Pions as spin waves: Chiral symmetry breaking in lattice gauge theory

In hamiltonian lattice gauge theory, the fermion vacuum at lowest order in 1/g² can be determined from degenerate perturbation theory plus mean field-spin wave techniques. Using compact QED as an example, we show that: (i) chiral symmetry is spontaneously broken; and (ii) $\text{m}{}_{\mathrm{<mtext>pseudoGoldstone</mtext>}}{}^2\text{∝ m}{}_{\mathrm{<mtext>fermion</mtext>}}\text{〈}\text{ψ}\text{ψ〉}$. The pseudoscalar pseudoGoldstone particles—the “pions” of this abelian theory—correspond to antiferromagnetic spin wave excitations of the fermion vacuum.     

Mimicking dihydroxy acetone phosphate-utilizing aldolases through organocatalysis: a facile route to carbohydrates and aminosugars

[reaction: see text] A practical and environmentally friendly organocatalytic strategy designed to mimic the DHAP aldolases has been developed and shown to be effective in the preparation of carbohydrates and aminosugars. (S)-Proline and (S)-2-pyrrolidine-tetrazole catalyzed the aldol reaction between dihydroxy acetone variants such as 1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one with aldehydes to give the corresponding polyols in good yields with very high ees.     

Trends in exchange coupling for trimethylenemethane-type Bis(semiquinone) biradicals and correlation of magnetic exchange with mixed valency for cross-conjugated systems

A magnetostructural correlation (conformational electron spin exchange modulation) within an isostructural series of biradical complexes is presented. X-ray crystal structures, variable-temperature electron paramagnetic resonance spectroscopy, zero-field splitting parameters, and variable-temperature magnetic susceptibility measurements were used to evaluate molecular conformation and electron spin exchange coupling in this series of molecules. Our combined results indicate that the ferromagnetic portion of the exchange couplings occurs via the cross-conjugated pi-systems, while the antiferromagnetic portion occurs through space and is equivalent to incipient bond formation. Thus, molecular conformation controls the relative amounts of ferro- and antiferromagnetic contributions to exchange coupling. In fact, the exchange parameter correlates with average semiquinone ring torsion angles via a Karplus-Conroy-type relation. Because of the natural connection between electron spin exchange coupling and electronic coupling related to electron transfer, we also correlate the exchange parameters in the biradical complexes to mixed valency in the corresponding quinone-semiquinone radical anions. Our results suggest that delocalization in the cross-conjugated, mixed-valent radical anions is proportional to the ferromagnetic contribution to the exchange coupling in the biradical oxidation states.     

Gd(III)[15-metallacrown-5] recognition of chiral α-amino acid analogues

Chiral Ln(III)[15-metallacrown-5] complexes with phenyl side chains have been shown to encapsulate aromatic carboxylates reversibly in their hydrophobic cavities. Given the importance of selective guest binding for applications of supramolecular containers in synthesis, separations, and materials design, the affinity of Gd(III)[15-metallacrown(Cu(II), L-pheHA)-5] hosts for a series of chiral carboxylate guests with varying substitutions on the α-carbon (phenylalanine, N-acetyl-phenylalanine, phenyllactate, mandelate, methoxyphenylacetate) has been investigated. Differential binding of S- and R-phenylalanine was revealed by X-ray crystallography, as the S-enantiomer exclusively forms associative hydrogen bonds with oxygen atoms in the metallacrown ring. Selective guest binding in solution was assessed with isothermal titration calorimetry, which measures the sequential guest binding in the hydrophobic cavity first and the hydrophilic face of the host, and a cyclic voltammetry assay, which quantifies guest binding strength in the hydrophobic cavity of the host exclusively. In solution, the Gd(III)[15-metallacrown(Cu(II), L-pheHA)-5] hydrophobic cavity exhibits modest chiral selectivity for enantiomers of phenylalanine (K(S)/K(R) = 2.4) and mandelate (K(S)/K(R) = 1.22). Weak binding constants of ～100 M(-1) were measured for neutral and -1 charged carboxylates with hydrophilic functional groups (ammonium, N-acetyl, methyl ether). Weaker binding relative to the unsubstituted guests is attributed to unfavorable interactions between the hydrophilic functionalities of the guest and the hydrophobic cavity of the host. In contrast, binding constants greater than 2000 M(-1) were measured for α-hydroxy analogues phenyllactate and mandelate. The significantly increased affinity likely arises from the guests being bound as a -2 anion upon metal-assisted deprotonation in the Gd(III)[15-metallacrown(Cu(II), l-pheHA)-5] cavity. It is established that guest binding affinity in the hydrophobic cavity of the host follows the general trend of neutral zwitterion < monoanion < dianion, with hydrophilic functional groups decreasing the binding affinity. These results have broad implications for the development of metallacrowns as supramolecular catalysts or in chiral separations.     

