Formation of 2-substituted benzofuran fragment ions from 6-alkyl- and 6-aryldibenzo(d,f)(1,3)dioxepine derivatives under electron ionization-a useful precursor ion for isomeric differentiation

Tandem mass spectrometry has been applied to differentiate three sets of o-, m- and p-methyl, -methoxy and -nitro-substituted-6-phenyl-dibenzo(d,f)(1,3)dioxepines. Collision-induced dissociation (CID) experiments have been carried out on 2-phenylbenzo[b]furan fragment ions, which originate from the decomposition of the molecular ions after their EI-induced isomerization to spirocyclic structures. With the exception of m- and p-methylphenylbenzo[b]furan isomers, which display identical CID mass spectra, the three isomeric methoxy- and nitrophenylbenzo[b]furan fragment ions display very characteristic CID behavior which allows unequivocal differentiation of the 6-phenyl-dibenzo(d,f)(1,3)dioxepine isomers. 6-(o-nitrophenyl)-dibenzo(d,f)(1,3)dioxepine isomer, does not form a 2-(o-nitrophenyl)benzo[b]furan ion and, therefore, it can be differentiated from the m- and p- isomers based on the mere EI mass spectra. Furthermore, it shows a characteristic ion most likely due to an ortho effect between the nitro group and the dioxepine ring. Multiple stage mass spectrometric techniques (MSn), labeled derivatives and reference compounds were used in order to gain additional information on the structures of product ion from the CID fragmentation.     

Unusual Cyclodextrin Derivatives as a New Avenue to Modulate Self‐ and Metal‐Induced Aβ Aggregation

Mounting evidence suggests an important role of cyclodextrins in providing protection in neurodegenerative disorders. Metal dyshomeostasis is reported to be a pathogenic factor in neurodegeneration because it could be responsible for damage involving oxidative stress and protein aggregation. As such, metal ions represent an effective target. To improve the metal‐binding ability of cyclodextrin, we synthesized three new 8‐hydroxyquinoline‐cyclodextrin conjugates with difunctionalized cyclodextrins. In particular, the 3‐difunctionalized regioisomer represents the first example of cyclodextrin with two pendants at the secondary rim, resulting in a promising compound. The derivatives have significant antioxidant capacity and the powerful activity in inhibiting self‐induced amyloid‐β aggregation seems to be led by synergistic effects of both cyclodextrin and hydroxyquinoline. Moreover, the derivatives are also able to complex metal ions and to inhibit metal‐induced protein aggregation. Therefore, these compounds could have potential as therapeutic agents in diseases related to protein aggregation and metal dyshomeostasis.     

Synthesis of carba analogs of 6-O-(benzyl)-d-allal- and -d-galactal-derived allyl epoxides and evaluation of the regio- and stereoselective behavior in nucleophilic addition reactions

The new racemic diastereoisomeric epoxides 6α and 6β, the carba analogs of the corresponding d-galactal- and d-allal-derived allyl epoxides have been synthesized and their regio- and stereoselective behavior examined in addition reactions with model O-, C-, N-, and S-nucleophiles. The results have indicated that epoxide 6β has a pronounced tendency toward anti-1,2-addition, whereas epoxide 6α shows interesting levels of syn- and/or anti-1,4-addition processes. A chiral recognition process found with epoxide 6β, turned out to be consistently reduced in epoxide 6α. All the results have been rationalized on the basis of conformational, steric, and stereoelectronic effects.     

Multifunctional cadmium single source precursor for the selective deposition of CdO or CdS by a solution route

We report on the interesting properties of a novel single precursor, Cd(tta)2 x tmeda (Htta = 2-thenoyl-trifluoroacetone, tmeda = N,N,N',N'-tetramethylethylenediamine), ideally suited for the selective and reproducible fabrication of pure quality films of CdS or CdO through a simple solution process.     

Search for melanoma markers in plasma and serum samples

Fourteen blood samples from patients with melanoma and eleven blood samples from healthy subjects were analyzed by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The study was focussed on species of low molecular weight, in the range 800-5000 Da, present in plasma and sera. While for healthy subjects plasma samples lead to the production of a higher number of ionic species, for melanoma patients a high number of diagnostic ions, present with high frequency and with quite high relative abundance, are present in particular in serum samples and to a lesser extent also in plasma. Since plasma samples are obtained more easily in comparison to sera, it is possible to suggest that also plasma can be used for these studies.     

