Acid-catalysed formation of tricyclic N,S-acetals in imidazolinone series based on the use of the unprecedented N-acyliminium ion cascade reaction involving transposition, heterocyclisation and pi-cyclisation

4-Hydroxy-5,5-dimethylimidazolines tethered at N-1 to an aryl sulfide undergo an unprecedented acid-catalysed domino reaction, involving double methyl transposition, heterocyclisation, isomerisation of thiazetidinium ion and, finally, pi-cyclisation. In this way a one-pot synthesis of original tricyclic N,S-acetals was developed. The same triheterocyclic products can be prepared also starting from the corresponding 5-hydroxy isomers (in this case the cascade of reactions does not involve methyl transposition).     

Synthesis of new fluorinated 1,5-benzoxazepine derivatives

A simple approach to the fluorinated 1,5-benzoxazepine ring system is described. By reacting commercially accessible aminophenols 1 and the trifluoroacetylvinyl ether 2, high yields of enaminones 3 were obtained. Functionalization of methyl group of compounds 3 gave rise to dieneamines 4 that were cyclized in acidic environment to benzoxazepine derivatives 5.     

Reactivity differences between molecular and surface silanols in the preparation of homogeneous and heterogeneous olefin metathesis catalysts

The reaction of Mo(N)(CH₂tBu)₃ (1) and SiO_2-(700) generates (SiO)Mo(NH)(CHtBu)(CH₂tBu) (2) when performed in C₆H₆ (material [1/SiO_2-(700)]_C6H6). The grafting occurs presumably by protonation of the nitrido ligand to form an intermediate (SiO)Mo(NH)(CH₂tBu)₃ (3), a pentacoordinated complex, which decomposes into 2 and 2,2-dimethylpropane. While [1/SiO_2-(700)]_C6H6 is highly active in olefin metathesis, [1/SiO_2-(700)]_CH2Cl2 and [1/SiO_2-(700)]_THF are poorly active or inactive catalysts respectively. In contrast, when Mo(N)(CH₂tBu)₃ reacts with a molecular silanol derivative, a soluble model of the surface of SiO_2-(700), it yields a very stable complex, (c-C₅H₉)₇Si₇O₁₂SiO-Mo(NH)(CH₂tBu)₃ (3m), which does not spontaneously generate 2,2-dimethylpropane and an alkylidene complex in contrast to the surface complex. Moreover, 3m does not catalyse olefin metathesis at room temperature as it does not already contain the initiating carbene ligand, and it is necessary to heat up the reaction mixture to 110 °C to obtain low catalytic activity. Nevertheless, the complex 3m generates well-defined metallocarbenes when heated in the presence of PMe₃: (c-C₅H₉)₇Si₇O₁₂SiO-Mo(N)(CHtBu)(P(CH₃)₃)₂ (4m) as a 10:1 mixture of its syn and anti rotamers with the loss of 2 equiv. of 2,2-dimethylpropane.     

Pharmacokinetics of the nitroxide PCA measured by in vivo EPR

PCA (2,2,5,5-tetramethylpiperidine-1-oxyl-3-carboxylic acid) is a relatively stable free radical which has been shown to be useful as a contrast agent for nuclear magnetic resonance imaging and as an imaging/spectroscopy agent for EPR. In an effort to determine the role of the liver and kidney in the pharmacokinetics of PCA, using low frequency in vivo EPR spectroscopy, we followed the clearance of PCA after intravenous injection in mice: under normal conditions, with a restricted blood supply to the kidneys, after exposure to an acute hepatotoxin CCl₄, and after exposure to lipopolysaccharide (endotoxin). The observed pharmacokinetics fit a two-component model. The fast component was dramatically affected when the renal vessels were restricted, while CCl₄ and endotoxin had a smaller but significant effect. The half times of the slow components were not significantly different (p>0.05) in the groups treated by renal blood flow occlusion, CCl₄, or LPS, compared with the control group. In conclusion, we find that the pharmacokinetics of PCA need to be completely described in term of a two component model: the fast component of the decay is mainly due to the elimination by the kidneys and also is affected by the time for the initial distribution; the slow component is related to the bioreduction of the nitroxide. In addition to the liver other tissues can also effectively metabolize PCA. The effect of oxygen on the rate of metabolism is modest at most.     

Acidobasic properties of molten potassium tetrahalogenogallates (X=Cl,I)

Molten potassium tetrachlorogallate and potassium tetraiodogallate were studied in terms of halogenoacidity, based on X^? ion-exchange. Titration of KX solution with GaX₃ were achieved and characterized by the shift of cathodic voltammetric curves. Autodissociation constants K_i,X/mol² kg^?1 were determined: ?log K_i,Cl=4.25±0.05 and ?log K_i,I=2.6±0.05, as well as the solubility values of KX: 0.41±0.02 and 0.80±0.02 mol kg^?1 for KCl and KI respectively.     