Solution self-assembly and adsorption at the air-water interface of the monorhamnose and dirhamnose rhamnolipids and their mixtures

The self-assembly in solution and adsorption at the air-water interface, measured by small-angle neutron scattering, SANS, and neutron reflectivity, NR, of the monorhamnose and dirhamnose rhamnolipids (R1, R2) and their mixtures, are discussed. The production of the deuterium-labeled rhamnolipids (required for the NR studies) from a Pseudomonas aeruginosa culture and their separation into the pure R1 and R2 components is described. At the air-water interface, R1 and R2 exhibit Langmuir-like adsorption isotherms, with saturated area/molecule values of about 60 and 75 ?(2), respectively. In R1/R2 mixtures, there is a strong partitioning of R1 to the surface and R2 competes less favorably because of the steric or packing constraints of the larger R2 dirhamnose headgroup. In dilute solution (<20 mM), R1 and R2 form small globular micelles, L(1), with aggregation numbers of about 50 and 30, respectively. At higher solution concentrations, R1 has a predominantly planar structure, L(α) (unilamellar, ULV, or bilamellar, BLV, vesicles) whereas R2 remains globular, with an aggregation number that increases with increasing surfactant concentration. For R1/R2 mixtures, solutions rich in R2 are predominantly micellar whereas solutions rich in R1 have a more planar structure. At an intermediate composition (60 to 80 mol % R1), there are mixed L(α)/L(1) and L(1)/L(α) regions. However, the higher preferred curvature associated with R2 tends to dominate the mixed R1/R2 microstructure and its associated phase behavior.     

Hydrodynamic chromatography of polystyrene microparticles in micropillar array columns

We report on the possibility to perform HDC in micropillar array columns and the potential advantages of such a system. The HDC performance of a pillar array column with pillar diameter = 5 μm and an interpillar distance of 2.5 μm has been characterized using both a low MW tracer (FITC) and differently sized polystyrene bead samples (100, 200 and 500 nm). The reduced plate height curves that were obtained for the different investigated markers all overlapped very well, and attained a minimum value of about h_min = 0.3 (reduction based on the pillar diameter), corresponding to 1.6 μm in absolute value and giving good prospects for high efficiency separations. The obtained reduced retention time values were in fair agreement with that predicted by the Di Marzio and Guttman model for a flow between flat plates, using the minimal interpillar distance as characteristic interplate distance.     

Trends in metal-biradical exchange interaction for first-row M(II)(nitronyl nitroxide-semiquinone) complexes

We report molecular structures and temperature-dependent magnetic susceptibility data for several new metal complexes of heterospin triplet ground-state biradical ligands. The ligands are comprised of both nitronyl-nitroxide (NN) and semiquinone (SQ) spin carriers. Five compounds are five-coordinate M(II) complexes (M = Mn, Co, Ni, Cu, and Zn), and one is a six-coordinate Ni(II) complex. Five compounds were structurally characterized. During copper complex formation a reaction with methanol occurs to form a unique methoxy-substituted SQ ring. Variable-temperature magnetic susceptibility studies are consistent with strong intraligand (NN-SQ and NN-PhSQ) ferromagnetic exchange coupling. For the five-coordinate Mn, Co, and Ni complexes, the S = 1 ligand is antiferromagnetically coupled to the metal. For both the five-coordinate Cu complex and the six-coordinate Ni complex, the ligand is ferromagnetically coupled to the metal spins in accordance with orbital symmetry arguments. Despite the low molecular symmetries, the predicted trend in metal-ligand exchange interactions is supported by spin dimer analysis based on extended Hückel calculations. For (NN-SQ)NiTp(Cum,Me)() (Tp(Cum,Me)() = hydro-tris(3-cumenyl-5-methylpyrazolyl)borate), an antisymmetric exchange term was required for the best fit of the magnetic susceptibility data. Antisymmetric exchange was less important for the other complexes due to inherently smaller Deltag. Finally, it is shown that intraligand exchange coupling is of paramount importance in stabilizing high-spin states of mixed metal-biradical complexes.     

High-throughput protein crystallography and drug discovery

Single crystal X-ray diffraction is the technique of choice for studying the interactions of small organic molecules with proteins by determining their three-dimensional structures; however the requirement for highly purified protein and lack of process automation have traditionally limited its use in this field. Despite these shortcomings, the use of crystal structures of therapeutically relevant drug targets in pharmaceutical research has increased significantly over the last decade. The application of structure-based drug design has resulted in several marketed drugs and is now an established discipline in most pharmaceutical companies. Furthermore, the recently published full genome sequences of Homo sapiens and a number of micro-organisms have provided a plethora of new potential drug targets that could be utilised in structure-based drug design programs. In order to take maximum advantage of this explosion of information, techniques have been developed to automate and speed up the various procedures required to obtain protein crystals of suitable quality, to collect and process the raw X-ray diffraction data into usable structural information, and to use three-dimensional protein structure as a basis for drug discovery and lead optimisation.This tutorial review covers the various technologies involved in the process pipeline for high-throughput protein crystallography as it is currently being applied to drug discovery. It is aimed at synthetic and computational chemists, as well as structural biologists, in both academia and industry, who are interested in structure-based drug design.