Synthesis and Reactions of Some Novel Triazolo‐, Azolo‐, Tetrazolo‐Pyridopyrimidine and Their Nucleoside Derivatives

Pyridopyrimidine reacted with aromatic aldehydes afforded the arylhydrazone 2a,b which could be cyclized into the pyrido[2,3‐d][1,2,4]triazolo[4,3‐a]pyrimidine 3a,b , with formic acid, and carbon disulphide to give pyrido[2,3‐d][1,2,4]traizolo[4,3‐a]pyrimidine 4, 5. Reaction of 1 with nitrous acid afforded tetrazolo[1,5‐a]pyrido[2,3‐d]pyrimidine 6 , which was reduced by zinc dust to give 2‐amino‐pyrido‐[2,3‐d]pyrimidine 7. Finally the reaction of 2‐hydrazino 1 with D‐xylose or D‐glucose afforded the acyclic N‐nucleoside 8, 11 which were converted into tetra/penta O‐acetate acyclic C‐nucleoside 9, 12 in acetic anhydride/pyridine. De‐acetylation of compounds 9, 12 afforded C‐nucleosides 10, 13.     

D3R Grand Challenge 2: blind prediction of protein–ligand poses,affinity rankings,and relative binding free energies

The Drug Design Data Resource (D3R) ran Grand Challenge 2 (GC2) from September 2016 through February 2017. This challenge was based on a dataset of structures and affinities for the nuclear receptor farnesoid X receptor (FXR), contributed by F. Hoffmann-La Roche. The dataset contained 102 IC50 values, spanning six orders of magnitude, and 36 high-resolution co-crystal structures with representatives of four major ligand classes. Strong global participation was evident, with 49 participants submitting 262 prediction submission packages in total. Procedurally, GC2 mimicked Grand Challenge 2015 (GC2015), with a Stage 1 subchallenge testing ligand pose prediction methods and ranking and scoring methods, and a Stage 2 subchallenge testing only ligand ranking and scoring methods after the release of all blinded co-crystal structures. Two smaller curated sets of 18 and 15 ligands were developed to test alchemical free energy methods. This overview summarizes all aspects of GC2, including the dataset details, challenge procedures, and participant results. We also consider implications for progress in the field, while highlighting methodological areas that merit continued development. Similar to GC2015, the outcome of GC2 underscores the pressing need for methods development in pose prediction, particularly for ligand scaffolds not currently represented in the Protein Data Bank (http://www.pdb.org), and in affinity ranking and scoring of bound ligands.     

Neutron scattering experiments on fully deuterated liquid N-methylformamide DCONDCD3 at various temperatures and under pressure. Comparison to X-ray results

Neutron scattering experiments are performed on fully deuterated liquid N-methylformamide (C2D5NO) at various temperatures and under pressure. The recorded data at atmospheric pressure and room temperature are analyzed to yield the molecular form factor and the distinct pair correlation function. Our measurements clearly show that the hydrogen-bond network, of which the parameters are deduced, persists locally in the liquid. The experimental structure factor could be explained in terms of short-range crystal structure. The r(N...O) distance decreases with increasing temperature from 293 to 398 K, whereas no significant variation of the intermolecular structure is detected when varying pressure from 1 bar to 4 kbar. Along the study, some comparison is made with complementary X-ray results.     

Inverse thermal analysis of the drying zone of the evaporator of an axially grooved heat pipe

An inverse approach is performed to characterize the thermal behaviour of an axially grooved heat pipe, in steady state, for various operating conditions. For this purpose, an experimental set up, as well as a network conduction model, are developed to simulate the heat transfer in the wall at the evaporator section. The minimization of an objective function, taking into account the discrepancy between measured temperatures and computed ones, allows then the estimation of a heat transfer coefficient as well as the drying out front positions for all the axial grooves. Hence, at the burnout point, the significant temperature increase in the evaporator extremity is considered to be a direct consequence of the restriction of the evaporative zone. Therefore, the distribution of liquid phase in the capillary structure of the heat pipe can be obtained through the analysis of the measured temperature gradient in the evaporator section where the dry out front was expected to occur. Furthermore, the dry out front expansion can be observed when the input heat load is increased or when the adiabatic temperature is decreased. Introducing an adverse tilt angle also shows the effect of the puddle.     

Action des Hydrazines Fluoroalkylées Sur Les α-Cetophosphonates: Synthèse des Hydrazones α-Phosphonylées N-Fluoroalkylées

In the present work, we study the reaction of fluorinated hydrazines H ₂ N-NHR _F with α-ketophosphonates 1, which lead to N-fluoroalkylated α-phosphonylated hydrazones 2. The stereochemistry of the hydrazones 2 was determined by multinuclear NMR experiments ( ¹ H, ¹³ C, ¹⁹ F, and ³¹ P) and IR spectroscopy.     

