Studies on the reaction of 2-aminoacetophenone with thiophosgene

The reaction of 3- and 4-aminoacetophenone with thiophosgene in a chloroform-water-calcium carbonate mixture at room temperature results in good yields of the related, known isothiocyanates. At first, however, we failed in all our attempts to produce 2-isothiocyanatoacetophenones with this reaction. Closer inspection of the reaction showed, that the product distribution depends upon the concentration of hydrogen ions pro-ducted and on the reaction time. When the reaction was followed with thin-layer chromatography, it was observed that the isothiocyanates formed first. In the further course of the reaction, they were converted to the 4-methylene-2-oxo-3,1-benzothiazines by the action of protons. The final products of the reaction were the 4-(3,1-benzothiazin-4-yl)-methylene-3,1-benzothiazines, formed from the monomer in a dimerization process. Depending upon the time the protons were removed from the reaction mixture, different products could be isolated.     

Solution and Solid‐State Studies on the Halide Binding Affinity of Perfluorophenyl‐Armed Uranyl–Salophen Receptors Enhanced by Anion–π Interactions

The enhancement of the binding between halide anions and a Lewis acidic uranyl–salophen receptor has been achieved by the introduction of pendant electron‐deficient arene units into the receptor skeleton. The association and the occurrence of the elusive anion–π interaction with halide anions (as tetrabutylammonium salts) have been demonstrated in solution and in the solid state, providing unambiguous evidence on the interplay of the concerted interactions responsible for the anion binding.     

On the bounded compact approximation property and measures of noncompactness

The Banach spaces with the bounded compact approximation property are characterized by the completeness of measures of noncompactness. Applications to the theory of semi-Fredholm operators and to the algebraic properties of their canonical images in the Calkin algebra are discussed.     

Semi-rotating cryogenic modulator for comprehensive two-dimensional gas chromatography

A laboratory-made cryogenic modulator for comprehensive two-dimensional gas chromatography (GCxGC) was constructed and evaluated. Analytes were trapped with carbon dioxide and desorbed with heated GC oven air. The GCxGC system included a non-polar first-dimension column and a semi-polar second-dimension column connected to a flame ionisation detector. A laboratory-written Matlab-based program was used for the data analysis. Peak widths at half height for n-alkanes, obtained with use of new modulator, were at narrowest 60 ms.     

An application of the method of conjugate gradients to the calculation of minimal basis set localized orbitals

Using an STO -3G basis set, energy localized molecular orbitals (LMO ) were determined for the ten electron series HF, H₂O, NH₃, and CH₄ as well as for CH₃OH and C₂H₂F₂. The method of conjugate gradients is shown to be a viable alternative to other non-eigenvalue methods. The characterization of the LMO in terms of first and second moment measures indicates that the STO -3G basis set LMO may be accurately correlated to larger sp basis set LMO . Also, it is shown that the first and second moment measures display a good linear correlation with the classical concept of electronegativity.     

Rethinking the application of the first nucleation theorem to particle formation

The critical cluster is the threshold size above which a cluster will be more likely to grow than to evaporate. In field and laboratory measurements of new particle formation, the number of molecules of a given species in the critical cluster is commonly taken to be the slope of the log-log plot of the formation rate versus the concentration of the species. This analysis is based on an approximate form of the first nucleation theorem, which is derived with the assumption that there are no minima in the free energy surface prior to the maximum at the critical size. However, many atmospherically relevant systems are likely to exhibit such minima, for example, ions surrounded by condensable vapour molecules or certain combinations of acids and bases. We have solved numerically the birth-death equations for both an electrically neutral one-component model system with a local minimum at pre-critical sizes and an ion-induced case. For the ion-induced case, it is verified that the log-log slope of the nucleation rate versus particle concentration plot gives accurately the difference between the cluster sizes at the free energy maximum and minimum, as is expected from the classical form of the ion-induced nucleation rate. However, the results show that applying the nucleation theorem to neutral systems with stable pre-nucleation clusters may lead to erroneous interpretations about the nature of the critical cluster.     

Model studies on a diastereoselective synthesis of the C(33)-C(37) fragment of Amphotericin B

A new, short and highly diastereoselective synthetic route aiming at the C(33)-C(37) fragment of Amphotericin B has been developed. Studies with a model aldehyde (benzaldehyde) have given very promising results: the desired stereochemistry of all four stereocenters of the target molecule has been achieved with high diastereoselection. The stereochemistry of three key intermediates and the target segment has been confirmed by X-ray crystallography.     

Proximity-induced catalysis by the protein kinase ERK2

Five hundred protein kinases phosphorylate 10 000 proteins in human cells. Frequently, more than one site in a protein is phosphorylated, and often by more than one protein kinase. The mechanistic basis underlying the overlapping specificity of the phospho-proteome is not well understood. We are interested in understanding why ERK2, a proline-directed protein kinase, phosphorylates only a fraction of the (S/T-P) sites found in the surface loops of proteins, at an appreciable rate. To address this fundamental question, we utilized a well-established protein substrate EtsDelta138, which comprises a globular ERK2-recognition domain (pnt domain) and an unstructured peptide-like N-terminal tail. This tail contains T38, the sole ERK2 phosphorylation site. We mutated the TP motif, which is recognized by the active site and found that mutagenesis of the T-38/P-39 motif to TD, TR, TA, TG, and TV has no effect on the stability of the ternary complex but does decrease kcat. We also investigated the effect of perturbing the binding between ERK2 and the pnt domain, which occurs outside the active site, to find that mutation of the pnt domain (F120A) leads to a 10-fold decrease in binding but the kcat remains the same. The data support a mechanism of proximity-mediated catalysis, where the docking of the pnt domain, outside the active site, increases the effective concentration of the TP motif near the active site. The data are consistent with the notion that the interaction between ERK2 and the pnt domain provides uniform binding energy and stabilizes each enzyme intermediate and transition state to an equal extent. While other steps on the reaction pathway contribute towards the specificity of the ERK2 reaction, a docking interaction provides the initial basis for substrate recognition. Those residues within the docked complex, which have the ability to access the active site with an appropriate geometry, can be phosphorylated at an efficient rate if followed by a proline or small hydrophobic amino acid.