Intramolecular Baylis-Hillman Reaction: A Pathway to Substituted Coumarins

The acrylate ester of salicylaldehyde, in the presence of DABCO, affords a crystalline coumarin salt. Formation of this derivative confirms a vital intermediate in the mechanism of the reaction. Salicylaldehyde, suitably protected, reacts with methyl acrylate to afford a novel coumarin not unlike the vasodilator chromonar.     

Effects of different composition ratio on the dielectric relaxation and dynamic mechanical properties of poly(ω‐dodecalactam‐co‐ε‐caprolactam‐co‐propylene oxide) copolymers

The molecular dynamics of new poly (ω‐dodecalactam‐co‐ε‐caprolactam‐co‐propylene oxide) copolymers (DL/CL/PAC) has been investigated by using dynamic mechanical thermal analysis (DMTA) and dielectric relaxation spectroscopy (DRS) measurements. The copolymers were synthesized via anionic polymerization of relevant lactams activated with carbamoyl derivatives of telechelic hydroxyl terminated polypropylene oxide with isophorone diisocyanate (PAC). The calorimetric, X‐ray diffraction, and DMTA measurements were performed to recognize the influence of the composition ratio and the type of PAC on the physical, thermal, and mechanical properties of the synthesized copolymers. The DRS was used to study the frequency dependence of the dielectric permittivity of some isotherms from ?110 to 145 °C. Copolymerization of ε‐caprolactam with about 10 wt % ω‐dodecalactam results in a copolymer that has lower water absorption, a melting point close to that of polyamide 6 and has a high enough degree of crystallinity in respect to high storage modulus. Five dielectric relaxations have been observed in the dielectric spectra, three at lower temperature and two at higher temperature. The copolymers have two glass transition temperatures for polyamide segments and polyether blocks, indicating microphase separation in the copolymers. Other studies directed toward molecular dynamics of polyamide DL/CL/PAC copolymers have not been reported. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2010     

A study of comparability in amplified fragment length polymorphism profiling using a simple model system

A simple amplified fragment length polymorphism (AFLP) model, using the bacteriophage lambda genome, was developed to test the reproducibility of this technique in an international comparative study. Using either non-selective or selective primers, nine fragments or subsets of two or three fragments, respectively, were predicted using in silico software. Under optimized conditions, all predicted fragments were experimentally generated. The reproducibility of the AFLP model was tested by submitting both "unknown" DNA template that had been restricted and ligated with AFLP linkers (R/L mixture) and corresponding primer pairs to nine laboratories participating in the study. Participants completed the final PCR step and then used either slab gel electrophoresis or CE to detect the AFLP fragments. The predicted fragments were identified by the majority of participants with size estimates consistently up to 3 base pair (bp) larger for slab gel electrophoresis than for CE. Shadow fragments, 3 bp larger than the predicted fragments, were often observed by study participants and organizers. The nine AFLP fragments exhibited relative intensities ranging from less than 3% to 22% and, apart from the two weakest fragments, with a % CV of 16 to 25. Fragments containing the highest guanine-cytosine (GC) content of 50-56% showed the greatest stability in the AFLP profiles.     

Rigid NON- and NSN-ligand complexes of tetravalent and trivalent uranium: comparison of U-OAr2 and U-SAr2 bonding

A rigid NSN-donor proligand, 4,5-bis(2,6-diisopropylanilino)-2,7-di-tert-butyl-9,9-dimethylthioxanthene (H(2)[TXA(2)], 1) was prepared by palladium-catalyzed coupling of 2,6-diisopropylaniline with 4,5-dibromo-2,7-di-tert-butyl-9,9-dimethylthioxanthene. Deprotonation of 1 using (n)BuLi provided Li(2)(DME)(2)[TXA(2)] (2), and subsequent reaction with UCl(4) afforded [Li(DME)(3)][(TXA(2))UCl(3)] (4). The analogous NON-donor ligated complex [(XA(2))UCl(3)K(DME)(3)] [3; XA(2) = 4,5-bis(2,6-diisopropylanilino)-2,7-di-tert-butyl-9,9-dimethylxanthene] was prepared by the reaction of K(2)(DME)(x)[XA(2)] with UCl(4). A cyclic voltammogram (CV) of 3 in THF/[NBu(4)][B(C(6)F(5))(4)] at 200 mV s(-1) showed an irreversible reduction to uranium(III) at E(pc) = -2.46 V versus FeCp(2)(0/+1), followed by a product wave at E(1/2) = -1.83 V. Complex 4 also underwent irreversible reduction to uranium(iii) [E(pc) = -2.56 V], resulting in an irreversible product peak at E(pa) = -1.83 V. One-electron reduction of complexes 3 and 4 using K(naphthalenide) under an argon atmosphere in DME yielded 6-coordinate [(XA(2))UCl(DME)] (5) and the thermally unstable 7-coordinate [(TXA(2))U(DME)Cl(2)Li(DME)(2)] (6), respectively. The U-S distances in 4 and 6 are uncommonly short, the C-S-U angles are unusually acute, and the thioxanthene backbone of the TXA(2) ligand is significantly bent. By contrast, the xanthene backbone in XA(2) complexes 3 and 5 is planar. However, κ(3)-coordination and an approximately meridional arrangement of the ancillary ligand donor atoms is maintained in all complexes. DFT and Atoms in Molecules (AIM) calculations were carried out on 3, 4, 5, 6, [(XA(2))UCl(3)](-) (3B), [(TXA(2))UCl(2)(DME)](-) (6B) and [(TXA(2))UCl(DME)] (6C) to probe the extent of covalency in U-SAr(2) bonding relative to U-OAr(2) bonding.     

