Organic synthesis with sulfones XXXII. A convenient route to α,β -unsaturated sulfones from saturated sulfones.

α-sulfonyl litiated anions are oxidized by cupric carboxylates into β, β-unsaturated sulfones. Primary sulfones lead to pure trans-vinylic sulfones.     

Two-step metal-mediated transformation of isoxazolidine-5-spirocyclopropanes into pyridone derivatives

[reaction: see text] The two-step metal-catalyzed overall transformation of isoxazolidine-5-spirocyclopropanes into the corresponding dihydro- and tetrahydropyridones is described. The first step is the chemoselective reduction of the N-O bond of the isoxazolidine ring preserving the fragile cyclopropanol moiety while the second transformation is the Pd(II) or Pd(0) conversion of the beta-aminocyclopropanol derivatives into the final compounds. The scope and limitations of this strategy are described.     

Phosphoramidate-mediated conversion of carbonyl ligands into isocyanide ligands: a new approach to chiral isocyanide ligands

Metal isocyanides have been used and studied by organometallic chemists for many years and, as a result, they have a rich and interesting chemistry. The nature of metal-free isocyanides and the methods of making isocyanide complexes, however, has resulted in the vast majority of studies to date being performed with structurally simple isocyanides. We report here a new approach to the synthesis of isocyanide ligands that involves the reaction of a metal carbonyl ligand with the anion of a phosphoramidate. As phosphoramidates can be synthesised in one step from amines, our method means that the structural diversity of readily available amines, particularly chiral amines, can now be incorporated into isocyanide ligands.     

Using Bioconjugated Nanoparticles To Monitor E. coli in a Flow Channel

A simple and portable flow channel optical detection system combined with bioconjugated luminescent nanoparticles allows the rapid detection of single bacterial cells without sample enrichment. The optical system is designed to have single‐molecule‐detection capability in a microcapillary flow channel by decreasing the laser excitation probe volume to a few picoliters, which consequently results in a low background. Specific monoclonal antibodies were immobilized on nanoparticles to form nanoparticle–antibody conjugates. The bioconjugated nanoparticles bind to the target bacteria when they recognize the antigen on the bacterium surface, thus providing a bright luminescent signal for the detection of individual bacteria cells. The high sensitivity provided by the luminescent and photostable silica nanoparticles eliminates the need for further enrichment of bacteria samples and signal amplification. This flow channel detection system is convenient and allows the detection of single bacterial cells within a few minutes.     

Study of the development of chemoresistance in melanoma cell lines using proteome analysis

Malignant melanomas have poor prognosis since treatment with anti-neoplastic agents is mostly ineffective. The biological mechanisms of this strong intrinsic therapy resistance are unknown. In order to identify new molecular factors potentially associated with the drug-resistant phenotype of malignant melanoma, a panel of human melanoma cell variants exhibiting low and high levels of resistance to four commonly used anticancer drugs in melanoma treatment, i.e., vindesine, etoposide, cisplatin, and fotemustine, was characterized using proteomic tools (two-dimensional electrophoresis for protein fractionation and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry for protein identification). In the neutral and weak acidic milieu (pH 4.0-8.0) a total number of 14 proteins showed alterations in expression whereas 20 proteins were differentially expressed in the basic milieu (pH 8.0-11.0). Besides proteins with unknown physiologic function, several factors were identified that show chaperone activity. Moreover, proteins involved in drug detoxification, metabolism, and regulation of apoptotic pathways could be identified. The possible role of these proteins in the development of chemoresistance is discussed, although detailed functional tests with these proteins have still to be performed. Nevertheless, it is clear that this proteomic approach for studying chemoresistance phenomena is a prerequisite before further investigation can yield insight into the biology and development of drug resistance in malignant melanoma.     

Detection of tetracysteine-tagged proteins using a biarsenical fluorescein derivative through dry microplate array gel electrophoresis

The design of an extended-run 96-well sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) system and the development of protein detection technology based upon fluorescein derivatives that bind to peptide epitope tags, allows the creation of a truly high-throughput analysis of protein expression, where less than 20 min are needed to separate proteins and analyze results. We demonstrate the overall capabilities of such a method combination in a complex cell lysate background, while comparing the specific results obtained using a biarsenical fluorescein-derivative and tetracysteine epitope-tagged proteins with total protein staining using a fluorescent gel stain and with Western blotting where an anti-oligohistidine (His) tag antibody has been employed. When applied on purified target proteins without extraneous protein background, the demonstrated sensitivity of the assay on the extended-run 96-array precast SDS-PAGE system allows detection of quantities of tagged protein as low as 1 pmol per band.     

Intramolecular electron transfer between tyrosine and tryptophan photosensitized by a chiral pi,pi* aromatic ketone

The photochemical reaction of Trp and Tyr and related peptides with Suprofen (SUP) as sensitizer in H2O/CH3CN (28:1 v/v) solutions has been studied by time-resolved spectroscopy. The results show that SUP induces oxidation of both Trp and Tyr, as well as intramolecular-ET reactions in the related peptides. The influence of photosensitizer configuration on the involved processes has been studied by using the enantiomerically pure compounds. A significant chiral recognition is observed in which the concentration of the radicals formed after triplet quenching depends on the configuration of the chiral center; the quenching process is higher when using the (R)-SUP enantiomer.     

Biomimetic methyl transfer to olefins

Conditions have been found under which trisubstituted olefins can be methylated with diaryl methyl sulfonium salts in 2,6-di-$\text{t}$-butylpyridine. The pattern of methylated compound's formed is similar to that of the enzymatic methylation of Δ²⁴ steroids side chains with $\text{S}$-adenosylmethionine as a methyl donor.     

Reaction of 3-benzylidene-2,4-pentanedione and 3-methoxymethylene-2,4-pentanedione with aroylhydrazines

Aroylhydrazines 2 reacted with 3-benzylidene-2,4-pentanedione ( 1 ) to give 1-aroyl-3,5-dimethyl-1H-pyrazoles 5 and benzaldehyde aroylhydrazones 6 . From the reaction of 3-methoxymethylene-2,4-pentanedione ( 7 ) with aroylhydrazines 2 the unknown N-aroyl-4-acetyl-1H-pyrazoles 9 were exclusively isolated in good yields.     

Fragmentation mechanisms of oligodeoxynucleotides studied by H/D exchange and electrospray ionization tandem mass spectrometry

We used solution-phase hydrogen/deuterium (H/D) exchange and multistage tandem mass spectrometry (MS/MS) experiments in an electrospray ion-trap mass spectrometer operating in the negative-ion mode to investigate the consequences of the loss of a high proton-affinity (PA) base from T-rich tetra and hexadeoxynucleotides. The T-rich oligodeoxynucleotides containing one or two other nucleobases take advantage of the mass spectral inertness of T because fragmentation of a T-rich oligomer is simple, allowing a tight focus on those processes of interest. Furthermore, determination of T-rich oligodeoxynucleotides may be a starting point in the development of a mass spectrometric scheme to understand the mutagenicity of various types of DNA damage by UV radiation. For nine oligodeoxynucleotides, the nucleobases were charged by nearly exclusive D transfer and then expelled as neutral bases. Loss of the base located at the 3' end is preferred over that from the 5' terminus when the two bases are identical. The observation of partially exchanged fragments from a completely exchanged precursor ion proves intramolecular H/D exchange between hydrogen atoms that can exchange in water and those that cannot. The multiplicity of the product-ion peaks provides information on decomposition pathways and origins of the product ions and shows that the loss of base is the first step in all fragmentation of hexanucleotides, but is a competitive process for tetranucleotide fragmentation.