I18-Microfocus Spectroscopy
|
Diamond Proposal Number(s):
[21484]
Open Access
Abstract: Using operando X-ray absorption spectroscopy in a continuous-flow microfluidic cell, we have investigated the nucleation of platinum nanoparticles from aqueous hexachloroplatinate solution in the presence of the reducing agent ethylene glycol. By adjusting flow rates in the microfluidic channel, we resolved the temporal evolution of the reaction system in the first few seconds, generating the time profiles for speciation, ligand exchange, and reduction of Pt. Detailed analysis of the X-ray absorption near-edge structure and extended X-ray absorption fine structure spectra with multivariate data analysis shows that at least two reaction intermediates are involved in the transformation of the precursor H2PtCl6 to metallic platinum nanoparticles, including the formation of clusters with Pt–Pt bonding before complete reduction to Pt nanoparticles.
|
May 2023
|
|
I04-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
|
Diamond Proposal Number(s):
[30015, 23316, 17844]
Open Access
Abstract: Sucrose import from photosynthetic tissues into the phloem is mediated by transporters from the low-affinity sucrose transporter family (SUC/SUT family). Furthermore, sucrose redistribution to other tissues is driven by phloem sap movement, the product of high turgor pressure created by this import activity. Additionally, sink organs such as fruits, cereals and seeds that accumulate high concentrations of sugar also depend on this active transport of sucrose. Here we present the structure of the sucrose–proton symporter, Arabidopsis thaliana SUC1, in an outward open conformation at 2.7 Å resolution, together with molecular dynamics simulations and biochemical characterization. We identify the key acidic residue required for proton-driven sucrose uptake and describe how protonation and sucrose binding are strongly coupled. Sucrose binding is a two-step process, with initial recognition mediated by the glucosyl moiety binding directly to the key acidic residue in a stringent pH-dependent manner. Our results explain how low-affinity sucrose transport is achieved in plants, and pinpoint a range of SUC binders that help define selectivity. Our data demonstrate a new mode for proton-driven symport with links to cation-driven symport and provide a broad model for general low-affinity transport in highly enriched substrate environments.
|
May 2023
|
|
I09-Surface and Interface Structural Analysis
|
Diamond Proposal Number(s):
[25739, 28742]
Abstract: The ability to control the structural properties of molecular layers is a key for the design and preparation of organic electronic devices. While microscopic growth studies of planar, rigid and symmetric π-conjugated molecules have been performed to a larger extent, this is less the case for elongated donor-acceptor molecules with flexible functional groups, which are particularly interesting due to their high dipole moments. Prototypical molecules of this type are merocyanines (MCs), which have been widely studied for the use as efficient absorbers in organic photodetectors. For maximized light absorption and optimized electronic properties the molecular arrangement which is affected by the initial assembly of the films at the supporting substrate interface is decisive. The situation deserves special attention, when the surface nucleation leads to so far not known and bulk-unlike aggregates. Here, we report on the growth of a typical MC (HB238) on the Ag(100) surface, serving as the substrate. In the energetically preferred phase, the molecules adsorb in a face-on geometry and organize in tetramers with a circular dipole arrangement. The tetramers further self-order in large, enantiopure domains with a periodicity that is commensurate to the Ag(100) surface, likely due to a specific bonding of the thiophene and thiazol rings to the Ag surface. Using scanning tunneling microscopy (STM) in combination with low energy electron diffraction we derive the detailed structure of the tetramers. The center of the tetramer, which is most prominent in STM images, consists of four upward pointing tert-butyl groups from four molecules. It is encircled by a ring of four hydrogen bonds between terminal CN-groups and thiophene rings on neighboring molecules. In parallel, the surface interaction modifies the intramolecular dipole, which is revealed from photoemission spectroscopy. Hence, this example shows how the surface template effect leads to an unforeseen molecular organization which is considerably more complex to that in the bulk phases of HB238, which feature paired dipoles.
|
May 2023
|
|
I03-Macromolecular Crystallography
|
David
Hargreaves
,
Rodrigo J.