Interaction between zigzag single-wall carbon nanotubes and polymers: a density-functional study

Density-functional all-electrons calculations within local-density approximation show that the two isoelectronic polymers poly(para-phenylene) and poly(para-borazylene) weakly interact with zigzag single-walled carbon nanotubes. The analysis of the electronic properties of the joint systems, both with the polymer inside and outside the nanotubes, reveals a physisorption process with small changes in band structures and densities of states with respect to the constituents. We evaluate the potential barrier arising between polymers and nanotubes. Finally, we remark a generic selectivity of poly(para-phenylene) with respect to the electronic behavior of nanotubes, leading to a change in the density of states of metallic tubules.     

Mesoionic compounds VIII. Synthesis of 3-phenylsydnonyl substituted alkenes. Some new photochromic sydnones

The reactions of 3-phenylsydnonyllithium with a variety of ketones to afford tertiary carbinols 4a-4i and their subsequent dehydration to 4-(3-phenylsydnonyl) alkenes 5a-5i are discussed. Among the alkenes, 2-[4-(3-phenylsydnonyl)]propene ( 5b ) and 1-[4-(3-phenylsydnonyl)]-1-cyclohexene ( 5i ) were photochromic. A Wittig reaction between ethyl-4-(3-phenylsydnonyl)-ketone and methylenetriphenylphosphorane afforded the photochromic 2-[4-(3-phenylsydnon-yl)]-1-butene(5j).     

Comparison of tridentate ligands in competition experiments for their ability to form a [Tc(CO)3] complex

In this study we have compared different ligands containing three or more hetero-atoms (N, O and/or S) with respect to their ability to form tridentate complexes with a Tc-tricarbonyl moiety. Comparison of each ligand in a competition reaction with histidine first and then with each other compound allowed to rank the ligands according to their ability of complex formation with the [^99mTc(CO)₃]⁺ precursor from diethylenetriamine (most efficient of the studied ligands) to nitrilotriacetic acid (weakest complexing properties). The results provide insight in the structural requirements for the formation of stable Tc-tricarbonyl complexes and suggest preferred combinations and arrangements of the hetero-atoms involved in the complex formation. They also give a good indication which type of ligand is most appropriate to modify biomolecules for an efficient and stable labelling with a Tc-tricarbonyl moiety.     

Characterization of Two Light-Harvesting Subunits Isolated from the Brown Alga Pelvetia canaliculata: Heterogeneity of Xanthophyll Distribution

The main light-harvesting fraction from Pelvetia canaliculata was isolated on a sucrose density gradient from digitonin-solubilized chloroplasts. After further solubilization by dodecyl maltoside, the bulk fraction was separated into two subunits by preparative isoelectric focusing. The more acidic brown fraction was mainly composed of 22 kDa polypeptides having an apparent pI of 4.55. Its pigment composition was very simple, containing chlorophyll (Chi) a, Chi c and fucoxanthin. The in vivo spectral properties of fucoxanthin, namely a shift in light absorption to the green and efficient energy transmission to Chi a, were conserved in this subunit. No xanthophyll associated with photoprotection was found in this band, even when obtained from photoinhibited thalli. The less acidic green band contained predominantly 22 kDa polypeptides that were resolved into numerous components by denaturing isoelectric focusing. Its pigment composition was more complex, containing, in addition, pigments of the so-called xanthophyll cycle. In photoinhibited thalli, about half of the violaxanthin was converted into antheraxanthin and zeaxanthin. All the pigments of the xanthophyll cycle were specifically associated with this subunit, and it may thus have a central role in the thermal dissipation of the absorbed light energy as postulated for light-harvesting complex II isolated from green plants.     

Cytotoxicity and Antiproliferative Effect of Hypericin and Derivatives after Photosensitization

The toxicity on three human tumor cell lines (A431, HeLa and MCF7) of five phenanthroperylenequinones (hypericin and derivatives) and two perylenequinones (cercosporin and calphostin C) was investigated after photosensitization (4 J/cm²). Furthermore, the antiproliferative effect on HeLa cells was studied for the phenanthroperylenequinones. Hypericin, 2,5-dibromohypericin, 2,5,9,12-tetrabromohypericin and perylenequinones displayed a potent cytotoxic and antiproliferative effect in the nanomolar range. Hypericin dicarboxylic acid exhibited no photoactivity. In general, the antiproliferative activity correlated well with the photocytotoxicity. However, the nonphotocytotoxic compound hexamethylhypericin showed potent antiproliferative activity in the nanomolar range, probably exerting its action by protein kinase C inhibition. Without light irradiation, no cytotoxic and antiproliferative effect was observed for any photocytotoxic phenanthroperylenequinone compound. Furthermore, confocal laser microscopy revealed that the subcellular localization in A431 cells was similar for the photoactive compounds; the photosensitizers were mainly concentrated in the perinuclear region, probably corresponding with the Golgi apparatus and the endoplasmic reticulum. In addition, the accumulation of the photosensitizers in HeLa cells was investigated. All compounds except hypericin dicarboxylic acid were found to concentrate to a large extent in the cells. The compound 2,5,9,12-tetrabromohypericin seemed intrinsically more effective than hypericin since the intracellular concentration of the bromoderivative was a magnitude of order lower than that of hypericin although both compounds showed similar photobiological activity.