Asymmetric Sulfur-Ylide-Mediated Formal [4+1]-Annulation Reaction: Scope and Mechanism.

A formal [4+1]-annulation strategy between sulfur ylides and 1,3-dienes was developed to afford functionalized cyclopentanoids. The process consists of a stereoselective cyclopropanation reaction followed, in situ, by a stereospecific MgI2 -catalyzed vinylcyclopropane-cyclopentene rearrangement. The use of chiral sulfur ylides provided cyclopentanoids with excellent enantiocontrol. A combined experimental and computational mechanistic study showed that the stereospecificity of the rearrangement could be accounted for by a double SN 2 reaction mechanism involving iodide.

Formal Asymmetric (4+1) Annulation Reaction between Sulfur Ylides and 1,3-Dienes.

A highly enantioselective synthesis of functionalized cyclopentanoids by a formal asymmetric (4+1) annulation strategy was developed. The methodology consists of a stereoselective cyclopropanation reaction between chiral sulfur ylides and 1,3-dienes followed by a, in situ, stereospecific MgI2 -catalyzed rearrangement of vinylcyclopropanes. This method is distinguished by a remarkable compatibility with functional groups and a high stereocontrol.

Nanoscale chemical and structural characterization of transient metallic nanowires using aberration-corrected STEM-EELS.

Direct chemical and structural characterization of transient iron-nickel alloy nanowires was performed at subnanometer spatial resolution using probe spherical aberration-corrected scanning transmission electron microscopy and electron energy-loss spectroscopy. Nanowires with diameter less than 2 nm retaining their nominal bulk alloy composition were observed. In some cases, the nanowires were oxidized. Before rupture, a nanojunction as thin as three atoms in width could be imaged. The time-dependent structural analyses revealed the nanowire rupture mechanisms. It is found that the atoms on the {111} planes were the easiest to be removed by electron irradiation and fluctuations between low-energy and high-energy facets were observed. The hitherto unknown rich variety of structural and chemical behavior in alloyed magnetic nanojunctions should be considered for understanding their physical properties.

High-Performance Implantable Sensors based on Anisotropic Magnetoresistive La0.67Sr0.33MnO3 for Biomedical Applications.

We present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La0.67Sr0.33MnO3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of ∼400%/T (with typical detectivity values of 2 nT·Hz-1/2 at a frequency of 1 Hz and 0.3 nT·Hz-1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo, support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues.

Functional expression of opioid receptors and other human GPCRs in yeast engineered to produce human sterols.

The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. However, some receptors, including the mu opioid receptor, are non-functional, which may be due to the presence of the fungal sterol ergosterol instead of cholesterol. Here we engineer yeast to produce cholesterol and introduce diverse mu, delta, and kappa opioid receptors to create sensitive opioid biosensors that recapitulate agonist binding profiles and antagonist inhibition. Additionally, human mu opioid receptor variants, including those with clinical relevance, largely display expected phenotypes. By testing mu opioid receptor-based biosensors with systematically adjusted cholesterol biosynthetic intermediates, we relate sterol profiles to biosensor sensitivity. Finally, we apply sterol-modified backgrounds to other human receptors revealing sterol influence in SSTR5, 5-HTR4, FPR1, and NPY1R signaling. This work provides a platform for generating human G protein-coupled receptor-based biosensors, facilitating receptor deorphanization and high-throughput screening of receptors and effectors.

Holistic engineering of Cal-A lipase chain-length selectivity identifies triglyceride binding hot-spot.

Through the application of a region-focused saturation mutagenesis and randomization approach, protein engineering of the Cal-A enzyme was undertaken with the goal of conferring new triglyceride selectivity. Little is known about the mode of triglyceride binding to Cal-A. Engineering Cal-A thus requires a systemic approach. Targeted and randomized Cal-A libraries were created, recombined using the Golden Gate approach and screened to detect variants able to discriminate between long-chain (olive oil) and short-chain (tributyrin) triglyceride substrates using a high-throughput in vivo method to visualize hydrolytic activity. Discriminative variants were analyzed using an in-house script to identify predominant substitutions. This approach allowed identification of variants that exhibit strong discrimination for the hydrolysis of short-chain triglycerides and others that discriminate towards hydrolysis of long-chain triglycerides. A clear pattern emerged from the discriminative variants, identifying the 217-245 helix-loop-helix motif as being a hot-spot for triglyceride recognition. This was the consequence of introducing the entire mutational load in selected regions, without putting a strain on distal parts of the protein. Our results improve our understanding of the Cal-A lipase mode of action and selectivity. This holistic perspective to protein engineering, where parts of the gene are individually mutated and the impact evaluated in the context of the whole protein, can be applied to any protein scaffold.

Strain-induced magnetic domain wall control by voltage in hybrid piezoelectric BaTiO3 ferrimagnetic TbFe structures.

This paper reports on the voltage dependence of the magnetization reversal of a thin amorphous ferromagnetic TbFe film grown on a ferroelectric and piezoelectric BaTiO3 single crystal. Magneto-optical measurements, at macroscopic scale or in a microscope, demonstrate how the ferroelectric BaTiO3 polarisation history influences the properties of the perpendicularly magnetized TbFe film. Unpolarised and twinned regions are obtained when the sample is zero voltage cooled whereas flat and saturated regions are obtained when the sample is voltage cooled through the ferroelectric ordering temperature of the BaTiO3 crystal, as supported by atomic force microscopy experiments. The two steps involved in the TbFe magnetization reversal, namely nucleation and propagation of magnetic domain walls, depend on the polarisation history. Nucleation is associated to coupling through strains with the piezoelectric BaTiO3 crystal and propagation to pinning with the ferroelastic surface patterns visible in the BaTiO3 topography.

Theoretical interpretation of the line shape of crystalline adipic acid.

A general quantum theoretical approach of the upsilon(X-H) IR line shape of cyclic dimers of weakly H-bonded species in the crystal state is proposed. In this model, the adiabatic approximation (allowing to separate the high-frequency motion from the slow one of the H-bond bridge) is performed for each separate H-bond bridge of the dimer and a strong nonadiabatic correction is introduced into the model via the resonant exchange between the fast-mode excited states of the two moieties. Quantum indirect damping and Fermi resonances are taken into account. The present model reduces satisfactorily to many models in the literature dealing with more special situations. It has been applied to the cyclic dimers of adipic acid in the crystal phase. It correctly fits the experimental line shape of the hydrogenated compound and predicts satisfactorily the evolution in the line shapes with temperature and the change in the line shape with isotopic substitution.

Theoretical interpretation of the line shape of the gaseous acetic acid cyclic dimer.

A general quantum theoretical approach of the nu(X-H) IR line shape of cyclic dimers of weakly H-bonded species in the gas phase is proposed. In this model, the adiabatic approximation (allowing to separate the high frequency motion from the slow one of the H-bond bridge), is performed for each separate H-bond bridge of the dimer and a strong nonadiabatic correction is introduced into the model via the resonant exchange between the fast mode excited states of the two moieties. The present model reduces satisfactorily to many models in the literature dealing with more special situations. It has been applied to the cyclic dimers (CD(3)CO(2)H)(2) and (CD(3)CO(2)D)(2) in the gas phase. It correctly fits the experimental line shape of the hydrogenated compound and predict satisfactorily the evolution in the line shapes, to the deuterated one by reducing simply the angular frequency of the H-bond bridge and the anharmonic coupling parameter by the factor 1/ square root of 2.