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Open Access
Abstract: We studied the impact of achiral substituents on the chiral supramolecular architectures of diketopyrrolo[3,4-c]pyrrole–1,2,3-1H-triazole (DPP) dyes. We decorated the same chiral DPP motif with substituent groups on the nitrogen atoms of the lactam moiety: the hydrophobic n-octyl alkyl chain, the hydrophilic triethylene glycol (TEG) chain and the thermo-cleavable t-butoxycarbonyl (t-Boc) carbamate group. In spite of identical conjugated chromophore and chiral appendage, in aggregated form the three dyes displayed profoundly different optical, chiroptical, electrochemical and thermal features. ECD measurements revealed differences in the aggregation modes, which would be inaccessible by most other techniques. We found strong chiroptical features, which would have major implications in the context of chiral organic opto-electronics and in the development of other highly innovative technological applications.
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Mar 2023
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Mona M.
Katariya
,
Matthew
Snee
,
Richard B.
Tunnicliffe
,
Madeline E.
Kavanagh
,
Helena I. M.
Boshoff
,
Cecilia N.
Amadi
,
Colin W.
Levy
,
Andrew W.
Munro
,
Chris
Abell
,
David
Leys
,
Anthony G.
Coyne
,
Kirsty J.
Mclean
Diamond Proposal Number(s):
[17773, 24447]
Open Access
Abstract: Mycobacterium tuberculosis (Mtb) was responsible for approximately 1.6 million deaths in 2021. With the emergence of extensive drug resistance, novel therapeutic agents are urgently needed, and continued drug discovery efforts required. Host-derived lipids such as cholesterol support Mtb growth, and are also suspected to function in immunomodulation, with links to persistence and immune evasion. Mtb cytochrome P450 (CYP) enzymes facilitate key steps in lipid catabolism and thus present potential targets for inhibition. Here we present a series of compounds based on an ethyl 5-(pyridin-4-yl)-1H-indole-2-carboxylate pharmacophore which bind strongly to both Mtb cholesterol oxidases CYP125 and CYP142. Using a structure-guided approach, combined with biophysical characterization, compounds with micromolar range in-cell activity against clinically relevant drug-resistant isolates were obtained. These will support further development of much-needed additional treatment options and provide routes to probe the role of CYP125 and CYP142 in Mtb pathogenesis.
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Mar 2023
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I19-Small Molecule Single Crystal Diffraction
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Abstract: The reactions of a terminal aluminium imide with a range of oxygen-containing substrates have been probed with a view to developing its use as a novel main group transfer agent for the [NR]2- fragment. We demonstrate transfer of the imide moiety to [N2], [CO] and [Ph(H)C] units driven thermodynamically by Al-O bond formation. N2O reacts rapidly to generate the organoazide DippN3 (Dipp = 2,6- iPr2C6H3), while CO2 (under dilute reaction conditions) yields the corresponding isocyanate, DippNCO. Mechanistic studies, using both experimental and quantum chemical techniques, identify a carbamate complex K2[(NON)Al{κ2-(N,O)-N(Dipp)CO2}]2 (formed via [2+2] cycloaddition) as an intermediate in the formation of DippNCO, and also in an alternative reaction leading to the generation of the amino-dicarboxylate complex K2[(NON)Al{κ2(O,O')-(O2C)2N(Dipp)}] (via the take-up of a second equivalent of CO2). In the case of benzaldehyde, a similar [2+2] cycloaddition process generates the metallacyclic hemi-aminal complex, Kn[(NON)Al{κ2-(N,O)-(N(Dipp)C(Ph)(H)O}]n. Extrusion of the imine, PhC(H)NDipp, via cyclo-reversion is disfavoured thermally, due to the high energy of the putative aluminium oxide co-product, K2[(NON)Al(O)]2. However, addition of CO2 allows the imine to be released, driven by the formation of the thermodynamically more stable aluminium carbonate co-product, K2[(NON)Al(κ2-(O,O')-CO3)]2.
