Structural, electronic, thermodynamic and optical properties of SrS1−xOx mixed crystals

The structural, electronic and thermodynamic properties of the SrS_1–xO_x ternary mixed crystals have been studied using the ab initio full potential linearized augmented plane wave (FP-LAPW) method within density functional theory. The effect of composition on lattice parameter, bulk modulus and band gap was investigated. The lattice constants from Vegard's law and the bulk modulus from linear concentration dependence were observed for the alloys. The microscopic origins of the gap bowing were explained by using the approach of Zunger and co-workers. The thermodynamic stability of these alloys was investigated by calculating the excess enthalpy of mixing ΔH_m as well as the phase diagram. In addition to FP-LAPW method, the composition dependence of the refractive index and the dielectric constant was studied by different models.     

Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I

A series of compounds based on the carboxyl-terminal CAAL sequence of PGGTase-I substrates was designed and synthesized. Using piperazin-2-one as a semi-rigid scaffold, we have introduced critical pharmacophores in a well-defined arrangement to mimic the CAAL sequence. High potency and exceptional selectivity were obtained for inhibition of PGGTase-I with structures such as 45 and 70. Potency of this series of GGTIs was dependent on the presence of an L-leucine residue with a free carboxyl terminus, as well as an S configuration of the 3-aryl group. The selectivity was significantly enhanced by 5-methyl substitution on the imidazole ring and fluorine substitution on the 3-aryl group. Modification of the 6-position of the piperazinone scaffold was found to be unfavorable. Compounds 44 and 69, the corresponding methyl esters of 45 and 70, were found to selectively block processing of Rap1A by PGGTase-I in whole cells with IC(50) values of 0.4 microM and 0.7 microM respectively.     

Structure-activity studies on a library of potent calix[4]arene-based PDGF antagonists that inhibit PDGF-stimulated PDGFR tyrosine phosphorylation

Platelet-derived growth factor (PDGF) and its receptor PDGFR are required for tumor growth and angiogenesis, so disruption of the PDGF-PDGFR interaction should lead to starvation of tumors and reduction of tumor growth. Potent PDGF antagonists have been discovered through the synthesis of a series of calix[4]arene-based compounds that are designed to bind to the three-loop region of PDGF. The effect of lower-rim alkylation, linker and number of interacting head groups on the calix[4]arene scaffold on PDGF affinity and cellular activity has been investigated.     

Structural,electronic,elastic,and thermal properties of CaNiH_3 perovskite obtained from first-principles calculations

A theoretical study of the structural, elastic, electronic, mechanical, and thermal properties of the perovskite-type hydride CaNiH_3 is presented. This study is carried out via first-principles full potential(FP) linearized augmented plane wave plus local orbital(LAPW+lo) method designed within the density functional theory(DFT). To treat the exchange–correlation energy/potential for the total energy calculations, the local density approximation(LDA) of Perdew–Wang(PW)and the generalized gradient approximation(GGA) of Perdew–Burke–Ernzerhof(PBE) are used. The three independent elastic constants(C_(11), C_(12), and C_(44)) are calculated from the direct computation of the stresses generated by small strains.Besides, we report the variation of the elastic constants as a function of pressure as well. From the calculated elastic constants, the mechanical character of CaNiH_3 is predicted. Pertaining to the thermal properties, the Debye temperature is estimated from the average sound velocity. To further comprehend this compound, the quasi-harmonic Debye model is used to analyze the thermal properties. From the calculations, we find that the obtained results of the lattice constant(a_0), bulk modulus(B_0), and its pressure derivative(B_0') are in good agreement with the available theoretical as well as experimental results. Similarly, the obtained electronic band structure demonstrates the metallic character of this perovskite-type hydride.     

First-principle calculations of the fundamental properties of CuBrxI1−x ternary alloy

Ab initio full-potential linearised augmented plane wave (FP-LAPW) method within density functional theory is applied to study the effect of composition on the structural, electronic and thermodynamic properties of CuBr_xI_1?x ternary alloy. The structural properties at equilibrium are investigated by using the new form of generalised gradient approximations that are based on the optimisation of total energy. For band structure calculations, both Engel–Vosko and modified Becke–Johnson of the exchange-correlation energy and potential, respectively, are used. Deviation of the lattice constants from Vegard's law and the bulk modulus from linear concentration dependence are observed. The microscopic origins of the gap bowing were explained by using the approach of Zunger and co-workers. On the other hand, the thermodynamic stability of this alloy was investigated by calculating the excess enthalpy of mixing ?Hm as well as the phase diagram by calculating the critical temperatures. A numerical first-principle calculations of the elastic constants as function of pressure is used to calculate C₁₁, C₁₂ and C₄₄.     

