Topological Groupoids

A groupoid is a set G in which a single valued product ab is defined for every pair of elements a, b ε G. If G is a groupoid and at the same time a Hausdorff topological space, and, moreover, the multiplication in the groupoid G is continuous in the topological space G, then G is called a topological groupoid. Our aim in this dissertation is two-fold: (1) to study topological groupoids for their own sake; (2) to investigate the relation of certain topological properties to associativity. We note, in relation to the first motif, that many authors have dealt with non-associative algebraic structures, i.e. Albert [1]*, Frink [4], Garrison [5], Etherington [2], Hausmann and Ore [7], and Stein [22]

Proteins that contain a functional Z-DNA-binding domain localize to cytoplasmic stress granules

Long double-stranded RNA may undergo hyper-editing by adenosine deaminases that act on RNA (ADARs), where up to 50% of adenosine residues may be converted to inosine. However, although numerous RNAs may undergo hyper-editing, the role for inosine-containing hyper-edited double-stranded RNA in cells is poorly understood. Nevertheless, editing plays a critical role in mammalian cells, as highlighted by the analysis of ADAR-null mutants. In particular, the long form of ADAR1 (ADAR1(p150)) is essential for viability. Moreover, a number of studies have implicated ADAR1(p150) in various stress pathways. We have previously shown that ADAR1(p150) localized to cytoplasmic stress granules in HeLa cells following either oxidative or interferon-induced stress. Here, we show that the Z-DNA-binding domain (Zα(ADAR1)) exclusively found in ADAR1(p150) is required for its localization to stress granules. Moreover, we show that fusion of Zα(ADAR1) to either green fluorescent protein (GFP) or polypyrimidine binding protein 4 (PTB4) also results in their localization to stress granules. We additionally show that the Zα domain from other Z-DNA-binding proteins (ZBP1, E3L) is likewise sufficient for localization to stress granules. Finally, we show that Z-RNA or Z-DNA binding is important for stress granule localization. We have thus identified a novel role for Z-DNA-binding domains in mammalian cells

Subtle Ligand Modification Inverts Guest Binding Hierarchy in M(II)8L6 Supramolecular Cubes.

Zinc(II), a dimolybdenum(II) paddlewheel tetramine A, and 2-formylpyridine self-assembled to generate a cubic Zn(II)8(L(A))6 assembly. The paddlewheel faces of this assembly exhibited two distinct conformations, whereas the analogous Fe(II)8(L(A))6 framework displayed no such perturbation to its structure. This variation in behavior is attributed to the subtle difference in ligand rotational freedom between the Zn(II)- and Fe(II)-cornered cubes. The incorporation of a fluorinated Mo(II)2 paddlewheel, B, into analogous Zn(II)8(L(B))6 and Fe(II)8(L(B))6 structures resulted in changes to the rotational dynamics of the ligands. These differing dynamics perturbed the energies of the frontier orbitals of these structures, as determined through spectroscopic and electrochemical methods. The result of these perturbations was an inversion of the halide binding preference of the Zn(II)8(L(B))6 host as compared to its Zn(II)8(L(A))6 congener, whereas the Fe(II)8(L(B))6 host maintained a similar binding hierarchy to Fe(II)8(L(A))6.Seventh Framework ProgrammeThis is the final version of the article. It first appeared from the American Chemical Society via http://dx.doi.org/10.1021/jacs.6b0385

Pyrene-edged Fe(II)4L6 cages adaptively reconfigure during guest binding.

Differential guest-binding behavior was observed between two pyrene-edged Fe4L6 cages, prepared from isomeric bis(4-aminophenyl)pyrene derivatives, 2-formylpyridine and iron(II). The cage based on a 1,6-pyrene scaffold possesses an enclosed cavity suitable for the encapsulation of large hydrophobic guests including fullerenes, polycyclic aromatic hydrocarbons, and large, structurally complex natural products such as steroids. Addition of the fullerenes C60 and C70 to the cage brought about a re-equilibration among the different cage diastereomers in order to maximize the binding affinity of the system. Density functional theory was employed to rationalize the experimentally observed energy differences for C60 binding within the cage diastereomers. In contrast, the cage isomer based on a 2,7-pyrene scaffold has a more porous cavity and did not show affinity for neutral hydrophobic guests.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) and the US National Science Foundation (NSF CHE-1124244)This is the final version of the article. It was first published by ACS at http://pubs.acs.org/doi/abs/10.1021/ja507617

Temperature Controls Guest Uptake and Release from Zn4L4 Tetrahedra.

