A Simulation Approach to Cost Estimation in the Project Contracting Industry

In the project contracting industry (particularly in Third World and developing economies) one of the basic requirements for a company to produce a bid is an accurate estimate of the overall costs. A typical contract will involve several hundred quotes from different suppliers, and some of the figures will be inherently more risky than others.This paper looks at the effect of component price uncertainties on the overall cost of a project and develops a company-based simulation model to evaluate this. The basic data is derived from the individual expertise existing within the company, and this is statistically tested for consistency.The application of the simulation model is demonstrated, and it is also used to test some simple hypotheses about the existing modus operandi.     

An alkylsilyl-tethered, high-capacity solid support amenable to diversity-oriented synthesis for one-bead, one-stock solution chemical genetics

The synthesis and use of an alkylsilyl-tethered large (500-600 microm) polystyrene resin (1) are disclosed. An optimized Suzuki coupling of bromine-functionalized polystyrene and a silicon-functionalized alkylborane generates the silicon-substituted polystyrene 1 in large scale (>100 g). Resin loading is accomplished by activation as the silyl triflate, which can accommodate even sterically encumbered secondary alcohols and phenols. Treatment with HF/pyridine for linker cleavage is mild, efficient, and amenable to an automated, large-scale distribution system. This platform delivers, minimally, 50 nmol of each small molecule derived from a diversity-oriented, split-pool synthesis on a per bead basis for use in both forward and reverse chemical genetic assays. This technology satisfies many requirements of a one bead-one stock solution approach to chemical genetics.     

Feasibility of a liquid-phase microextraction sample clean-up and liquid chromatographic/mass spectrometric screening method for selected anabolic steroid glucuronides in biological samples

Anabolic androgenic steroids (AAS) are metabolized extensively in the human body, resulting mainly in the formation of glucuronide conjugates. Current detection methods for AAS are based on gas chromatographic/mass spectrometric (GC/MS) analysis of the hydrolyzed steroid aglycones. These analyses require laborious sample preparation steps and are therefore time consuming. Our interest was to develop a rapid and straightforward method for intact steroid glucuronides in biological samples, using liquid-phase microextraction (LPME) sample clean-up and concentration method combined with liquid chromatographic/tandem mass spectrometric (LC/MS/MS) analysis. The applicability of LPME was optimized for 13 steroid glucuronides, and compared with conventional liquid-liquid extraction (LLE) and solid-phase extraction (SPE) procedures. An LC/MS/MS method was developed for the quantitative detection of AAS glucuronides, using a deuterium-labeled steroid glucuronide as the internal standard. LPME, owing to its high specificity, was shown to be better suited than conventional LLE and SPE for the clean-up of urinary AAS glucuronides. The LPME/LC/MS/MS method was fast and reliable, offering acceptable reproducibility and linearity with detection limits in the range 2-20 ng ml(-1) for most of the selected AAS glucuronides. The method was successfully applied to in vitro metabolic studies, and also tested with an authentic forensic urine sample. For a urine matrix the method still has some unsolved problems with specificity, which should be overcome before the method can be reliably used for doping analysis, but still offering additional and complementary data for current GC/MS analyses.     

Synthetic studies related to diketopyrrolopyrrole (DPP) pigments. Part 2: The use of esters in place of nitriles in standard DPP syntheses: Claisen-type acylations and furopyrrole intermediates

Ethyl 2-aryl-4,5-dihydro-5-oxopyrrole-3-carboxylates react with esters or acyl halides in the presence of a strong base to give 4-acyl derivatives, which exist predominantly as either E- or Z-enols. These are cyclised, either in solution at temperatures >200 °C or by microwave irradiation, to 3,6-disubstituted 1H-furo[3,4-c]pyrrolediones which, after N-protection, are convertible by reaction with primary amines into novel N,N′-disubstituted DPP derivatives.     

Controlling the outcome of an N-alkylation reaction by using N-oxide functional groups

Covalent modifiers of proteins are of importance in chemical proteomics, an emerging chemical technology used to assign protein function. In this study, high-field (1)H NMR techniques were used to analyze the reaction of the bioactive compound, 2,3-bis(bromomethyl)quinoxaline 1,4-dioxide, with amines (a model system for proteins containing nitrogen-based nucleophiles). Unexpectedly, the results show that a double nucleophilic substitution reaction involving 2 equiv of the amine is preferred to an intramolecular cyclization pathway. A direct comparison with the reaction carried out on a substrate lacking the N-oxide functional groups is also provided. X-ray crystal structures and computational studies are used to rationalize the observed differences in reactivity between the two systems.     

The microwave spectrum of bromine isocyanate,Brnco: Determination of rotational constants from quadrupole hyperfine structure

A novel method has been developed to evaluate accurate rotational constants from the microwave spectrum of the unstable molecule bromine isocyanate, using perturbations in nuclear quadrupole hyperfine structure. It has been applied to this prolate near-symmetric rotor to determine A_v and x_ab accurately, entirely from a-type R branches. The method has been made possible by the development of a special computer program for global léast-squares fitting to rotational and centrifugal distortion constants, along with all components of the Br nuclear quadrupole coupling tensor.     

Benzyl vs. tropylium ions in the decomposition of some alkylnitrobenzenes

The [NO₂C₇H₆]⁺ ions generated from m-alkylnitrobenzenes have been shown to be different in their decomposition from those generated from p-alkylnitrobenzenes, even when the alkyl group is methyl and the departing fragment a hydrogen radical. Thus, in these cases even molecular ions of relatively high internal energy do not reversibly ring-expand to cycloheptatriene structures. In addition, the [NO₂C₇H₆]⁺ ions, assumed to be benzylic, do not ring-expand to nitrotropylium ions at internal energies sufficient to cause subsequent loss of NO or NO₂ from the p- and m-isomers, respectively.     

Copper-Mediated Conversion of Complex Ethers to Esters: Enabling Biopolymer Depolymerisation under Mild Conditions

Selective processing of the β-O-4 unit in lignin is essential for the efficient depolymerisation of this biopolymer and therefore its successful integration into a biorefinery set-up. An approach is described in which this unit is modified to incorporate a carboxylic ester with the goal of enabling the use of mild depolymerisation conditions. Inspired by preliminary results using a Cu/TEMPO/O₂ system, a protocol was developed that gave the desired β-O-4-containing ester in high yield using certain dimeric model compounds. The optimised reaction conditions were then applied to an oligomeric lignin model system. Extensive 2D NMR analysis demonstrated that analogous chemistry could be achieved with the oligomeric substrate. Mild depolymerisation of the ester-containing oligomer delivered the expected aryl acid monomer.