2-Butyl-11-phenyl-5,10-dihydro-1H-benzo[e]imidazo[1,5-a][1,4]diazepine-1,3(2H)-dione

The title compound, C21H21N3O2, was obtained following a five-step synthetic procedure yielding weakly diffracting rod and needle-shaped crystals which crystallized concomitantly. Structural analysis of a rod-shaped crystal showed that the central seven-membered heterocyclic ring adopts a conformation that is perhaps best described as a distorted boat, with the H-bearing (CH2 and NH) atoms lying well out of the least-squares mean plane fitted through the other five atoms in the ring (r.m.s. deviation 0.075 Å). In the crystal, the compound packs as a twisted chain, which propagates along the b axis by means of an R 1 2(6) motif formed by one of the carbonyl O atoms acting as a bifurcated acceptor in an N—H⋯O and C—H⋯O inter­action. No diffraction was observed from the needle-shaped crystals

4-(Piperidin-1-yl)-4H-benzo[b]tetra­zolo[1,5-d][1,4]diazepin-5(6H)-one

There are two crystallographically unique mol­ecules present in the asymmetric unit of the title compound, C14H16N6O; in both mol­ecules, the seven-membered diazepinone ring adopts a boat-like conformation and the chair conformation piperidine ring is an axial substituent on the diazepinone ring. In the crystal, each mol­ecule forms hydrogen bonds with its respective symmetry equivalents. Hydrogen bonding between mol­ecule A and symmetry equivalents forms two ring motifs, the first formed by inversion-related N—H⋯O inter­actions and the second formed by C—H⋯O and C—H⋯N inter­actions. The combination of both ring motifs results in the formation of an infinite double tape, which propagates in the a-axis direction. Hydrogen bonding between mol­ecule B and symmetry equivalents forms one ring motif by inversion-related N—H⋯O inter­actions and a second ring motif by C—H⋯O inter­actions, which propagate as a single tape parallel with the c axis

The thermal stability of bulk nanocrystalline steels

Nanocrystalline bainite, commonly known as “superbainite”, is a novel class of steel that utilises careful alloy design to reduce the bainite transformation temperature to below 300℃. This results in grains that are tens of nanometres in width, which make steel strong and tough. The structure can be produced in large volumes without the need for rapid cooling or severe deformation. The presence of austenite in nanocrystalline bainite is largely responsible for the toughness. Unfortunately, the austenite is metastable and previous work has shown that it decomposes into cementite and ferrite upon heating. This decomposition makes the material weak and brittle. The present work aims to develop new alloys that form nanocrystalline bainite, but which are able to survive heating. Previous work has shown that cementite precipitation is the first stage in the decomposition process and so the first alloys developed aimed to suppress cementite precipitation. This resulted in a noticeable improvement in thermal stability, although the austenite does eventually decompose at higher temperatures. Subsequent work led to an alloy which was designed not to resist cementite precipitation, but to tolerate it without the associated loss of austenite. This was achieved by the addition of large quantities of nickel to stabilise the austenite even if its carbon content is depleted. This alloy is able to survive exposure to elevated temperatures with the majority of austenite being retained. The thermal stability of the alloys was assessed using time-resolved synchrotron X-ray diffractometry at both the Deutsches Elektronen Synchrotron (DESY) and Diamond Light Source. The high-quality data that were collected allowed the symmetry of the ferrite lattice to be investigated and it was found that the lattice was best-described using a body-centred tetragonal crystal structure. This is the first evidence of its kind. Mechanical properties were investigated in the as-transformed condition at ambient temperature and at a temperature representative of aeronautic applications. The alloys developed in this project have comparable strength, toughness and fatigue performance to existing nanocrystalline bainitic steels. Mechanical properties were also measured after heating at 480℃ for 8 d and this was found to reduce strength and toughness, consistent with the measured loss of austenite

Chemokine receptors in the rheumatoid synovium: upregulation of CXCR5

In patients with rheumatoid arthritis (RA), chemokine and chemokine receptor interactions play a central role in the recruitment of leukocytes into inflamed joints. This study was undertaken to characterize the expression of chemokine receptors in the synovial tissue of RA and non-RA patients. RA synovia (n = 8) were obtained from knee joint replacement operations and control non-RA synovia (n = 9) were obtained from arthroscopic knee biopsies sampled from patients with recent meniscal or articular cartilage damage or degeneration. The mRNA expression of chemokine receptors and their ligands was determined using gene microarrays and PCR. The protein expression of these genes was demonstrated by single-label and double-label immunohistochemistry. Microarray analysis showed the mRNA for CXCR5 to be more abundant in RA than non-RA synovial tissue, and of the chemokine receptors studied CXCR5 showed the greatest upregulation. PCR experiments confirmed the differential expression of CXCR5. By immunohistochemistry we were able to detect CXCR5 in all RA and non-RA samples. In the RA samples the presence of CXCR5 was observed on B cells and T cells in the infiltrates but also on macrophages and endothelial cells. In the non-RA samples the presence of CXCR5 was limited to macrophages and endothelial cells. CXCR5 expression in synovial fluid macrophages and peripheral blood monocytes from RA patients was confirmed by PCR. The present study shows that CXCR5 is upregulated in RA synovial tissue and is expressed in a variety of cell types. This receptor may be involved in the recruitment and positioning of B cells, T cells and monocytes/macrophages in the RA synovium. More importantly, the increased level of CXCR5, a homeostatic chemokine receptor, in the RA synovium suggests that non-inflammatory receptor–ligand pairs might play an important role in the pathogenesis of RA

Optimizing the Readout of Lanthanide-DOTA Complexes for the Detection of Ligand-Bound Copper(I)

The CuAAC ‘click’ reaction was used to couple alkyne-functionalized lanthanide-DOTA complexes to a range of fluorescent antennae. Screening of the antenna components was aided by comparison of the luminescent output of the resultant sensors using data normalized to account for reaction conversion as assessed by IR. A maximum 82-fold enhanced signal:background luminescence output was achieved using a Eu(III)-DOTA complex coupled to a coumarin-azide, in a reaction which is specific to the presence of copper(I). This optimized complex provides a new lead design for lanthanide-DOTA complexes which can act as irreversible ‘turn-on’ catalytic sensors for the detection of ligand-bound copper(I)

A catch-and-release approach to selective modification of accessible tyrosine residues

The tyrosine side chain is amphiphilic leading to significant variations in the surface exposure of tyrosine residues in the folded structure of a native sequence protein. This variability can be exploited to give residue-selective functionalization of a protein substrate by using a highly reactive diazonium group tethered to an agarose-based resin. This novel catch-and-release approach to protein modification has been demonstrated for proteins with accessible tyrosine residues, which are compared with a control group of proteins in which there are no accessible tyrosine residues. MS analysis of the modified proteins showed that functionalization was highly selective, but reactivity was further attenuated by the electrostatic environment of any individual residue. Automated screening of PDB structures allows identification of potential candidates for selective modification by comparison with the accessibility of the tyrosine residue in a benchmark peptide (GYG)

2-Propyl 3,3-dibromo-2-hydroxy­pyrrolidine-1-carboxyl­ate

The title compound, C8H13Br2NO3, crystallizes as a non-merohedral twin with twin law −0.6 0 0.4/0 − 1 0 /1.6 0 0.6, and the structure has a refined twin domain ratio of 0.546 (5). The structure shows a compact conformation, with the ester unit roughly coplanar with a mean plane fitted through the non-H atoms of the pyrrolidine ring [dihedral angle = 8.23 (9)°]. In the crystal, inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate an R 2 2(12) motif