| 1. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 2. |
|
|
| 3. |
- Simons, Matthew C., et al.
(författare)
-
Beyond Radical Rebound : Methane Oxidation to Methanol Catalyzed by Iron Species in Metal–Organic Framework Nodes
- 2021
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 143:31, s. 12165-12174
-
Tidskriftsartikel (refereegranskat)abstract
- Recent work has exploited the ability of metalorganic frameworks (MOFs) to isolate Fe sites that mimic the structures of sites in enzymes that catalyze selective oxidations at low temperatures, opening new pathways for the valorization of underutilized feedstocks such as methane. Questions remain as to whether the radical-rebound mechanism commonly invoked in enzymatic and homogeneous systems also applies in these rigid-framework materials, in which resisting the overoxidation of desired products is a major challenge. We demonstrate that MOFs bearing Fe(II) sites within Fe-3-mu(3)-oxo nodes active for conversion of CH4 + N2O mixtures (368-408 K) require steps beyond the radical-rebound mechanism to protect the desired CH3OH product. Infrared spectra and density functional theory show that CH3OH(g) is stabilized as Fe(III)-OCH3 groups on the MOF via hydrogen atom transfer with Fe(III)-OH groups, eliminating water. Consequently, upon addition of a protonic zeolite in inter- and intrapellet mixtures with the MOF, we observed increases in (CHOH)-O-3 selectivity with increasing ratio and proximity of zeolitic H+ to MOF-based Fe(II) sites, as methanol is protected within the zeolite. We infer from the data that (CHOH)-O-3( g) is formed via the radical-rebound mechanism on Fe(II) sites but that subsequent transport and dehydration steps are required to protect (CHOH)-O-3( g) from overoxidation. The results demonstrate that the radical-rebound mechanism commonly invoked in this chemistry is insufficient to explain the reactivity of these systems, that the selectivity-controlling steps involve both chemical and physical rate phenomena, as well as offering a strategy to mitigate overoxidation in these and similar systems.
|
|
| 4. |
- Simons, Matthew C., et al.
(författare)
-
Structure, Dynamics, and Reactivity for Light Alkane Oxidation of Fe(II) Sites Situated in the Nodes of a Metal–Organic Framework
- 2019
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 141:45, s. 18142-18151
-
Tidskriftsartikel (refereegranskat)abstract
- Metal organic frameworks (MOFs), with their crystalline, porous structures, can be synthesized to incorporate a wide range of catalytically active metals in tailored surroundings. These materials have potential as catalysts for conversion of light alkanes, feedstocks available in large quantities from shale gas that are changing the economics of manufacturing commodity chemicals. Mononuclear high-spin (S = 2) Fe(II) sites situated in the nodes of the MOF MIL-100(Fe) convert propane via dehydrogenation, hydroxylation, and overoxidation pathways in reactions with the atomic oxidant N2O. Pair distribution function analysis, N-2 adsorption isotherms, X-ray diffraction patterns, and infrared and Raman spectra confirm the single-phase crystallinity and stability of MIL-100(Fe) under reaction conditions (523 K in vacuo, 378-408 K C3H8 + N2O). Density functional theory (DFT) calculations illustrate a reaction mechanism for the formation of 2-propanol, propylene, and 1-propanol involving the oxidation of Fe(II) to Fe(III) via a high-spin Fe(IV)=O intermediate. The speciation of Fe(II) and Fe(III) in the nodes and their dynamic interchange was characterized by in situ X-ray absorption spectroscopy and ex situ Mossbauer spectroscopy. The catalytic relevance of Fe(II) sites and the number of such sites were determined using in situ chemical titrations with NO. N-2 and C3H6 production rates were found to be first-order in N2O partial pressure and zero-order in C3H8 partial pressure, consistent with DFT calculations that predict the reaction of Fe(II) with N2O to be rate determining. DFT calculations using a broken symmetry method show that Fe-trimer nodes affecting reaction contain antiferromagnetically coupled iron species, and highlight the importance of stabilizing high-spin (S = 2) Fe(II) species for effecting alkane oxidation at low temperatures (<408 K).
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Babucci, Melike, et al.
(författare)
-
Characterization of a Metal–Organic Framework Zr6O8 Node-Supported Atomically Dispersed Iridium Catalyst for Ethylene Hydrogenation by X-ray Absorption Near-Edge Structure and Infrared Spectroscopies
- 2021
-
Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 125:31, s. 16995-17007
-
Tidskriftsartikel (refereegranskat)abstract
- The catalytic properties of atomically dispersed supported metals depend on the supports as ligands. We report metal-organic frameworks in the UiO-66 family, synthesized with various ligands that influence the electron-donor properties of the Zr6O8 nodes, including benzene-1,4-dicarboxylate linkers (some with substituents) and formate, acetate, benzoate, and trifluoroacetate. Catalytically active iridium species on the nodes were made by chemisorption of Ir(CO)(2)(acetylacetonato), giving Ir(CO) 2 groups, identified by infrared (IR) and extended X-ray absorption fine structure spectroscopies. The electronic properties of the iridium centers, which are sensitive to the supports as ligands, were characterized with high-energy-resolution fluorescence detection X-ray absorption near-edge spectroscopy (HERFD XANES), distinguishing the supports and giving results correlated with the nu(CO) IR spectra and catalytic activities of partially decarbonylated iridium sites for ethylene hydrogenation at 313 K and atmospheric pressure. The IR spectra of the working catalyst incorporating linkers with NH2 substituents show an initial induction period as reactants changed the iridium ligand environment, after which the catalyst operating in a once-through flow reactor underwent no measurable deactivation for 48 h. Among the results, we emphasize the value of HERFD XANES spectroscopy for the sensitive assessment of the effects of supports as ligands that determine the catalytic properties of atomically dispersed metals.
