Predictable Selectivity in Remote C−H Oxidation of Steroids: Analysis of Substrate Binding Mode

Predictability is a key requirement to encompass late‐stage C?H functionalization in synthetic routes. However, prediction (and control) of reaction selectivity is usually challenging, especially for complex substrate structures and elusive transformations such as remote C(sp³)?H oxidation, as it requires distinguishing a specific C?H bond from many others with similar reactivity. Developed here is a strategy for predictable, remote C?H oxidation that entails substrate binding to a supramolecular Mn or Fe catalyst followed by elucidation of the conformation of the host‐guest adduct by NMR analysis. These analyses indicate which remote C?H bonds are suitably oriented for the oxidation before carrying out the reaction, enabling prediction of site selectivity. This strategy was applied to late‐stage C(sp³)?H oxidation of amino‐steroids at C15 (or C16) positions, with a selectivity tunable by modification of catalyst chirality and metal.     

Micro-Raman analysis of Fe-diffused lithium niobate waveguides

The photorefractive properties of LiNbO₃ are closely related to the defect structure which strongly depends on the conditions of sample preparation. By means of micro-Raman scattering measurements we investigate the influence of the thermal treatment in the preparation of Fe-diffused waveguides. We underline the role of intrinsic defects and discuss the mechanism of incorporation of iron in the lattice. We especially emphasize the specific role of three phonon modes which are able to separately probe the Li, Nb or O sublattice.     

Quantitative analysis of two-dimensional gel-separated proteins using isotopically marked alkylating agents and matrix-assisted laser desorption/ionization mass spectrometry

We describe a simple approach for the relative quantification of individual proteins within a mixture. The method is based on the differential labelling of the mixtures by use of a commercially available acrylamide and deuterium-labelled [2,3,3'-d(3)]-acrylamide to alkylate proteins prior to two-dimensional (2-D) gel electrophoresis. The tryptic digests of the separated proteins were subjected to reflector matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis and the relative peak heights of cysteine-containing peptides were used to quantify their precursor proteins. This approach was tested for the relative quantification of proteins within an artificial mixture of standard proteins and for proteins observed in a 2-D map of rat serum. A good correlation was found between the measured ratios derived from MALDI-TOF data and those theoretically calculated prior to 2-D analysis via known mixing ratios of the two alkylating reagents. The described procedure has proved to be effective for comparative measurements of protein abundances within the investigated mixtures.     

Spot overlapping in two-dimensional polyacrylamide gel electrophoresis separations: a statistical study of complex protein maps

A statistical approach able to extract the information contained in a two-dimenisional polyacrylamide gel electrophoresis (2-D PAGE) separation is here reported. The method is based on the quantitative theory of peak overlapping, a procedure previously developed by the authors and here extended to 2-D separations. The whole map is divided into many strips in order to obtain 1-D separations on which the statistic procedure is applied: the developed algorithms, on the basis of spot experimental data (intensity and spatial coordinates) permit to estimate the intrinsic number of components and to single out the specific order present in spot positions. The procedure was validated on computer-simulated maps. Its applicability to real samples was tested on maps obtained from literature sources. The following important information on protein mixtures can be extracted: (i) the number of proteins can be accurately estimated, on the basis of the spatial coordinates and intensities of spots detected in the 2-D PAGE map; (ii) the model describing distribution of interdistance between adjacent spots can be identified in both the separation dimensions; (iii) the presence of repeated interdistances in spot positions in the maps can be easily singled out: these regularities suggest specific protein modifications.     

Monitoring folding transitions of synthetic,branched-chain polypeptides by capillary zone electrophoresis

The coil/helix transition of a synthetic, branched-chain polymeric polypeptide (poly (Lys(Glu(1)-DL-Ala(3))EAK), 50-Lys residues long in the backbone, as a function of increasing molarities of methanol in solution, is here studied by both, circular dichroism (CD) and capillary zone electrophoresis. CD spectra showed that, at 75% v/v methanol, the transition from random coil to fully helical structure was obtained, in a pH 1.1 HCI solution in the presence of 20 mM NaCI. CZE studies, run in parallel, exhibited the classical unfolding to folding sigmoidal transition, with mid-point at 60% v/v methanol concentration, plateauing at ca. 80% v/v organic solvent. Surprisingly, though, such unfolding to folding transition was accompanied by an expansion, rather than a contraction, of the resulting ordered polypeptide. As the charge of the polypeptide (a pure polycation at a pH of 2.1 in CZE) was kept rigorously constant, a plot of the radius of the polymer along the sigmoidal transition clearly showed that the radius of gyration of the helical, structured polypeptide was in fact larger than that of the random coil. Such results were confirmed by molecular dynamics simulations, which indicated that the dimensions of such polypeptide, in alpha-helix configuration, were 8.5 nm (in length) and 3.2 nm (in diameter), whereas those of the corresponding random coil were 7.2 nm (in length) and 5.1 nm (length of shorter axis). It would thus appear that the randomized structure assumes the shape of a more compact object, roughly resembling a "rugby ball".     

Comparative enantioseparations with native beta-cyclodextrin,randomly acetylated beta-cyclodextrin and heptakis-(2,3-di-O-acetyl)-beta-cyclodextrin in capillary electrophoresis

Comparative enantioseparations were performed with three neutral cyclodextrins (CDs) in capillary electrophoresis (CE). In particular, native beta-CD was compared with single component heptakis(2,3-di-O-acetyl)-beta-CD (HDA-beta-CD) and randomly acetylated beta-CD (Ac-beta-CD) with the emphasis on the enantiomer migration order. The opposite affinity of the enantiomers of several chiral analytes was observed towards native beta-CD and its acetylated derivatives. The enantiomer affinity pattern of some chiral analytes was also opposite towards the two acetylated derivatives of beta-CD. In the case of the chiral drug clenbuterol (CL) an attempt was made to evaluate the possible structural reasons of the affinity reversal using one- and two-dimensional as well as transverse rotating frame nuclear Overhauser effect spectroscopy (ROESY). Significant differences were observed between the structure of the CL complexes with beta-CD and HDA-beta-CD.     

Cycloaddition reactions of 2,4-diphenyl-1,3-diazabuta-1,3-dienes with isocyanates and isothiocyanates

The cycloaddition reactions of 1-p-tolyl and 1-benzyl- 2,4-diphenyl-1,3-diazabuta-1,3-dienes with a variety of aryl and alkyl isocyanate and isothiocyanate are described. The reaction mechanism is also discussed.     

Novel intramolecular cyclization of N-alkynyl heterocycles containing proximate nucleophiles

Intramolecular cyclization of 2-acyl-1-propargyl-1H-indoles in the presence of ammonia provides an easy entry to pyrazino[1,2-a]indole nucleus.     

Novel heteroaromatic-based multi-branched dyes with enhanced two-photon absorption activity

The first examples of heterocycle-based multi-branched dyes with efficient two-photon absorption (TPA) activity are reported; the novel chromophores exhibit large TPA cross sections (as high as 1600 x 10(-50) cm4 s photon(-1) molecule(-1), measured with 150 fs laser pulses at 800 nm); a strong cooperative enhancement in the branched systems with respect to the one-dimensional sub-units is found.