A stereodivergent approach to substituted 4-hydroxypiperidines

A stereodivergent route toward both diastereomeric forms of functionalized 4-hydroxypiperidines has been successfully developed. This route involves biocatalytic generation of the enantiopure starting materials followed by functionalization via N-acyliminium ion-mediated CC-bond formation.     

Spermine participates in oxidative damage of guanosine and 8-oxoguanosine leading to deoxyribosylurea formation

Oxidation of single- or double-stranded DNA containing a 7,8-dihydro-8-oxoguanosine lesion with the one-electron oxidant Na2IrCl6 in the presence of spermine led to formation of a covalent adduct that was analyzed by gel electrophoresis, HPLC, ESI-MS, and UV-vis. The adduct was labile to heat, exhibiting a t1/2 of 12 h at 37 degrees C, and the ultimate hydrolysis product was characterized as a deoxyribosylurea lesion. Data from model studies with 1,3-diaminopropane vs 1,4-diaminobutane are consistent with initial formation of a C5 spermine adduct from a dehydro-8-oxoguanosine intermediate, followed by rearrangement to a spiroaminal subject to slow hydrolysis at C4 of the purine. Spermine adducts could also be formed from oxidation of the analogous G-containing oligomer from reaction with singlet oxygen, albeit in lower yield. These results are surprising in light of the traditional view that spermine is radioprotective against DNA oxidation.     

Solid-phase synthesis of lidocaine and procainamide analogues using backbone amide linker (BAL) anchoring

New solid-phase strategies have been developed for the synthesis of lidocaine (1) and procainamide (2) analogues, using backbone amide linker (BAL) anchoring. Both sets were prepared starting from a common resin-bound intermediate, followed by four general steps: (i) attachment of a primary aliphatic or aromatic amine to the solid support via reductive amination (as monitored by a novel test involving reaction of 2,4-dinitrophenylhydrazine with residual aldehyde groups); (ii) acylation of the resultant secondary amine; (iii) displacement of halide with an amine; and (iv) trifluoroacetic acid-mediated release from the support. A manual parallel strategy was followed to provide 60 novel compounds, of which two dozen have not been previously described. In most cases, initial crude purities were >80%, and overall isolated yields were in the 40-88% range.     

Polyelectrolyte complex formation between poly(diallyldimethyl-ammonium chloride) and copolymers of acrylamide and sodium-acrylate

 The interaction between oppositely charged polyelectrolytes, in this study poly(diallyldimethylammonium chloride) (PDADMAC) and copolymers of acrylamide and sodium-acrylate differing in their chain length and charge density parameter (ξ) was investigated in relation to the molar charge ratio of anionic to cationic charges (n ₋/n ₊). The molecular weights of the polyelectrolytes used were 2.9·10⁵g/mol for PDADMAC and for the polyacrylamide copolymers 14 ·10⁶g/mol as well as 5·10⁵g/mol obtained by ultrasonic degradation of the high molecular weight copolymers. The charge density parameters of the polyanions used (ξ ^PR ) varied between 0.14 and 0.64. Complexation between PDADMAC and high molecular weight polyanions leads mainly to macroscopic phase separation whereas the degraded polyanions and PDADMAC formed soluble complexes as well as stable dispersions, if charge excess was available. Precipitates and dispersions were characterized by several methods such as element analysis, thermogravimetry, pyrolysis-GC/MS, PEL titration, ζ-potential measurements, determination of turbidity, particle size measurements and determination of carbon content (TOC).  All precipitated complexes include about 20% water and are of 1:1 stoichiometry concerning ionic binding. Investigations of dispersions confirm 1:1 stoichiometry of complex particles stabilized by excess polyelectrolyte and soluble complexes. It was also found that the particle size can be varied via the charge density parameter of the polyanions used in the range of negative charge excess. Received: 21 June 2001 Accepted: 9 October 2001     

Charge transfer at F<Subscript>16</Subscript>CoPc and CoPc interfaces to Au

We analyze the electronic properties of the interfaces between cobalt phthalocyanine (CoPc), as well as fluorinated cobalt phthalocyanine (F₁₆CoPc), and an Au(100) single-crystal using X-ray photoemission spectroscopy and valence band ultraviolet photoemission spectroscopy. Our data demonstrate that for the monolayers of both materials a charge transfer occurs from the substrate to the center of the organic molecules resulting in a central Co(I) ion. This leads to the conclusion that this effect essentially is fluorination- and ligand-independent.     

Phosphatidylcholine dimers can be easily misinterpreted as cardiolipins in complex lipid mixtures: a matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometric study of lipids from hepatocytes

The liver is an important organ that is particularly involved in the lipid metabolism of the organism. Thus, high interest is nowadays focused on the lipid composition of the liver and particularly the liver parenchymal cells, the hepatocytes. Hepatocytes contain common phospholipids (PL) such as phosphatidylcholines, ‐ethanolamines and ‐inositols, for instance, that can be easily analyzed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS) even without previous separation of the PL mixture. However, in addition to common PL, hepatocytes possess also significant amounts of cardiolipin (CLP). The MS analysis of this PL is quite challenging because it (a) has a higher mass than common lipids and (b) possesses a higher negative charge. We will show here that caution is required if CLP is analyzed directly from the total lipid extract because PC dimers may be interpreted as cardiolipins if the positive ion MALDI mass spectra are analyzed. Copyright © 2011 John Wiley & Sons, Ltd.     

Nanoscopic optical sensors based on functional supramolecular hybrid materials

This review highlights how the combination of supramolecular principles and nanoscopic solid structures enables the design of new hybrid sensing ensembles with improved sensitivity and/or selectivity and for the targeting of analytes for which selectivity is hard to achieve by conventional methods. Such ideas are bridging the gap between molecules, materials sciences and nanotechnology. Relevant examples will be detailed, taking into account functional aspects such as (1) enhanced coordination of functionalized solids, (2) enhanced signalling through preorganization, (3) signalling by assembly–disassembly of nanoscopic objects, (4) biomimetic probes utilizing discrimination by polarity and size and (5) distinct switching and gating protocols. These strategies are opening new prospects for sensor research and signalling paradigms at the frontier between nanotechnology, smart materials and supramolecular chemistry.