Functionalized 2-azabicyclo[3.3.1]nonanes. IV. synthesis of the indolo[3,2-f]morphan system.

A short route to the 2-azabicyclo[3.3.1]nonan-7-one system is described. Condensation of 4-piperidones with diethyl 2-oxopropylphosphonate, followed by catalytic hydrogenation furnished the corresponding piperidylpropanones $\text{6}$ which were cyclized with mercuric acetate in acetic acid to the target target bicyclic ketones $\text{1}$. The Fischer indole synthesis from $\text{1}$$\text{a}$ afforded regioselectively the indole [3,2-f]morphan $\text{2}$, a new heteromorphan type.     

Spin control in ladderlike hexanuclear copper(II) complexes with metallacyclophane cores

Two new hexanuclear oxamatocopper(II) complexes 3 and 4 have been synthesized from the binuclear copper(II) complexes of the meta- and para-phenylenebis(oxamate) ligands, respectively. Complexes 3 and 4 possess an overall ladderlike structure made up of two oxamate-bridged linear trinuclear units ("rails") connected through two phenylenediamidate bridges ("rungs") between the central copper atoms to give metallacyclic cores of the meta- and para-cyclophane type, respectively. They show different ground spin states, S = 1 (3) or S = 0 (4), depending on the substitution pattern in the aromatic spacers. The triplet state molecule 3 containing two spin doublet Cu(II)3 units connected by two m-phenylenediamidate bridges represents a successful extension of the concept of "ferromagnetic coupling units" to metal complexes, which is a well-known approach toward high spin organic radicals.     

Preparation and nanoscale mechanical properties of self-assembled carboxylic acid functionalized pentathiophene on mica

The oligothiophene derivative 4-(5' " '-decyl-[2,2';5',2' ';5' ',2' ";5' ",2' " '] pentathiophen-5-yl)-butyric acid (D5TBA) was synthesized by Stille cross-coupling methods using functionalized thiophene monomers. The structural and mechanical properties of D5TBA self-assembled monolayers on mica have been studied by atomic force microscopy (AFM). The self-assembled films were prepared by immersing the mica in dilute chloroform or tetrahydrofuran (THF) solutions. The films were predominantly of monolayer thickness with molecules packed in nearly upright orientations. In regions covered with multilayers, the molecules in each monolayer were oriented opposite to those in the neighboring ones, that is, with COOH-COOH and CH3-CH3 contact. The nature of the end group in contact with the substrate depended on the solvent used and the degree of hydration of the substrate, with hydrophobic chloroform solvent favoring the methyl end down and hydrophilic THF favoring the acid group end down. The orientation could also be controlled by dipping using the Langmuir-Blodgett technique.     

From metal to ligand electroactivity in nickel(II) oxamato complexes

The locus of oxidation in square-planar nickel(ii) oxamato complexes can be continuously shifted from the metal to the ligand by an appropriate choice of electron-donating substituents on the aromatic moiety of the ligand.     

Hydroxyl radical reactivity with nitrobenzene in subcritical and supercritical water

The bimolecular rate constants of the addition reaction between hydroxyl radical (*OH) and nitrobenzene (C(6)H(5)NO(2)) were measured in subcritical and supercritical water (SCW) at temperatures between ambient and 390 degrees C. The measured bimolecular rate constants showed distinctly non-Arrhenius behavior (i.e., essentially no increase with temperature) from ambient to 350 degrees C, but increased in the slightly subcritical and supercritical region between 350 and 390 degrees C. These data were modeled reasonably well over the entire temperature range with a three-step reaction mechanism, originally proposed by Ashton et al.(1) This model includes the formation of a pi-complex intermediate as the precursor of the nitrohydroxycyclohexadienyl radical.     

Comparison of different sample treatments for the analysis of ochratoxin A in must, wine and beer by liquid chromatography

Ochratoxin A (OTA) is a mycotoxin produced by some species of Aspergillus and Penicillium verrucosum. It has been found in foods and feed all over the world. There is a great concern about OTA because it is nephrotoxic and probably, carcinogenic to humans. Most of analytical methods developed for OTA in wine, beer and other products are based on LC with fluorescence detection (LC-FLD). In the present work, various procedures for extraction and/or clean-up for determination of OTA in musts, wine and beer by LC-FLD were compared: (1) dilution with polyethylen glycol 8000 and NaHCO3 solution and clean-up an on immunoaffinity column (IAC); (2) extraction with chloroform and IAC clean-up; solid-phase extraction (SPE) on (3) reversed-phase (RP) C18; (4) RP phenylsilane and (5) Oasis HLB cartridges. SPE on phenylsilane and Oasis HLB have not been reported for OTA analysis in beverages. The same LC-FLD conditions and concentration ratio were used. The former procedure was simple, rapid and provided flat baselines, free from most impurity peaks, high OTA recoveries and quite repeatable results. RP C18 using methanol-acetic acid (99.5:0.5) as elution solvent provided good recoveries and precision, thus becoming a cheaper but interesting alternative at 0.1-1 ng/ml spiking levels. Oasis HLB cartridges were usually better than phenylsilane. Possible binding of OTA to proteins or other components was tested by acid treatment before extraction but no significant differences with controls appeared.     

