Synthesis of substituted 4-pyridones and 4-aminopyridinium salts via a one-pot pyridine synthesis

Synthesis of substituted 4-benzyloxypyridinium salts by the addition of Grignard reagents to pyridine N-oxides provides an efficient route for obtaining substituted 4-pyridones or 4-aminopyridinium salts.     

Determination of the activity of a molecular solute in saturated solution

Prediction of the solubility of a solid molecular compound in a solvent, as well as, estimation of the solution activity coefficient from experimental solubility data both require estimation of the activity of the solute in the saturated solution. The activity of the solute in the saturated solution is often defined using the pure melt at the same temperature as the thermodynamic reference. In chemical engineering literature also the activity of the solid is usually defined on the same reference state. However, far below the melting temperature, the properties of this reference state cannot be determined experimentally, and different simplifications and approximations are normally adopted. In the present work, a novel method is presented to determine the activity of the solute in the saturated solution (=ideal solubility) and the heat capacity difference between the pure supercooled melt and solid. The approach is based on rigorous thermodynamics, using standard experimental thermodynamic data at the melting temperature of the pure compound and solubility measurements in different solvents at various temperatures. The method is illustrated using data for ortho-, meta-, and para-hydroxybenzoic acid, salicylamide and paracetamol. The results show that complete neglect of the heat capacity terms may lead to estimations of the activity that are incorrect by a factor of 12. Other commonly used simplifications may lead to estimations that are only one-third of the correct value.     

Analysis of trace elements in trunk wood by thick-target PIXE using dry ashing for preconcentration

Thick-target Particle Induced X-ray Emission (TTPIXE) was used for the quantitative determination of trace-element concentrations in trunk wood. The wood samples were preconcentrated by dry ashing to improve the reliability of the sampling and the sensitivity of the analytical method. Samples of Scots pine (Pinus sylvestris) and Norway spruce (Picea abies) were collected from a polluted area (Harjavalta) as well as from a relatively nonpolluted area (Merimasku) in southwestern Finland. The elements studied were P, S, K, Ca, Mn, Fe, Ni, Cu, Pb, Rb, Sr, Ba, Cd and Ag. TTPIXE combined with dry ashing is a sensitive and reliable analytical technique for most elements studied. The method was validified by using several certified reference materials and also by ICP-MS analysis. Due to the low ash content (0.2–0.4%) in wood a high preconcentration factor can be obtained. Differences in trace-element uptake were observed between the two tree species studied. Trunk wood from the polluted area contained higher concentrations of heavy metal ions. Received: 30 August 1996 / Revised: 11 October 1996 / Accepted: 3 November 1996     

Fluorescence contrast and threshold limit: implications for photodynamic diagnosis of basal cell carcinoma

This study was designed to evaluate what application time of delta-5-aminolaevulinic acid (ALA) results in highest contrast between tumour and normal skin, in the interval 1-4 h, when using photodynamic diagnosis (PDD) of basal cell carcinomas (BCC) located on the face. Moreover, a value of the demarcation limit has been derived based on the fluorescence variation in normal skin adjacent to the tumour. Forty patients were included in the study, randomly allocated to four different groups with varying ALA application time in the range 1-4 h. The contrast, defined as the ratio between the fluorescence intensity in ALA-treated tumour tissue and normal skin, was calculated for each patient, and the mean values in each group were evaluated as a function of ALA application time. In addition, the fluorescence intensity variation in ALA-treated normal skin adjacent to the tumour was assessed. The results from this study show a peak of the mean contrast values after 3 h ALA application, but due to large interpatient variation, the mean contrast did not differ significantly in the interval 2-4 h. After 2 h ALA application, the fluorescence intensity variation in the normal ALA-treated skin was found to be at a maximum, which suggests that 2 h ALA application is not preferable when using PDD. Based on data of the fluorescence variation in ALA-treated normal skin after 3 and 4 h ALA application, a tolerance interval was calculated implying that values above 1.4 times the mean normal fluorescence indicate an abnormal condition. This tolerance limit agrees well with results obtained in a former study.     

Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm)

This article describes the applicability of multivariate projection techniques, such as principal-component analysis (PCA) and partial least-squares (PLS) projections to latent structures, to the large-volume high-density data structures obtained within genomics, proteomics, and metabonomics. PCA and PLS, and their extensions, derive their usefulness from their ability to analyze data with many, noisy, collinear, and even incomplete variables in both X and Y. Three examples are used as illustrations: the first example is a genomics data set and involves modeling of microarray data of cell cycle-regulated genes in the microorganism Saccharomyces cerevisiae. The second example contains NMR-metabonomics data, measured on urine samples of male rats treated with either of the drugs chloroquine or amiodarone. The third and last data set describes sequence-function classification studies in a set of G-protein-coupled receptors using hierarchical PCA.     