1,2-Addition of Activated Vinyl Carbanions to α,β-Unsaturated Carbonyls

Methyl acrylate reacts with α,β-unsaturated aldehydes in the presence of a tertiary amine to afford 1,2-addition products.     

Triphenylene analogues with B2N2C2 cores: synthesis, structure, redox behavior, and photophysical properties

A series of alkyl (1-3), aryl (6), and benzo-annulated (4, 5) heteroaromatic triphenylene analogues with B(2)N(2)C(2) cores have been synthesized via chelation of pyridazine derivatives using difunctional Lewis acidic diborabiphenyl precursors. In contrast to triphenylene, NICS(1) calculations on 1 suggested high aromaticities for the central (-11.3 ppm) and outer borabenzene rings (-7.7 ppm), along with nonaromatic behavior for the pyridazine ring (-0.7 ppm). Crystal structure analyses supported this analysis. When the a- and c-faces of the pyridazine moiety were free of substitution (1, 3), planar structures resulted, but upon substitution, a twisted B(2)N(2)C(2) core was observed due to steric repulsion of neighboring hydrogen atoms (e.g., 5). The increase of steric bulk from H (1) to (i)Pr (3) in the planar species was found to result in a dimeric, head-to-tail herringbone packing motif, held together by close intermolecular B...N interactions of 3.39 Angstrom. One-electron reduction by Cp(2)Co was found to afford the radical anions of 3 and 5, which were characterized by broad, featureless singlets in the EPR spectra; [3](.)(-)[Cp(2)Co](+) was characterized by X-ray crystallography. While the planar structures (1-4) were observed to possess weak fluorescence (Phi(F) = 0.02-0.08) with either yellow-orange (ca. 555 nm) or green emission (521 nm), the twisted structures (5, 6) were found to be nonfluorescent.     

DNA methylation ratio variability may impede clinical application of cancer diagnostic markers

Hypermethylation at promoter regions of tumour suppressor genes is diagnostic for many cancers. Many genomic regions that may be the targets for clinical diagnostic assays have been identified through use of measuring systems reliant on bisulphite conversion, but few of these promising markers are in clinical use. The comparability of a widely used DNA methylation measuring system involving bisulphite conversion was evaluated by supplying three experienced centres with methylated DNA reference material mixtures that were independently prepared and characterised by mass spectrometry and high-pressure liquid chromatography. A replication scheme was designed to evaluate reproducibility of key analytical steps within and between laboratories by regression analysis. In general, methylation was underestimated and methylation ratio values were highly variable. The difference in methylation ratio between CpG sites was the key contributor to variable results. The CpG site effect followed a similar pattern at all centres and at all methylation levels examined indicating that sequence context had a major effect on methylation ratio measurement using the bisulphite conversion process. The magnitude of underestimation combined with the variability of measurements between CpG sites compromises the concept of measuring genomic regional methylation by averaging the methylation ratios of many CpG sites. There were no significant differences in replicate bisulphite conversions or sample work-up and instrument analysis at each centre thus making this technique suitable for comparative intralaboratory investigations. However, it may not be suitable for a routine diagnostic assay without extensive standardisation efforts.     

A standard additions method reduces inhibitor-induced bias in quantitative real-time PCR

A method of calibration for real-time quantitative polymerase chain reaction (qPCR) experiments based on the method of standard additions combined with non-linear curve fitting is described. The method is tested by comparing the results of a traditionally calibrated qPCR experiment with the standard additions experiment in the presence of 2 mM EDTA, a known inhibitor chosen to provide an unambiguous test of the principle by inducing an approximately twofold bias in apparent copy number calculated using traditional calibration. The standard additions method is shown to substantially reduce inhibitor-induced bias in quantitative real-time qPCR.     

Estimation of slow diffusion rates in confined systems: CCl4 in zeolite NaA

Often the rate of passage of gaseous molecules through model zeolites is too small to be computed directly. An estimate for the rate of passage of CCl₄ through the 8-ring window in a model of zeolite A has been obtained by combining a direct evaluation of the free energy profile and an adaptation of the rare events method. First the free energy profile is found from a direct evaluation of the canonical partition function at high dilution and the transition state theory rate constant obtained. The dynamic correction factor is then estimated from molecular dynamics runs and used to compute the actual rate k_eff. The method is used to estimate the rate of passage through the 8-ring window in a rigid model of zeolite A, and the results are compared with those obtained from rigid models with expanded windows and from the flexible model. Even a small expansion in the 8-ring window diameter increases the rate significantly, but the changes associated with a flexible cage are small.