Fluorine detected 2D NMR experiments for the practical determination of size and sign of homonuclear F-F and heteronuclear C-F multiple bond J-coupling constants in multiple fluorinated compounds.

The use of fluorine in molecules obtained from chemical synthesis has become increasingly important within the pharmaceutical and agricultural industry. NMR characterization of these compounds is of great value with respect to their structure elucidation, their screening in metabolomics investigations and binding studies. The favorable NMR properties of the fluorine nucleus make NMR with fluorine detection of great value in this respect.

Interpretation and visualization of non-linear data fusion in kernel space: study on metabolomic characterization of progression of multiple sclerosis.

Background: In the last decade data fusion has become widespread in the field of metabolomics. Linear data fusion is performed most commonly. However, many data display non-linear parameter dependences.

Simultaneous analysis of plasma and CSF by NMR and hierarchical models fusion.

Because cerebrospinal fluid (CSF) is the biofluid which interacts most closely with the central nervous system, it holds promise as a reporter of neurological disease, for example multiple sclerosis (MScl). To characterize the metabolomics profile of neuroinflammatory aspects of this disease we studied an animal model of MScl-experimental autoimmune/allergic encephalomyelitis (EAE). Because CSF also exchanges metabolites with blood via the blood-brain barrier, malfunctions occurring in the CNS may be reflected in the biochemical composition of blood plasma.

Determination of size and sign of hetero-nuclear coupling constants from 2D 19F-13C correlation spectra.

Fluorinated organic compounds have become increasingly important within the polymer and the pharmaceutical industry as well as for clinical applications. For the structural elucidation of such compounds, NMR experiments with fluorine detection are of great value due to the favorable NMR properties of the fluorine nucleus. For the investigation of three fluorinated compounds, triple resonance 2D HSQC and HMBC experiments were adopted to fluorine detection with carbon and/or proton decoupling to yield F-C, F-C{H}, F-C{C(acq)} and F-C{H,C(acq)} variants.

NMR and pattern recognition can distinguish neuroinflammation and peripheral inflammation.

Multiple Sclerosis (MScl) is a neurodegenerative disease of the CNS, associated with chronic neuroinflammation. Cerebrospinal fluid (CSF), being in closest interaction with CNS, was used to profile neuroinflammation to discover disease-specific markers. We used the commonly accepted animal model for the neuroinflammatory aspect of MScl: the experimental autoimmune/allergic encephalomyelitis (EAE).

Fusion of metabolomics and proteomics data for biomarkers discovery: case study on the experimental autoimmune encephalomyelitis.

Background: Analysis of Cerebrospinal Fluid (CSF) samples holds great promise to diagnose neurological pathologies and gain insight into the molecular background of these pathologies. Proteomics and metabolomics methods provide invaluable information on the biomolecular content of CSF and thereby on the possible status of the central nervous system, including neurological pathologies. The combined information provides a more complete description of CSF content.

Application of fluorine NMR for structure identification of steroids.

Fluorinated steroids were examined using 1D and 2D homo- and heteronuclear (19)F NMR, such as (19)F-(1) H and (19)F-(13)C. The utilization of fluorine NMR accounted for spectral simplification and resulted in a straightforward pathway for the determination of structures including the configuration of these compounds; these steroids present an illustrative example for other types of fluorinated compounds, which are increasingly encountered in drug discovery. The potential of (19)F NMR is elaborated on in detail for two compounds containing diastereotopic fluorines with different coupling patterns.

Quantitative proteomics and metabolomics analysis of normal human cerebrospinal fluid samples.

The analysis of cerebrospinal fluid (CSF) is used in biomarker discovery studies for various neurodegenerative central nervous system (CNS) disorders. However, little is known about variation of CSF proteins and metabolites between patients without neurological disorders. A baseline for a large number of CSF compounds appears to be lacking.

Determination and identification of estrogenic compounds generated with biosynthetic enzymes using hyphenated screening assays, high resolution mass spectrometry and off-line NMR.

