Microwave-assisted acylation of 7-amino-5-aryl-6-cyanopyrido[2,3-d]pyrimidines

A microwave-assisted method is described for monoacylating 7-amino-5-aryl-6-cyanopyrido[2,3-d]pyrimidines using excess acid chlorides in pyridine. A diacylated intermediate is effectively deacylated to the product amide by a macroporous-Tris resin. A small library of 17 amides was prepared to validate the method. The integration of commercial microwave technology into the ArQule chemistry platform is also discussed.     

A Counterexample to a Conjecture of Akemann and Anderson

Akemann and Anderson made a conjecture about ‘paving’projections in finite-dimensional matrix algebras which, iftrue, would settle the well-known Kadison–Singer problem.Their conjecture is falsified in this paper by an explicit sequenceof counterexamples.     

Crystal structure and spectroscopy of a hydrogen-bridged one-dimensional Cu(II) complex containing both octahedral and square pyramidal geometries in the same unit cell

Single crystals of the helical hydrogen-bridged one-dimensional Cu(II) complex, [Cu(stpy)₂(CH₃COO)₂(H₂O)₂] (1) [Cu(stpy)₂(CH₃COO)₂(H₂O)] (2), are prepared and characterized by elemental and thermal analyses, IR, electronic and X-ray crystal structure determination. The crystals are monoclinic, of space group C2/c, with unit cell parameters a = 31.842(7) Å, b = 5.9829(10) Å, c = 30.970(14) Å, = 111.78(3)°, Z = 4. The asymmetric unit contains two different types of Cu(II) polyhedra, namely, octahedron and square pyramid within the same unit cell. 1 has elongated octahedral geometry with two nitrogen atoms from stpy and two oxygen atoms from synmonodentate acetate ligands, transcoordinated to Cu(II) in the basal plane. The oxygen atoms of the two water molecules occupy the axial positions. 2 has Cu(II) coordination polyhedra similar to 1, except that only one of the apical positions is occupied by a water molecule. The structure consists of two independent linear chains, one involving octahedral (1) and the other involving square-pyramidal (2) polyhedra, held by hydrogen bridges. The Cu–Cu intra- and interchain separations in both 1 and 2 are 5.983 and 8.214 Å. The unit cell packing shows weak -stacking between adjacent coordinated stpy ligands in the chain, resulting in ladder-type structure. Further, the extended packing reveals helical arrangement of Cu(II) polyhedra in the lattice.     

Ab initio simulation of the BaZrO3 (0 0 1) surface structure

Electronic and atomic structures of different terminations of the (0 0 1) non-polar orientation of BaZrO₃ surfaces have been studied using first-principles calculations. We found that surface energies at both possible surface terminations, BaO and ZrO₂, were very close. The (0 0 1)-BaO and (0 0 1)-ZrO₂ terminated surfaces have bandgap values smaller than that of a bulk BaZrO₃ crystal. In addition, the relative surface stability has been analyzed as a function of chemical environment.     

Low temperature synthesis of ITO nanoparticles using polyol process

A low temperature synthesis technique to prepare indium tin oxide (ITO) nanoparticles by the polyol process is proposed. On examining the phase formation of ITO nanoparticles in polyols and alcohols such as ethylene glycol, trimethylene glycol, and 1-heptanol, it was found that ITO nanoparticles could be synthesized directly without any post--annealing treatments at 175 °C in 1-heptanol. The morphology of the particles is influenced by the type of polyol. The composition of Sn in the ITO system could be easily controlled by simply varying the In/Sn precursor ratio in 1-heptanol. The low temperature synthesis method has enabled the formation of highly crystalline ITO nanoparticles with diameters less than 25 nm even at annealing temperatures as high as 700 °C.     

Collisional activation of protein complexes: Picking up the pieces

Mass spectrometry is fast becoming a vital approach not only for the identification and quantification of proteins, but also for the study of the noncovalent assemblies they form. Approaches for ionizing, transmitting, and detecting protein complexes intact in the mass spectrometer are now well established. The challenge has therefore shifted to developing and applying mass spectrometry approaches to elucidate the structure of such species. A crucial aspect to this goal is inducing their disassembly in the gas phase to mine information as to their composition and organization. Here the consequences of collisionally activating protein complexes are illustrated through ion mobility mass spectrometry measurements and discussed in the context of the current literature. Although a consensus view of the mechanism of dissociation is starting to emerge, it is also clear that a number of aspects remain unresolved. These outstanding questions and frontier challenges must be addressed if gas-phase dissociative approaches are to reach their full potential in the study of protein assemblies.     

MAOS ls for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines

General, high-yielding MAOS protocols for the expedient synthesis of functionalized 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines are described amenable to an iterative analog library synthesis strategy for the lead optimization of an M1 antagonist screening hit. Optimized compounds proved to be highly selective M1 antagonists.     

Monitoring the heterogeneity in single cell responses to drugs using electrochemical impedance and electrochemical noise

Impedance spectroscopy is a widely used technique for monitoring cell–surface interactions and morphological changes, typically based on averaged signals from thousands of cells. However, acquiring impedance data at the single cell level, can potentially reveal cell-to-cell heterogeneity for example in response to chemotherapeutic agents such as doxorubicin. Here, we present a generic platform where light is used to define and localize the electroactive area, thus enabling the impedance measurements for selected single cells. We firstly tested the platform to assess phenotypic changes in breast cancer cells, at the single cell level, using the change in the cell impedance. We next show that changes in electrochemical noise reflects instantaneous responses of the cells to drugs, prior to any phenotypical changes. We used doxorubicin and monensin as model drugs and found that both drug influx and efflux events affect the impedance noise signals. Finally, we show how the electrochemical noise signal can be combined with fluorescence microscopy, to show that the noise provides information on cell susceptibility and resistance to drugs at the single cell level. Together the combination of electrochemical impedance and electrochemical noise with fluorescence microscopy provides a unique approach to understanding the heterogeneity in the response of single cells to stimuli where there is not phenotypic change.

A light addressable single-cell impedance technique for cell adhesion monitoring and measurement of a cell''s drug response based on electrochemical noise is introduced.     

Optical nonlinearity of organic dyes as studied by Z-scan and transient grating techniques

The excited state absorption cross-section of 5,5′-dichloro-11-diphenyl-amino-3,3′-diethyl-10, 12-ethylinethiatricarbocyanine perchlorate (IR140) have been measured by using a single beam transmission technique. Z-scan experiments have been used to find out a few nonlinear parameters. The excited state relaxation times have also been measured by using laser induced transient grating (LITG) technique.     

Synthesis of highly substituted 2,6-anti-configured tetrahydropyrans. First steps towards an efficient access to amphidinol 3 ring system

Highly functionalised and polysubstituted tetrahydropyrans, akin to the middle core of the amphidinols, can be efficiently synthesised, with full stereocontrol and in good yields, using as key steps an anti-allylation reaction coupled with an intramolecular Sakurai cyclisation. Three approaches were devised in order to reach a broad range of substitution patterns.