A simple and stereodivergent strategy for the synthesis of 3′-C-branched 2′,3′-dideoxynucleosides exploiting (Z)-but-2-en-1,4-diol and (R)-2,3-cyclohexylideneglyceraldehyde

Barbier type additions of allylic bromide 4, derived from (Z)-but-2-en-1,4-diol 2 to (R)-2,3-cyclohexylideneglyceraldehyde 1 were performed through mediation with Zn employing Luche’s procedure and also with low valent Cu, Co, and Fe which were produced via bimetal redox strategy in THF to afford 5c,d as the major products. From these, 5a,b were prepared following an oxidation-reduction protocol. Compound 5c was exploited as a representative starting material to develop a simple and inexpensive strategy toward the synthesis of 3′-C-branched 2′,3′-dideoxynucleosides having stereodiversity at 3′- and 4′-positions.     

Microfluidic discharge-based optical sources for detection of biochemicals

This paper reports a discharge-based optical source for fluorescence of biochemicals in microfluidic systems. Its efficacy is demonstrated using a stacked microchip that integrates a microfluidic wavelength-tunable optical source, a biochemical sample reservoir and optical filters. It is shown to excite fluorescence in l-tryptophan and DNA samples labeled by SYBR green dye. The discharge is struck in ambient air, between a metal anode and a cathode cavity that is filled with an aqueous solution, which is doped with a metal salt selected for its emission characteristics. The characteristic line spectra, which arise from energetic transitions of the metal ions that are sputtered into the glow region of the discharge, are optically filtered and guided to the biochemical sample that resides in a separate on-chip reservoir. For DNA fluorescence, a barium chloride solution is used to emit light at 454 and 493 nm. For tryptophan fluorescence, the cathode contains lead (ii) nitrate solution to provide a 280 nm emission. The resulting fluorescence from the DNA and tryptophan samples is compared to reference data. This technique can also be used to excite other fluorophores by using appropriately doped liquid cathodes having the desired emission characteristics.     

Ultrafast excited state relaxation dynamics of branched donor-pi-acceptor chromophore: evidence of a charge-delocalized state

Excited-state dynamics and complete transient absorption features of the trimer tris-4,4',4' '-(4-nitrophenyleethynyl)triphenylamine and the monomer 4-N,N-(dimethylamino)-4'-nitrotolane have been obtained from femtosecond pump-probe spectroscopy. The measurements are carried out to understand the mechanism behind enhanced two-photon absorption cross-sections of branched systems over their linear counterparts. Absorption and emission transition dipole moments of monomer and trimer in toluene have suggested that the emitting state of trimer is different from the monomer and probably is arising from the charge-delocalized C(3) symmetry state. Ultrafast transient absorption measurements on these molecules have spectroscopically validated the presence of an initial electron delocalized state with the C(3) symmetry state in the trimer molecule. The results have shown that there is a slower rate of internal conversion from the C(3) symmetry state to intramolecular charge transfer of trimer suggesting a barrier between them. Also, presence of a charge-stabilized state and involvement of a nonemissive state in the excited-state deactivation has been observed for both monomer and trimer.     

Characterisation of a series of acetals/ketals of bis(2-nitrophenyl) ethanediol and bis(4,5-dimethoxy-2-nitrophenyl) ethanediol under APCI mass spectrometric conditions

A series acetals/ketals of aldehydes and ketones formed by the reaction of two photolabile protecting groups, bis(2-nitrophenyl) ethanediol and bis(4,5-dimethoxy-2-nitrophenyl) ethanediol (I and II, respectively), were analysed under EI, LSIMS, ESI and APCI conditions to obtain molecular weights as well as structural information. The EI and LSIMS techniques failed to give molecular weight information. The positive ESI yielded [M + H](+) ions only for I; however, with added Na(+) both I and II formed [M + Na](+) adducts. But upon decomposition, the [M + Na](+) ions yielded Na(+) ion as the only product ion. Similarly, under negative ion ESI conditions both I and II gave molecular weight information by forming adduct ions with halide anions (F(-), Cl(-), Br(-) and I(-)); however, they did not give structural information as they resulted in only the halide anion as the abundant fragment ion upon dissociation. All the compounds formed abundant M(-*) ions under negative ion APCI conditions, and their MS/MS spectra showed characteristic fragment ions; hence the acetals/ketals of I and II could be successfully characterized under negative ion APCI conditions.     

