Proof of the local REM conjecture for number partitioning. II. Growing energy scales

We continue our analysis of the number partitioning problem with n weights chosen i.i.d. from some fixed probability distribution with density ρ. In Part I of this work, we established the so‐called local REM conjecture of Bauke, Franz and Mertens. Namely, we showed that, as n → ∞, the suitably rescaled energy spectrum above some fixed scale α tends to a Poisson process with density one, and the partitions corresponding to these energies become asymptotically uncorrelated. In this part, we analyze the number partitioning problem for energy scales α_n that grow with n, and show that the local REM conjecture holds as long as n^‐1/4α_n → 0, and fails if α_n grows like κn^1/4 with κ > 0. We also consider the SK‐spin glass model, and show that it has an analogous threshold: the local REM conjecture holds for energies of order o(n), and fails if the energies grow like κn with κ > 0. © 2008 Wiley Periodicals, Inc. Random Struct. Alg., 2009     

A Carbene‐Extended ATRA Reaction

Atom‐transfer radical addition (ATRA) reactions have gained a strong foothold in organic synthesis by virtue of their operational simplicity, synthetic versatility, and perfect atom economy. A rich chemical space can be accessed through clever combinations of the simple starting materials. Many variations of this general motif have been reported. However, the vast majority involve the addition of an organic halide across a C=C double bond, resulting in the formation of 1,2‐bifunctional products. This report introduces a significant expansion of this general reactivity concept to give 1,3‐bifunctional adducts through the combination of 1,1‐ATRA to a carbenoid and 1,2‐ATRA to an alkyne. Both processes operate under mild conditions (RT, 5 h) with the same commercial catalyst (CoBr₂, dppbz).     

Syntheses of the Stemona alkaloids (+/-)-stenine, (+/-)-neostenine, and (+/-)-13-epineostenine using a stereodivergent Diels-Alder/azido-Schmidt reaction

A tandem Diels-Alder/azido-Schmidt reaction sequence provides rapid access to the core skeleton shared by several Stemona alkaloids including stenine, neostenine, tuberostemonine, and neotuberostemonine. The discovery and evolution of inter- and intramolecular variations of this process and their applications to total syntheses of (+/-)-stenine and (+/-)-neostenine are described. The stereochemical outcome of the reaction depends on both substrate type and reaction conditions, enabling the preparation of both (+/-)-stenine and (+/-)-neostenine from the same diene/dienophile combination.     

Determination of binding selectivities in host-guest complexation by electrospray/quadrupole ion trap mass spectrometry

The quantifiable relationship between the equilibrium solution composition and electrospray (ESI) mass spectral peak intensities of simple host-guest complexes was investigated. Specifically, host-guest complexes of simple crown ethers or glymes with alkali metals and ammonium ions were studied. Comparisons were made between the theoretical concentrations of host-guest complexes derived in solution from known stability constants and the peak intensities for the complexes observed by ESI mass spectrometry (ESI-MS). Two types of complexation experiments were undertaken. First, complexation of a single guest ion, such as an alkali metal, and two crown ethers was studied to evaluate the determination of binding selectivities. Second, complexation of two different guest ions by a single polyether host was also examined. In general, solvation was found to play an integral part in the ability to quantify binding selectivities by ESI-MS. The more similar the solvation energies of the two complexes in the mixture, the more quantifiable their binding selectivities by ESI-MS. In some cases, excellent correlation was obtained between the theoretically predicted selectivity ratios and the ESI mass spectral ratios, in particular when the ESI ratios were adjusted based on evaluation of ESI response factors for the various host-guest complexes.     

The CK2 alpha/CK2 beta interface of human protein kinase CK2 harbors a binding pocket for small molecules

The Ser/Thr kinase CK2 (previously called casein kinase 2) is composed of two catalytic chains (CK2 alpha) attached to a dimer of noncatalytic subunits (CK2 beta). CK2 is involved in suppression of apoptosis, cell survival, and tumorigenesis. To investigate these activities and possibly affect them, selective CK2 inhibitors are required. An often-used CK2 inhibitor is 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). In a complex structure with human CK2 alpha, DRB binds to the canonical ATP cleft, but additionally it occupies an allosteric site that can be alternatively filled by glycerol. Inhibition kinetic studies corroborate the dual binding mode of the inhibitor. Structural comparisons reveal a surprising conformational plasticity of human CK2 alpha around both DRB binding sites. After local rearrangement, the allosteric site serves as a CK2 beta interface. This opens the potential to construct molecules interfering with the CK2 alpha/CK2 beta interaction.     

