices such as nanorobots. Additionally, biotechnology applications have shown the prospective use of NDs for bioanalytical purposes, such as protein purification or fluorescent biolabeling. This review critically examines the use of NDs for biomedical applications based on type (i.e., high-pressure high-temperature [HPHT], CVD diamond, detonation ND [DND]), post-synthesis processing and modifications, and resultant properties including bio-interfacing. The discussion focuses on nanodiamond material in the form of nanoparticles, while the biomedical uses of nanodiamond coatings and thin films are discussed rather briefly. Specific use of NDs in both non-conjugated and conjugated forms as enterosorbents or solid phase carriers for small molecules including lysozyme, vaccines, and drugs is also considered. The use of NDs as human anti-cancer agents and in health care products is already showing promising results for further development. The review concludes with a look to the future directions and challenges involved in maximizing the potential of these exciting little carbon-based gems in the fields of engineering, medicine, and biotechnology.     

Simple and Sensitive Determination of Sibutramine in Slimming Tea Beverages Using a Carbon Screen‐printed Electrode with Adsorptive Stripping Voltammetry

The stimulant sibutramine is an anorexic agent found as an adulterant in natural products and multivitamins supplements used for weight‐loss. In this work, a carbon graphite screen‐printed electrode (SPE‐Gr) with adsorptive stripping pulse differential voltammetry (AdSDPV) is presented for the sensitive and simple detection of sibutramine in slimming tea beverages. The proposed electrochemical method shows a linear working range from 2.0 to 120 μM with a low LOD (0.3 μM) for sibutramine determination in slimming tea samples. The analytical performance of the SPE‐Gr with AdSDPV for sibutramine detection suggests its possible application as an easy, fast and low‐cost method to analyse adulterated tea samples with this stimulant at low levels (<0.1 %).     

Formation and hydrolysis of gas‐phase [UO2(R)]+: R═CH3, CH2CH3, CH═CH2, and C6H5

The goals of the present study were (a) to create positively charged organo‐uranyl complexes with general formula [UO₂(R)]⁺ (eg, R═CH₃ and CH₂CH₃) by decarboxylation of [UO₂(O₂C─R)]⁺ precursors and (b) to identify the pathways by which the complexes, if formed, dissociate by collisional activation or otherwise react when exposed to gas‐phase H₂O. Collision‐induced dissociation (CID) of both [UO₂(O₂C─CH₃)]⁺ and [UO₂(O₂C─CH₂CH₃)]⁺ causes H⁺ transfer and elimination of a ketene to leave [UO₂(OH)]⁺. However, CID of the alkoxides [UO₂(OCH₂CH₃)]⁺ and [UO₂(OCH₂CH₂CH₃)]⁺ produced [UO₂(CH₃)]⁺ and [UO₂(CH₂CH₃)]⁺, respectively. Isolation of [UO₂(CH₃)]⁺ and [UO₂(CH₂CH₃)]⁺ for reaction with H₂O caused formation of [UO₂(H₂O)]⁺ by elimination of ·CH₃ and ·CH₂CH₃: Hydrolysis was not observed. CID of the acrylate and benzoate versions of the complexes, [UO₂(O₂C─CH═CH₂)]⁺ and [UO₂(O₂C─C₆H₅)]⁺, caused decarboxylation to leave [UO₂(CH═CH₂)]⁺ and [UO₂(C₆H₅)]⁺, respectively. These organometallic species do react with H₂O to produce [UO₂(OH)]⁺, and loss of the respective radicals to leave [UO₂(H₂O)]⁺ was not detected. Density functional theory calculations suggest that formation of [UO₂(OH)]⁺, rather than the hydrated U^VO₂⁺, cation is energetically favored regardless of the precursor ion. However, for the [UO₂(CH₃)]⁺ and [UO₂(CH₂CH₃)]⁺ precursors, the transition state energy for proton transfer to generate [UO₂(OH)]⁺ and the associated neutral alkanes is higher than the path involving direct elimination of the organic neutral to form [UO₂(H₂O)]⁺. The situation is reversed for the [UO₂(CH═CH₂)]⁺ and [UO₂(C₆H₅)]⁺ precursors: The transition state for proton transfer is lower than the energy required for creation of [UO₂(H₂O)]⁺ by elimination of CH═CH₂ or C₆H₅ radical.     

Mechanistic insights into intramolecular phosphate group transfer during collision induced dissociation of phosphopeptides

We report on the rearrangement chemistry of model phosphorylated peptides during collision‐induced dissociation (CID), where intramolecular phosphate group transfers are observed from donor to acceptor residues. Such “scrambling” could result in inaccurate modification localization, potentially leading to misidentifications. Systematic studies presented herein provide mechanistic insights for the unusually high phosphate group rearrangements presented some time ago by Reid and coworkers (Proteomics 2013, 13 [6], 964‐973). It is postulated here that a basic residue like histidine can play a key role in mediating the phosphate group transfer by deprotonating the serine acceptor site. The proposed mechanism is consistent with the observation that fast collisional activation by collision‐cell CID and higher‐energy collisional dissociation (HCD) can shut down rearrangement chemistry. Additionally, the rearrangement chemistry is highly dependent on the charge state of the peptide, mirroring previous studies that less rearrangement is observed under mobile proton conditions.