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The emergence of untreatable drug-resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity ( K D ). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl ( 10 f ) and tert -butyl ( 10 g ) compounds displaying optimal activity (MIC 1.562 μg/mL, K D 0.22 μM ( 10 f ) and 4.81 μM ( 10 g )). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H-bond acceptors/H-bond donors 4/0, number of rotatable bonds 5-6, molecular volume >340 Å 3 , topological polar surface area <40 Å 2 ., Competing Interests: The authors declare no conflict of interest.

We describe a general model to explore responsive adsorption processes in flexible porous materials. This model combines mean field formalism of the osmotic potential, classical density functional theory of adsorption in slit pore models and generic potential functions which represent the Helmholtz free energy landscape of a porous system. Using this model, we focus on recreating flexible adsorption phenomena observed in prototypical metal-organic frameworks, especially the recently discovered effect of negative gas adsorption (NGA). We identify the key characteristics required for the model to generate unusual adsorption processes and subsequently employ an extensive parametric study to outline conditions under which gate-opening and NGA are observed. This powerful approach will guide the design of responsive porous materials and the discovery of entirely new adsorption processes.

Directional, micron-scale honeycomb pores in Li-ion battery electrodes were fabricated using a layer-by-layer, self-assembly approach based on spray-printing of carbon nanofibers. By controlling the drying behavior of each printed electrode layer through optimization of (i) the volume ratio of fugitive bisolvent carriers in the suspension and (ii) the substrate temperature during printing, self-assembled, honeycomb pore channels through the electrode were created spontaneously and reliably on current collector areas larger than 20 cm × 15 cm. The honeycomb pore structure promoted efficient Li-ion dynamics at high charge/discharge current densities. Incorporating an optimum fraction (2.5 wt %) of high-energy-density Si particulate into the honeycomb electrodes provided a 4-fold increase in deliverable discharge capacity at 8000 mA/g. The spray-printed, honeycomb pore electrodes were then investigated as negative electrodes coupled with similar spray-printed LiFePO 4 positive electrodes in a full Li-ion cell configuration, providing an approximately 50% improvement in rate capacity retention over half-cell configurations of identical electrodes at 4000 mA/g.

A new mesoporous metal-organic framework (MOF; DUT-60) was conceptually designed in silico using Zn 4 O 6+ nodes, ditopic and tritopic linkers to explore the stability limits of framework architectures with ultrahigh porosity. The robust ith-d topology of DUT-60 provides an average bulk and shear modulus (4.97 GPa and 0.50 GPa, respectively) for this ultra-porous framework, a key prerequisite to suppress pore collapse during desolvation. Subsequently, a cluster precursor approach, resulting in minimal side product formation in the solvothermal synthesis, was used to produce DUT-60, a new crystalline framework with the highest recorded accessible pore volume (5.02 cm 3  g -1 ) surpassing all known crystalline framework materials., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly porous metal-organic framework DUT-48, isoreticular to DUT-49, is reported with a high surface area of 4560 m 2 ·g -1 and methane storage capacity up to 0.27 g·g -1 (164 cm 3 ·cm -3 ) at 6.5 MPa and 298 K. The flexibility of DUT-48 and DUT-49 under external and internal (adsorption-induced) pressure is analyzed and rationalized using a combination of advanced experimental and computational techniques. While both networks undergo a contraction by mechanical pressure, only DUT-49 shows adsorption-induced structural transitions and negative gas adsorption of n -butane and nitrogen. This adsorption behavior was analyzed by microcalorimetry measurements and molecular simulations to provide an explanation for the lack of adsorption-induced breathing in DUT-48. It was revealed that for DUT-48, a significantly lower adsorption enthalpy difference and a higher framework stiffness prevent adsorption-induced structural transitions and negative gas adsorption. The mechanical behavior of both DUT-48 and DUT-49 was further analyzed by mercury porosimetry experiments and molecular simulations. Both materials exhibit large volume changes under hydrostatic compression, demonstrating noteworthy potential as shock absorbers with unprecedented high work energies., Competing Interests: The authors declare no competing financial interest.

Composed from discrete units, porous molecular materials (PMMs) possess unique properties not observed for conventional, extended, solids, such as solution processibility and permanent porosity in the liquid phase. However, identifying the origin of porosity is not a trivial process, especially for amorphous or liquid phases. Furthermore, the assembly of molecular components is typically governed by a subtle balance of weak intermolecular forces that makes structure prediction challenging. Accordingly, in this review we canvass the crucial role of molecular simulations in the characterisation and design of PMMs. We will outline strategies for modelling porosity in crystalline, amorphous and liquid phases and also describe the state-of-the-art methods used for high-throughput screening of large datasets to identify materials that exhibit novel performance characteristics.

