Fluorine-NMR experiments for high-throughput screening: theoretical aspects,practical considerations,and range of applicability

Competition ligand-based NMR screening experiments have recently been introduced to overcome most of the problems associated with traditional ligand-based NMR screening. Molecules with marginal solubility and high affinity for a given target can be easily identified in a high-throughput manner by screening chemical mixtures against the target in the presence of a weak- to medium-affinity ligand of known binding constant. While the original competition-based approaches utilized (1)H detection, significant advantages are obtained using (19)F detection. The absence of spectral overlap permits the screening of large chemical mixtures and allows for automated analysis of the spectra, even in the presence of protonated buffers, solvents, and detergents. The large chemical shift anisotropy of fluorine and the significant exchange contribution allow for the selection of a weak-affinity spy molecule, thus resulting in a lower binding affinity threshold for the identified NMR hits. The method, labeled FAXS (fluorine chemical shift anisotropy and exchange for screening) is rapid and requires only a limited amount of protein and, therefore, compares favorably with the other established non-NMR techniques used in high-throughput screening. Herein the theoretical aspects of this powerful (19)F-based approach are presented and discussed in detail. The experimental conditions together with the detection limits and binding constant measurements are investigated using human serum albumin as the target.     

Minimally almost periodic totally disconnected groups

In this paper we prove that every closed noncompact group of isometries of a homogeneous tree which acts transitively on the tree boundary contains a normal closed cocompact subgroup which is minimally almost periodic. Moreover we prove that is a topologically simple group.

     

Synthesis and Study of the Photophysical Properties of a New Eu<Superscript>3+</Superscript> Complex with 3-Hydroxypicolinamide

This work reports on the synthesis and characterization of a new complex of Eu³⁺ with the 3-hydroxypicolinamide ligand (Hhpa). Here we present an approach for obtaining bis[2-carbamoyl(κO)pyridin-3-olato(κO’)] lanthanide complexes, which were characterized through elemental analysis, thermal analysis, infrared and photoluminescence spectroscopies (emission, excitation, luminescence lifetimes, quantum efficiencies, Judd-Ofelt parameters and quantum yields). Although hpa can act as a bidentate ligand in different conformations, the results attest for the occurrence of a unique coordination site of low symmetry for the Eu³⁺ ions, in which two anionic hpa ligands coordinate the cations through an O/O chelating system. The phosphorescence of the synthesized gadolinium complex provides the energy of the triplet state, which is determined to be at 20,830 cm^-1 over the ground state. This makes the Hhpa ligand very adequate for sensitizing the Eu³⁺ luminescence, which leads to a very efficient antenna effect and opens a wide range of applications for the complex in light emitting organic-inorganic devices.     

Complex dynamics and configurational entropy of spatial optical solitons in nonlocal media

Intense light propagating in a nonlinear medium can generate an ensemble of interacting filaments of light, or spatial solitons. Using nematic liquid crystals, we demonstrate that the filaments exhibit collective behavior typical of complex systems, including the formation of clusters and soundlike vibrations, as well as the reduction of the configurational entropy, controlled by the degree of nonlocality of the medium.     

Synthesis, antimicrobial and antiproliferative activity of novel silver(I) tris(pyrazolyl)methanesulfonate and 1,3,5-triaza-7-phosphadamantane complexes