|
|
| 8. |
- Babucci, Melike, et al.
(författare)
-
Controlling catalytic activity and selectivity for partial hydrogenation by tuning the environment around active sites in iridium complexes bonded to supports
- 2019
-
Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6520 .- 2041-6539. ; 10:9, s. 2623-2632
-
Tidskriftsartikel (refereegranskat)abstract
- Single-site Ir(CO)(2) complexes bonded to high-surface-area metal oxide supports, SiO2, TiO2, Fe2O3, CeO2, MgO, and La2O3, were synthesized by chemisorption of Ir(CO)(2)(acac) (acac = acetylacetonate) followed by coating with each of the following ionic liquids (ILs): 1-n-butyl-3-methylimidazolium tetrafluoroborate, [BMIM][BF4], 1-n-butyl-3-methylimidazolium acetate, [BMIM][Ac], and 1-(3-cyanopropyl)-3-methylimidazolium dicyanamide, [CPMIM][DCA]. Extended X-ray absorption fine structure spectroscopy showed that site-isolated iridium was bonded to oxygen atoms of the support. Electron densities on the iridium enveloped by each IL sheath/support combination were characterized by carbonyl infrared spectroscopy of the iridium gem-dicarbonyls and by X-ray absorption near-edge structure data. The electron-donor/acceptor tendencies of both the support and IL determine the activity and selectivity of the catalysts for the hydrogenation of 1,3-butadiene, with electron-rich iridium being selective for partial hydrogenation. The results resolve the effects of the IL and support as ligands; for example, the effect of the IL becomes dominant when the support has a weak electron-donor character. The combined effects of supports and ILs as ligands offer broad opportunities for tuning catalytic properties of supported metal catalysts.
|
|
| 9. |
- Babucci, Melike, et al.
(författare)
-
Tuning the Selectivity of Single-Site Supported Metal Catalysts with Ionic Liquids
- 2017
-
Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435 .- 2155-5435. ; 7:10, s. 6969-6972
-
Tidskriftsartikel (refereegranskat)abstract
- 1,3-Dialkylimidazolium ionic liquid coatings act as electron donors, increasing the selectivity for partial hydrogenation of 1,3-butadiene catalyzed by iridium complexes supported on high-surface-area gamma-Al2O3. High-energy-resolution fluorescence detection X-ray absorption near-edge structure (HERFD XANES) measurements quantify the electron donation and are correlated with the catalytic activity and selectivity. The results demonstrate broad opportunities to tune electronic environments and catalytic properties of atomically dispersed supported metal catalysts.
|
|
| 10. |
- Babucci, Melike, et al.
(författare)
-
Unraveling the individual influences of supports and ionic liquid coatings on the catalytic properties of supported iridium complexes and iridium clusters
- 2020
-
Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517 .- 1090-2694. ; 387, s. 186-195
-
Tidskriftsartikel (refereegranskat)abstract
- Supported iridium complexes were synthesized by the reaction of Ir(CO)(2) (acac) (acac = acetylacetonato) with SiO2, gamma-Al2O3, and MgO. Extended X-ray absorption fine structure (EXAFS) and infrared (IR) spectra demonstrate that the iridium was present as atomically dispersed species anchored to each support. The samples were treated in flowing H-2 at 673 K to form supported iridium clusters. EXAFS spectra and highangle annular dark-field scanning transmission electron microscopy images demonstrate that the average diameter of the iridium clusters on each support was approximately 1.2 nm. The catalysts before and after cluster formation were coated with each of a family of 1,3-dialkylimidazolium ionic liquids (ILs) having varying electron-donor tendencies probed by their nu(C2H) frequencies determined by IR spectroscopy. The coated and uncoated samples were tested as catalysts for partial hydrogenation of 1,3-butadiene in a flow reactor at 333 K, with turnover frequencies determined from differential conversions. The individual influences of the IL coatings and supports on the catalyst performance were found to depend strongly on whether the iridium was site-isolated complexes or present in clusters. The IL coatings as ligands exerted dominant effects on the clusters as catalysts, whereas the supports exerted dominant effects on the isolated iridium atoms. The results indicate how to tune the effects of metal nuclearity, IL coatings, and supports on the electronic environments and catalytic properties of the metals
|
|