Soft microporous materials exhibit properties, such as gated adsorption and breathing, which are highly desirable for many applications. These properties are largely studied for single crystals; however, many potential applications expect to construct structured or composite systems, examples of which include monoliths and mixed-matrix membranes. Herein, we use finite element methods to predict the macroscopic mechanical response of composite microporous materials. This implementation connects the microscopic treatment of crystalline structures to the response of a macroscopic sample. Our simulations reveal the bulk modulus of an embedded adsorbent within a composite is affected by the thickness and properties of the encapsulating layer. Subsequently, we employ this methodology to examine mixed-matrix membranes and materials of negative linear compressibility. This application of finite element methods allows for unprecedented insight into the mechanical properties of real-world systems and supports the development of composites containing mechanically anomalous porous materials.

The synthesis and characterisation of two novel, functionalised porous organic cages are presented. We demonstrate that a step-wise approach to the synthesis of these robust C-C bonded cages allows for the introduction of a controlled number of endohedral pyridine functional groups. In addition, kinetic processing is used to access permanently porous morphologies.

The recently reported process of chiral induction in a metal-organic framework (MOF) by nonchiral guest adsorption, demonstrated on the prototypical MOF-5, may revolutionize the production of MOFs for enantioselective separation and catalysis. Herein, we describe an investigation employing multiscale molecular simulation to discover the microscopic mechanism of chiral induction and investigate the stability of the resulting framework. Our results explain how the molecular size and chemical nature of N-methyl-2-pyrrolidone (NMP) give rise to the chiral transformation in MOF-5, whereas it cannot occur for other guest molecules, such as N,N-dimethylformamide (DMF). Moreover, we show that the guest-free CMOF-5 structure is energetically unstable, with either the achiral conventional structure or a closed pore structure preferred, demonstrating that chirality will not be retained upon activation of CMOF-5. While this limits the usability of chiral induction in MOFs, our study opens new avenues for the use of other guest molecules and provides microscopic insight into this unexpected outcome of guest-framework interactions in a soft porous crystal.

Porous metal-organic polyhedra (MOPs), constructed from heterometallic Pd(II)-M(II) (M = Cu, Ni, Zn) paddlewheel nodes and 5-tert-butyl-1,3-benzenedicarboxylate organic links, were prepared in which the Pd(II) ions preferentially line the inner surface of the cage molecules. Careful activation produces co-ordinatively unsaturated 3d transition metal sites on the external MOP surfaces giving rise to H2 adsorption enthalpies in excess of -12 kJ mol(-1).

Post-synthetic metalation (PSMet) offers expansive scope for a targeted approach to tailoring the properties of MOFs. Numerous methods for carrying-out PSMet chemistry have been reported, however, these can be categorized into three general strategies: (a) addition to coordinating groups; (b) counter-ion exchange in charged frameworks; or, (c) host-guest encapsulation of metal-containing entities within the pores of the framework. PSMet has been applied to enhance the performance characteristics of parent MOFs for gas storage and separation, and catalysis. Notably, PSMet is a prominent strategy in the field of MOF catalysis as it offers a route to design size-selective catalysts, based on the premise of reticular chemistry in MOFs and the ability to incorporate a range of catalytically-active metal centres. Other applications for materials produced via or utilising PSMet strategies include enhancing gas storage or molecular separations, the triggered release of drugs, sensing and tunable light emission for luminescent materials. This review surveys seminal examples of PSMet to highlight the broad scope of this technique for enhancing the performance characteristics of MOFs and to demonstrate how the PSMet concept can be developed for future applications.