Chemistry of mangana- and rhenatricarbadecaboranyl tricarbonyl complexes: evidence for an associative mechanism of ligand substitution involving an eta6-eta4 cage-slippage process analagous to eta5-eta3-cyclopentadienyl ring-slippage

The reaction of the tricarbadecaboranyl anion, 6-Ph-nido-5,6,9-C(3)B(7)H(9)(-), with M(CO)(5)Br [M = Mn, Re] or [(eta(6)-C(10)H(8))Mn(CO)(3)(+)]BF(4)(-) yielded the half-sandwich metallatricarbadecaboranyl analogues of (eta(5)-C(5)H(5))M(CO)(3) [M = Mn, Re]. For both 1,1,1-(CO)(3)-2-Ph-closo-1,2,3,4-MC(3)B(7)H(9) [M = Mn (2) and Re (3)], the metal is eta(6)-coordinated to the puckered six-membered open face of the tricarbadecaboranyl cage. Reactions of 2 and 3 with isocyanide at room temperature produced complexes 8-(CNBu(t))-8,8,8-(CO)(3)-9-Ph-nido-8,7,9,10-MC(3)B(7)H(9) [M = Mn (4), Re (5)], having the cage eta(4)-coordinated to the metal. Photolysis of 4 and 5 then resulted in the loss of CO and the formation of 1-(CNBu(t))-1,1-(CO)(2)-2-Ph-closo-1,2,3,4-MC(3)B(7)H(9) [M = Mn, Re (6)], where the cage is again eta(6)-coordinated to the metal. Reaction of 2 and 3 with 1 equiv of phosphine at room temperature produced the eta(6)-coordinated monosubstituted complexes 1,1-(CO)(2)-1-P(CH(3))(3)-2-Ph-closo-1,2,3,4-MC(3)B(7)H(9) [M = Mn (7), Re (9)] and 1,1-(CO)(2)-1-P(C(6)H(5))(3)-2-Ph-closo-1,2,3,4-MC(3)B(7)H(9) [M = Mn (8), Re (10)]. NMR studies of these reactions at -40 degrees C showed that substitution occurs by an associative mechanism involving the initial formation of intermediates having structures similar to those of the eta(4)-complexes 4 and 5. The observed eta(6)-eta(4) cage-slippage is analogous to the eta(5)-eta(3) ring-slippage that has been proposed to take place in related substitution reactions of cyclopentadienyl-metal complexes. Reaction of 9 with an additional equivalent of P(CH(3))(3) gave 8,8-(CO)(2)-8,8-(P(CH(3))(3))(2)-9-Ph-nido-8,7,9,10-ReC(3)B(7)H(9) (11), where the cage is eta(4)-coordinated to the metal. Photolysis of 11 resulted in the loss of CO and the formation of the disubstituted eta(6)-complex 1-CO-1,1-(P(CH(3))(3))(2)-2-Ph-closo-1,2,3,4-ReC(3)B(7)H(9) (12).     

High-throughput sequence determination of cyclic peptide library members by partial Edman degradation/mass spectrometry

Cyclic peptides provide attractive lead compounds for drug discovery and excellent molecular probes in biomedical research. Large combinatorial libraries of cyclic peptides can now be routinely synthesized by the split-and-pool method and screened against biological targets. However, post-screening sequence determination of hit peptides has been problematic. In this report, a high-throughput method for the sequence determination of cyclic peptide library members has been developed. TentaGel microbeads (90 mum) were spatially segregated into outer and inner layers; cyclic peptides were displayed on the bead surface, whereas the inner core of each bead contained the corresponding linear peptide as the encoding sequence. After screening of the cyclic peptide library against a macromolecular target, the identity of hit peptides was determined by sequencing the linear encoding peptides inside the bead using a partial Edman degradation/mass spectrometry method. On-bead screening of an octapeptide library (theoretical diversity of 160 000) identified cyclic peptides that bind to streptavidin. A 400-member library of tyrocidine A analogues was synthesized on TentaGel macrobeads and solution-phase screening of the library directly against bacterial cells identified a tyrocidine analogue of improved antibacterial activity. Our results demonstrate that the new method for cyclic peptide sequence determination is reliable, operationally simple, rapid, and inexpensive and should greatly expand the utility of cyclic peptides in biomedical research.     

