Dichlorido{N‐[2‐(diphenylphosphanyl)benzylidene]‐2‐methylaniline}palladium(II) acetonitrile monosolvate

The title imino–phosphine compound, [PdCl₂(C₂₆H₂₂NP)]·CH₃CN, was prepared by reaction of N‐[2‐(diphenylphosphanyl)benzylidene]‐2‐methylaniline with dichlorido(cycloocta‐1,5‐diene)palladium(II) in dry CH₂Cl₂. The Pd^II cation is coordinated by the P and N atoms of the bidentate chelating ligand and by two chloride anions, generating a distorted square‐planar coordination geometry. There is a detectable trans influence for the chloride ligands. The methyl group present in this structure has an influence on the crystal packing.     

Fluorescence biosensing micropatterned surfaces based on immobilized human acetylcholinesterase

Human acetylcholinesterase (AChE) is a widely studied target enzyme in drug discovery for Alzheimer’s disease (AD). In this paper we report evaluation of the optimum structure and chemistry of the supporting material for a new AChE-based fluorescence sensing surface. To achieve this objective, multilayered silicon wafers with spatially controlled geometry and chemical diversity were fabricated. Specifically, silicon wafers with silicon oxide patterns (SiO₂/Si wafers), platinum-coated silicon wafers with SiO₂ patterns (SiO₂/Pt/Ti/Si wafers), and Pt-coated wafers coated with different thicknesses of TiO₂ and SiO₂ (SiO₂/TiO₂/Pt/Ti/Si wafers) were labelled with the fluorescent conjugation agent HiLyte Fluor 555. Selection of a suitable material and the optimum pattern thickness required to maximize the fluorescence signal and maintain chemical stability was performed by confocal laser-scanning microscopy (CLSM). Results showed that the highest signal-to-background ratio was always obtained on wafers with 100 nm thick SiO₂ features. Hence, these wafers were selected for covalent binding of human AChE. Batch-wise kinetic studies revealed that enzyme activity was retained after immobilization. Combined use of atomic-force microscopy and CLSM revealed that AChE was homogeneously and selectively distributed on the SiO₂ microstructures at a suitable distance from the reflective surface. In the optimum design, efficient fluorescence emission was obtained from the AChE-based biosensing surface after labelling with propidium, a selective fluorescent probe of the peripheral binding site of AChE.

Spin-exchange dynamical structure factor of the S=1/2 Heisenberg chain

We determine the spin-exchange dynamical structure factor of the Heisenberg spin chain, as is measured by indirect resonant inelastic x-ray scattering (RIXS). We find that two-spin RIXS excitations nearly entirely fractionalize into two-spinon states. These share the same continuum lower bound as single-spin neutron scattering excitations, even if the relevant final states belong to orthogonal symmetry sectors. The RIXS spectral weight is mainly carried by higher-energy excitations, and is beyond the reach of the low-energy effective theories of Luttinger liquid type.     

First principle kinetic studies of zeolite-catalyzed methylation reactions

Methylations of ethene, propene, and butene by methanol over the acidic microporous H-ZSM-5 catalyst are studied by means of state of the art computational techniques, to derive Arrhenius plots and rate constants from first principles that can directly be compared with the experimental data. For these key elementary reactions in the methanol to hydrocarbons (MTH) process, direct kinetic data became available only recently [J. Catal.2005, 224, 115-123; J. Catal.2005, 234, 385-400]. At 350 °C, apparent activation energies of 103, 69, and 45 kJ/mol and rate constants of 2.6 × 10(-4), 4.5 × 10(-3), and 1.3 × 10(-2) mol/(g h mbar) for ethene, propene, and butene were derived, giving following relative ratios for methylation k(ethene)/k(propene)/k(butene) = 1:17:50. In this work, rate constants including pre-exponential factors are calculated which give very good agreement with the experimental data: apparent activation energies of 94, 62, and 37 kJ/mol for ethene, propene, and butene are found, and relative ratios of methylation k(ethene)/k(propene)/k(butene) = 1:23:763. The entropies of gas phase alkenes are underestimated in the harmonic oscillator approximation due to the occurrence of internal rotations. These low vibrational modes were substituted by manually constructed partition functions. Overall, the absolute reaction rates can be calculated with near chemical accuracy, and qualitative trends are very well reproduced. In addition, the proposed scheme is computationally very efficient and constitutes significant progress in kinetic modeling of reactions in heterogeneous catalysis.     