Five new silver(I) complexes of formulas [Ag(Tpms)] (1), [Ag(Tpms)(PPh(3))] (2), [Ag(Tpms)(PCy(3))] (3), [Ag(PTA)][BF(4)] (4), and [Ag(Tpms)(PTA)] (5) {Tpms = tris(pyrazol-1-yl)methanesulfonate, PPh(3) = triphenylphosphane, PCy(3) = tricyclohexylphosphane, PTA = 1,3,5-triaza-7-phosphaadamantane} have been synthesized and fully characterized by elemental analyses, (1)H, (13)C, and (31)P NMR, electrospray ionization mass spectrometry (ESI-MS), and IR spectroscopic techniques. The single crystal X-ray diffraction study of 3 shows the Tpms ligand acting in the N(3)-facially coordinating mode, while in 2 and 5 a N(2)O-coordination is found, with the SO(3) group bonded to silver and a pendant free pyrazolyl ring. Features of the tilting in the coordinated pyrazolyl rings in these cases suggest that this inequivalence is related with the cone angles of the phosphanes. A detailed study of antimycobacterial and antiproliferative properties of all compounds has been carried out. They were screened for their in vitro antimicrobial activities against the standard strains Enterococcus faecalis (ATCC 29922), Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Streptococcus pyogenes (SF37), Streptococcus sanguinis (SK36), Streptococcus mutans (UA159), Escherichia coli (ATCC 25922), and the fungus Candida albicans (ATCC 24443). Complexes 1-5 have been found to display effective antimicrobial activity against the series of bacteria and fungi, and some of them are potential candidates for antiseptic or disinfectant drugs. Interaction of Ag complexes with deoxyribonucleic acid (DNA) has been studied by fluorescence spectroscopic techniques, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA-EB system on addition of Ag complexes shows that the fluorescence quenching of DNA-EB complex occurs and compound 3 is particularly active. Complexes 1-5 exhibit pronounced antiproliferative activity against human malignant melanoma (A375) with an activity often higher than that of AgNO(3), which has been used as a control, following the same order of activity inhibition on DNA, i.e., 3 > 2 > 1 > 5 > AgNO(3)? 4.     

Estimation of the degree of asphericity of a glass sphere using a vectorial shearing interferometer

The degree of asphericity is estimated by determining the average radius of curvature in different sections, at various points on the surface of a sphere, and the deviation from it. We employ the vectorial shearing interferometer (VSI) as the instrument to determine the radius of curvature from two subapertures of the transparent glass sphere. We incorporate the sphere as a thick lens into the interferometric setup, illuminating it with an expanded beam. The spherical aberration, introduced by the sphere in the wave front, depends on the local sphere radius, on the refraction index of the glass, and on the cone angle of the source. The wave front aberrated by the sphere impinges on the VSI. Here, the wave front is divided in two in amplitude, it is sheared vectorially, and it is superimposed with itself. The fringe pattern is formed in the intersection of the wave fronts. The shape of the resulting fringe pattern is directly related to spherical aberration. We estimate qualitatively the degree of asphericity, comparing the phase gradients in different sections of the sphere. Here, we report on the experimental setup to test the asphericity, the results with different vectorial shearing (magnitude and direction). Finally, we perform a comparison with the theoretical predictions.     

Reactivity of the tetrahydroborate copper(I) complexes [(PR3)2Cu(η2-BH4)] (R = Ph,Cy) toward CO2, COS,and SCNPh

CO₂, COS, and SCNPh react under very mild conditions with the copper(I)-tetrahydroborate complexes [(PR₃)₂Cu(η²-BH₄)] (R = Ph, Cy); CO₂ and COS give the complexes [(PR₃)₂Cu(η²-O₂CH)] and [(PR₃)₂Cu(η²-OSCH)] respectively, whereas SCNPh gives the η²-dithiocarbamate complexes [(PR₃)₂Cu-(η²-S₂CNHPh)]. Addition of PPh₃ under CO₂ to solutions of [(PPh₃)₂Cu-(η²-BH₄)] gives [(PPh₃)₃Cu(η¹-O₂CH)] while addition of PPh₃ and NBu₄ClO₄ under CO₂ gives [(PPh₃)₃Cu(η-O₂CH)Cu(PPh₃)₃] ClO₄.     

Synthesis of bis(2-chloroethyl)amino-1,8-naphthyridines for evaluation as anticancer agents

Some 1,8-naphthyridine nitrogen mustards have been synthesized for studies of their antitumor potentialities. All the tested intermediate and target compounds are devoid of antitumor properties.