This paper describes the determination and identification of active and inactive estrogenic compounds produced by biosynthetic methods. A hyphenated screening assay towards the human estrogen receptor ligand binding domain (hER)alpha and hERbeta integrating target-ligand interactions and liquid chromatography-high resolution mass spectrometry was used. With this approach, information on both biologic activity and structure identity of compounds produced by bacterial mutants of cytochrome P450s was obtained in parallel.

The unstable part of the apical stem of duck hepatitis B virus epsilon shows enhanced base pair opening but not pico- to nanosecond dynamics and is essential for reverse transcriptase binding.

Hepatitis B virus (HBV) replication starts with binding of reverse transcriptase (RT) to the apical stem-loop region of epsilon, a conserved element of the RNA pregenome. For duck HBV, an in vitro replication system has provided molecular details of this interaction. Further insights can be obtained from the structure and dynamics of the duck and human apical stem-loops.

A microfluidic high-resolution NMR flow probe.

A microfluidic high-resolution NMR flow probe based on a novel stripline detector chip is demonstrated. This tool is invaluable for the in situ monitoring of reactions performed in microreactors. As an example, the acetylation of benzyl alcohol with acetyl chloride was monitored.

Low temperature in situ UV irradiation of [(eta 5-C5H5)Co(C2H4)2] in the NMR probe: formation of Co(III) silyl hydride complexes.

Low temperature in situ UV irradiation of [(eta(5)-C(5)H(5))Co(C(2)H(4))(2)] in the presence of silanes enables the characterisation of unstable fluxional Co(III) silyl hydride complexes [(eta(5)-C(5)H(5))Co(SiR(3))(H)(C(2)H(4))] (SiR(3) = SiEt(3), SiMe(3) or SiHEt(2)) by NMR spectroscopy; the reaction of [Co(eta(5)-C(5)H(5))(C(2)H(4))(2)] with HSiR(3) proceeds thermally to reach an equilibrium when SiR(3) = Si(OMe)(3) or SiClMePh.

Thermodynamics and NMR studies on Duck, Heron and Human HBV encapsidation signals.

Hepatitis B virus (HBV) replication is initiated by binding of its reverse transcriptase (P) to the apical stem-loop (AL) and primer loop (PL) of epsilon, a highly conserved RNA element at the 5'-end of the RNA pregenome. Mutation studies on duck/heron and human in vitro systems have shown similarities but also differences between their P-epsilon interaction. Here, NMR and UV thermodynamic data on AL (and PL) from these three species are presented.

Photochemical isomerization of N-heterocyclic carbene ruthenium hydride complexes: in situ photolysis, parahydrogen, and computational studies.

Low-temperature UV irradiation of the N-heterocyclic carbene complex Ru(IEt2Me2)(PPh3)2(CO)H2 (IEt2Me2 = 1,3-bis(ethyl)-4,5-dimethylimidazol-2-ylidene) leads to a remarkable photoisomerization reaction. By combining in situ photolysis and parahydrogen experiments to characterize the ultimate photoproducts and DFT calculations to interrogate the structures of the key 16-electron intermediates, the importance of both PPh3 and H2 loss pathways has been established.

Photochemical reactions of (eta 5-cyclopentadienyl)bis(t-butylacrylate) rhodium with silanes: dynamics of isomer interconversion via Rh(eta 2-silane) species.

The compound CpRh(C(2)H(3)CO(2)(t)Bu)(2) 1 has been synthesised as a mixture of two pairs of interconverting isomers which differ in the relative orientations of the alkene substituents. The four isomers have been fully characterised by NMR spectroscopy. When complex 1 is photolysed in the presence of a silane, HSiR(2)R'R(2)R'= Et(3), Me(3), HEt(2), (OMe)(3) and Me(2)Cl] the corresponding Si-H oxidative addition products CpRh(SiR(2)R')(H)(C(2)H(3)CO(2)(t)Bu) and CpRh(H)(2)(SiR(2)R')(2) are formed.