Carbajo
,
Michael S.
Bodnarchuk
,
Kevin
Embrey
,
Philip B.
Rawlins
,
Martin
Packer
,
Sébastien L.
Degorce
,
Alexander W.
Hird
,
Jeffrey W.
Johannes
,
Elisabetta
Chiarparin
,
Markus
Schade
Abstract: The structure-based design of small-molecule inhibitors targeting protein–protein interactions (PPIs) remains a huge challenge as the drug must bind typically wide and shallow protein sites. A PPI target of high interest for hematological cancer therapy is myeloid cell leukemia 1 (Mcl-1), a prosurvival guardian protein from the Bcl-2 family. Despite being previously considered undruggable, seven small-molecule Mcl-1 inhibitors have recently entered clinical trials. Here, we report the crystal structure of the clinical-stage inhibitor AMG-176 bound to Mcl-1 and analyze its interaction along with clinical inhibitors AZD5991 and S64315. Our X-ray data reveal high plasticity of Mcl-1 and a remarkable ligand-induced pocket deepening. Nuclear Magnetic Resonance (NMR)-based free ligand conformer analysis demonstrates that such unprecedented induced fit is uniquely achieved by designing highly rigid inhibitors, preorganized in their bioactive conformation. By elucidating key chemistry design principles, this work provides a roadmap for targeting the largely untapped PPI class more successfully.
|
May 2023
|
|
|
|
Open Access
Abstract: Herein, the alcoholysis of furfuryl alcohol in a series of SBA-15-pr-SO3H catalysts with different pore sizes is reported. Elemental analysis and NMR relaxation/diffusion methods show that changes in pore size have a significant effect on catalyst activity and durability. In particular, the decrease in catalyst activity after catalyst reuse is mainly due to carbonaceous deposition, whereas leaching of sulfonic acid groups is not significant. This effect is more pronounced in the largest-pore-size catalyst C3, which rapidly deactivates after one reaction cycle, whereas catalysts with a relatively medium and small average pore size (named, respectively, C2 and C1) deactivate after two reaction cycles and to a lesser extent. CHNS elemental analysis showed that C1 and C3 experience a similar amount of carbonaceous deposition, suggesting that the increased reusability of the small-pore-size catalyst can be attributed to the presence of SO3H groups mostly present on the external surface, as corroborated by results on pore clogging obtained by NMR relaxation measurements. The increased reusability of the C2 catalyst is attributed to a lower amount of humin being formed and, at the same time, reduced pore clogging, which helps to maintain accessible the internal pore space.
|
May 2023
|
|
I14-Hard X-ray Nanoprobe
|
Gea T.
Van De Kerkhof
,
Jessica M.
Walker
,
Surabhi
Agrawal
,
Stuart M.
Clarke
,
Mobbassar H.
Sk
,
Dominic J.
Craske
,
Robert
Lindsay
,
Michael
Dowhyj
,
Ayomide
Osundare
,
Manfred E.
Schuster
,
Julia E.
Parker
Diamond Proposal Number(s):
[28835]
Open Access
Abstract: Studying chemical reactions in an environment that closely mimics the system’s natural operating conditions can offer crucial insights into dynamic oxidation processes. Transmission Electron Microscopes (TEMs) and X-ray Nanoprobes allow the use of imaging and spectroscopy to access nanoscale chemical and structural information about these processes. However, the controlled operating conditions and constraints make the design and implementation of in situ sample environments challenging. Here, we outline the setup of an in situ liquid sample environment for the Hard X-ray Nanoprobe beamline (I14) at Diamond Light Source. The liquid environment allows for the imaging and spectroscopic analysis of samples exposed to liquid flow, with heating up to 80℃. The capability is demonstrated with an example experiment studying iron corrosion. The design of the sample cell offers the prospect of combining X-ray and electron microscopy for the in situ multi-length scale imaging and spectroscopy of samples in liquid.