Phase stability and electronic properties of silver halides

In this work, we study the phase stability and electronic properties of silver halides ( AgBr, AgCl and AgI) using the full-potential linearized augmented plane wave method within the density functional theory. In this approach, the Wu–Cohen generalized gradient approximation was used for the exchange–correlation potential. Moreover, the modified Becke–Johnson approximation was also used for band-structure calculations. Various structural phase transitions were considered here in order to confirm the most stable structure and to predict the phase transition under hydrostatic pressure. In addition, we have studied the band structures of the stable phases of these compounds which reveal that the three compounds exhibit semiconducting behavior. The results obtained are compared with other calculations and experimental measurements.     

Le phosphate naturel modifié au vanadium : un nouveau catalyseur pour l’oxydation des cycloalcanones et des α-cétols en présence de l’oxygène moléculaire

In this work, we have studied the catalytic oxidative cleavage of C-C bonds of cycloalkanones and α-ketols, in the presence of natural phosphate (NP) type fluorapatite, Ca₁₀(PO₄)₆F₂, and dioxygen. The aim was to find a heterogeneous system clean and efficient alternative to the industrial oxidation of cyclohexanone to adipic acid with nitric acid. The modification of the NP by vanadium leads to the preparation of a new catalyst V/PN. The latter was characterized by: XRD, FTIR, SEM and BET. It appears that vanadium is well dispersed on the surface of the NP. Using 2-methylcyclohexanone as model substrate, we optimized the conditions of reaction in order to make the system ‘V/PN/O₂’ more performance. The comparative study between the two catalytic systems ‘PN/O₂’ and ‘V/PN/O₂’ shows that the latter is more active. Finally, the system ‘V/PN/O₂’ has been recycled but low leaching of vanadium was observed in the first use of the catalyst.     

Natural microphosphate as a catalyst for Knoevenagel condensation: specific surface effect

The effect of specific surface of natural phosphate on Knoevenagel condensations involving aldehydes and activated methylene is studied. The best catalytic activities were observed with catalyst micronised (NPm). This revised version was published online in June 2006 with corrections to the Cover Date.     

Protein farnesyltransferase: Flexible docking studies on inhibitors using computational modeling

Summary Using MacroModel, peptide, peptidomimetic and non-peptidomimetic inhibitors of the zinc metalloenzyme, farnesyltransferase (FTase), were docked into the enzyme binding site. Inhibitor flexibility, farnesyl pyrophosphate substrate flexibility, and partial protein flexibility were taken into account in these docking studies. In addition to CVFM and CVIM, as well as our own inhibitors FTI-276 and FTI-2148, we have docked other farnesyltransferase inhibitors (FTIs) including Zarnestra, which presently is in advanced clinical trials. The AMBER* force field was employed, augmented with parameters that were derived for zinc. A single binding site model that was derived from the crystal structure of CVFM complexed with farnesyltransferase and farnesylpyrophosphate was used for these studies. The docking results using the lowest energy structure from the simulation, or one of the lowest energy structures, were generally in excellent agreement with the X-ray structures. One of the most important findings of this study is that numerous alternative conformations for the methionine side chain can be accommodated by the enzyme suggesting that the methionine pocket can tolerate groups larger than methionine at the C-terminus of the tetrapeptide and suggesting alternative locations for the placement of side chains that may improve potency.     

Terphenyl-Based Bak BH3 alpha-helical proteomimetics as low-molecular-weight antagonists of Bcl-xL

We describe a general method for the mimicry of one face of an alpha-helix based on a terphenyl scaffold that spatially projects functionality in a manner similar to that of two turns of an alpha-helix. The synthetic scaffold reduces the flexibility and molecular weight of the mimicked protein secondary structure. We have applied this design to the development of antagonists of the alpha-helix binding protein Bcl-x(L). Using a sequential synthetic strategy, we have prepared a library of terphenyl derivatives to mimic the helical region of the Bak BH3 domain that binds Bcl-x(L). Fluorescence polarization assays were carried out to evaluate the ability of terphenyl derivatives to displace the Bcl-x(L)-bound Bak peptide. Terphenyl 14 exhibited good in vitro affinity with a K(i) value of 0.114 muM. These terphenyl derivatives were more selective at disrupting the Bcl-x(L)/Bak over the HDM2/p53 interaction, which involves binding of the N-terminal alpha-helix of p53 to HDM2. Structural studies using NMR spectroscopy and computer-aided docking simulations suggested that the helix binding area on the surface of Bcl-x(L) is the target for the synthetic ligands. Treatment of human embryonic kidney 293 (HEK293) cells with terphenyl derivatives resulted in the disruption of the binding of Bcl-x(L) to Bax in intact cells.