The absence of surface dipole contributions to metal work functions

A simple model, derived from a linear approximation to the ionization potentials of atoms, is used to compute the work functions of some 43 metals, mostly within their experimental uncertainties. The computation does not make use of a surface dipole contribution. In this respect, it departs from the current literature of many-body theoretical calculations in which the surface dipole plays a major role. Even without the use of surface dipoles, the model can still count for small differences observed on different crystal faces. The model also accounts for the experimental correlations of work functions with half the ionization potential and yields a simple formalism for computing the work functions of metallic clusters. Finally, the model yields the work functions of ions in terms of the same parameter used for the work functions of electrons.     

A new nucleophilic addition/ring-closure sequence. Enantioselective synthesis of 3-deoxy-8-oxatropanes

[reaction: see text] A study of new nucleophilic addition/ring-closure (NARC) sequences has resulted in the development of a stereoselective synthetic route to 3-deoxy-8-oxatropanes. The new sequences consisted of either a syn or anti aldol addition, employing an omega-alkenoyl sultam, followed by two-step bicyclic ring construction involving, consecutively, ring-closing metathesis and intramolecular oxymercuration.     

Investigations into a free radical-mediated 1,2-imino migration

The radical reactions of a series of bromides 9a-c and selenides 12-15 have been investigated to determine the factors that are important for a successful radical-mediated 1,2-imino migration.     

Electronic and steric effects in thermal denitrosation of N-nitrosoamides

N-Alkyl-N-nitrosoamides undergo competitive reactions whose rates are dependent upon the interplay of a number of factors. There already exists a significant body of work delineating the effects of pH on the partitioning of the nitrosoamides along their deaminative (-N(2)) and denitrosative (-"NO(+)") pathways. In this paper, the issue of pH dependence is discussed with particular attention to nitrosoamide decompositions in nonaqueous media. The role of the acidity of the medium in the partitioning of the nitrosoamide between deamination and denitrosation and in the choice of deaminative pathways is revisited. In nonaqueous media under near-neutral conditions, the partitioning's pH dependence is evidently accompanied by a sensitivity to structural features in the nitrosoamide. Thus, diminution of steric crowding around the N-nitroso moiety as well as the presence of strongly electron-withdrawing acyl units (i.e., those derived from strong acids, e.g., tosyl and trifyl) increase the relative yield of amides by encouraging the denitrosative pathway. A mechanism for thermal denitrosation of nitrosoamides under near-neutral conditions is proposed in which rapid protonation at the acyl O rather than slow protonation at the amidic N is the first step in the reaction profile. A rate-limiting, bimolecular reaction between the O-conjugate acid and adventitious nucleophiles at the nitrosyl group then occurs followed by rapid tautomerization to amide.     

Flow-induced beam steering in a single laser hot spot

The transmitted angular distribution of a 527 nm nearly diffraction-limited laser is measured after it propagates through a plasma with supersonic transverse flow. The laser beam is deflected by as much as 10 degrees and exhibits bowlike features in the flow direction, which is attributed to flow-induced beam steering. The finite interaction volume allows for direct comparison with a 3D hydrodynamic simulation, which is in good agreement with details of the experiment.     

Discrete and dipole-mode gap solitons in higher-order nonlinear photonic lattices

We investigate the formation of fundamental discrete solitons and dipole-mode gap solitons in triangular photonic lattices imprinted in photorefractive nonlinear media. These lattices are strongly affected by the photorefractive anisotropy, resulting in orientation-dependent refractive index structures with reduced symmetry. It is demonstrated that two different orientations of the lattice wave enable the formation of fundamental discrete solitons in the total internal reflection gap. Furthermore, it is shown that one lattice orientation additionally supports dipole-mode solitons in the Bragg reflection gap. The experimental results are corroborated by numerical simulations using the full anisotropic model. PACS 42.65.Tg; 42.65.Wi; 42.70.Qs     

Triflic anhydride mediated cyclization of 5-hydroxy-substituted pyrrolidinones for the preparation of alpha-trifluoromethylsulfonamido furans

The reaction of alpha-angelica lactone with alkylamines under aqueous conditions afforded 5-hydroxy-5-methylpyrrolidinones in high yield. When the reaction was carried out under anhydrous conditions, the only products obtained were the corresponding 4-oxopentanoic acid amides. Treatment of either class of compound with triflic anhydride (Tf(2)O) in pyridine resulted in the formation of various substituted sulfonamidofurans. The suggested mechanism involves initial formation of an iminium ion which is subsequently transformed into a transient imino triflate. Cyclization of the highly electrophilic imine onto the oxygen atom of the adjacent carbonyl group generates an imino dihydrofuran intermediate. This species reacts further with another equivalent of Tf(2)O to give the observed product. The nature of the Lewis acid used was found to affect the outcome of the cyclization reaction. In certain cases, the sulfonamide furan was utilized as a cycloaddition substrate for the synthesis of indolines and related heterocyclic systems.     

An Optimised Small‐Molecule Stabiliser of the 14‐3‐3–PMA2 Protein–Protein Interaction

Modulation of protein–protein interactions (PPIs) is a highly demanding, but also a very promising approach in chemical biology and targeted drug discovery. In contrast to inhibiting PPIs with small, chemically tractable molecules, stabilisation of these interactions can only be achieved with complex natural products, like rapamycin, FK506, taxol, forskolin, brefeldin and fusicoccin. Fusicoccin stabilises the activatory complex of the plant H⁺‐ATPase PMA2 and 14‐3‐3 proteins. Recently, we have shown that the stabilising effect of fusicoccin could be mimicked by a trisubstituted pyrrolinone (pyrrolidone1, 1 ). Here, we report the synthesis, functional activity and crystal structure of derivatives of 1 that stabilise the 14‐3‐3–PMA2 complex. With a limited compound collection three modifications that are important for activity enhancement could be determined: 1) conversion of the pyrrolinone scaffold into a pyrazole, 2) introduction of a tetrazole moiety to the phenyl ring that contacts PMA2, and 3) addition of a bromine to the phenyl ring that exclusively contacts the 14‐3‐3 protein. The crystal structure of a pyrazole derivative of 1 in complex with 14‐3‐3 and PMA2 revealed that the more rigid core of this molecule positions the stabiliser deeper into the rim of the interface, enlarging especially the contact surface to PMA2. Combination of the aforementioned features gave rise to a molecule ( 37 ) that displays a threefold increase in stabilising the 14‐3‐3–PMA2 complex over 1 . Compound 37 and the other active derivatives show no effect on two other important 14‐3‐3 protein–protein interactions, that is, with CRaf and p53. This is the first study that describes the successful optimisation of a PPI stabiliser identified by screening.     

Nanomolar Inhibitors for Two Distinct Biological Target Families from a Single Synthetic Sequence: A Next Step in Combinatorial Library Design?

One common synthetic route creates small-molecule libraries directed toward two functionally distinct target families. The novel structural template 1 can independently display the necessary pharmacophore patterns for inhibition of members of two different biomolecular target families, the matrix metalloproteinases (MMPs) or the phosphodiesterases (PDEs). The incorporation of multiple target family directed design elements into combinatorial library design could help expedite the pharmaceutical lead discovery process. Z=OR′ (PDE4), H (MMPs).