Fine Tuning of β‐Peptide Foldamers: a Single Atom Replacement Holds Back the Switch from an 8‐Helix to a 12‐Helix

Cyclic homologated amino acids are important building blocks for the construction of helical foldamers. N‐aminoazetidine‐2‐carboxylic acid (AAzC), an aza analogue of trans‐2‐aminocyclobutanecarboxylic acid (tACBC), displays a strong hydrazino turn conformational feature, which is proposed to act as an 8‐helix primer. tACBC oligomers bearing a single N‐terminal AAzC residue were studied to evaluate the ability of AAzC to induce and support an 8‐helix along the oligopeptide length. While tACBC homooligomers assume a dominant 12‐helix conformation, the aza‐primed oligomers preferentially adopt a stabilized 8‐helix conformation for an oligomer length up to 6 residues. The (formal) single‐atom exchange at the N terminus of a tACBC oligomer thus contributes to the sustainability of the 8‐helix, which resists the switch to a 12‐helix. This effect illustrates atomic‐level programmable design for fine tuning of peptide foldamer architectures.     

Cobalt‐Catalyzed Cross‐Coupling of 3‐ and 4‐Iodopiperidines with Grignard Reagents

A cobalt‐catalyzed cross‐coupling between 3‐ and 4‐iodopiperidines and Grignard reagents is disclosed. The reaction is an efficient, cheap, chemoselective, and flexible way to functionalize piperidines. This coupling was used as the key step to realize a short synthesis of (±)‐preclamol. Some mechanistic investigations were conducted that highlight the formation of radical intermediates.     

Formation of the Main Cores Present in Natural Products by Tandem Additions

A rapid route to 5,5‐ and 5,6‐ bicyclic systems is provided by an 1,3‐alkyl‐shift process mediated by a hypervalent iodine reagent on aromatics. The structures obtained contain several unsaturations with different behaviors and reactivities. Such diversity allows further elaborations for the rapid formation of compact systems present in a variety of natural products. The potential for further transformations has been demonstrated by performing a double Michael addition. This cyclization process is regio‐ and stereoselective due to the presence of a former benzylic substituent. Furthermore, an extension of this approach has been accomplished on indole derivatives.     

A fluorescence anisotropy method for measuring protein concentration in complex cell culture media

The rapid, quantitative analysis of the complex cell culture media used in biopharmaceutical manufacturing is of critical importance. Requirements for cell culture media composition profiling, or changes in specific analyte concentrations (e.g. amino acids in the media or product protein in the bioprocess broth) often necessitate the use of complicated analytical methods and extensive sample handling. Rapid spectroscopic methods like multi-dimensional fluorescence (MDF) spectroscopy have been successfully applied for the routine determination of compositional changes in cell culture media and bioprocess broths. Quantifying macromolecules in cell culture media is a specific challenge as there is a need to implement measurements rapidly on the prepared media. However, the use of standard fluorescence spectroscopy is complicated by the emission overlap from many media components. Here, we demonstrate how combining anisotropy measurements with standard total synchronous fluorescence spectroscopy (TSFS) provides a rapid, accurate quantitation method for cell culture media. Anisotropy provides emission resolution between large and small fluorophores while TSFS provides a robust measurement space. Model cell culture media was prepared using yeastolate (2.5 mg mL^–1) spiked with bovine serum albumin (0 to 5 mg mL^–1). Using this method, protein emission is clearly discriminated from background yeastolate emission, allowing for accurate bovine serum albumin (BSA) quantification over a 0.1 to 4.0 mg mL^–1range with a limit of detection (LOD) of 13.8 μg mL^–1.     

Self-templating polythiophene derivatives: electronic decoupling of conjugated strands through staggered packing

Whereas molecular electronics needs well-controlled 3D geometries for decoupling or interconnecting individual molecules, conjugated polymers form disordered structures when deposited on a substrate. We show that this trend can be overcome in polythiophene derivatives designed so as to exploit weak sulfur-bromine interactions. A self-template effect follows, leading to staggered organizations of well-aligned electronically decoupled conjugated strands, as observed in situ by scanning tunneling microscopy and spectroscopy on graphite.     

Synthese et isomerisation de methoxycarbonyl-5 dihydropyrannones-2

Condensation of dimethyl 3-methylglutaconate with ketones provides a one pot route for the preparation of 5-methoxycarbonyl-4-methyldihydropyran-2-ones. The experimental conditions to give selectively pyran-2-ones isomers are discussed. The structure of the different products was established on the basis of ¹H and ¹³C nmr spectral data.     

A structurally guided method for the decomposition of expression in music performance

A method for separating, profiling, and quantifying the contributions of different structural components to expressive musical performance is described. The method is demonstrated through its application to a set of expert piano performances of a short piece from the classical period. The results show that the output of the method aids in the understanding of how the different structural components in a piece of music combine in the generation of an expressive performance. A second demonstration applies the method to performances at different tempi to illustrate its effectiveness in pinpointing the structural features responsible for small but statistically significant differences between performances. The method is compared with other approaches to the analysis and modeling of musical performance, and a number of potential applications are identified.     

Lithium environment in dilute poly(ethylene oxide)/lithium triflate polymer electrolyte from REDOR NMR spectroscopy

The role of the lithium ion environment is of fundamental interest regarding transport and conductivity in lithium polymer electrolytes. X-ray crystallography has been used to characterize the lithium environment in completely crystalline poly(ethylene oxide) (PEO) electrolytes, but this approach cannot be used with dilute PEO electrolytes. Here, using solid-state NMR data collected with the rotational-echo double-resonance 13C[7Li] (REDOR) pulse sequence, we have been able to characterize the crystalline microdomains of a PEO-lithium triflate sample with an oxygen/lithium ratio of 20:1. Our data clearly demonstrates that the lithium crystalline microdomains are nearly identical to those of a completely crystalline 3:1 sample, for which the crystal structure is known.     

L'Étude de la Structure Électronique des Métaux des Terres Rares

In rare earth metals, one can neglect interactions between 4f shells centred on neighbouring sites. The conduction band is occupied by three sd electrons (eventually two in europium and ytterbium). These sd electrons are coupled to the f electrons through an interaction of the form where s _e is the spin of a conduction electron and Sf _i the spin of the ith f electron of a given ion. It is therefore possible to consider two groups of properties:

1. The ones, related to the nature of the conduction electrons, change very little through the series: this is the case of the crystalline structure, of the atomic volume.

2. The others, such as the magnetic properties, are related to the internal shells and vary with the filling of the 4f shell. Experiment shows a correlation between those two groups of properties. De Gennes formalism, essentially valid in the hypothesis of tightly bound 4f electrons, gives a satisfactory picture of the properties of the metals in the second half of the series, but it does not give as good a picture for the first rare earth metals, especially for cerium. In the cerium free atom, the 4f, 5d, 6s states have comparable energies and one might think that, in the trivalent metal, the 4f states are broadened in energy by resonances with the extended sd states, but still do not overlap from one atom to the other. They would then occupy virtual bound states analogous to the virtual bound states described by Blandin and Friedel for the transition impurities in noble metals.

An identical situation seems to occur in ytterbium under pressure: one observes a huge increase of the electrical resistivity which goes back to low values at very high pressures. This might also be the case of the actinide metals, especially of Plutonium, in which the 5f states begin to stabilize. So we have to consider two cases:

1. The 4f electrons occupy bound states.

2. The 4f electrons occupy virtual bound states.

In the first part (§ 2), we use de Gennes formalism for 4f bound states. The energy related to magnetic interactions is computed making the assumption of a spherical Fermi surface. A correlation between the crystalline structure and the magnetic properties shows up. In the second half of the series, one can neglect the crystalline field effects and the total energy is the sum of the magnetic term and of the elastic term due to the contribution of the conduction electrons. For every state of magnetic order, the crystalline structure is well defined, corresponding to the minimum of the total energy, and conversely. It is possible to explain in this manner:

1. The b.c.c. structure of europium, which is unusual for a divalent transition metal.

2. The variation of the c/a ratio of the h.c.p. structure both through the series and with temperature.

3. The anomalies in the thermal expansion coefficient observed below the magnetic order-disorder transitions.

4. The helix pitch of the magnetic configurations of this type.

The anomalies of the thermoelectric power observed at the transition points are related to the different dependences of the spin correlations above and below the transition temperatures. The agreement between theory and experiment is satisfactory. Some discrepancy can be attributed to the rather crude approximation of a spherical Fermi surface.

In the second part (§ 3), we deal with a situation where the 4f electrons occupy virtual bound states. These levels are very narrow, about 10^?2 ev wide, and separated in energy by the correlations between electrons. Using Blandin's formalism we calculate the electrical and magnetic properties associated with such a situation. Calculations lead to very strong magnetic coupling; the indirect interaction between magnetic ions is antiferromagnetic for first nearest neighbours, whereas in the case of 4f bound states it is ferromagnetic. Finally, it is possible to explain the properties of cerium and ytterbium.

1. In Cerium, the two first levels overlap at the Fermi level, in such a way that the f electron be almost entirely distributed in the first level.

2. In ytterbium, under pressure, the fourteenth level comes across and above the Fermi level. The maximum resistivity is obtained for a half filling of this level.

In the third part (§ 4), we attempt to apply this model of virtual bound states to plutonium, although in this metal, the 5f shells have a larger spatial extension than the 4f orbitals in rare earths. Anomalies in several physical properties of plutonium seem to indicate a magnetic transition at about 65° K, but no anomaly shows up in the magnetic susceptibility. Using a virtual bound state model associated with a very small polarization of the 5f states, it is possible to explain all the physical properties of plutonium. This model leads to a very small magnetic moment, that cannot be detected by experiment.