I20-Scanning-X-ray spectroscopy (XAS/XES)
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Diamond Proposal Number(s):
[24399]
Open Access
Abstract: The catalytic conversion of C–H to C–F bonds is a critical synthetic transformation of relevance to the pharmaceutical, agrochemical, and medicinal chemical industries. When coupled with an oxidant and a fluorine donor, biomimetic Mn-porphyrins have been shown to be capable of achieving this reaction. However, the definition of the active forms of these fluorinating Mn-porphyrins remains an unsolved challenge, which limits mechanistic understanding of the process and makes it challenging to systematically design better catalytic materials. Herein, we present a combination of kinetic, spectroscopic, and theoretical studies focused on alkane fluorination over Mn-containing porphyrins. Specifically, by correlating kinetic studies with resonance Raman, UV–vis, and high-energy resolution fluorescence detected X-ray absorption spectroscopic analysis of the various states of the catalyst, we provide evidence that a 6-coordinated Mn(IV) complex with −F and −OI(F)Ar axial ligands is the active species responsible for selective fluorination via Hydrogen Atom Transfer. This active state is distinct from the Mn═O species previously proposed to be the active intermediates for alkane fluorination and oxidation.
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Mar 2025
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B18-Core EXAFS
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Diamond Proposal Number(s):
[34632]
Open Access
Abstract: Ethylene produced from steam cracking includes an acetylene impurity of 0.5–3%, harming the downstream polymerization process. To achieve polymer-grade ethylene, acetylene must be removed by chemoselective hydrogenation to ethylene without overhydrogenation to ethane. The current state-of-the-art process uses supported Pd nanoparticles (NPs) and toxic CO injections to poison the active sites, which is expensive and shows poor ethylene selectivity. To tackle this issue, the use of single-atom catalysts can offer a way to simultaneously improve selectivity through preferential desorption of ethylene over its hydrogenation and minimize cost. In particular, single-atom cobalt catalysis can address both of these issues. However, to date, single-atom cobalt has not been tested for this reaction. Herein, we present a cost-effective monometallic, cobalt-anchored zeolite Y (Co1@Y) catalyst, synthesized via an in situ hydrothermal method, holding isolated active cobalt atoms that efficiently and selectively hydrogenate acetylene to ethylene. Characterization techniques proved the absence of NPs and the presence of single-atom cobalt sites. The catalyst achieved an ethylene selectivity of 90 ± 2% at full acetylene conversion, with a stable performance for over 400 h. Co1@Y achieved TOFethylene greater than the previously reported zeolite-supported single-atom catalysts by ∼5 times. Varying the dispersion of cobalt from an NP to a single atom modified the reaction mechanism from associative to dissociative, remarkably improving catalytic activity and selectivity. This strategy can be extended to other relatively inactive metals and other hydrogenation reactions.
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Feb 2025
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E02-JEM ARM 300CF
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Diamond Proposal Number(s):
[32035]
Open Access
Abstract: Bimetallic manganese–ruthenium nanoparticles of defined Mn:Ru ratios were prepared on an imidazolium-based supported ionic liquid phase. Characterization of the resulting MnxRu100–x@SILP materials by electron microscopy evidenced the formation of small (1.3–3.6 nm) and well-dispersed nanoparticles (NPs) containing Mn and Ru in the expected ratios. X-ray absorption spectroscopy (XAS) studies revealed that no significant levels of alloying occurred in these NPs that contain mainly oxidized Mn species and metallic Ru, consistent with the immiscibility of the two metals and the high oxophilicity of Mn. The hydrogenation performance of MnxRu100–x@SILP materials was probed using benzylideneacetone as model substrate containing three distinct reducible moieties. Albeit the two metals are present in distinct phases, the Mn:Ru ratio was found to have a strong impact on activity and selectivity with trends similar to what was previously reported for alloyed FexRu100–x@SILP and CoxRu100–x@SILP catalysts. In particular, a sharp switch of 6-membered aromatic ring hydrogenation between Mn15Ru85 (full ring hydrogenation) and Mn25Ru75 (no ring hydrogenation) was observed. These results demonstrate that alloying is not a requirement to observe synergistic effects from the combination of 3d metals and noble metals in NPs, opening new opportunities for the development of bimetallic catalysts for selective hydrogenation.
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Feb 2025
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
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Diamond Proposal Number(s):
[37236]
Open Access
Abstract: Reductive amination is one of the most synthetically direct routes to access chiral amines. Several Imine Reductases (IREDs) have been discovered to catalyze reductive amination (Reductive Aminases or RedAms), yet they are dependent on the expensive phosphorylated nicotinamide adenine dinucleotide cofactor NADPH and usually more active at basic pH. Here, we describe the discovery and synthetic potential of an IRED from Rhodococcus erythropolis (RytRedAm) that catalyzes reductive amination between a series of medium to large carbonyl and amine compounds with conversions of up to >99% and 99% enantiomeric excess at neutral pH. RytRedAm catalyzes the formation of a substituted γ-lactam and N-methyl-1-phenylethanamine with stereochemistry opposite to that of fungal RedAms, giving the (S)-enantiomer. This enzyme remarkably uses both NADPH and NADH cofactors with KM values of 15 and 247 μM and turnover numbers kcat of 3.6 and 9.0 s–1, respectively, for the reductive amination of hexanal with allylamine. The crystal structure obtained provides insights into the flexibility to also accept NADH, with residues R35 and I69 diverging from that of other IREDs/RedAms in the otherwise conserved Rossmann fold. RytRedAm thus represents a subfamily of enzymes that enable synthetic applications using NADH-dependent reductive amination to access complementary chiral amine products.
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Dec 2024
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I03-Macromolecular Crystallography
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Abstract: The assembly of artificial metalloenzymes (ArMs) provides a second coordination sphere around a metal catalyst. Such a well-defined microenvironment can lead to an enhancement of the activities and selectivity of the catalyst. Herein, we present the development of artificial hydroxylase (ArHase) by embedding an Fe-TAML (TAML = tetraamide macrocyclic ligand) catalyst into a human carbonic anhydrase II (hCAII). Incorporation of the Fe-TAML catalyst ([BS-Fe-bTAML]–) within hCAII enhanced the total turnover number (TTON) for the hydroxylation of benzylic C–H bonds. After engineering a thermostable variant of hCAII (hCAIITS), the resulting ArHase, [BS-Fe-bTAML]–·hCAIITS, was subjected to directed evolution using cell lysates in a 384-well format. After three rounds of laboratory evolution, the best-performing variants exhibited enhancement in the initial rate (124.4 min–1) and in the TTON (2629 TTON) for the hydroxylation of benzylic C–H bonds compared to that of the free cofactor. We surmise that an arginine residue introduced in the course of directed evolution engages in hydrogen bonding with [BS-Fe-bTAML]–. This study highlights the potential of relying on a thermostable host protein to improve the catalytic performance of hCAII-based ArMs.
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Nov 2024
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I03-Macromolecular Crystallography
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Diamond Proposal Number(s):
[20303]
Open Access
Abstract: Ene reductases (EREDs) catalyze asymmetric reduction with exquisite chemo-, stereo-, and regioselectivity. Recent discoveries led to unlocking other types of reactivities toward oxime reduction and reductive C–C bond formation. Exploring nontypical reactions can further expand the biocatalytic knowledgebase, and evidence alludes to yet another variant reaction where flavin mononucleotide (FMN)-bound ERs from the old yellow enzyme family (OYE) have unconventional activity with α,β-dicarbonyl substrates. In this study, we demonstrate the nonconventional stereoselective monoreduction of α,β-dicarbonyl to the corresponding chiral hydroxycarbonyl, which are valuable building blocks for asymmetric synthesis. We explored ten α,β-dicarbonyl aliphatic, cyclic, or aromatic compounds and tested their reduction with five OYEs and one nonflavin-dependent double bond reductase (DBR). Only GluER reduced aliphatic α,β-dicarbonyls, with up to 19% conversion of 2,3-hexanedione to 2-hydroxyhexan-3-one with an R-selectivity of 83% ee. The best substrate was the aromatic α,β-dicarbonyl 1-phenyl-1,2-propanedione, with 91% conversion to phenylacetylcarbinol using OYE3 with R-selectivity >99.9% ee. Michaelis–Menten kinetics for 1-phenyl-1,2-propanedione with OYE3 gave a turnover kcat of 0.71 ± 0.03 s–1 and a Km of 2.46 ± 0.25 mM. Twenty-four EREDs from multiple classes of OYEs and DBRs were further screened on 1-phenyl-1,2-propanedione, showing that class II OYEs (OYE3-like) have the best overall selectivity and conversion. EPR studies detected no radical signal, whereas NMR studies with deuterium labeling indicate proton incorporation at the benzylic carbonyl carbon from the solvent and not the FMN hydride. A crystal structure of OYE2 with 1.5 Å resolution was obtained, and docking studies showed a productive pose with the substrate.
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Oct 2024
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I03-Macromolecular Crystallography
I04-Macromolecular Crystallography
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Sandeep
Bhosale
,
Sachin
Kandalkar
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Pierre-André
Gilormini
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Oluwafemi
Akintola
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Rhianna
Rowland
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Pal John Pal
Adabala
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Dustin
King
,
Matthew C.
Deen
,
Xi
Chen
,
Gideon J.
Davies
,
David J.
Vocadlo
,
Andrew J.
Bennet
Diamond Proposal Number(s):
[18598, 24948]
Open Access
Abstract: Mutations in many members of the set of human lysosomal glycoside hydrolases cause a wide range of lysosomal storage diseases. As a result, much effort has been directed toward identifying pharmacological chaperones of these lysosomal enzymes. The majority of the candidate chaperones are active site-directed competitive iminosugar inhibitors but these have met with limited success. As a first step toward an alternative class of pharmacological chaperones we explored the potential of small molecule mechanism-based reversible covalent inhibitors to form transient enzyme–inhibitor adducts. By serial synthesis and kinetic analysis of candidate molecules, we show that rational tuning of the chemical reactivity of glucose-configured carbasugars delivers cyclohexenyl-based allylic carbasugar that react with the lysosomal enzyme β-glucocerebrosidase (GCase) to form covalent enzyme-adducts with different half-lives. X-ray structural analysis of these compounds bound noncovalently to GCase, along with the structures of the covalent adducts of compounds that reacted with the catalytic nucleophile of GCase, reveal unexpected reactivities of these compounds. Using differential scanning fluorimetry, we show that formation of a transient covalent intermediate stabilizes the folded enzyme against thermal denaturation. In addition, these covalent adducts break down to liberate the active enzyme and a product that is no longer inhibitory. We further show that the one compound, which reacts through an unprecedented SN1′-like mechanism, exhibits exceptional reactivity–illustrated by this compound also covalently labeling an α-glucosidase. We anticipate that such carbasugar-based single turnover covalent ligands may serve as pharmacological chaperones for lysosomal glycoside hydrolases and other disease-associated retaining glycosidases. The unusual reactivity of these molecules should also open the door to creation of new chemical biology probes to explore the biology of this important superfamily of glycoside hydrolases.
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Sep 2024
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B18-Core EXAFS
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Danial
Farooq
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Matthew E.
Potter
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Sebastian
Stockenhuber
,
Jay
Pritchard
,
Antonios
Vamvakeros
,
Stephen W. T.
Price
,
Jakub
Drnec
,
Ben
Ruchte
,
James
Paterson
,
Mark
Peacock
,
Andrew
Beale
Diamond Proposal Number(s):
[29271]
Open Access
Abstract: X-ray diffraction/scattering computed tomography (XRS-CT) was used to create two-dimensional images, with 20 μm resolution, of passivated Co/TiO2/Mn Fischer–Tropsch catalyst extrudates postreaction after 300 h on stream under industrially relevant conditions. This combination of scattering techniques provided insights into both the spatial variation of the different cobalt phases and the influence that increasing Mn loading has on this. It also demonstrated the presence of a wax coating throughout the extrudate and its capacity to preserve the Co/Mn species in their state in the reactor. Correlating these findings with catalytic performance highlights the crucial phases and active sites within Fischer–Tropsch catalysts required for understanding the tunability of the product distribution between saturated hydrocarbons or oxygenate and olefin products. In particular, a Mn loading of 3 wt % led to an optimum equilibrium between the amount of hexagonal close-packed Co and Co2C phases resulting in maximum oxygenate selectivity. XRS-CT revealed Co2C to be located on the extrudates’ periphery, while metallic Co phases were more prevalent toward the center, possibly due to a lower [CO] ratio there. Reduction at 450 °C of a 10 wt % Mn sample resulted in MnTiO3 formation, which inhibited carbide formation and alcohol selectivity. It is suggested that small MnO particles promote Co carburization by decreasing the CO dissociation barrier, and the Co2C phase promotes CO nondissociative adsorption leading to increased oxygenate selectivity. This study highlights the influence of Mn on the catalyst structure and function and the importance of studying catalysts under industrially relevant reaction times.
