The Newman-Kwart rearrangement re-evaluated by microwave synthesis

The Newman-Kwart rearrangement (NKR) has been re-evaluated by microwave heating. Microwave technology has proven to be ideal for investigating this high temperature rearrangement and facilitated the confirmation of many aspects of this valuable reaction. Comparisons between thermal and microwave results indicate no evidence of a significant microwave effect.     

Homologation and alkylation of boronic esters and boranes by 1,2‐metallate rearrangement of boron ate complexes

Organoboranes and boronic esters readily undergo nucleophilic addition, and if the nucleophile also bears an α‐leaving group, 1,2‐metallate rearrangement of the ate complex results. Through such a process a carbon chain can be extended, usually with high stereocontrol and this is the focus of this review. A chiral boronic ester (substrate control) can be used for stereocontrolled homologations with (dichloromethyl)lithium in the presence of ZnCl₂. Subsequent alkylation by an organometallic reagent also occurs with high levels of stereocontrol. Chiral lithiated carbanions (reagent control) can also be used for the reaction sequence with achiral boronic esters and boranes. Aryl‐stabilized sulfur ylide derived chiral carbanions can be homologated with a range of boranes including vinyl boranes in good yield and high diastereo‐ and enantioselectivity. Lithiated alkyl chlorides react with boronic esters, again with high stereocontrol, but both sets of reactions are limited in scope. Chiral lithiated carbamates show the greatest substrate scope and react with both boronic esters and boranes with excellent enantioselectivity. Furthermore, iterative homologation with chiral lithiated carbamates allows carbon chains to be “grown” with control over relative and absolute stereochemistry. The factors responsible for stereocontrol are discussed. © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 24–39; 2009: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20168     

Forward flux sampling-type schemes for simulating rare events: efficiency analysis

We analyze the efficiency of several simulation methods which we have recently proposed for calculating rate constants for rare events in stochastic dynamical systems in or out of equilibrium. We derive analytical expressions for the computational cost of using these methods and for the statistical error in the final estimate of the rate constant for a given computational cost. These expressions can be used to determine which method to use for a given problem, to optimize the choice of parameters, and to evaluate the significance of the results obtained. We apply the expressions to the two-dimensional nonequilibrium rare event problem proposed by Maier and Stein [Phys. Rev. E 48, 931 (1993)]. For this problem, our analysis gives accurate quantitative predictions for the computational efficiency of the three methods.     

Sampling rare switching events in biochemical networks

Bistable biochemical switches are widely found in gene regulatory networks and signal transduction pathways. Their switching dynamics are difficult to study, however, because switching events are rare, and the systems are out of equilibrium. We present a simulation method for predicting the rate and mechanism of the flipping of these switches. We apply it to a genetic switch and find that it is highly efficient. The path ensembles for the forward and reverse processes do not coincide. The method is widely applicable to rare events and nonequilibrium processes.     

Formation of enamine Schiff bases by ring cleavage of pyridine

On treatment with diphenyldichloromethane or anisal chloride in the presence of acetone and aqueous sodium hydroxide, pyridine undergoes condensation and ring cleavage to yield the enamine Schiff bases 1,1-diphenyl-2-azadeca-1,3Z,5Z,7E-tetraen-9-one (1) and 1-(4-methoxyphenyl)-2-azadeca-1E,3Z,5Z,7E-tetraen-9-one (7). The reaction proceeds through attack of acetonyl carbanion on the initially formed bis-pyridinium salt, followed by ring scission with elimination of one equivalent of pyridine. The structure and stereochemistry of the 2-azatetraene (1) was confirmed by X-ray crystallography.     

Eliminating fast reactions in stochastic simulations of biochemical networks: a bistable genetic switch

In many stochastic simulations of biochemical reaction networks, it is desirable to "coarse grain" the reaction set, removing fast reactions while retaining the correct system dynamics. Various coarse-graining methods have been proposed, but it remains unclear which methods are reliable and which reactions can safely be eliminated. We address these issues for a model gene regulatory network that is particularly sensitive to dynamical fluctuations: a bistable genetic switch. We remove protein-DNA and/or protein-protein association-dissociation reactions from the reaction set using various coarse-graining strategies. We determine the effects on the steady-state probability distribution function and on the rate of fluctuation-driven switch flipping transitions. We find that protein-protein interactions may be safely eliminated from the reaction set, but protein-DNA interactions may not. We also find that it is important to use the chemical master equation rather than macroscopic rate equations to compute effective propensity functions for the coarse-grained reactions.     

Designing compound subsets: comparison of random and rational approaches using statistical simulation

Compound subsets, which may be screened where it is not feasible or desirable to screen all available compounds, may be designed using rational or random selection. Literature on the relative performance of random versus rational selection reports conflicting observations, possibly because some random subsets might be more representative than others and perform better than subsets designed by rational means, or vice versa. In order to address this likelihood, we simulated a large number of rationally designed subsets for evaluation against an equally large number of randomly generated subsets. We found that our rationally designed subsets give higher mean hit rates compared to those of the random ones. We also compared subsets comprising random plates with subsets of random compounds and found that, while the mean hit rate of both is the same, the former demonstrates more variation in the hit rate. The choice of compound file, rational subset method, and ratio of the subset size to the compound file size are key factors in the relative performance of random and rational selection, and statistical simulation is a viable way to identify the selection approach appropriate for a subset.     

Raman spectroscopic analysis of the enigmatic Comper pigments

An early church decoration project carried out by Sir Ninian Comper in 1896–98, involving the rood screen and canopy in St. Mary’s, Egmanton, is currently undergoing restoration. Despite the rather prolific works of this famous ecclesiastical architect, there is little information available about the actual pigments that he used in his projects that gave rise to the special nomenclature “Comper green” and “Comper red”. Specimens of green, red, black, grey, white and blue paint from this work have been made available for Raman spectroscopic analysis, and their identification has been achieved for the first time. The characteristic red and green pigments used in Comper’s work, Comper green and Comper red, are both seen to be mixtures; in the former, Raman bands from chrome yellow (lead(II) chromate) and Prussian blue are identified, and the latter is confirmed as being a mixture of vermilion (mercury(II) sulfide) and barytes (barium sulfate). The other colours are found to represent a rich diversity of palette and include haematite, lead tin yellow (type II), lamp black, gypsum, anhydrite, hydrocerussite and calcite. The information from this first Raman spectroscopic study of Comper’s palette will assist the conservation and restoration of an important nineteenth century church decoration.     

Hydrothermal calcium-carbonate veins reveal past ocean chemistry

Records of past ocean chemistry provide an integrated history of fundamental Earth processes, including the evolution of its continents, climate, and life. Here, we describe a recent dramatic shift in appreciation of the value and the application of studies of ocean crustal hydrothermal processes, which can be used to both reconstruct records of past ocean chemistry and decipher the past changes to global conditions responsible for any variations in these records. In particular, we describe a recently developed method for the determination of past seawater cation ratios using hydrothermal calcium-carbonate veins precipitated from seawater-derived fluids in the upper ocean crust.