Synthesis and Structural Analysis of Aspergillus fumigatus Galactosaminogalactans Featuring α‐Galactose, α‐Galactosamine and α‐N‐Acetyl Galactosamine Linkages

Galactosaminogalactan (GAG) is a prominent cell wall component of the opportunistic fungal pathogen Aspergillus fumigatus. GAG is a heteropolysaccharide composed of α‐1,4‐linked galactose, galactosamine and N‐acetylgalactosamine residues. To enable biochemical studies, a library of GAG‐fragments was constructed featuring specimens containing α‐galactose‐, α‐galactosamine and α‐N‐acetyl galactosamine linkages. Key features of the synthetic strategy include the use of di‐tert‐butylsilylidene directed α‐galactosylation methodology and regioselective benzoylation reactions using benzoyl‐hydroxybenzotriazole (Bz‐OBt). Structural analysis of the Gal, GalN and GalNAc oligomers by a combination of NMR and MD approaches revealed that the oligomers adopt an elongated, almost straight, structure, stabilized by inter‐residue H‐bonds, one of which is a non‐conventional C?H???O hydrogen bond between H5 of the residue (i+1) and O3 of the residue (i). The structures position the C‐2 substituents almost perpendicular to the oligosaccharide main chain axis, pointing to the bulk solvent and available for interactions with antibodies or other binding partners.     

Induced‐Fit Mechanism in Class I Terpene Cyclases

We present crystallographic and functional data of selina‐4(15),7(11)‐diene synthase (SdS) from Streptomyces pristinaespiralis in its open and closed (ligand‐bound) conformation. We could identify an induced‐fit mechanism by elucidating a rearrangement of the G1/2 helix‐break motif upon substrate binding. This rearrangement highlights a novel effector triad comprising the pyrophosphate sensor Arg178, the linker Asp181, and the effector Gly182‐O. This structural motif is strictly conserved in class I terpene cyclases from bacteria, fungi, and plants, including epi‐isozizaene synthase (3KB9), aristolochene synthase (4KUX), bornyl diphosphate synthase (1N20), limonene synthase (2ONG), 5‐epi‐aristolochene synthase (5EAT), and taxa‐4(5),11(12)‐diene synthase (3P5R). An elaborate structure‐based mutagenesis in combination with analysis of the distinct product spectra confirmed the mechanistic models of carbocation formation and stabilization in SdS.     

Iterative tandem catalysis of racemic AB monomers

Racemic AB monomers encompassing a secondary hydroxy group and a methyl ester moiety were synthesized and converted to chiral polyesters by iterative tandem catalysis (ITC). The concurrent action of an enantioselective acylation catalyst (Novozym 435) and a racemization catalyst (Ru(Shvo)) results in the high conversion of the racemic monomers to enantio‐enriched polymers. Several factors are important for attaining high ee's and high molecular weights. The enantioselectivities observed for the novel AB monomers by Novozym 435 are high enough at 70 °C (E ratio ≥ 200) for the monomers to be useful for ITC. ITC of methyl 6‐hydroxyheptanoate showed that a catalyst loading of ～1.4 mol % Ru(Shvo), 25 mg Novozym 435/mmol AB monomer, and 0.5 mmol DMP/mmol monomer employing a monomer concentration of 1 mol/L gave a monomer conversion of 94%, an ee of 91%, and an M_p of 6.0 kg/mol. Application of these conditions to the other AB monomers revealed the sensitivity of the system. Reduced enantioselectivities were observed when longer reaction times were required for attaining high conversions. These long reaction times were necessary due to the slow (or absent) racemization activity of the Ru(Shvo) catalyst as a result of catalyst deactivation. Since quantitative conversions are crucial to attain high molecular weight polymers in polycondensation reactions, we could significantly improve the system by switching to isopropyl esters of the AB monomers and/or by strict exclusion of oxygen during the ITC. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2721–2733, 2008     

Normal form theory for relative equilibria and relative periodic solutions

We show that in the neighbourhood of relative equilibria and relative periodic solutions, coordinates can be chosen so that the equations of motion, in normal form, admit certain additional equivariance conditions up to arbitrarily high order.

In particular, normal forms for relative periodic solutions effectively reduce to normal forms for relative equilibria, enabling the calculation of the drift of solutions bifurcating from relative periodic solutions.

     

Exact and heuristic methodologies for scheduling in hospitals: problems, formulations and algorithms

This text summarizes the PhD thesis defended by the author in January 2006 under the supervision of Professor Erik Demeulemeester at the Katholieke Universiteit Leuven. The thesis is written in English and is available from the author’s website (http://www.econ.kuleuven.be/jeroen.belien). In this research we propose a number of exact and heuristic algorithms for various scheduling problems encountered in hospitals. The emphasis lies on the design of new methodologies as well as on the applicability of the algorithms in real-life environments. The main contributions include a new decomposition approach for a particular class of staff scheduling problems, an extensive study of master surgery scheduling algorithms that aim at leveling the resultant bed occupancy and an innovative method for integrating nurse and surgery scheduling.