Multi-selective one dimensional proton NMR experiments for rapid screening and binding affinity measurements

High-throughput ligand-based proton NMR screening performed in the presence of a spy molecule and a control molecule is a valuable tool for identifying drug leads. A limitation of the technique is represented by the severe overlap encountered in the screening of large chemical mixtures. An approach for overcoming this overlap problem is the use of multi-selective R(1) filtered and COSY or TOCSY experiments. Application of this methodology to compounds binding to the Sudlow site I of human serum albumin is presented. The screening is performed by simply monitoring the intensity of two signals. The precise measurement of the relative intensity of the two resonances permits determination of the binding constant of the NMR-hit. For a simple competition binding mechanism, the rapidly-derived NMR binding constants are in good agreement with the values derived from full-titration ITC and fluorescence spectroscopy measurements.     

Nanofocusing of optical energy in tapered plasmonic waveguides

We predict theoretically that surface plasmon polaritons propagating toward the tip of a tapered plasmonic waveguide are slowed down and asymptotically stopped when they tend to the tip, never actually reaching it (the travel time to the tip is logarithmically divergent). This phenomenon causes accumulation of energy and giant local fields at the tip. There are various prospective applications in nano-optics and nanotechnology.     

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.     

Femtosecond optical responses of disordered clusters, composites, and rough surfaces: "the ninth wave" effect

We predict that in the course of femtosecond excitation of random clusters, composites, or rough surfaces in the optically linear regime, ultrafast giant fluctuations of local fields occur. These fluctuations cause transient (on a femtosecond scale) formation of highly enhanced fields localized in nanometer-size regions ("the ninth wave effect"). The spatial distribution of those fields is dramatically different from the case of steady-state excitation. We discuss manifestations of this effect and possible experiments.     

Plasmonic enhancing nanoantennas for photodetection

This paper discusses the use of plasmonic nanostructured systems as nanoantennas for photodetection. Even though semiconductors and their heterostructures have many useful properties and widely used in photodetection, their electron density is very small compared to that of metals and, therefore, they have low absorption cross sections. The idea of using metal nanostructured antennas is to combine the high optical responses of metals with the functional electric properties of semiconductors.     

Some Isoperimetric Inequalities in Electrochemistry and Hele Shaw Flows

Isoperimetric inequalities are applied to a moving-boundaryproblem for doubly-connected domains. This problem occurs forexample in electrochemistry, in which case the domains in questionare the electrolyte of an electrolytic cell. The two electrodessurrounding the electrolyte are assumed to grow or dissolve,at different rates in general, by electrochemical reaction.We obtain optimal estimates showing, for example, that the leastchange in volume of each electrode always occurs in sphericalsymmetry.     

On the utility of S-mesitylsulfinimines for the stereoselective synthesis of chiral amines and aziridines

The synthetic utility of S-mesitylsulfinimines for the synthesis of chiral amines and aziridines was examined through their reactions with Grignard reagents, with the ylides derived from trimethylsulfonium iodide and S-allyl-tetrahydrothiophenium bromide and through an aza-Darzens manifold, affording convenient access to a diverse range of highly substituted chiral amines and aziridines in high yields and excellent stereoselectivities.     

A two-directional approach to the anatoxin alkaloids: second synthesis of homoanatoxin and efficient synthesis of anatoxin-a

Total syntheses of the potent neurotoxins, environmental hazards, and biochemical probes anatoxin-a and homoanatoxin have been achieved from a common intermediate using a combined two-directional synthesis-tandem reaction strategy which includes key advances in oxidative desymmetrisation, tandem Michael-intramolecular Mannich cyclisations and a new method for deprotection of N-tosyl anatoxin-a.     

Versatile C(sp2)−C(sp3) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes

The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron‐deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross‐couplings, and circumvents common issues associated with proto‐demetalation and β‐hydride elimination.     

Combining two-directional synthesis and tandem reactions: a short formal synthesis of halichlorine

A short and efficient synthesis of an advanced intermediate (1) in the Clive route to halichlorine has been achieved in 12 steps and 13.2% yield by a combined two-directional synthesis/tandem reaction strategy.