Biomolecular materials based on sol-gel encapsulated proteins

The proteins copper-zinc superoxide dismutase (CuZnSOD), cytochrome c, myoglobin, hemoglobin, and bacterio-rhodopsin are encapsulated in stable, optically transparent, porous, silica glass matrices prepared by the sol-gel method such that the biomolecules retain their characteristic reactivities and spectroscopic properties. The resulting glasses allow transport of small molecules into and out of the glasses at reasonable rates but retain the protein molecules within their pores. The transparency of the glasses enables the chemical reactions of the immobilized proteins to be monitored by means of changes in their visible absorption spectra. Silica glasses containing the immobilized proteins have similar reactivities and spectroscopic properties to those found for the proteins in solution. The enzymes glucose oxidase and peroxidase were also encapsulated in transparent silica glass matrices. Upon exposure to glucose solutions, a colored glass is formed that can be used as the active element in a solid state optically based glucose sensor.     

In the first proven SN2' fullerene reaction,both C3 and C1 C60F36 hydrolyse to C1 isomers of C60F35OH that eliminate HF to give epoxides C60F34O; C60F36O oxides are shown to be ethers,and a fourth isomer of C60F36 exists

On standing in organic solvents containing traces of water, C3 and C1 isomers of C60F36 slowly convert to C1 isomers of C60F35OH. Both fluorofullerenols eliminate HF during EI mass spectrometry to give C60F34O epoxides, one fullerenol being much less stable than the other to the extent that the mass spectrum shows only the epoxide. Both C60F35OH isomers have C1 symmetry, one being identified by the remarkable linear relationship between chemical shifts in its 19F NMR spectrum and those in the spectrum of C1 C60F36; the spectrum of the other shows the pattern of C3 C60F36 rendered asymmetrical by the replacement of one F by OH. The reactions are facilitated by the presence of isolated double bonds, and provide the first proven examples of an SN2' reaction of a fullerene derivative. Our observation explains why only a limited number of fluorines are readily replaced in C60F36 and why C60F18 is by contrast much more resistant to hydrolysis. We have isolated also a pure isomer of C60F36O, which is shown to be an oxahomofullerene (ether) apparently derived from C1 C60F36, and an impure fraction comprising a fourth isomer of C60F36, a trifluoromethyl derivative of C60F36, a second isomer of C60F36O, and an unknown species of 1392 u.     

Dynamic kinetic resolution of racemic gamma-aryl-delta-oxoesters. Enantioselective synthesis of 3-arylpiperidines

Cyclodehydration of racemic gamma-aryl-delta-oxoesters with (R)- or (S)-phenylglycinol stereoselectively affords bicyclic delta-lactams, in a process that involves a dynamic kinetic resolution. Subsequent reduction of these lactams leads to enantiopure 3-arylpiperidines. Starting from racemic aldehyde esters, this short sequence has been applied to the synthesis of (R)-3-phenylpiperidine and the antipsychotic drug (-)-3-PPP (an (S)-3-arylpiperidine), whereas starting from racemic ketone esters enantiopure cis-2-alkyl-3-arylpiperidines are prepared.     

Kinetic assay for high-throughput screening of in vitro transthyretin amyloid fibrillogenesis inhibitors

Stabilization of tetrameric transthyretin (TTR) by binding of small ligands is a current strategy aimed at inhibiting amyloid fibrillogenesis in transthyretin-associated pathologies, such as senile systemic amyloidosis (SSA) and familial amyloidotic polyneuropathy (FAP). A kinetic assay is developed for rapid evaluation of compounds as potential in vitro inhibitors in a high-throughput screening format. It is based on monitoring the time-dependent increase of absorbance due to turbidity occurring by acid-induced protein aggregation. The method uses the highly amyloidogenic Y78F mutant of human transthyretin (heterogously expressed in Escherichia coli cells). Initial rates of protein aggregation at different inhibitor concentrations follow a monoexponential dose-response curve from which inhibition parameters are calculated. For the assay development, thyroid hormones and nonsteroidal antiinflamatory drugs were chosen among other reference compounds. Some of them are already known to be in vitro inhibitors of TTR amyloidogenesis. Analysis time is optimized to last 1.5 h, and the method is implemented in microtiter plates for screening of libraries of potential fibrillogenesis inhibitors.