Crystal Structure Analyses of Organic and Organometallic Compounds

The thesis is divided into three parts: the first part is a brief review of the theory and methods of x-ray crystallography, the second part describes a number of computer programmes devised either wholly or partly by the author, and in the third part accounts of three structure analyses are presented. The computer programmes described in Part II are written in ALGOL for the English Electric KDP9 Computer. The molecular functions system is a group of six programmes for interpreting the results of a structure analysis: bond lengths and interbond angles with their standard deviations, intermolecular contacts, and mean plane equations may be calculated and rigid-body vibrational analysis can be carried out. The automatic structure solution (ASS) system allows semi-automatic Fourier refinement to be performed. The minimum residual programme permits crystal structures to be refined in projection by direct calculation of the minimum R-factor. The structure analyses presented in Part III are applications of the x-ray method to organic and organo-metallic structural problems. It has been known for more than twenty years that indene can form a 1:2 adduct with dimethylacetylene-dicarboxylate. Earlier chemical and spectroscopic studies on the adduct did not lead to a successful structure determination. The molecular structure of the adduct has now been definitely established by x-ray analysis of its dibromo-derivative. The structure analyses of phenanthrenechromium tricarbonyl, C14H10Cr(CO)3, and of 9,10-dihydrophenanthrenechromium tricarbonyl, C14H12Cr(CO)3, were undertaken to obtain accurate dimensions for aromatic rings bonded to chromium. In both analyses the standard deviations of the C-C bonds range from 0.006 to 0.010 A. The results suggest that the chromium atom causes a slight increase in the mean bond length of the bonded ring without alteration of the ring symmetry. Structural studies on related arenechromium complexes are discussed

A Novel Pt(II)-Pt(IV) Mixed Valence Complex: The Crystal and Molecular Structure of [LPt(μ-l)(μ-Me2PCH2PMe2)2PtMe3] [h], L = 0.451 + 0.55Me

X-ray structure determination of the title compound has shown that iodination of [Pt2Me4 (,u-Me2PCH2PMe2)2] involves an oxidative addition reaction accompanied by methyl group transfer between the two platinum atoms. The crystal structure is built of symmetrical, linear [Isl- anions and partially disordered cations, in which I- or CH3- ligands occupy the L sites with nearly equal propability. In the cations the Pt(II) and Pt(IV) centres are characterised by square planar and octahedral coordination geometries; they are locked into close proximity [Pt ... Pt 386.3(1) pm] by two bridging Me2PCH2PMe2 ligands. The L-shaped LPt(μ -I)PtMe fragment [Pt-I-Pt 91.2(1)0 ] is perpendicular to the Pt(l)P2L(μ -I) and Pt(2)P2C2 coordination planes. The overall geometry of the cation approximates to C8 symmetry. Crystals of the title compound are triclinic, space group Pl, with two formula units in a unit cell of dimensions a = 924.0(2), b = 932.8(4), c = 1804.4(7) pm, a = 102.39(4), fl = 94.63(3) and y = = 96.93(3)0 . Lecrst-squares refinement of the structural model defined by 221 parameters converged at a conventional R index on F of 0.049 for 5045 reflections with I ~ 3 a (I)

Crystal Structure of the Phosphinyl-stabilised Ylide Me3NNP(=O)Ph2 ⋅ H2O

Crystals of trimethylammonio-P,P-diphenylphosphinamidate hydrate, Me3NNP(=O)Ph2 ⋅ H2O, are held together by hydrogen bonds which link two Me3NNP(=O)Ph2 and two water molecules to form a centrosymmetric O4H4 ring belonging to graph set R2 4(8). Each P=O oxygen atom can thereby act as acceptor to two hydrogen bonds, rather than to only one, as in the two-fold symmetric P=O⋅⋅⋅H–O–H⋅⋅⋅O=P motif commonly found in phosphine oxide hemihydrates. The unusual P–N bond in Me3NNP(=O)Ph2 is short enough 1.614(3) Å to indicate some multiple character

