A scaleable formal total synthesis of dehydrogliotoxin

A formal total synthesis of the epidithiodiketopiperazine natural product, dehydrogliotoxin (2), utilizing an intramolecular ring closure to form key intermediate 5 is described.     

Low-magnesium, <Emphasis Type="Italic">trans</Emphasis>-cleavage activity by type III,tertiary stabilized hammerhead ribozymes with stem 1 discontinuities

Background  

Low concentrations of free magnesium in the intracellular environment can present critical limitations for hammerhead ribozymes, especially for those that are designed for intermolecular (trans) cleavage of a host or pathogen RNA. Tertiary stabilizing motifs (TSM's) from natural and artificial ribozymes with a "type I" topology have been exploited to stabilize trans-cleaving hammerheads. Ribozymes with "type II" or "type III" topologies might seem incompatible with conversion to trans-cleavage designs, because opening the loop at the end of stem 1 or stem 2 to accommodate substrate binding is expected to disrupt the TSM and eliminate tertiary stabilization.     

Novel fragmentation pathway for CID of (b<Subscript>n</Subscript>−1+Cat)<Superscript>+</Superscript> ions from model,metal cationized peptides

We report a new fragmentation pathway for the CID of (b3 - 1 + Cat)+ product ions derived from the model peptide AXAG, where X = beta-alanine, gamma-aminobutyric acid, epsilon-amino-n-caproic acid, or 4-aminomethylbenzoic acid. By changing the amino acid to the C-terminal side of the amino acid X, and incorporating 15N and 13C labeled residues at the same position, we conclude that the dissociation pathway most likely leads to a metal cationized nitrile. With respect to the various amino acids at position X, the putative nitrile product becomes more prominent, relative to the conventional (a3 - 1 + Cat)+ species, in the order beta-alanine < gamma-aminobutyric acid < epsilon-aminocaproic acid < 4-aminomethylbenzoic acid. The pathway is not observed for peptides with alpha-amino acids at position X. The product ion is observed most prominently during the CID of Li+ and Na+ cationized peptides, only to a small extent for Ag+ cationized peptides, and not at all from protonated analogues.     

In situ measurements of the spectral emittance of coal ash deposits

The spectral emittance of deposits left by bituminous and sub-bituminous coals under oxidizing conditions have been measured in situ. Pulverized coal is injected into a down-fired entrained-flow reactor. Ash accumulates on a probe in the reactor effluent and radiation emitted by the ash layer is recorded using a Fourier transform infrared (FTIR) spectrometer. Values for the spectral emissive power emitted by the ash and the surface temperature of the ash are extracted from these data. These results are then used to calculate the spectral emittance of the deposit. The spectral emittances of ash deposits formed by burning Illinois #6 (bituminous) coal and Powder River Basin (sub-bituminous) coal were measured between 3000 and 500 wavenumbers. The spectral emittance of the deposit left by the bituminous coal has a constant value of approximately 0.46 between 3000 and 2400 wavenumbers. Between 2200 and 1200 wavenumbers, the spectral emittance of the deposit increases from approximately 0.47 to approximately 0.61. Between 1200 and 500 wavenumbers, the spectral emittance is relatively constant at 0.61. The spectral emittance of the deposit left by the sub-bituminous coal is also relatively constant between 3000 and 2400 wavenumbers at a value of 0.29. Between 2200 and 500 wavenumbers, the spectral emittance of deposits from the sub-bituminous coal increases from approximately 0.29 to 0.55. Differences between these spectral emittance measurements and those measured ex situ illustrate the importance of making in situ measurements. Band emittances were calculated using the measured spectral emittances, and band emittances of the deposits are reported as functions of temperature.     

Solution-phase counterion effects in supramolecular and mechanostereochemical systems

The self-assembly of molecular components into complex superstructures involves the subtle interplay of various noncovalent forces. Charged species are often utilised in self-assembly processes as a result of the favorable π-π, cation-π, electrostatic, and hydrogen bonding interactions that form between these species. Although the counterions associated with these charged species can exert significant effects on the synthesis, stability, and operation of superstructures in solution, rarely are the counterions considered, leading to misinterpretations and misunderstandings of the studied systems. In this tutorial review, we discuss a variety of solution-phase counterion effects, from the fundamental origins to innovative ways in which these effects are exploited for useful functions.     

In vitro evolution of ligands to the membrane protein caveolin

Membrane proteins comprise a third of the human genome, yet present challenging targets for reverse chemical genetics. For example, although implicated in numerous diseases including multiple myeloma, the membrane protein caveolin-1 appears to offer a poor target for the discovery of synthetic ligands due to its largely unknown structure and insolubility. To break this impasse and identify new classes of caveolae controlling lead compounds, we applied phage-based, reverse chemical genetics for the discovery of caveolin-1 ligands derived from the anti-HIV therapeutic T20. Substitution of homologous residues into the T20 sequence used a process analogous to medicinal chemistry for the affinity maturation to bind caveolin. The resultant caveolin-1 ligands bound with >1000-fold higher affinity than wild-type T20. Two types of ELISAs and isothermal titration calorimetry (ITC) measurements demonstrated high affinity binding to caveolin by the T20 variants with K(d) values in the 150 nM range. Microscopy experiments with the highest affinity caveolin ligands confirmed colocalization of the ligands with endogenous caveolin in NIH 3T3 cells. The results establish the foundation for targeting caveolin and caveolae formation in living cells.     

Catalytic oxidative cleavage of olefins promoted by osmium tetroxide and hydrogen peroxide

Hydrogen peroxide was employed as the terminal oxidant in the osmium tetroxide mediated oxidative cleavage of olefins, producing the corresponding aldehyde and ketone products. Aryl olefins are cleaved in good to excellent yield regardless of arene electronics. Alkyl olefins cleave in moderate to good yield for di- and tri-substituted alkenes.     

A cubic, 12-connected, microporous metal-organometallic phosphate framework sustained by truncated tetrahedral nodes

A rare example of a microporous metal-organic phosphate, [Co(12)(L)(6)(μ(3)-PO(4))(4)(μ(3)-F)(4)(μ-H(2)O)(6)][NO(3)](2) (1), is synthesized by the reaction of a [(η(5)-C(5)H(5))Fe(II)](+)-functionalized terephthalate ligand with Co(NO(3))(2)·6H(2)O and phosphate and fluoride ions generated from the in situ hydrolysis of hexafluorophosphate. 1 is a cubic, 12-connected, face-centered cubic framework sustained by the linear connection of unprecedented, dodecanuclear truncated tetrahedral coordination clusters.