'On-the-fly' hydrogen/deuterium exchange liquid chromatography/mass spectrometry using a dual-sprayer atmospheric pressure ionisation source

In-source 'on-the-fly' hydrogen/deuterium (H/D) exchange liquid chromatography mass spectrometry (LC/MS) has been investigated. The work was performed using a dual-sprayer source. The analyte was introduced through an electrospray ionisation sprayer and D2O was introduced through an atmospheric pressure chemical ionisation sprayer. To achieve H/D exchange sufficient to determine the number of exchangeable H atoms of a compound, a saturated 'steady-state' D2O atmosphere had to be created in the ion source by having a 2:1 or higher D2O-to-analyte flow rate ratio. Under these conditions H/D exchange levels of 32-90% were achieved. In most cases the H/D exchange was sufficient to measure the number of exchangeable H atoms in some antiulcerative and anthelmintic pharmaceuticals. The concept of in-source 'on-the-fly' H/D exchange by introducing the deuterating agent via a second sprayer has been shown. It allows the integrity of the chromatographic separation to be kept, since the H/D exchange takes place post-separation.     

Molecular precursor route to bulk and silica-supported Nb2Mo3O14 using water-soluble oxo-oxalato complexes

The catalytically relevant Nb2Mo3O14 phase has been prepared in bulk and silica-supported forms via the so-called "multiple molecular precursors method" from water-soluble oxo-oxalato complexes of Nb and Mo, (NH4)3[NbO(ox)3].H2O, and (NH4)2[MoO3(ox)].H2O. Thermal treatment of the mixed Nb-Mo precursor has been optimized for the formation of the pure Nb2Mo3O14 phase, either as bulk oxide or a silica-supported phase with high specific surface area. A characterization of the bulk phase obtained via the conventional ceramic route has also been carried out and a comparison has been made with the precursors route. According to this route, the Nb2Mo3O14 phase is shown to be formed in a pure form at 700 degrees C (i.e., 100 degrees C below the lowest temperature reported so far for the formation of the phase by the ceramic method). The supported samples have appreciable specific surface areas of 60-70 m(2) g(-1), much larger than those reached in the previous attempts under vacuum in sealed vials. The SEM and EDX analyses reveal a high dispersion of the desired phase on the silica support.     

The neutron star zoo

Neutron stars are a very diverse population, both in their observational and their physical properties. They prefer to radiate most of their energy at X-ray and gamma-ray wavelengths. But whether their emission is powered by rotation, accretion, heat, magnetic fields or nuclear reactions, they are all different species of the same animal whose magnetic field evolution and interior composition remain a mystery. This article will broadly review the properties of inhabitants of the neutron star zoo, with emphasis on their high-energy emission.     

In Silico Identification of Tripeptides as Lead Compounds for the Design of KOR Ligands

The kappa opioid receptor (KOR) represents an attractive target for the development of drugs as potential antidepressants, anxiolytics and analgesics. A robust computational approach may guarantee a reduction in costs in the initial stages of drug discovery, novelty and accurate results. In this work, a virtual screening workflow of a library consisting of ~6 million molecules was set up, with the aim to find potential lead compounds that could manifest activity on the KOR. This in silico study provides a significant contribution in the identification of compounds capable of interacting with a specific molecular target. The main computational techniques adopted in this experimental work include: (i) virtual screening; (ii) drug design and leads optimization; (iii) molecular dynamics. The best hits are tripeptides prepared via solution phase peptide synthesis. These were tested in vivo, revealing a good antinociceptive effect after subcutaneous administration. However, further work is due to delineate their full pharmacological profile, in order to verify the features predicted by the in silico outcomes.     

FDR,an easier way to NNLO calculations: a two-loop case study

In this paper we illustrate the simplifications produced by FDR in NNLO computations. We show with an explicit example that—due to its four-dimensionality—FDR does not require an order-by-order renormalization and that, unlike the one-loop case, FDR and dimensional regularization generate intermediate two-loop results which are no longer linked by a simple subtraction of the ultraviolet (UV) poles in $\epsilon $ . Our case study is the two-loop amplitude for $H \rightarrow \gamma \gamma $ , mediated by an infinitely heavy top loop, in the presence of gluonic corrections. We use this to elucidate how gauge invariance is preserved with no need of introducing counterterms in the Lagrangian. In addition, we discuss a possible four-dimensional approach to the infrared problem compatible with the FDR treatment of the UV infinities.     

Photophysical properties of 4,4'-di-tert-butyl-2,2'-bipyridine supported 6-membered 2,2'-diphenyl-X platinacycles (X = CH2, NMe, O)

The six-membered platinacycle complex, Pt((t)Bu(2)bpy)(C(6)H(4)OC(6)H(4)) (6) ((t)Bu(2)bpy = 4,4'-di-tert-butyl-2,2'-bipyridine) has been prepared from Pt((t)Bu(2)bpy)Cl(2) and 2,2'-dilithio-diphenyl ether. Platinacycle 6 and its analogs with X = CH(2) (4) and NMe (5) exhibit intense solid-state photoluminescence and nearly identical crystal structures. The photophysical properties of 4-6 in the visible range are dominated by mixed metal-ligand-to-ligand charge transfer (MLL'CT) transitions involving high-lying filled mixed metal-ligand orbitals (ML), composed primarily of platinacyclic ring-based d- and π-orbitals, and a low lying vacant π* orbital (L') of the (t)Bu(2)bpy ligand. Lone pair donation from the bridging oxygen atom and especially the NMe group increases the energy of the mixed metal-ligand orbital (ML) without altering the energy of the (t)Bu(2)bpy π* orbital. As a result, the MLL'CT state energy decreases and the absorption and emission wavelengths are red-shifted. DFT and TD-DFT calculations support the experimental results. Additional calculations on the unknown platinacycles with X = CO (7) and SO(2) (8) predict a blue-shift for the MLL'CT absorption and emission. Two nearly equal energy triplet minima were located on the DFT triplet surface for 4-6. One of these (4T-6T) has a geometry very similar to the ground-state singlet (as represented by 4-6) and is associated with the emissive (3)MLL'CT excited state. The other triplet-state (4T'-6T') has a distorted structure where the platinacycle ring is twisted out of the Pt((t)Bu(2)bpy) plane. Thermal access to this distorted triplet may be responsible for the loss of photoluminescence in room temperature solutions of 4-6.     

Diels-Alder cycloaddition for fluorophore targeting to specific proteins inside living cells

The inverse-electron-demand Diels-Alder cycloaddition between trans-cyclooctenes and tetrazines is biocompatible and exceptionally fast. We utilized this chemistry for site-specific fluorescence labeling of proteins on the cell surface and inside living mammalian cells by a two-step protocol. Escherichia coli lipoic acid ligase site-specifically ligates a trans-cyclooctene derivative onto a protein of interest in the first step, followed by chemoselective derivatization with a tetrazine-fluorophore conjugate in the second step. On the cell surface, this labeling was fluorogenic and highly sensitive. Inside the cell, we achieved specific labeling of cytoskeletal proteins with green and red fluorophores. By incorporating the Diels-Alder cycloaddition, we have broadened the panel of fluorophores that can be targeted by lipoic acid ligase.