Study of the oxidative half‐reaction catalyzed by a non‐heme ferrous catalytic center by means of structural and computational methodologies

Deacetoxycephalosporin C synthase (DAOCS) is a mononuclear ferrous enzyme that catalyzes the expansion of the five‐membered thiazolidine ring of the penicillin nucleus into the six‐membered dihydrothiazine ring of the cephalosporins. In the first half‐reaction with dioxygen and 2‐oxoglutarate, a reactive iron–oxygen species is produced that can subsequently react with the penicillin substrate to yield the cephalosporin. We describe quantum mechanical calculations of the first part of the reaction based on the high‐resolution structures of the active site of DAOCS and its complexes with ligands. These studies are aimed at understanding how the reactive species can be produced and contained in the active site of the enzyme. The results demonstrate the priming of the active site by the co‐substrate for oxygen binding and hint to the presence of a stable iron–peroxo intermediate in equilibrium with a more reactive ferryl species and the formation of CO₂ as a leaving group by decarboxylation of 2‐oxoglutarate. A conclusion from these studies is that substitution of CO₂ by the penicillin substrate triggers the oxidation reaction in a booby‐trap‐like mechanism. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Hexagonal-to-cubic phase transformation in composite thin films induced by FePt nanoparticles located at PS/PEO interfaces

The organization process of asymmetric poly(styrene-block-ethylene oxide) (PS-b-PEO) copolymer thin films blended with FePt nanoparticles is studied. In a first step, it is shown that FePt nanoparticles stabilized by oleic acid ligands are distributed within the PS matrix phase, whereas the same particles partially covered with short dopamine-terminated-methoxy poly(ethylene oxide) (mPEO-Dopa) are located at PS/PEO interfaces. The swelling of PS domains, induced by FePt_oleic acid nanoparticles during the solvent annealing process, results in formation of a disordered microstructure in comparison to the well-organized hexagonally close-packed (HCP) cylinder phase formed in the neat PS-b-PEO copolymer. The evolution of the microstructure of PS-b-PEO/FePt_mPEO-Dopa composite has been investigated for different solvent annealing treatments. Under high-humidity conditions during the vapor annealing process, the addition of FePt nanoparticles results in formation of spheres in the film split into terraces. The upper and lower terraces are occupied by spheres organized in an unusual square and HCP phases, respectively. Under low-humidity conditions, undulated PEO cylinders oriented parallel to substrate are formed in the presence of FePt nanoparticles. In this case, we observe that most of the nanoparticles accumulate within the core of topological defects, which induces a low nanoparticle concentration at the PS/PEO interfaces and so stabilizes an intermediate undulated cylinder phase.     

Intramolecular weak interactions in the thermodynamic stereoselectivity of copper(II) complexes with carnosine-trehalose conjugates

The interactions of metal ions with chiral molecules are of particular interest for relevant biochemical processes, as many of them are made possible only with a selected chirality of the stereocenters. In this work we report a study of the stereoselectivity of copper(II) complexes with D-trehalose-L-carnosine and D-trehalose-D-carnosine as a prototypical case of natural chirality selection. The interest in L-carnosine dipeptide is compounded by its antioxidant and antitumor properties, which are further enhanced when combined with D-trehalose. Potentiometric, calorimetric, and UV/circular dichroism (CD) spectroscopic measurements show that the copper(II) dimer of D-trehalose-L-carnosine is more stable than the D-trehalose-D-carnosine diastereoisomeric copper(II) dimer (log β(L)(22-2) - log β(D)(22-2) = 3.6). Free-energy calculations highlight that the cause of this different behavior lies with different intramolecular weak interactions between the diastereoisomers. The different pattern of hydrogen bonds and the different CH-π interactions between the π-electron-rich imidazole and the α-glucose rings are more favorable by 5 kcal mol(-1) in the L dimer.     

Intramolecular Inclusion of L-tryptophan within 3-functionalized Cyclodextrins

Abstract

The synthesis of L-tryptophan attached to the C3 group of a β-cyclodextrin through amide linkages with ethylenediamine or propylenediamine is reported. Circular dichroism and fluorescence investigations were carried out showing great differences between the two derivatives. The derivative containing the propylenediamine chain shows clear self-inclusion and exhibits spectral variations upon guest inclusion detected both by circular dichroism or by fluorescence. The difference in conformation of the two derivatives could be explained on the basis of the chain length.