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Jan 2023
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B23-Circular Dichroism
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Diamond Proposal Number(s):
[30755, 31552]
Abstract: The correlation between size of nanoparticles and structure and shape of mesogenic ligands and the ensuing assembly behaviour is not really understood and closer inspection shows very surprising features. Here 2 and 4 nm gold nanoparticles (NP) were synthesized, grafted with a forked ligand containing two rod-like mesogens in its two branches: one with cholesterol and the other with azobenzene. The 4 nm NPs also contained n-hexylthiol as co-ligand. They were found to form an FCC cubic superlattice, while the 2 nm NPs form hexagonal HCP with weak birefringence, hence with partially oriented ligands. The structures were compared with those of related systems containing a range of different azobenzene-to-cholesterol ratios, all giving body-centered tetragonal superlattices with various degrees of anisotropy. Geometric analysis is presented in terms of asphericity of NP surrounding, requirement for space-filling and structural anisotropy. Some general rules are derived to help design the soft corona around the NPs in order to obtain superlattices with desired structure and anisotropy.
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Dec 2022
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[15059]
Abstract: Four bis [2-{pyrazol-1-yl}-6-{pyrazol-3-yl}pyridine] ligands have been synthesized, with butane-1,4-diyl ( L 1 ), pyrid-2,6-diyl ( L 2 ), benzene-1,2-dimethylenyl ( L 3 ) and propane-1,3-diyl ( L 4 ) linkers between the tridentate metal-binding domains. L 1 and L 2 form [Fe 2 ( μ - L ) 2 ]X 4 (X ‒ = BF 4 ‒ or ClO 4 ‒ ) helicate complexes when treated with the appropriate iron(II) precursor. Solvate crystals of [Fe 2 ( μ - L 1 ) 2 ][BF 4 ] 4 exhibit three different helicate conformations, which differ in the torsions of their butanediyl linker groups. The solvates exhibit gradual thermal spin-crossover, with examples of stepwise switching and partial spin-crossover to a low temperature mixed-spin form. Salts of [Fe 2 ( μ - L 2 ) 2 ] 4+ are high-spin, which reflects their highly twisted iron coordination geometry. The composition and dynamics of assembly structures formed by iron(II) with L 1 - L 3 vary with the ligand linker group, by mass spectrometry and 1 H NMR. Gas phase DFT calculations imply the butanediyl linker conformation in [Fe 2 ( μ - L 1 ) 2 ] 4+ influences its spin state properties, but show anomalies attributed to intramolecular electrostatic repulsion between the iron atoms.
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Nov 2022
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I11-High Resolution Powder Diffraction
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Open Access
Abstract: A family of seven silver(I)-perfluorocarboxylate-quinoxaline coordination polymers, [Ag 4 (O 2 CR F ) 4 (quin) 4 ] 1 - 5 (R F = (CF 2 ) n-1 CF 3 ) 4 , n = 1 to 5); [Ag 4 (O 2 C(CF 2 ) 2 CO 2 ) 2 (quin) 4 ] 6 ; [Ag 4 (O 2 CC 6 F 5 ) 4 (quin) 4 ] 7 (quin = quinoxaline), denoted by composition as 4:4:4 phases , was synthesised from reaction of the corresponding silver(I) perfluorocarboxylate with excess quinoxaline. Compounds 1 - 7 adopt a common 2D layered structure in which 1D silver-perfluorcarboxylate chains are crosslinked by ditopic quinoxaline ligands. Solid-state reaction upon heating, involving loss of one equivalent of quinoxaline, yielding new crystalline 4:4:3 phases [Ag 4 (O 2 C(CF 2 ) n-1 CF 3 ) 4 (quin) 3 ] n ( 8 - 10 , n = 1 to 3), was followed in situ by PXRD and TGA studies. Crystal structures were confirmed by direct syntheses and structure determination. The solid-state reaction converting 4:4:4 to 4:4:3 phase materials involves cleavage and formation of Ag–N and Ag–O bonds to enable the structural rearrangement. One of the 4:4:3 phase coordination polymers ( 10 ) shows the remarkably high dielectric constant in the low electric field frequency range.
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Jun 2022
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I11-High Resolution Powder Diffraction
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Shanshan
Liu
,
Yinlin
Chen
,
Bin
Yue
,
Chang
Wang
,
Bin
Qin
,
Yuchao
Chai
,
Guangjun
Wu
,
Jiangnan
Li
,
Xue
Han
,
Ivan
Da Silva
,
Pascal
Manuel
,
Sarah J.
Day
,
Naijia
Guan
,
Stephen P.