Design and synthesis of potential new apoptosis agents: hybrid compounds containing perillyl alcohol and new constrained retinoids

Novel retinoids 1-3 containing perillyl alcohol were synthesized through the addition of perillyl alcohol to the activated carboxylic acids (retinoids) promoted by DCC (N,N′-dicyclohexyl carbodiimide). A set of structurally and functionally diverse perillyl alcohol derivatives of retinoids were obtained in good yields (78-82%). Biological evaluation of these novel hybrid compounds (containing retinoids and perillyl alcohol) is currently underway in our laboratory.     

Studies on the effect of different levels of toughener and flame retardants on thermal stability of epoxy resin

A thermoplastic toughener, polyether sulphone (PES) and a number of different types of flame retardants were blended in different ratios with a commercial epoxy resin triglycidyl-p-aminophenol (TGAP) and 4,4-diamino diphenyl sulphone (DDS) a curing agent. The effect of type and levels of flame retardants (FR) and the toughening agent on the curing, thermal decomposition and char oxidation behaviour of the epoxy resin was studied by the simultaneous differential thermal analysis and thermogravimetric techniques. It was observed that the toughener slightly increases the curing temperature (by up to 20 °C) but had minimal effect on the decomposition temperature of the resin. Flame retardants, however affected all stages depending upon the type of flame retardant used. The curing peak for samples containing tougher and flame retardants although slightly changed depending upon the type of FR, was not more than ± 20 °C compared to that of samples containing toughener only. All flame retardants lowered the decomposition temperature of the epoxy resin. Phosphorus- and nitrogen-containing flame retardants reduced the char oxidation leading to more residual char, whereas halogen- containing flame retardants had less effect on this stage.     

An effective quantum parameter for strongly correlated metallic ferromagnets

The correlated motion of electrons in metallic ferromagnets is investigated in terms of a realistic interacting-electron model with N-fold orbital degeneracy and intra-orbital (U) and inter-orbital (J) Coulomb interactions. Correlation-induced self-energy and vertex corrections are incorporated systematically to provide a non-perturbative Goldstone-mode-preserving scheme. An effective quantum parameter [U2+(N-1)J2]/[U+(N-1)J]2 is obtained which determines, in analogy with 1/S for quantum spin systems and 1/N for the N-orbital Hubbard model, the strength of correlation-induced quantum corrections to magnetic excitations. The rapid suppression of this quantum parameter with Hund's coupling J, especially for large N, provides fundamental insight into the phenomenon of strong stabilization of metallic ferromagnetism by orbital degeneracy and Hund's coupling. Correlation effects are investigated for spin stiffness, magnon dispersion, electronic spectral function, density of states, and finite-temperature spin dynamics using realistic bandwidth, interaction, and lattice parameters for iron.     

Stereospecific Photoredox-Catalyzed Vinylations to Functionalized Alkenes and C-Glycosides**

We report an efficient radical-mediated C−C coupling through photoredox-catalyzed reactions of 4-alkyl-dihydropyridines (DHPs) and vinylbenziodoxol(on)es (VBX, VBO). This transition-metal-free and mild photocatalytic method has excellent functional group tolerance and affords vinylated products in good yields, with complete retention of the alkene configuration. The utility of the methodology is demonstrated by the diastereoselective synthesis of C-vinyl glycosides. Preliminary mechanistic studies suggest that the C−C bond formation is stereospecific and proceeds through a concerted radical coupling transition state.