|
May 2023
|
|
I19-Small Molecule Single Crystal Diffraction
|
Diamond Proposal Number(s):
[21053]
Abstract: N-9-Fluorenylmethyloxycarbonyl (Fmoc)- and C-tertiary butyl (t-Bu)-protected glutamate (L-2), bearing a phenanthroline moiety at the side residue, forms 1D supramolecular assemblies via H-bonding as well as undergoing π-stacking interactions to afford crystals or gels that depend on the shape-complementarity of coexisting alcohols, as demonstrated by structural analyses on these assemblies by means of single-crystal X-ray diffractometry and supplemented with small- and wide-angle X-ray scattering data. Moreover, the rheological measurements on the gels help to define a model for when gels and crystals are expected and found. These observations and conclusions highlight an important, but not very appreciated, aspect of solute–solvent interactions within supramolecular assemblies that can allow the constituent-aggregating molecules in some systems to exhibit high selectivity toward the structures of their solvents. The consequences of this selectivity, as demonstrated here by single-crystal and powder X-ray diffraction data, can lead to self-assembled structures which alter completely the bulk phase properties and morphology of the materials. In that regard, rheological measurements have helped to develop a model to explain when gels and phase-separated mixtures of crystals and solvents are expected.
|
May 2023
|
|
B18-Core EXAFS
E01-JEM ARM 200CF
|
Diamond Proposal Number(s):
[21795, 15151]
Open Access
Abstract: Catalytic allylic alcohol oxidation to aldehydes is an industrial process that necessitates chemoselectivity. Surface PdO (on Pd) enables this transformation but does not represent optimal metal utilisation. Here we report a facile synthesis route to produce isolated surface PdO catalytic sites on an earth-abundant metal (NiO) for cinnamyl alcohol oxidation.
|
May 2023
|
|
B21-High Throughput SAXS
I24-Microfocus Macromolecular Crystallography
|
Diamond Proposal Number(s):
[31323, 31668]
Open Access
Abstract: The allosteric regulation of biomolecules, such as enzymes, enables them to adapt and alter their conformation to fit specific substrates, expressing different functionalities in response to stimuli. Different stimuli can also trigger synthetic coordination cages to change their shape, size, and nuclearity by reconfiguring the dynamic metal–ligand bonds that hold them together. Here we demonstrate an abiological system consisting of different organic subcomponents and ZnII metal ions, which can respond to simple stimuli in complex ways. A ZnII20L12 dodecahedron transforms to give a larger ZnII30L12 icosidodecahedron through subcomponent exchange, as an aldehyde that forms bidentate ligands is displaced in favor of one that forms tridentate ligands together with a penta-amine subcomponent. In the presence of a chiral template guest, the same system that produced the icosidodecahedron instead gives a ZnII15L6 truncated rhombohedral architecture through enantioselective self-assembly. Under specific crystallization conditions, a guest induces a further reconfiguration of either the ZnII30L12 or ZnII15L6 cages to yield an unprecedented ZnII20L8 pseudo-truncated octahedral structure. The transformation network of these cages shows how large synthetic hosts can undergo structural adaptation through the application of chemical stimuli, opening pathways to broader applications.
|
May 2023
|
|
B21-High Throughput SAXS
|
Ália
Dos Santos
,
Daniel E.
Rollins
,
Yukti
Hari-Gupta
,
Hannah
Mcarthur
,
Mingxue
Du
,
Sabrina Yong Zi
Ru
,
Kseniia
Pidlisna
,
Ane
Stranger
,
Faeeza
Lorgat
,
Danielle
Lambert
,
Ian
Brown
,
Kevin
Howland
,
Jesse
Aaron
,
Lin
Wang
,
Peter J. I.
Ellis
,
Teng-Leong
Chew
,
Marisa
Martin-Fernandez
,
Alice L. B.
Pyne
,
Christopher P.
Toseland
Diamond Proposal Number(s):
[16207]
Open Access
Abstract: NDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear functions for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We find that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover nuclear roles for NDP52 in gene expression and DNA structure regulation.
|
May 2023
|
|