Cation-deficient lanthanum manganite oxides: Experimental and theoretical studies

Cation-deficient lanthanum manganite oxides with 0.8 ≤ La/Mn ≤ 1.25 were synthesized using a multi-step decomposition of gel precursors and investigated from experimental and theoretical point of view. The XRD (X-Ray Diffraction) analysis of the mixed LaMnO₃ oxide crystal concludes to a hexagonal structure, space group R-3c, excluding the presence of pure oxides such as La₂O₃, Mn₂O₃, or MnO₂ whatever the ratio La/Mn is. Oxides with nominal formulae La_1?xMnO_3+y and LaMn_1?x′O_3+y contain more than one defect structure involving valence defect (holes h), anionic vacancies as well as cationic vacancies in A and B sublattices of the perovskite structure. With the increase of La or Mn non-stoichiometry, the oxygen content y decreases more with La-deficient compositions than with Mn-deficient ones. The La/Mn ratio influences strongly the relationship between [h], [V_O], [V_La^?] and [V_Mn^?].The DFT-GGA (Density functional Theory, Generalized-Gradient Approximation) simulation of these compounds using VASP (Vienna Ab-initio Simulation Package) concludes that the electronic structure for the optimized stoichiometric La₆Mn₆O₁₈ is not optimal, relative to that expected considering Mn(III) ions with four alpha electrons each. The non-stoichiometry is the easiest way of reducing the Jahn–Teller instability by depopulating the half-filled e_g orbitals. A partial oxidation is then stabilizing. Creation of defects, either an O insertion or a cationic vacancy, allows finding an ideal count. In the case of pure cationic defects (missing a La(III) or a Mn(III) cation), the amount of vacancies is one missing cation upon twelve. The compact nature of lanthanum manganite oxide does not allow oxygen insertion within the bulk structure and oxidation can only be achieved at the surface without O penetration. The formation of antisites is endothermic. The creation of mixed vicinal vacancies, one oxygen and one cationic vacancy (La or Mn), is exothermic for a concentration of defects of one defect per twelve cations.     

Using Electron Induced Dissociation (EID) on an LC Time-Scale to Characterize a Mixture of Analogous Small Organic Molecules

LC ESI FTICR MS of a sample of cediranib identified this pharmaceutical target molecule plus an additional 10 compounds of interest, all of which were less than 10% total ion current (TIC) peak intensity relative to cediranib. LC FTICR tandem mass spectrometry using electron induced dissociation (EID) has been achieved and has proven to be the best way to generate useful product ion information for all of these singly protonated molecules. Cediranib [M + H]⁺ fragmented by EID to give 29 product ions whereas QTOF-CID generated only one very intense product ion, and linear ion trap-CID, which generated 10 product ions, but all with poor S/N. Twenty-six of the EID product ions were unique to this fragmentation technique alone. By considering the complementary LC-EID and LC-CID data together, all 10 unknown compounds were structurally characterized and proven to be analogous to cediranib. Of particular importance, EID produced unique product ion information for one of the low level cediranib analogues that enabled full characterization of the molecule such that the presence of an extra propylpyrrolidine group was discovered and proven to be located on the pyrrolidine ring of cediranib, solving an analytical problem that could not be solved by collision induced dissociation (CID). Thus, it has been demonstrated that EID is in harmony with the chromatography duty-cycle and the dynamic concentration range of synthetic compounds containing trace impurities, providing crucial analytical information that cannot be obtained by more traditional methodologies.     

Antifungal effects of secondary metabolites isolated from marine organisms collected from the Tunisian coast

Phallusides 1,2,3 (1), Fasciculatin (2), Acanthelline (3), Axisonitrile (4), Oroïdin (5) and the Novel bromopyrolimidazolic compound Axinellizine (6) were evaluated for their antifungal effects against several phytopatogenic fungi and were found to possess considerable activities. Insecticidal effect of only Acanthellin (3) against the major pest of stored products Tribolium confusum Duv has been carried out using direct contact application method showing a significant inhibitory effect of the test material on the T. confusum Duv larvae growth. Forty-five percent mortality of the adults was achieved 8 days after treatment.     

On Odd Perturbations of Free Fermion Fields

We study the scattering theory of fermion systems subject to a smooth local perturbation with a non-vanishing odd part. We introduce a modified free fermion fields which have an appropriate commutation relations with the free Fock fermion fields. We construct the wave operators using the modified field and prove asymptotic completeness. Our work extends former results on Hilbert space asymptotic completeness.