Basic Salts with »Very Short« Hydrogen Bonds; the Crystal Structure of a-Picoline-N-oxide Hemihydrochloride Sesquihydrate (Dunlop\u27s Salt)

Type A acid salts of many simple carboxylic acids (HX) crystallise with anions, XHx-, which are symmetrical and which contain »very short« OHO-bonds with O . .. 0 less than 250 pm. Such compounds also reveal anomalous IR spectra. The Glasgow work on such crystal structures has benefited from a long collaboration with Hadzi\u27s spectroscopic group at Ljubljana. The importance of such joint studies in helping the understanding of strong hydrogen bonding is discussed. Some organic bases form analogous basic salts, which have similarly anomalous spectra. An example, discovered by Hadzi in 1962, is the hemihydrobromide of a.-picoline-N-oxide, B · 1/2HBr, where B = CoH7NO, for which he predicted the formula BHB+ Br-. Preliminary X-ray work confirmed this and the presence of a »very short« OHO-bond. Hitherto unpublished crystallographic work is summarised. Dunlop\u27s salt is the sesquihydrated hemihydrochloride of the same base. A careful X-ray study has been made (1040 reflexions; R = 3.70/o): B · 1/2HCl · 3/2H20 has a structure corresponding to BHB+ c1- · 3H20; the cation lies across a centre of symmetry, with O ... O = 241.4(3) pm. At one stage the salt was supposed to include a symmetrical ClHc1- anion; but our more precise work shows the anion to be c1- ... H-OH (or HO-H ... en symmetrised by disorder across a twofold axis of the crystal, with c1- ... O = = 297(1) pm. The spectrum of DSALT is almost identical with that of the hemihydrobromide

Anthrax lethal toxin induced lysosomal membrane permeabilization and cytosolic cathepsin release is Nlrp1b/Nalp1b-dependent.

NOD-like receptors (NLRs) are a group of cytoplasmic molecules that recognize microbial invasion or 'danger signals'. Activation of NLRs can induce rapid caspase-1 dependent cell death termed pyroptosis, or a caspase-1 independent cell death termed pyronecrosis. Bacillus anthracis lethal toxin (LT), is recognized by a subset of alleles of the NLR protein Nlrp1b, resulting in pyroptotic cell death of macrophages and dendritic cells. Here we show that LT induces lysosomal membrane permeabilization (LMP). The presentation of LMP requires expression of an LT-responsive allele of Nlrp1b, and is blocked by proteasome inhibitors and heat shock, both of which prevent LT-mediated pyroptosis. Further the lysosomal protease cathepsin B is released into the cell cytosol and cathepsin inhibitors block LT-mediated cell death. These data reveal a role for lysosomal membrane permeabilization in the cellular response to bacterial pathogens and demonstrate a shared requirement for cytosolic relocalization of cathepsins in pyroptosis and pyronecrosis

Generation of Functional Beta-Like Cells from Human Exocrine Pancreas

<div><p>Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin⁺ cells. The resultant β-like cells expressed insulin protein levels at ~15–30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants.</p></div

Using a private 5G network to support the international broadcast of the coronation of HM King Charles III

Wireless cameras for news contribution feeds regularly use “bonded-cellular” devices, which connect to and split the encoded video across multiple public mobile network SIMs. However, in high demand density environments with large crowds, the public networks can quickly become saturated and unable to sustain the necessary bitrates to support high-definition video. To overcome this and provide uncontested wireless connectivity, the largest pop-up 5G standalone non-public (private) network of its type was deployed outside Buckingham Palace and along The Mall to Admiralty Arch to support news contributions for domestic and foreign broadcasters at the Coronation of HM King Charles III, without changing the contribution workflow. (This paper first appeared in the Proceedings of the 2024 NAB Broadcast Engineering and Information Technology Conference, and is reprinted with permission. https://nabpilot.org/beitc-proceedings/

Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe