Chiral discrimination within disordered adlayers on metal surfaces

Using a novel non-linear optical technique enantiomeric excess within a translationally disordered overlayer on a metal surface has been monitored for the first time.     

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.     

Helical tubulate inclusion compounds of ferrocene and squalene

The inclusion compounds of 2,8-dimethyltricyclo[5.3.1.1^3,9]dodecane-syn-2,syn-8-diol,3, with ferrocene and with squalene have been prepared. The crystal structures of these helical tubulate compounds: (3)₃·(ferrocene)_0.75 [P3₁21,a=b=13.7480(6),c=7.0312(5) Å,Z=1,R=0.038] and (3)₃·(squalene)_0.23 [P3₁21,a=b=13.677(1),c=7.0533(9) Å,Z=1,R=0.042] are described. Supplementary Data relating to this article are deposited with the British Library as supplementary publication No. SUP 82151 (16 pages).     

A novel catalytic heme cofactor in SfmD with a single thioether bond and a bis-His ligand set revealed by a de novo crystal structural and spectroscopic study

SfmD is a heme-dependent enzyme in the biosynthetic pathway of saframycin A. Here, we present a 1.78 Å resolution de novo crystal structure of SfmD, which unveils a novel heme cofactor attached to the protein with an unusual Hx_nHxxxC motif (n ∼ 38). This heme cofactor is unique in two respects. It contains a single thioether bond in a cysteine–vinyl link with Cys317, and the ferric heme has two axial protein ligands, i.e., His274 and His313. We demonstrated that SfmD heme is catalytically active and can utilize dioxygen and ascorbate for a single-oxygen insertion into 3-methyl-l-tyrosine. Catalytic assays using ascorbate derivatives revealed the functional groups of ascorbate essential to its function as a cosubstrate. Abolishing the thioether linkage through mutation of Cys317 resulted in catalytically inactive SfmD variants. EPR and optical data revealed that the heme center undergoes a substantial conformational change with one axial histidine ligand dissociating from the iron ion in response to substrate 3-methyl-l-tyrosine binding or chemical reduction by a reducing agent, such as the cosubstrate ascorbate. The labile axial ligand was identified as His274 through redox-linked structural determinations. Together, identifying an unusual heme cofactor with a previously unknown heme-binding motif for a monooxygenase activity and the structural similarity of SfmD to the members of the heme-based tryptophan dioxygenase superfamily will broaden understanding of heme chemistry.

The de novo crystal structure of SfmD reveals a novel c-type heme cofactor for promoting a monooxygenation reaction in the biosynthetic pathway of saframycin A.     

Evaluation of new single crystal piezoelectric materials for surface acoustic-wave applications

Surface acoustic waves (SAW), or Rayleigh waves, bound to the surfaces of piezoelectric materials are becoming rapidly significant in electronic device applications, particularly as VHF-UHF frequency filters and versatile time-domain processors. The majority of available devices utilize either signle crystalline quartz or lithium niobate as the piezoelectric medium. This paper describes briefly the growth and critical evaluation of SAW impedance and propagation properties for certain new single crystal piezoelectric materials. Crystals discussed are Czochralski-grown bismuth germanium oxide, films of zinc oxide and aluminum nitride both epitaxially grown on single crystal sapphire, and flux-grown beryllium oxide. It is concluded that bismuth germanium oxide may prove an important cost-effective alternative to both quartz and lithium niobate, and that either zinc oxide or aluminum nitride is destined to prove invaluable in the realization of monolithic circuits such as programmable tapped delay lines, in which SAW will be interfaced with metal-oxide semiconductor (large scale integrated) technology, and active SAW elements employing functional integration.     

The cohomology of invariant variational bicomplexes

Let: E M be a fiber bundle and let be an infinitesimal Lie transformation group acting onE. We announce various new results concerning the cohomology of the invariant variational bicomplex ( ^*,* (J(E)), d_H, d_V) and the associated invariant Euler-Lagrange complex. As one application of our general theory, we completely solve the local invariant inverse problem of the calculus of variations for finite-dimensional infinitesimal Lie transformation groups.     

Vortex shedding from a ring in shear flow

Vortex shedding from a bluff ring in a linear shear flow has been investigated experimentally. The shedding frequency, measured using a hot wire in various positions within the near wake of the ring, was found to be remarkably insensitive to a mean flow shear parameter, , defined by (d/U _o).U/y, where d is the mean ring diameter and U _o is the undisturbed upstream velocity on the ring axis; even for = 0.41, corresponding to a velocity variation of about ±24% across the outer ring diameter, the Strouhal number was only about 5% lower than in uniform flow. However, the strong axisymmetric shedding which dominates the flow for = 0 is significantly affected by shear. Indeed, spatial correlation measurements demonstrated that the shedding actually becomes anti-symmetric at the highest values of . The implication of these results is that vortex flowmeters constructed using a ring as the shedding body would be relatively unaffected by changes in the upstream mean flow profile.