Dynamically porous metal-organic frameworks (MOFs) with a chiral quartz-based structure have been synthesized from the multidentate ligand 2,2'-dihydroxybiphenyl-4,4'-dicarboxylate (H2diol). Compounds [Ni(II)(H2diol)(S)2]·xS (where S = DMF or DEF) show marked changes in 77 K N2 uptake between partially desolvated [Ni(II)(H2diol)(S)2] (only the pore solvent is removed) and fully desolvated [Ni(II)(H2diol)] forms. Furthermore, [Ni(II)(H2diol)(DMF)2] displays additional solvent-dependent porosity through the rotation of DMF molecules attached to the axial coordination sites of the Ni(II) centre. A unique feature of the four coordinate Ni(II) centre in [Ni(II)(H2diol)] is the dynamic response to its chemical environment. Exposure of [Ni(II)(H2diol)] to H2O and MeOH vapour leads to coordination of both axial sites of the Ni centres and to the generation of a solvated framework, whereas exposure to EtOH, DMF, acetone, and MeCN does not lead to any change in metal coordination or structure metrics. MeOH vapour adsorption was able to be tracked by time-dependent magnetometry as the solvated and desolvated structures have different magnetic moments. Solvated and desolvated forms of the MOF show remarkable differences in their thermal expansivities; [Ni(II)(H2diol)(DMF)2]·DMF displays marked positive thermal expansion (PTE) in the c-axis, yet near to zero thermal expansion, between 90 and 450 K, is observed for [Ni(II)(H2diol)]. These new MOF architectures demonstrate a dynamic structural and colourimetric response to selected adsorbates via a unique mechanism that involves a reversible change in the coordination environment of the metal centre. These coordination changes are mediated throughout the MOF by rotational mobility about the biaryl bond of the ligand.

Objective: The goal of this study was to characterize hospital antimicrobial stewardship practices nationwide and to identify factors associated with the presence of these programs., Methods: The first web-based survey was sent in 2009 to members of the Yankee Alliance and the Premier Healthcare Alliance, nationwide organizations of health-care providers. The second survey, a slightly modified version of the first, was sent in 2010 to a commercially purchased list of hospital pharmacy director e-mail addresses., Results: A total of 406 responses were received from ~5890 providers targeted, for an overall response rate of ~7%. More than one half (206 of 406) of the respondents reported having what they considered to be a formal antimicrobial stewardship program (ASP). Among all respondents regardless of presence or absence of an ASP, 96.4% (351 of 364) were using some form of antimicrobial stewardship technique. Of those respondents working in hospitals without an ASP, 63.3% (114 of 180) had considered implementing one. After controlling for all significant variables, those that remained which were significantly associated with having an ASP were survey (Premier vs commercial), having an infectious disease consultation service, and having an infectious disease pharmacist., Conclusions: In this survey of 406 respondents from across the country, we found that just more than one half of hospitals had what they considered to be formal ASPs; however, the vast majority were using stewardship techniques to optimize the use of antibiotics. Common barriers to implementation of ASPs included staffing constraints and insufficient funding., (Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.)

Coordination polymers and discrete metallo-supramolecular assemblies of hexaaryl[3]radialene compounds exhibit intriguing structures with short anion to π-centroid distances in the solid-state. Furthermore, these [3]radialene compounds display useful photophysical and electrochemical properties that make them ideal as potential platforms for anion receptors. In this study, hexafluoro[3]radialene was optimized to the MP2/aug-cc-pVTZ level of theory, and its complexes with halide anions were optimized to HF/6-31G++(d,p), MP2/6-31G++(d,p), M06-2X/6-31G++(d,p), and M06-2X/6-311G++(d,p) levels of theory. Hexafluoro[3]radialene was shown to have properties (large positive Qzz and areas of positive electrostatic surface potential) comparable to other compounds that show anion-π interactions. The interaction energies of complexes of hexafluoro[3]radialene with halide anions were calculated and found to be favorable and equivalent to those of fluorinated aromatic compounds. A series of synthetically accessible hexaaryl[3]radialenes were optimized to HF/6-31G++(d,p) theory and their complexes with halides optimized to the M06-2X/6-31G++(d,p) level of theory. The calculated properties of the electron-deficient hexaaryl[3]radialenes also show large positive Qzz quadrupole moments and two areas of positive potential; at the [3]radialene core and the acidic aryl hydrogen atoms. The interaction energies of the complexes of hexaaryl[3]radialenes and halide anions were found to follow the trend F(-) > Cl(-) ≈ Br(-) and correlate with the electron-deficient nature of the [3]radialene. Close contacts were observed between the anion and the radialene core and the aryl hydrogen atoms, suggesting a combination of anion-π and hydrogen bonding is important. Mass spectrometry was used to experimentally observe the complexes of a number of hexaaryl[3]radialenes with F(-), Cl(-), and Br(-) predicted computationally. Anion-[3]radialene complexes were successfully detected, and the stability of the complexes in tandem MS/MS experiments was found to support the computational results.