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

Two-stage directed self-assembly of a cyclic [3]catenane.

Interlocked molecules possess properties and functions that depend upon their intricate connectivity. In addition to the topologically trivial rotaxanes, whose structures may be captured by a planar graph, the topologically non-trivial knots and catenanes represent some of chemistry's most challenging synthetic targets because of the three-dimensional assembly necessary for their construction. Here we report the synthesis of a cyclic [3]catenane, which consists of three mutually interpenetrating rings, via an unusual synthetic route. Five distinct building blocks self-assemble into a heteroleptic triangular framework composed of two joined Fe(II)3L3 circular helicates. Subcomponent exchange then enables specific points in the framework to be linked together to generate the cyclic [3]catenane product. Our method represents an advance both in the intricacy of the metal-templated self-assembly procedure and in the use of selective imine exchange to generate a topologically complex product.This work was supported by the UK Engineering and Physical Sciences Research Council (EPSRC) and a Marie Curie fellowship for J.J.H. (ITN-2010–264645). The authors thank the Diamond Light Source (UK) for synchrotron beamtime on I19 (MT7984 and MT8464).This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.220

Up Rising:Rehabilitating J.G. Ballard’s High-Rise with R.D. Laing and Lauren Berlant

High-Rise by J.G. Ballard intriguingly contains a pivotal character named Dr. Robert Laing, surely an allusion to the then influential psychiatric writer, Dr. R.D. Laing. Re-reading Ballard's classic text through the prism of Laing’s theories, with further explication of the role of flat affect via Lauren Berlant, this article presents a new interpretation of a classic text that argues that Ballard ingeniously misdirected his readers into making identifications with precisely the wrong characters and the wrong actions. Re-focusing a subject gaze in accordance with these theoretical analyses, allows for an entirely alternative understanding of the text in which Ballard was more than a pessimistic prophet of inexorable urban breakdown, he foretold societal rehabilitation as well. High-Rise is read as a classic of psychogeography, an established genre which is argued to be of great relevance to the study of society and space. This article therefore engages in a reading of a psychogeographical text via theory implicitly alluded to by the text itself

Extreme managers, extreme workplaces: capitalism, organizations and corporate psychopaths

This paper reports on in-depth, qualitative research carried out in England in 2013 among five organizational directors and two senior managers who had worked with other senior directors or managers who were Corporate Psychopaths, as measured by a management psychopathy measure. The Corporate Psychopaths reported on in this research displayed remarkable consistency in their approach to management to the extent that they could be called “text book examples” of managerial psychopathy. They were seen as being organizational stars and as deserving of performance awards by those above them, while the Corporate Psychopaths simultaneously subjected those below them to extreme forms of behavior, including bullying, intimidation and coercion and also engaged in extreme forms of mismanagement; such as very poor levels of personnel management, directionless leadership, miss-management of resources and outright fraud

Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries

Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest’s surface area: the change in ΔG for binding is 0.3 kJ mol–1 Å–2, corresponding to 5 kJ mol–1 for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant is K = 1.2 × 106 M–1 for cycloundecanone, whose volume is approximately 50% of the cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones differing in shape but not size, ΔG for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek’s 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganized cyclic ketones all have association constants of 104–105 M–1. A crystal structure of the cage·cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak hydrogen-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudospherical cage cavity despite the slight mismatch in shape

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

Coordination Cages Selectively Transport Molecular Cargoes Across Liquid Membranes.

Chemical purifications are critical processes across many industries, requiring 10-15% of humanity's global energy budget. Coordination cages are able to catch and release guest molecules based upon their size and shape, providing a new technological basis for achieving chemical separation. Here, we show that aqueous solutions of FeII4L6 and CoII4L4 cages can be used as liquid membranes. Selective transport of complex hydrocarbons across these membranes enabled the separation of target compounds from mixtures under ambient conditions. The kinetics of cage-mediated cargo transport are governed by guest binding affinity. Using sequential transport across two consecutive membranes, target compounds were isolated from a mixture in a size-selective fashion. The selectivities of both cages thus enabled a two-stage separation process to isolate a single compound from a mixture of physicochemically similar molecules

Sequential induction of three recombination directionality factors directs assembly of tripartite integrative and conjugative elements

Tripartite integrative and conjugative elements (ICE3) are a novel form of ICE that exist as three separate DNA regions integrated within the genomes of Mesorhizobium spp. Prior to conjugative transfer the three ICE3 regions of M. ciceri WSM1271 ICEMcSym1271 combine and excise to form a single circular element. This assembly requires three coordinated recombination events involving three site-specific recombinases IntS, IntG and IntM. Here, we demonstrate that three excisionases–or recombination directionality factors—RdfS, RdfG and RdfM are required for ICE3 excision. Transcriptome sequencing revealed that expression of ICE3 transfer and conjugation genes was induced by quorum sensing. Quorum sensing activated expression of rdfS, and in turn RdfS stimulated transcription of both rdfG and rdfM. Therefore, RdfS acts as a “master controller” of ICE3 assembly and excision. The dependence of all three excisive reactions on RdfS ensures that ICE3 excision occurs via a stepwise sequence of recombination events that avoids splitting the chromosome into a non-viable configuration. These discoveries expose a surprisingly simple control system guiding molecular assembly of these novel and complex mobile genetic elements and highlight the diverse and critical functions of excisionase proteins in control of horizontal gene transfer

Radiation techniques for acromegaly

Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques