New developments in the Pd-catalysed cyclisation-coupling reaction of alkene-containing carbonucleophiles with organic halides (and triflates). The first examples of asymmetric catalysis.

The results of our preliminary investigations directed toward asymmetric catalysis of the cyclocarbopalladation of alkenes bearing a proximate nucleophile with organic halides (or triflates) are disclosed. A series of bidentate phosphine ligands were evaluated in intramolecular versions of this reaction using (E)-2-[7-(2-bromophenyl)-hept-4-enyl]-malonic acid dimethyl ester (1) and (Z)-2-[7-(2-trifluoromethanesulfonyloxy-phenyl)-hept-4-enyl]-malonic acid dimethyl ester (9) as model substrates. The highest enantioselective induction was obtained with aryl triflate 9 which produced the corresponding cyclopentylindane as a single diastereomer in 54% chemical yield and 43% ee by using PdCl₂[S-(−)-TolBINAP] as chiral catalyst and K₂CO₃ as base.     

De novo synthesis of 4'-ethoxy nucleoside analogues

Butenolides 5a and 13 were used as optically active templates in the de novo synthesis of 4'-disubstituted nucleoside analogues. The butenolides were reduced and acylated in situ to give acetates 10 and 14. Vorbrüggen coupling gave the protected nucleoside analogues 11 and 15. Reduction of 11 gave 4'-ethoxy-2',3'-dideoxythymidine (6) and deprotection of 15 gave 4'-ethoxy-2',3'-dideoxydidehydrothymidine (7). The cis-dihydroxylation of a variety of butenolides occurred with the major product formed from oxidation of the beta-face.     

Targeting cell surface receptors with ligand-conjugated nanocrystals

To explore the potential for use of ligand-conjugated nanocrystals to target cell surface receptors, ion channels, and transporters, we explored the ability of serotonin-labeled CdSe nanocrystals (SNACs) to interact with antidepressant-sensitive, human and Drosophila serotonin transporters (hSERT, dSERT) expressed in HeLa and HEK-293 cells. Unlike unconjugated nanocrystals, SNACs were found to dose-dependently inhibit transport of radiolabeled serotonin by hSERT and dSERT, with an estimated half-maximal activity (EC(50)) of 33 (dSERT) and 99 microM (hSERT). When serotonin was conjugated to the nanocrystal through a linker arm (LSNACs), the EC(50) for hSERT was determined to be 115 microM. Electrophysiology measurements indicated that LSNACs did not elicit currents from the serotonin-3 (5HT(3)) receptor but did produce currents when exposed to the transporter, which are similar to those elicited by antagonists. Moreover, fluorescent LSNACs were found to label SERT-transfected cells but did not label either nontransfected cells or transfected cells coincubated with the high-affinity SERT antagonist paroxetine. These findings support further consideration of ligand-conjugated nanocrystals as versatile probes of membrane proteins in living cells.     

Chemical structure of cow kappa-casein: study of the soluble tryptic peptides

The sequences of 13 tryptic peptides of cow ?_A-casein (accounting for about one half of the amino acid residues present in the protein) were established. The rennin sensitive linkage could be located in a large fragment (36 residues). ?-casein consists of a hydrophilic part (?-caseino-glycopeptide) and of a hydrophobic moiety (para-?-casein); in this latter, however, several quite hydrophilic sequences were characterized. Another feature of the ?-casein structure is the frequent duplication or triplication of certain amino acids (Pro-Pro; Phe-Phe; Gln-Gln-Gln-Asn-Glu-Glu-Glu; Pro-Pro-Lys-Lys-Asn-Gln-; etc. …).     

An efficient way to 1,7-enynes and ethyl 8-yn-2-enoates from aldohexoses and to polyhydroxylated 1-vinylcyclohexenes

In this paper, we report the synthesis of carbohydrate-derived 1,7-enynes and subsequent metathesis to yield polyhydroxylated 1-vinylcyclohexenes. For example, we converted D-glucose 2 to the (6,7)-dideoxy-D-gluco-hept-6-ene-pyranose 7, which led to the desired 1,7-enyne 16. The ring-closing metathesis of this 1,7-enyne 16 with the second generation Grubbs catalyst, under Mori's conditions, gave the corresponding polyhydroxylated 1-vinylcyclohexene 25 in 76% yield. The conversion of several aldohexoses into polyhydroxylated 1-vinylcyclohexenes was carried out with satisfying yields. We report also the synthesis of two carbohydrate-derived ethyl 8-yn-2-enoates from D-glucose derivatives.     