Thompson
,
Sihai
Yang
,
Landong
Li
Diamond Proposal Number(s):
[29649]
Abstract: The development of cost-effective sorbents for direct capture of trace CO 2 (<1%) from the atmosphere is an important and challenging task. Natural or commercial zeolites are promising sorbents, but their performance in adsorption of trace CO 2 has been poorly explored to date. Herein, we report a systematic study on capture of trace CO 2 by commercial faujasite zeolites, where we found that the extra-framework cations played a key role on their performance. Under dry conditions, Ba-X displays high dynamic uptake of 1.79 and 0.69 mmol g -1 at CO 2 concentrations of 10000 and 1000 ppm, respectively, and shows excellent recyclability in the temperature-swing adsorption processes. K-X exhibits perfect moisture resistance, and >95 % dry CO 2 uptake can be preserved under relative humidity of 74%. In situ solid-state NMR spectroscopy, synchrotron X-ray diffraction and neutron diffraction reveal two binding sites for CO 2 in these zeolites, namely the basic framework oxygen atoms and the divalent alkaline earth metal ions. This study unlocks the potential of low-cost natural zeolites for applications in direct air capture.
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Jun 2022
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I19-Small Molecule Single Crystal Diffraction
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Diamond Proposal Number(s):
[22411]
Abstract: Extremely high electrophilic metal complexes, composed by a metal cation and very electron poor σ–donor ancillary ligands, are expected to be privileged catalysts for oxidation reactions in organic chemistry. However, their low lifetime prevents any use in catalysis. Here we show the synthesis of fluorinated pyridine–Pd 2+ coordinate cages within the channels of an anionic tridimensional metal organic framework (MOF), and their use as efficient metal catalysts for the aerobic oxidation of aliphatic alcohols to carboxylic acids without any additive. Mechanistic studies strongly support that the MOF–stabilized coordination cage with perfluorinated ligands unleashes the full electrophilic potential of Pd 2+ to dehydrogenate primary alcohols, without any base, and also to activate O 2 for the radical oxidation to the aldehyde intermediate. This study opens the door to design catalytic perfluorinated complexes for challenging organic transformations, where an extremely high electrophilic metal site is required.
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Dec 2021
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B23-Circular Dichroism
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Diamond Proposal Number(s):
[17621, 19225]
Abstract: Solid-state ECD (ss-ECD) spectra of a model microcrystalline solid, finasteride, dispersed into a KCl pellet were recorded by using the synchrotron radiation source at the Diamond B23 beamline. Scanning a surface of 36 mm2 with a step of 0.5 mm, we measured a set of ECD imaging (ECDi) spectra very different from each other and from the ss-ECD recorded with a bench-top instrument (1 cm2 area). This is due to the anisotropic part of the ECD (ACD), which averages to zero in solution or on a large number of randomly oriented crystallites, but can otherwise be extremely large. Two-way singular value decomposition (SVD) analysis, through experimental and simulated TDDFT spectra, disclosed that the measured and theoretical principal components are in line with each other. This finding demonstrates that the observed isotropic ss-ECD spectrum is governed by the anisotropy of locally oriented crystals. It also introduces a new quality for ss-ECD measurements and opens a new future for probing and mapping chiral materials in the solid state such as active pharmaceutical ingredients (APIs).
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Dec 2021
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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)
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David J.
Fallon
,
Stephanie
Lehmann
,
Chun‐wa
Chung
,
Alex
Phillipou
,
Christian
Eberl
,
Ken G. M.
Fantom
,
Francesca
Zappacosta
,
Vipulkumar K.
Patel
,
Marcus
Bantscheff
,
Christopher J.
Schofield
,
Nicholas C. O.
Tomkinson
,
Jacob T.
Bush
Diamond Proposal Number(s):
[20024]
Abstract: We present a one-step Ugi reaction protocol for the expedient synthesis of photoaffinity probes for live-cell MS-based proteomics. The reaction couples an amine affinity function with commonly used photoreactive groups, and a variety of handle functionalities. Using this technology, a series of pan-BET (BET: bromodomain and extra-terminal domain) selective bromodomain photoaffinity probes were obtained by parallel synthesis. Studies on the effects of photoreactive group, linker length and irradiation wavelength on photocrosslinking efficiency provide valuable insights into photoaffinity probe design. Optimal probes were progressed to MS-based proteomics to capture the BET family of proteins from live cells and reveal their potential on- and off-target profiles.
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Sep 2021
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