Asymmetric Synthesis XXIII.1 A 100% cis Diastereoselectivity in the SYnthesis of Enantiomerically Pure 2,6-Dialkylpiperidines

Enantiomerically pure (+)-(2S,6R)-2-propyl-6-methyl-piperidine 6 has been obtained in 4 steps, 66% overall yield and without separation of diastereomers from the chiral 2-cyano-6-oxazolopiperidine synthon 1c derived from (+)-1,2-diphenyl-2-aminoethanol     

Size and sequence and the volume change of protein folding

The application of hydrostatic pressure generally leads to protein unfolding, implying, in accordance with Le Chatelier's principle, that the unfolded state has a smaller molar volume than the folded state. However, the origin of the volume change upon unfolding, ΔV(u), has yet to be determined. We have examined systematically the effects of protein size and sequence on the value of ΔV(u) using as a model system a series of deletion variants of the ankyrin repeat domain of the Notch receptor. The results provide strong evidence in support of the notion that the major contributing factor to pressure effects on proteins is their imperfect internal packing in the folded state. These packing defects appear to be specifically localized in the 3D structure, in contrast to the uniformly distributed effects of temperature and denaturants that depend upon hydration of exposed surface area upon unfolding. Given its local nature, the extent to which pressure globally affects protein structure can inform on the degree of cooperativity and long-range coupling intrinsic to the folded state. We also show that the energetics of the protein's conformations can significantly modulate their volumetric properties, providing further insight into protein stability.     

Asymmetric Synthesis IX1: Preparation of Chiral α-Substituted Phenethylamines

(S)-N-methyl-α-methyl-phenethylamines 5a-d were obtai-ned in 56–62% e.e. from the chiral synthoh (-)-N-cyano-methyl-4-phenyl-1,3-oxazolidine-1.     

Sur un transformation inattendue de l'amino-3 nitro-2 benzofuranne par l'acide acétique

Pure or highly concentrated acetic acid slowly transforms 3-amino-2- nitrobenzofuran into 3-diazo-2,3-dihydro-2-benzofuranone, the structure of which has been confirmed by its spectroscopic characters as well as by its chemical reactivity     

GEOMETRIC REQUIREMENTS FOR THE INTRAMOLECULAR QUENCHING OF INDOLE FLUORESCENCE BY AMIDE AND CARBOXYLIC ACID GROUPS IN RIGID MOLECULES WITH THE [2,2,1]BICYCLOHEPTENYL SKELETON

Abstract— The geometric requirements for intramolecular fluorescence quenching of indole by carboxylic acid and amide functions have been determined in rigid norbornyl ([2.2,1]bicycloheptenyl) skeleton: trans and cis 3-(3'-indolyl) norbornene 2-dimethylcarboxamides or carboxylic acids. The reference compound was the 3-(3'-indolyl) N-dimethylpropionamide or -propanoic acid. The quenching occurs mainly in protic solvents. In the cis compounds, the quantum yields are strongly decreased when compared to the trans and open chain compounds. As determined by the pH dependence of fluorescence of the acids, it is in the acid form—COOH that the fluorescence is quenched; in the ionized species -CO⁻₂, only small quenching is observed. The K_s of Stern-Volmer equations are very small for the cis bicyclic acid and amide, the indole nucleus being shielded on one side only. The results support the hypothesis that small rearrangement of the peptide bond in protein conformation changes may be detected by fluorescence.     

Improved oxygen mobility in nanosized mixed-oxide particles synthesized using a simple nanocasting route

This work reports the synthesis of homogeneously dispersed mixed-oxide nanoparticles (<5 nm) exhibiting improved lattice oxygen mobility (ca. two times higher than on bulk samples), using a novel synthesis procedure of nanocasting in mesoporous silica host support.     

Towards a Quantitative Understanding of Protein Hydration and Volumetric Properties

Herein, we probe by pressure perturbation calorimetry (PPC) the coefficient of thermal expansion, the volumetric and the hydration properties of variants of a hyperstable variant of staphylococcal nuclease (SNase), Δ+PHS. The temperature‐dependent volumetric properties of the folded and unfolded states of the wild‐type protein are calculated with previously published data. The present PPC results are used to interpret the volume diagram and expansivity at a molecular level. We conclude that the expansivity of the unfolded state is, to a first approximation, temperature independent, while that of the folded state decreases with increasing temperature. Our data suggest that at low temperature the defining contribution to ΔV comes mainly from excluded volume differences and ΔV for unfolding is negative. In contrast, at high temperatures, differential solvation due to the increased exposed surface area of the unfolded state and, in particular, its larger thermal volume linked to the increased conformational dynamics of the unfolded state ensemble takes over and ΔV for unfolding eventually becomes positive.