Tetrahedral nickel nitrosyl complexes with tripodal [N3] and [Se3] donor ancillary ligands: structural and computational evidence that a linear nitrosyl is a trivalent ligand

Linear nickel nitrosyl compounds supported by tridentate nitrogen and selenium ligands, namely the tris(3,5-dimethylpyrazolyl)hydroborato and tris(2-seleno-1-mesitylimidazolyl)hydroborato complexes, [TpMe2]NiNO and [TseMes]NiNO, have been synthesized and structurally characterized by X-ray diffraction. Computational studies demonstrate that the linear nitrosyl ligand behaves as a trivalent X3 ligand such that the Ni-N interaction has multiple bond character.     

Nonenzymatic Hydrolysis of Cocaine via Intramolecular Acid Catalysis

The spontaneous hydrolysis of the methyl-ester group of cocaine ( 1 ) in vivo contributes to the metabolic clearance of the drug in man. Neighboring-group participation by the tropane N-atom of cocaine in this hydrolysis was suggested by the normal stability of the methyl-ester groups of pseudococaine and N-acylnorcocaine. For cocaine, the relative rate of methyl-ester to benzoyl-ester hydrolysis was ca. 10:1 at pH≤7.4, and, although absolute rates increased with increasing pH, their ratio collapsed at pH>pK_a (8.6). These data are consistent with intramolecular acid catalysis of alkaline hydrolysis of the cocaine methyl-ester group under physiologic conditions.     

Solidification/stabilization of lead with the aid of bagasse as an additive to Portland cement

Solidification/stabilization (S/S) of hazardous waste is a widely used technology; therefore, it is crucial to evaluate its effectiveness and make attempts to improve the technique. A better matrix for S/S of hazardous waste was designed that is effective and economically feasible. This was accomplished by adding bagasse (byproduct of milling or diffusing sugar cane) to the waste/cement matrix. Lead nitrate was used as the model heavy metal waste with a 10 or 15% lead by weight to cement loading. Samples were cured for 7, 14, and 28 days at 24°C. Samples containing bagasse typically resulted in TCLP (modified) extract lead concentrations of approximately 0.5 mg/l of lead for all samples, while samples containing no bagasse had lead extract concentrations of approximately 5 mg/l for 10% samples and 45 mg/l for 15%. Results indicate that using bagasse as an additive to cement effectively improved the S/S of lead.     

Structure and bonding of KSiH3 and its 18-crown-6 derivatives: unusual ambidentate behavior of the SiH3(-) anion

Density functional theory (DFT) calculations of [K(18-crown-6)SiH(3)] (1) and KSiH(3) (2) have shown that both the classical tet and non-classical inv coordination modes of the [SiH(3)](-) anion to the K(+) ion are energetically accessible. Single-crystal X-ray structures of the tet and inv derivatives [K(18-crown-6)SiH(3)·THF] (1a) and [K(18-crown-6)SiH(3)·HSiPh(3)] (1b) confirm this conclusion, showing that small changes in the coordination sphere of the metal are sufficient to alter the orientation of the anion. A topological analysis of the calculated electron densities for 1 and 2 reveals that the K···Si interaction in the tet conformer of 2 possesses a significant amount of covalent character. In contrast, the inv form of 2 displays primarily electrostatic character for the K···Si and K···H interactions. Incorporation of the 18-crown-6 ligand in 1 reduces the polarizing power of the K(+) cation, hardening the cation-anion interaction in both conformers. The experimental structures of 1a and 1b bear out these conclusions, with the strongly bound tetrahydrofuran (THF) ligand softening the K(+) ion in 1a and favoring the tet conformer, while the weakly interacting HSiPh(3) ligand in 1b has minimal effect on the K(+) center, resulting in an inv orientation.     

On an efficient implementation and mass boundedness conditions for a discrete Dirichlet problem associated with a nonlinear system of singular partial differential equations

In this work, we propose an efficient implementation of a finite-difference method employed to approximate the solutions of a system of partial differential equations that appears in the investigation of the growth of biological films. The associated homogeneous Dirichlet problem is discretized using a linear approach. This discretization yields a positivity- and boundedness-preserving implicit technique which is represented in vector form through the multiplication by a sparse matrix. A straightforward implementation of this methodology would require a substantial amount of computer memory and time, but the problem is conveniently coded using a continual reduction of the zero sub-matrices of the representing matrix. In addition to the conditions that guarantee the positivity and the boundedness of the numerical approximations, we establish some parametric constraints that assure that the same properties for the discrete total mass at each point of the mesh-grid and each discrete time are actually satisfied. Some simulations are provided in order to illustrate both the performance of the implementation, and the preservation of the positivity and the boundedness of the numerical approximations.     

Convenient Pd‐Catalyzed Synthesis of Large Unimolecular Star Polyethylene Nanoparticles

A simplistic convenient “arm‐first” catalytic synthesis method is demonstrated to render soft unimolecular star polyethylene nanoparticles. Low‐dispersity polyethylene arms of controllable length and topology are first synthesized via Pd‐catalyzed “living” ethylene poly­merization. The subsequent addition of norbornadiene as a unique cross‐linker renders the block polymer containing a short polynorbornadiene (PNBD) sequence. Efficient and rapid catalytic cross‐linking of the PNBD sequences occurs in the polymer precipitation and drying steps to give rise to star polyethylene nanoparticles. The star polymers are featured with tunable arm length and topology, high molecular weight (as high as 1770 kg mol⁻¹), high arm numbers (as high as 88), and desirable average nano­particle size (29−72 nm).

     

Distinct functional and conformational states of the human lymphoid tyrosine phosphatase catalytic domain can be targeted by choice of the inhibitor chemotype

The lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, has recently been identified as a promising drug target for human autoimmunity diseases. Like the majority of protein-tyrosine phosphatases LYP can adopt two functionally distinct forms determined by the conformation of the WPD-loop. The WPD-loop plays an important role in the catalytic dephosphorylation by protein-tyrosine phosphatases. Here we investigate the binding modes of two chemotypes of small molecule LYP inhibitors with respect to both protein conformations using computational modeling. To evaluate binding in the active form, we built a LYP protein structure model of high quality. Our results suggest that the two different compound classes investigated, bind to different conformations of the LYP phosphatase domain. Binding to the closed form is facilitated by an interaction with Asp195 in the WPD-loop, presumably stabilizing the active conformation. The analysis presented here is relevant for the design of inhibitors that specifically target either the closed or the open conformation of LYP in order to achieve better selectivity over phosphatases with similar binding sites.     

Model validation in operations research

Numerous articles have appeared in the literature expressing different degrees of concern with the methodology of OR in general and with the validation of OR models in particular. Suggestions have been formulated to remove some of the shortcomings of the methodology as currently practised and to introduce modifications in the approach because of the changing nature of the problems tackled. Advances in modeling capabilities and solution techniques have also had considerable impact on the way validation is perceived. Large scale computer-based mathematical models and especially simulation models have brought new dimensions to the notion of validation. Terms like ‘confidence’, ‘credibility and reliability’, ‘model assessment and evaluation’, ‘usefulness and usability of the model’ have become rather common. This paper is an attempt, through an interpretation of the literature, to put model validation and related issues in a framework that may be of use both to model-builders and to decision-makers.