Investigating bidentate and tridentate carbamoylmethylphosphine oxide ligand interactions with rare-Earth elements using electrospray ionization quadrupole ion trap mass spectrometry

Electrospray ionization (ESI) quadrupole ion trap mass spectrometry (QIT-MS) and collisionally activated dissociation (CAD) were used to evaluate the rare-earth binding properties of two hydrophobic carbamoylmethylphosphine oxide (CMPO) ligands, the normal bidentate variety, (t-BuC6H4)2P(O)CH2C(O)N(i-Bu)2 (A), a new potentially tridentate extractant, (t-BuC6H4)2P(O)CH[CH2C(O)N(i-Bu)2]C(O)N(i-Bu)2 (B), and tributyl phosphate. The mass spectral results obtained from analysis of 1% HNO3/methanol solution containing the ligands and dissolved lanthanide salts reveal that the favorable stoichiometries of the ligand/metal/nitrate complexes are 2:1:2 for the bidentate ligand A, 1:1:2 for the tridentate ligand B, and 3:1:2 for the monodentate tributyl phosphate. These observed stoichiometries correlate with the number of available binding sites on each ligand as well as with potential steric effects. Energy-variable collisionally activated dissociation experiments showed that for the 2:1:2 complexes involving ligand A or B, as the ionic radius of the bound metal decreased, the removal of nitric acid required less energy and resulted in less extensive spontaneous solvent coordination. This experimental trend suggests that, as the ionic radius of the lanthanide ion decreases, a pair of the carbamoylmethylphosphine ligands is able to more completely solvate the bound metal ion thereby weakening the nitrate-metal interaction.     

The cyano nitronyl nitroxide radical: experimental and theoretical evidence for the fourth case of the McConnell-I mechanism

The nitronyl nitroxide 2-cyano-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (1) crystallises in the tetragonal P42(1)m space group with a=7.4050(7), c=8.649(1) A. In the crystal the molecules form layers parallel to the ab plane in which they are orthogonal to each other. In the layers there are close contacts, 2.953(2) A, between the NO groups and the bridging carbon atoms of the O-N-C-N-O fragment of neighbouring radicals. The calculated spin density shows a positive population mainly and equally localised on the NO groups and small but significant negative spin densities on the bridging carbon atom and the cyano nitrogen. Absorption spectra show temperature-dependent transitions related to the magnetic behaviour. The temperature dependence of the magnetic susceptibility in the range 2-300 K reveals that couplings between the radicals are antiferromagnetic, and is interpreted by considering a two-dimensional square array of spin S=1/2 antiferromagnetically coupled (J=-10 cm(-1) and g=2.01). This is interpreted as an exchange coupling through close contact between positive and negative spin densities in orthogonal orbitals on oxygen and carbon atoms, respectively.     

New mono- and bis-carbene samarium complexes: synthesis, X-ray crystal structures and reactivity

New samarium carbene complexes have been synthesized and characterized by X-ray diffraction analysis; the carbenic nature was assessed by reactivity studies.     

The dependence of the variances of the parameters in non-linear regression analysis on the number of data points

In designing an experimentin which non-linear regression analysis is used to evaluate the physicochemical parameters that chracterize the behavior of the system being studied, it would be useful to be able to predict how the number of data points affects th reliabilities of the values obtained. The relation between these depends on hos the points are distributed as well as on the nature of the equation to which thd data are fitted. Weighted non-linear regression analysis has been applied to six common equations involving a total of fourteen parameters, using a number of n of points that was varied from 4 to     

Substitution effects enhancing the lasing ability of organic compounds

Simple calculations can help to predict which derivatives in a series of organic compounds are potential lasing material. In conjugated systems, a necessary condition for lasing is that there is not less than a specific minimum energy difference between a first excited allowed and a second excited forbidden transition. This order of transition and energy spacing can be obtained by judicious substitutions even in molecules that do not meet these conditions. Lasing action in the near UV has been observed in five new compounds.