We report the preparation of triazatruxene-faced tetrahedral cage 1, which exhibits two diastereomeric configurations (T1 and T2) that differ in the handedness of the ligand faces relative to that of the octahedrally coordinated metal centers. At lower temperatures, T1 is favored, whereas T2 predominates at higher temperatures. Host-guest studies show that T1 binds small aliphatic guests, whereas T2 binds larger aromatic molecules, with these changes in binding preference resulting from differences in cavity size and degree of enclosure. Thus, by a change in temperature the cage system can be triggered to eject one bound guest and take up another.This work was supported by the European Research Council (695009) and the UK Engineering and Physical Sciences Research Council (EPSRC EP/M008258/1). The authors thank the Department of Chemistry NMR Facility at the University of Cambridge for performing some NMR experiments and the EPSRC UK National Mass Spectrometry Facility at Swansea University for carrying out high-resolution mass spectrometry. D.Z. acknowledges a Herchel Smith Research Fellowship from the University of Cambridge. J.D.T. acknowledges the Rashkind Family Endowment and the Chenery Endowment from Randolph-Macon College

Unexpected Nickel Complex Speciation Unlocks Alternative Pathways for the Reactions of Alkyl Halides with dppf-Nickel(0)

The mechanism of the reactions between dppf-Ni0 complexes and alkyl halides has been investigated using kinetic and mechanistic experiments and DFT calculations. The active species is [Ni(κ2-dppf)(κ1-dppf)], which undergoes a halide abstraction reaction with alkyl halides and rapidly captures the alkyl radical that is formed. The rates of the reactions of [Ni(COD)(dppf)] with alkyl halides and the yields of prototypical nickel-catalyzed Kumada cross-coupling reactions of alkyl halides are shown to be significantly improved by the addition of free dppf ligand

Sterics and Hydrogen Bonding Control Stereochemistry and Self-Sorting in BINOL-Based Assemblies

Here we demonstrate how the hydrogen-bonding ability of a BINOL-based dialdehyde subcomponent dictated the stereochemical outcome of its subsequent self-assembly into one diastereomeric helicate form when bearing free hydroxy groups, and another in the case of its methylated congener. The presence of methyl groups also altered the self-sorting behavior when mixed with another, short linear dialdehyde subcomponent, switching the outcome of the system from narcissistic to integrative self-sorting. In all cases, the axial chirality of the BINOL building block also dictated helicate metal center handedness during stereospecific self-assembly. A new family of stereochemically pure heteroleptic helicates were thus prepared using the new knowledge gained. We also found that switching from FeII to ZnII, or the incorporation of a longer linear ligand, favored heteroleptic structure formation

Selective Anion Extraction and Recovery Using a FeII4L4 Cage

Selective anion extraction is useful for the recovery and purification of valuable chemicals, and in the removal of pollutants from the environment. Here we report that FeII4L4 cage 1 is able to extract an equimolar amount of ReO4−, a high-value anion and a nonradioactive surrogate of TcO4−, from water to nitromethane. Importantly, the extraction was efficiently performed even in the presence of 10 other common anions in water, highlighting the high selectivity of 1 for ReO4−. The extracted guest could be released into water as the cage disassembled in ethyl acetate, and then 1 could be recycled by switching the solvent to acetonitrile. The versatile solubility of the cage also enabled complete extraction of ReO4− (as the tetrabutylammonium salt) from an organic phase into water by using the sulfate salt of 1 as the extractant.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC EP/M008258/1). The authors thank the Department of Chemistry NMR facility, University of Cambridge for performing some NMR experiments, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for carrying out high resolution mass spectrometry. D. Z. acknowledges the Herchel Smith Research Fellowship from the University of Cambridge

Signal transduction in a covalent post-assembly modification cascade

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels–Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels–Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.B.S.P. acknowledges the Herchel Smith Research Fellowship, the Royal Commission for the Exhibition of 1851 Research Fellowship and the Fellowship from Corpus Christi College, Cambridge. D.A.R. acknowledges support from the Gates Cambridge Trust. This work was also supported by the UK Engineering and Physical Sciences Research Council (EPSRC, EP/M008258/1). The authors thank Diamond Light Source (UK) for synchrotron beamtime on I19 (MT11397), the NMR facility at the University of Cambridge Chemistry Department, and the EPSRC UK National Mass Spectrometry Facility at Swansea University

Metallo-cryptophane cages from cis-linked and trans-linked strategies.

Data supporting study of Pd(II) metallo-cage species from cyclotriguaiacylene derived ligands