Catalyst and ring size effects on periselectivity of oxonium ylide rearrangements

Diazoketones were subjected to carbene-transfer with Rh(II) or Cu(II) catalysts to probe the selectivity for rearrangement via five- or six-membered oxonium ylides. 4,5-Bis(benzyloxy) and 4-allyloxy-5-benzyloxy substrates 3a,b showed a large preference for rearrangement via the five-membered ylide under all conditions. However, a sharp divergence was seen with 5-allyloxy-4-benzyloxy substrate 3c, which underwent predominantly a [2,3]-shift to pyran 5c via the six-membered ylide with Cu(II) catalysis and a [1,2]-shift to furan 4c via the five-membered ylide with Rh(II) catalysis.     

Enantioselective luminescence quenching of DNA light-switch [Ru(phen)2dppz]2+ by electron transfer to structural homologue [Ru(phendione)2dppz]2+

The quenching of the luminescence of [Ru(phen)(2)dppz](2+) by structural homologue [Ru(phendione)(2)dppz](2+), when both complexes are bound to DNA, has been studied for all four combinations of Delta and Lambda enantiomers. Flow linear dichroism spectroscopy (LD) indicates similar binding geometries for all the four compounds, with the dppz ligand fully intercalated between the DNA base pairs. A difference in the LD spectrum observed for the lowest-energy MLCT transition suggests that a transition, potentially related to the final localization of the excited electron to the dppz ligand in [Ru(phen)(2)dppz](2+), is overlaid by an orthogonally polarized transition in [Ru(phendione)(2)dppz](2+). This would be consistent with a low-lying LUMO of the phendione moiety of [Ru(phendione)(2)dppz](2+) that can accept the excited electron from [Ru(phen)(2)dppz](2+), thereby quenching the emission of the latter. The lifetime of excited Delta-[Ru(phen)(2)dppz](2+) is decreased moderately, from 664 to 427 ns, when bound simultaneously with the phendione complex to DNA. The 108 ns lifetime of opposite enantiomer, Lambda-[Ru(phen)(2)dppz](2+), is only shortened to 94 ns. These results are consistent with an average rate constant for electron transfer of approximately 1.10(6) s(-1) between the phenanthroline- and phendione-ruthenium complexes. At binding ratios close to saturation of DNA, the total emission of the two enantiomers is lowered equally much, but for the Lambda enantiomer, this is not paralleled by a decrease in luminescence lifetime. A binding isotherm simulation based on a generalized McGhee-von Hippel approach shows that the Delta enantiomer binds approximately 3 times stronger to DNA both for [Ru(phendione)(2)dppz](2+) and [Ru(phen)(2)dppz](2+). This explains the similar decrease in total emission, without the parallel decrease in lifetime for the Lambda enantiomer. The simulation also does not indicate any significant binding cooperativity, in contrast to the case when Delta-[Rh(phi)(2)bipy](3+) is used as quencher. The very slow electron transfer from [Ru(phen)(2)dppz](2+) to [Ru(phendione)(2)dppz](2+), compared to the case when [Rh(phi)(2)phen](3+) is the acceptor, can be explained by a much smaller driving free-energy difference.     

Heat capacity and other thermodynamic properties of CoTe2 from 5 to 1 030 K and of CoTe2.315 from 300 to 1 040 K

The heat capacity of orthorhombic (marcasite-type structure) cobalt ditelluride has been measured from 5 to 1 030 K by adiabatic-shield calorimetry with alternate energy inputs and equilibrations. Above 900 K a marked increase in heat capacity occurs which probably signals a change in the composition of the CoTe₂-phase towards higher tellurium content. Values at 298.15 and 1 000 K in J K^–1 mol^–1 of the heat capacity (C _p,m), entropy [S _m ^° (T)–S _m ^° (0)], andGibbs energy function – [G _m ^° (T)–H _m ^° (0)]T ^–1 are 75.23, 114.5, 49.93, and 132.4, 216.2, 139.17, respectively. Consistent with the metallic behavior of CoTe₂, deviation of the heat capacity from theDebye T ³-law was found at low temperatures. Comparison with the heat capacity of FeTe₂ shows aSchottky-like deviation with a maximum of 7.3 J K^–1 mol^–1 at 80 K and evidences the influence of the additional 3 d-electron in cobalt compared to iron. Heat capacity measurements were made on CoTe_2.33 to ascertain the existence range of the CoTe_2+x -phase and the entropy of the associated structural disorder.The portion of this research done at Ann Arbor was supported in part by the Structural Chemistry and Chemical Thermodynamics Program of the Division of Chemistry of the National Science Foundation under Grant No. CHE-7710049.