Expanding dialogues: from natural autoinducers to non-natural analogues that modulate quorum sensing in Gram-negative bacteria

Bacteria are capable of "communicating" their local population densities via a process termed quorum sensing (QS). Gram-negative bacteria use N-acylated l-homoserine lactones (AHLs), in conjunction with their cognate LuxR-type receptors, as their primary signalling circuit for QS. In this critical review, we examine AHL signalling in Gram-negative bacteria with a primary focus on the design of non-natural AHLs, their structure-activity relationships, and their application in chemical biological approaches to study QS (72 references).     

A lattice model of vitrification and gelation

In this work we introduce a simple lattice model with T-shaped molecules in two dimensions that exhibits a rich range of morphological behaviors. Depending on the volume fraction and quench path, this system can adopt uniform liquid, solution, and phase-separated states, as well as inhomogeneous glass or gel-like states, as revealed by dynamic mean-field simulations. An important characteristic of this system is the existence of a large number of degenerate low-energy states with small barriers that leads to a broad, kinetically explored landscape. The mean-field stability and phase diagram of this model is constructed and provides a useful guide for understanding the complex behaviors of the system. One striking feature is that there is a cascade of instabilities that converge to mark the onset of what we identify as the glass transition. Both dynamic mean-field and Monte Carlo simulations reveal glass-like relaxation dynamics. Our results lead to a picture of gelation as a continuation of the glass transition into the two-phase region, or equivalently, as an incomplete phase separation arrested by the onset of the glass transition.     

Tight binding inhibitors of N-acyl amino sugar and N-acyl amino acid deacetylases

Very potent inhibitors were synthesized for the enzymatic deacetylation of N-acetyl-d-glucosamine-6-phosphate (NagA) and N-acetyl-d-glutamate (DGD). The methyl phosphonamidate derivative of d-glucosamine-6-phosphate bound to N-acetyl-d-glucosamine-6-phosphate deacetylase with an equilibrium dissociation constant of 34 +/- 5 nM at pH 7.5 and an association rate constant of 6.1 x 103 M-1 s-1. The inhibition constant is 4000-fold lower than the Michaelis constant for the substrate N-acetyl-d-glucosamine-6-phosphate. N-Acetyl-d-glutamate deacetylase was inhibited by the methyl phosphonamidate derivative of d-glutamate with an inhibition constant of 460 +/- 70 pM at pH 7.6. The inhibitor bound to the enzyme 500 000-fold tighter than the Michaelis constant for N-formyl-d-glutamate. These compounds mimic the putative tetrahedral intermediate formed upon nucleophilic attack of an activated water molecule on the amide bond of the target substrate. These inhibitors should prove useful in the elucidation of the enzyme-substrate interactions for enzymes within the amidohydrolase superfamily.     

Growth mechanism of textured MgO thin films via SSCVD

Magnesium oxide thin films have been deposited with use of single source chemical vapor deposition (SSCVD). The resultant films were examined by using transmission electron microscopy, X-ray texture analysis, and pole figure analysis. Due to the nature of the chemical reactions occurring at the surface during SSCVD growth, which result in a high growth rate/low flux environment, films of (111) orientation have been achieved without an amorphous underlayer, an unusual result for films of this orientation. Moreover the films have a strong degree of biaxial texturing in the x-y plane as found with X-ray texture analysis. These findings have important implications for buffer layers in perovskite thin film devices. The mechanism producing these structures has been revealed by using TEM and is discussed here.     

Divergent reactivity of allene-containing α-diazoesters using Cu and Rh catalysis

A versatile intramolecular reaction of allene-containing diazomalonates that exhibits excellent chemoselectivity for either allenic C–H insertion or cyclopropanation is demonstrated. The identity of the product depends on the transition metal catalyst that is employed for the reaction. Rh catalysts promote exclusive C–H insertion with good diastereoselectivity for the trans product, while Cu catalysis enables intramolecular cyclopropanation to yield methylenecyclopropanes with moderate to good E:Z ratios.