Fluorinated Retinoids via Crossed Aldol Condensation of 1,1,1-Trifluoroacetone

Piperidine-acetic acid catalysed crossed aldol condensation of 1,1,1-trifluoroacetone with aryl or α,β-unsaturated aldehydes was found to be a useful method for the preparation of unsaturated trifluoromethyl ketones. Chain extension of these ketones led to several new fluorinated retinoids including the hitherto elusive all-trans isomers of 19,19,19- and 20,20,20-trifluororetinal.     

Reaction of pentadienyliron tricarbonyl cations with hydride donors

A series of pentadienyliron tricarbonyl cations has been prepared and reacted with the hydride ion donors sodium borohydride, sodium cyanoborohydride, and lithium triethylborohydride in order to determine steric and electronic effects in these reduction reactions. Sodium cyanoborohydride yields products of retained configuration whereas lithium triethylborohydride yields dieneiron tricarbonyl compounds of inverted configuration. Kinetic and thermodynamic considerations are used to account for these results.     

Silver-colloid-nucleated cytochrome c superstructures encapsulated in silica nanoarchitectures

We recently discovered that self-organized superstructures of the heme protein cytochrome c (cyt. c) are nucleated in buffer by gold nanoparticles. The protein molecules within the superstructure survive both silica sol-gel encapsulation and drying from supercritical carbon dioxide to form air-filled biocomposite aerogels that exhibit gas-phase binding activity for nitric oxide. In this investigation, we report that viable proteins are present in biocomposite aerogels when the nucleating metal nanoparticle is silver rather than gold. Silver colloids were synthesized via reduction of an aqueous solution of Ag+ using either citrate or borohydride reductants. As determined by transmission electron microscopy and UV-visible absorption spectroscopy, the silver nanoparticles vary in size and shape depending on the synthetic route, which affects the fraction of cyt. c that survives the processing necessary to form a biocomposite aerogel. Silver colloids synthesized via the citrate preparation are polydisperse, with sizes ranging from 1 to 100 nm, and lead to low cyt. c viability in the dried bioaerogels (approximately 15%). Protein superstructures nucleated at approximately 10-nm Ag colloids prepared via the borohydride route, including citrate stabilization of the borohydride-reduced metal, retain significant protein viability within the bioaerogels (approximately 45%).     

Synthesis of tetrahydro-1,4-benzodiazepine-2-ones on hydrophilic polyamide SynPhase lanterns

Solid-phase synthesis is greatly dependent on the solid support. Here, we report the use of a new hydrophilic grafted surface on SynPhase lanterns in solid-phase organic chemistry. A convenient and facile solid-phase synthesis of disubstituted 1,4-benzodiazepine-2-ones on polyamide SynPhase lanterns is described. The key step of the synthesis involved a reduction-cyclization of a nitroaryl methyl ester with a mixture of tin(II) chloride dihydrate and ammonium acetate in water and ethanol at elevated temperature to give the desired target compounds. A library of 21 disubstituted 1,4-benzodiazepine-2-ones was prepared.     

Theoretical examination of Mg(2+)-mediated hydrolysis of a phosphodiester linkage as proposed for the hammerhead ribozyme

The hammerhead ribozyme is an RNA molecule capable of self-cleavage at a unique site within its sequence. Hydrolysis of this phosphodiester linkage has been proposed to occur via an in-line attack geometry for nucleophilic displacement by the 2'-hydroxyl on the adjoining phosphorus to generate a 2',3'-cyclic phosphate ester with elimination of the 5'-hydroxyl group, requiring a divalent metal ion under physiological conditions. The proposed S(N)2(P) reaction mechanism was investigated using density functional theory calculations incorporating the hybrid functional B3LYP to study this metal ion-dependent reaction with a tetraaquo magnesium (II)-bound hydroxide ion. For the Mg(2+)-catalyzed reaction, the gas-phase geometry optimized calculations predict two transition states with a kinetically insignificant, yet clearly defined, pentacoordinate intermediate. The first transition state located for the reaction is characterized by internal nucleophilic attack coupled to proton transfer. The second transition state, the rate-determining step, involves breaking of the exocyclic P-O bond where a metal-ligated water molecule assists in the departure of the leaving group. These calculations demonstrate that the reaction mechanism incorporating a single metal ion, serving as a Lewis acid, functions as a general base and can afford the necessary stabilization to the leaving group by orienting a water molecule for catalysis.     

Accurate potential energy curves for HeO-, NeO-, and ArO-: spectroscopy and transport coefficients

We calculate accurate potential energy curves for HeO(-), NeO(-), and ArO(-), including the full counterpoise correction and allowing for spin-orbit effects. Comparison with previous curves is presented, where these are available. The three curves, (2)Sigma(12) (+), (2)Pi(12), and (2)Pi(32), are used to derive spectroscopic constants and to calculate the transport coefficients for O(-) moving in a bath of the respective rare gas. Conclusions are made based on a comparison with the available data.     

On the Gittins index in the M/G/1 queue

For an M/G/1 queue with the objective of minimizing the mean number of jobs in the system, the Gittins index rule is known to be optimal among the set of non-anticipating policies. We develop properties of the Gittins index. For a single-class queue it is known that when the service time distribution is of type Decreasing Hazard Rate (New Better than Used in Expectation), the Foreground–Background (First-Come-First-Served) discipline is optimal. By utilizing the Gittins index approach, we show that in fact, Foreground–Background and First-Come-First-Served are optimal if and only if the service time distribution is of type Decreasing Hazard Rate and New Better than Used in Expectation, respectively. For the multi-class case, where jobs of different classes have different service distributions, we obtain new results that characterize the optimal policy under various assumptions on the service time distributions. We also investigate distributions whose hazard rate and mean residual lifetime are not monotonic.     

Synthesis of fluorinated cyclic s-trans vinylogous acid and amide ester derivatives

A two-step procedure for the preparation of ethyl 4-amino-2-oxo-6-(trifluoromethyl)cyclohex-3-ene-1-carboxylate (enaminone) and methyl 4-hydroxy-2-oxo-6-(trifluoromethyl)cyclohex-3-ene-1-carboxylate (vinylogous acid) has been accomplished, using reactive Michael acceptors under basic condition. In addition, acyclic trifluoromethylated ester derivatives were isolated as competing by-products. The above compounds represent novel synthetically useful trifluoromethyl building blocks.