Methylxanthine drugs are chitinase inhibitors: investigation of inhibition and binding modes

Family 18 chitinases play key roles in a range of pathogenic organisms and are overexpressed in the asthmatic lung. By screening a library of marketed drug molecules, we have identified methylxanthine derivatives as possible inhibitor leads. These derivatives, theophylline, caffeine, and pentoxifylline, are used therapeutically as antiinflammatory agents, with pleiotropic mechanisms of action. Here it is shown that they are also competitive inhibitors against a fungal family 18 chitinase, with pentoxifylline being the most potent (K(i) of 37 microM). Crystallographic analysis of chitinase-inhibitor complexes revealed specific interactions with the active site, mimicking the reaction intermediate analog, allosamidin. Mutagenesis identified the key active site residues, conserved in mammalian chitinases, which contribute to inhibitor affinity. Enzyme assays also revealed that these methylxanthines are active against human chitinases.     

Synthesis and study of 4‐(4′‐n‐alkoxybenzoyloxybenzoyl)‐4′′‐n‐butoxyanilides

Thirteen compounds with ester and amide linkages were synthesized and their mesogenic properties evaluated. Methyl to n‐propyl derivatives exhibit nematic phases, n‐butyl to n‐decyl derivatives exhibit smectic and nematic mesophases, whereas n‐dodecyl to n‐octadecyl derivatives exhibit only smectic phases. All the smectic homologues exhibit smectic C phases. Middle members of the homologous series exhibit polymorphism of smectic mesophase. A plot of transition temperatures versus number of carbon atoms in the alkoxy chain reveals an odd–even effect for nematic–isotropic transition temperatures. Nematic–isotropic and smectic–cholesteric thermal stabilities of the prepared compounds (series I) are higher compared to those of previously reported compounds, series A, B and C. The results indicate that a simple reversal of a central linkage has a dramatic effect on the appearance of smectic mesophase in a homologous series. The structures of the synthesized compounds were characterized using elemental analysis, thin‐layer chromatography and spectral data.     

Rhodium(II)‐Catalyzed Nondirected Oxidative Alkenylation of Arenes: Arene Loading at One Equivalent

A bimetallic Rh^II catalyst promoted the C? H alkenylation of simple arenes at 1.0 equivalent without the use of a directing group. A phosphine ligand as well as cooperative reoxidation of Rh^II with Cu(TFA)₂ and V₂O₅ proved essential in providing monoalkenylated products in good yields and selectivities, especially with di‐ and trisubstituted arenes.     

Synthesis of pyrrolo[2,3-b]azepine-4,7-dione derivatives

The Dieckmann reaction has been successfully applied for the first time in the synthesis of pvrrolo[2,3-b)]azepines.     

A generic mathematical model of single point cutting tools in terms of grinding parameters

The paper presents the analytical geometric details of the mathematical modeling of a single point cutting tool with a generic profile. The grinding angles and the ground depths on the tool are allowed to vary along the tool flanks and face, altering the cutting angles from point to point. The surface modeling begins with the creation of a tool blank model. Then unbounded surfaces are considered and transformed to get the cutting tool surfaces. The intersection of these surfaces gives the complete model of the tool. Starting from the basic model where the tool face and flank are planar, the generalization of the geometric design has been done in two steps to give free-form shapes to the tool surfaces, termed as the two generations of the generic profile. Then a forward and inverse mapping has been presented for the basic model and the two generations of the generic tool to relate the grinding angles with the prevalent nomenclatures (ASA, ORS and NRS). The model has been validated and the variation of tool angles with the grinding parameters has been illustrated with an example.     

On the hyperfine spectral lines of an atomic copper vapor laser

The hyperfine structure of energy levels of copper atom and its transition probabilities were considered. The resonance and metastable levels of the copper atom are split into hyperfine structures, due to the magnetic dipole moment and the electric quadrupole moment. In this paper, a succinct introduction to the relevant theory of the hyperfine spectral structure and experimental observations of elemental copper vapor laser is presented.     

Vibrational dynamics of Co<Subscript>67</Subscript>Zr<Subscript>33</Subscript> semiconductor glassy alloy

The computation of vibrational dynamics of semiconductor Co₆₇Zr₃₃ glassy alloy has been reported for the first time that uses a different theoretical model potential formalism with Wills-Harrison (WH) form. Various local field correction functions are used to study the screening influence. The thermodynamic and elastic properties are also estimated from the elastic limits of the phonon dispersion curves (PDC). The dispersion frequency with respect to the wavenumber is found to be influenced by the dielectric screening due to the conduction electrons. Values obtained using the S-local field correction function and BS approach tend to be greater than other values calculated. The text was submitted by the authors in English. Zhurnal Strukturnoi Khimii, Vol. 50, No. 2, pp. 235–242, March–April, 2009.     

Screening-dependent superconducting state parameters of transition metals-based binary alloys

Study of the screening-dependent superconducting state parameters, namely, electron-phonon coupling strength λ, Coulomb pseudopotential μ*, transition temperature T _C , isotope effect exponent α, and effective interaction strength N ₀ V of 3d-transition metals-based binary alloys is made extensively using a model potential. A considerable influence of different exchange and correlation functions on λ and μ* is found. The obtained results are in qualitative agreement with the available experimental data wherever exist.