104 research outputs found
Pore Shape Modification of a Microporous Metal-Organic Framework Using High Pressure:Accessing a New Phase with Oversized Guest Molecules
The authors thank the Royal Society of Edinburgh and the Scottish Government for a fellowship to S.A.M. The authors thank EPSRC (EP/J02077X/1) and Leverhulme Trust for a research project grant (RPG-209) for financial support. They also thank the UK Carr Parinello consortium for allocation of computing time on the EPSRC high performance computing resource ARCHER (managed by the Edinburgh Parallel Computing Centre, the EaSTCHEM Research Computing Facility and the University of Edinburgh ECDF facility).Pressures up to 0.8 GPa have been used to squeeze a range of sterically "oversized" C5-C8 alkane guest molecules into the cavities of a small-pore Sc-based metal?organic framework. Guest inclusion causes a pronounced reorientation of the aromatic rings of one-third of the terephthalate linkers, which act as "torsion springs", resulting in a fully reversible change in the local pore structure. The study demonstrates how pressure-induced guest uptake can be used to investigate framework flexibility relevant to "breathing" behavior and to understand the uptake of guest molecules in MOFs relevant to hydrocarbon separation.PostprintPeer reviewe
Molecular simulations studies of gas adsorption in metal–organic frameworks
Using computational tools ranging from molecular simulations – including
both Monte Carlo and molecular dynamics methods – to quantum
mechanical (QM) calculations (primarily at density functional theory (DFT)
level), this work focuses on addressing some of the challenges faced in
molecular simulations of gas adsorption in metal–organic frameworks
(MOFs). This work consists of two themes: one concerns gas adsorption in
MOFs with coordinatively unsaturated metal sites (cus’s), and the other one
deals with predicting and understanding the breathing behaviour of the
flexible MOF MIL-53(Sc).
It has been shown experimentally that incorporation of cus’s – also known as
“open” metal sites or unsaturated metal centres – into MOFs significantly
enhances the uptake of certain gases such as CO2 and CH4. As a result of the
considerably enhanced, localized guest-molecule interactions with the cus’s,
it, however, remains a challenge to predict correctly adsorption isotherms
and/or mechanisms in MOFs with cus’s using grand-canonical Monte Carlo
(GCMC) simulations based on generic classical force fields. To address this
problem, two multi-scale modelling approaches – which combine GCMC
simulations with QM calculations – have been proposed in this work. The
first approach is based on the direct implementation of a fluid–framework
potential energy surface, calculated by a hybrid DFT/ab initio method, in the
GCMC simulations. The second approach involves parameterization of ab
initio force fields for GCMC simulations of gas adsorption in MOFs with
cus’s. This approach focuses on the generation of accurate ab initio reference
data, selection of semiempirical model potentials, and force-field fitting
through a multi-objective genetic algorithm approach. The multi-scale
simulation strategy not only yields adsorption isotherms in very good
agreement with experimental data but also correctly captures adsorption
mechanisms, including the adsorption on the cus’s, observed experimentally
but absent from GCMC simulations based on generic force fields.
The second challenge that this work aims to address concerns the “breathing”
phenomenon of MOFs, in which the framework structure adapts its pore
opening to accommodate guest molecules, for example. The breathing effect
gives rise to some exceptional properties of these MOFs and hence promising
applications. However, framework flexibility often poses a challenge for
computational studies of such MOFs, because suitable flexible force fields for
frameworks are lacking and the effort involved in developing a new one is
no less a challenge. Here, an alternative to the force-field-based approach is
adopted. Ab initio molecular dynamics (AIMD) simulations – which combine
classical molecular dynamics simulations with electronic-structure
calculations “on the fly” – have been deployed to study structural changes of
the breathing MOF MIL-53(Sc) in response to changes in temperature over
the range 100–623 K and adsorption of CO2 at 0–0.9 bar at 196 K. AIMD
simulations employing dispersion-corrected DFT accurately simulated the
experimentally observed closure of MIL-53(Sc) upon solvent removal and the
transition of the empty MOF from the closed-pore phase to the very-narrow-pore
phase with increasing temperature. AIMD simulations were also used to
mimic the CO2 adsorption of MIL-53(Sc) in silico by allowing the MIL-53(Sc)
framework to evolve freely in response to CO2 loadings corresponding to the
two steps in the experimental adsorption isotherm. The resulting structures
enabled the structure determination of the two CO2-containing intermediate
and large-pore phases observed by experimental synchrotron X-ray diffraction
studies with increasing CO2 pressure; this would not have been possible for
the intermediate structure via conventional methods because of diffraction
peak broadening. Furthermore, the strong and anisotropic peak broadening
observed for the intermediate structure could be explained in terms of
fluctuations of the framework predicted by the AIMD simulations.