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Aug 2024
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I03-Macromolecular Crystallography
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Florence J.
Hardy
,
Matthew G.
Quesne
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Emilie F.
Gérard
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Jingming
Zhao
,
Mary
Ortmayer
,
Christopher J.
Taylor
,
Hafiz S.
Ali
,
Jeffrey W.
Slater
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Colin W.
Levy
,
Derren J.
Heyes
,
J. Martin
Bollinger
,
Sam P.
De Visser
,
Anthony P.
Green
Diamond Proposal Number(s):
[24447]
Open Access
Abstract: The ability to introduce noncanonical amino acids as axial ligands in heme enzymes has provided a powerful experimental tool for studying the structure and reactivity of their FeIV═O (“ferryl”) intermediates. Here, we show that a similar approach can be used to perturb the conserved Fe coordination environment of 2-oxoglutarate (2OG) dependent oxygenases, a versatile class of enzymes that employ highly-reactive ferryl intermediates to mediate challenging C–H functionalizations. Replacement of one of the cis-disposed histidine ligands in the oxygenase VioC with a less electron donating Nδ-methyl-histidine (MeHis) preserves both catalytic function and reaction selectivity. Significantly, the key ferryl intermediate responsible for C–H activation can be accumulated in both the wildtype and the modified protein. In contrast to heme enzymes, where metal-oxo reactivity is extremely sensitive to the nature of the proximal ligand, the rates of C–H activation and the observed large kinetic isotope effects are only minimally affected by axial ligand replacement in VioC. This study showcases a powerful tool for modulating the coordination sphere of nonheme iron enzymes that will enhance our understanding of the factors governing their divergent activities.
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Jul 2024
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I15-1-X-ray Pair Distribution Function (XPDF)
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Liudmyla
Masliuk
,
Kyeonghyeon
Nam
,
Maxwell W.
Terban
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Yonghyuk
Lee
,
Pierre
Kube
,
Daniel
Delgado
,
Frank
Girgsdies
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Karsten
Reuter
,
Robert
Schlögl
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Annette
Trunschke
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Christoph
Scheurer
,
Mirijam
Zobel
,
Thomas
Lunkenbein
Diamond Proposal Number(s):
[20578]
Open Access
Abstract: The interface between a solid catalyst and the reacting medium plays a crucial role in the function of the material in catalysis. In the present work, we show that the surface termination of isostructural molybdenum–vanadium oxides is strongly linked to the real structure of the bulk. This conclusion is based on comparing (scanning) transmission electron microscopy images with pair distribution function (PDF) data obtained for (Mo,V)Ox and (Mo,V,Te,Nb)Ox. Distance-dependent analyses of the PDF results demonstrate that (Mo,V,Te,Nb)Ox exhibits stronger deviations from the averaged orthorhombic crystal structure than (Mo,V)Ox in the short and intermediate regimes. These deviations are explained by higher structural diversity, which is facilitated by the increased chemical complexity of the quinary oxide and in particular by the presence of Nb. This structural diversity is seemingly important to form intrinsic bulk-like surface terminations that are highly selective in alkane oxidation. More rigid (Mo,V)Ox is characterized by defective surfaces that are more active but less selective for the same reactions. In line with machine learning interatomic potential (MLIP) calculations, we highlight that the surface termination of (Mo,V,Te,Nb)Ox is characterized by a reconfiguration of the pentagonal building blocks, causing a preferential exposure of Nb sites. The presented results foster hypotheses that chemical complexity is superior for the performance of multifunctional catalysts. The underlying principle is not the presence of multiple chemically different surface centers but instead the ability of structural diversity to optimally align and distribute the elements at the surface and, thus, to shape the structural environment around the active sites. This study experimentally evidences the origin of the structure-directing impact of the real structure of the bulk on functional interfaces and encourages the development of efficient surface engineering strategies toward improved high-performance selective oxidation catalysts.
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May 2024
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