Fundamental insights from the molecular-level interactions further revealed
the origin of the breathing of MIL-53(Sc) upon temperature variation and
CO2 adsorption.
Both the multi-scale simulation strategy for gas adsorption in MOFs with
cus’s and the AIMD study of the stimuli-responsive breathing behaviour of
MIL-53(Sc) illustrate the power and promise of combining molecular
simulations with quantum mechanical calculations for the prediction and
understanding of MOFs
The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis
Perfluorocarbon liquid under pressure:A medium for gas delivery
The authors thank the Royal Society of Edinburgh and the Scottish Government for a fellowship to Dr Stephen A. Moggach, and the Leverhulme Trust for financial support.A novel method for CO2 delivery to a porous material is reported, wherein a perfluorocarbon containing dissolved CO2 has been used as a pressure-transmitting liquid in a high-pressure single-crystal X-ray diffraction experiment. Pressure causes the gas to be squeezed out of the liquid into the host crystal, monitored via a single-crystal to single-crystal phase transition on uptake of CO2.PostprintPeer reviewe
Stabilization of Scandium Terephthalate MOFs against Reversible Amorphization and Structural Phase Transition by Guest Uptake at Extreme Pressure
Previous high-pressure experiments have shown that pressure-transmitting fluids composed of small molecules can be forced inside the pores of metal organic framework materials, where they can cause phase transitions and amorphization and can even induce porosity in conventionally nonporous materials. Here we report a combined high-pressure diffraction and computational study of the structural response to methanol uptake at high pressure on a scandium terephthalate MOF (Sc2BDC3, BDC = 1,4-benzenedicarboxylate) and its nitro-functionalized derivative (Sc2(NO2–BDC)3) and compare it to direct compression behavior in a nonpenetrative hydrostatic fluid, Fluorinert-77. In Fluorinert-77, Sc2BDC3 displays amorphization above 0.1 GPa, reversible upon pressure release, whereas Sc2(NO2–BDC)3 undergoes a phase transition (C2/c to Fdd2) to a denser but topologically identical polymorph. In the presence of methanol, the reversible amorphization of Sc2BDC3 and the displacive phase transition of the nitro-form are completely inhibited (at least up to 3 GPa). Upon uptake of methanol on Sc2BDC3, the methanol molecules are found by diffraction to occupy two sites, with preferential relative filling of one site compared to the other: grand canonical Monte Carlo simulations support these experimental observations, and molecular dynamics simulations reveal the likely orientations of the methanol molecules, which are controlled at least in part by H-bonding interactions between guests. As well as revealing the atomistic origin of the stabilization of these MOFs against nonpenetrative hydrostatic fluids at high pressure, this study demonstrates a novel high-pressure approach to study adsorption within a porous framework as a function of increasing guest content, and so to determine the most energetically favorable adsorption sites
Development of a Series of Kynurenine 3-Monooxygenase Inhibitors Leading to a Clinical Candidate for the Treatment of Acute Pancreatitis
Recently,
we reported a novel role for KMO in the pathogenesis
of acute pancreatitis (AP). A number of inhibitors of kynurenine 3-monooxygenase
(KMO) have previously been described as potential treatments for neurodegenerative
conditions and particularly for Huntington’s disease. However,
the inhibitors reported to date have insufficient aqueous solubility
relative to their cellular potency to be compatible with the intravenous
(iv) dosing route required in AP. We have identified and optimized
a novel series of high affinity KMO inhibitors with favorable physicochemical
properties. The leading example is exquisitely selective, has low
clearance in two species, prevents lung and kidney damage in a rat
model of acute pancreatitis, and is progressing into preclinical development
Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis
Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base
Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine
Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy in developing countries than in developed countries. Here I describe studies with a live oral cholera vaccine that include older children no longer deriving immune support from breast milk or maternal antibodies and that identify some of the factors accounting for the lower immunogenicity, as well as suggesting counter-measures that may enhance the effectiveness of oral immunization in developing countries. The fundamental breakthrough is likely to require reversing effects of the 'environmental enteropathy' that is often present in children living in fecally contaminated, impoverished environments
'Sadly forgotten'?: Newspaper coverage of the first men to fly the Atlantic non-stop, Alcock and Brown
This article centres on John Alcock and Arthur Whitten Brown, two Mancunians who were the first people to fly the Atlantic non-stop, yet are largely neglected as a subject of acclaim or study and even the centenary of their historic flight from Newfoundland to Ireland went by virtually uncelebrated in Britain in 2019. Alcock died six months after their ground-breaking flight and Brown, an understated character, was not comfortable with fame, but their circumstances and disposition do not explain why they have been forgotten. This article will try to explain why by examining the coverage of three newspapers, one provincial and two national, through the lens of news values
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