| 1. |
- Andersson, Jenny Marie, et al.
(författare)
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The Impact of Nonequilibrium Conditions in Lung Surfactant : Structure and Composition Gradients in Multilamellar Films
- 2018
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:10, s. 1315-1325
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Tidskriftsartikel (refereegranskat)abstract
- The lipid-protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air-liquid interfaces.
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| 2. |
- Aspuru-Guzik, Alan, et al.
(författare)
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The Matter Simulation (R)evolution
- 2018
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Ingår i: ACS CENTRAL SCIENCE. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:2, s. 144-152
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Tidskriftsartikel (refereegranskat)abstract
- To date, the program for the development of methods and models for atomistic and continuum simulation directed toward chemicals and materials has reached an incredible degree of sophistication and maturity. Currently, one can witness an increasingly rapid emergence of advances in computing, artificial intelligence, and robotics. This drives us to consider the future of computer simulation of matter from the molecular to the human length and time scales in a radical way that deliberately dares to go beyond the foreseeable next steps in any given discipline. This perspective article presents a view on this future development that we believe is likely to become a reality during our lifetime.
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| 3. |
- Bosque, Irene, et al.
(författare)
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Redox Catalysis Facilitates Lignin Depolymerization
- 2017
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7951 .- 2374-7943. ; 3:6, s. 621-628
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Tidskriftsartikel (refereegranskat)abstract
- Lignin is a recalcitrant and underexploited natural feedstock for aromatic commodity chemicals, and its degradation generally requires the use of high temperatures and harsh reaction conditions. Herein we present an ambient temperature one-pot process for the controlled oxidation and depolymerization of this potent resource. Harnessing the potential of electrocatalytic oxidation in conjugation with our photocatalytic cleavage methodology, we have developed an operationally simple procedure for selective fragmentation of β-O-4 bonds with excellent mass recovery, which provides a unique opportunity to expand the existing lignin usage from energy source to commodity chemicals and synthetic building block source.
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| 4. |
- Emilsson, Gustav, 1989, et al.
(författare)
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Gating Protein Transport in Solid State Nanopores by Single Molecule Recognition
- 2018
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7951 .- 2374-7943. ; 4:8, s. 1007-1014
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Tidskriftsartikel (refereegranskat)abstract
- Control of molecular translocation through nanoscale apertures is of great interest for DNA sequencing, biomolecular filters, and new platforms for single molecule analysis. However, methods for controlling the permeability of nanopores are very limited. Here, we show how nanopores functionalized with poly(ethylene glycol) brushes, which fully prevent protein translocation, can be reversibly gated to an "open" state by binding of single IgG antibodies that disrupt the macromolecular barrier. On the basis of surface plasmon resonance data we propose a two-state model describing the antibody-polymer interaction kinetics. Reversibly (weakly) bound antibodies decrease the protein exclusion height while irreversibly (strongly) bound antibodies do not. Our results are further supported by fluorescence readout from pore arrays and high-speed atomic force microscopy on single pores. This type of dynamic barrier control on the nanoscale provides new possibilities for biomolecular separation and analysis.
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| 5. |
- Gemmi, Mauro, et al.
(författare)
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3D Electron Diffraction : The Nanocrystallography Revolution
- 2019
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Ingår i: ACS central science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 5:8, s. 1315-1329
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Tidskriftsartikel (refereegranskat)abstract
- Crystallography of nanocrystalline materials has witnessed a true revolution in the past 10 years, thanks to the introduction of protocols for 3D acquisition and analysis of electron diffraction data. This method provides single-crystal data of structure solution and refinement quality, allowing the atomic structure determination of those materials that remained hitherto unknown because of their limited crystallinity. Several experimental protocols exist, which share the common idea of sampling a sequence of diffraction patterns while the crystal is tilted around a noncrystallographic axis, namely, the goniometer axis of the transmission electron microscope sample stage. This Outlook reviews most important 3D electron diffraction applications for different kinds of samples and problematics, related with both materials and life sciences. Structure refinement including dynamical scattering is also briefly discussed.
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| 6. |
- Gentile, Francesco, et al.
(författare)
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Deep Docking : A Deep Learning Platform for Augmentation of Structure Based Drug Discovery
- 2020
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Ingår i: ACS central science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 6:6, s. 939-949
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Tidskriftsartikel (refereegranskat)abstract
- Drug discovery is a rigorous process that requires billion dollars of investments and decades of research to bring a molecule from bench to a bedside. While virtual docking can significantly accelerate the process of drug discovery, it ultimately lags the current rate of expansion of chemical databases that already exceed billions of molecular records. This recent surge of small molecules availability presents great drug discovery opportunities, but also demands much faster screening protocols. In order to address this challenge, we herein introduce Deep Docking (DD), a novel deep learning platform that is suitable for docking billions of molecular structures in a rapid, yet accurate fashion. The DD approach utilizes quantitative structure-activity relationship (QSAR) deep models trained on docking scores of subsets of a chemical library to approximate the docking outcome for yet unprocessed entries and, therefore, to remove unfavorable molecules in an iterative manner. The use of DD methodology in conjunction with the FRED docking program allowed rapid and accurate calculation of docking scores for 1.36 billion molecules from the ZINC15 library against 12 prominent target proteins and demonstrated up to 100-fold data reduction and 6000-fold enrichment of high scoring molecules (without notable loss of favorably docked entities). The DD protocol can readily be used in conjunction with any docking program and was made publicly available.
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| 7. |
- Guimond, S. E., et al.
(författare)
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Synthetic Heparan Sulfate Mimetic Pixatimod (PG545) Potently Inhibits SARS-CoV-2 by Disrupting the Spike-ACE2 Interaction
- 2022
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:5, s. 527-545
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) is a cell surface polysaccharide recently identified as a coreceptor with the ACE2 protein for the S1 spike protein on SARS-CoV-2 virus, providing a tractable new therapeutic target. Clinically used heparins demonstrate an inhibitory activity but have an anticoagulant activity and are supply-limited, necessitating alternative solutions. Here, we show that synthetic HS mimetic pixatimod (PG545), a cancer drug candidate, binds and destabilizes the SARS-CoV-2 spike protein receptor binding domain and directly inhibits its binding to ACE2, consistent with molecular modeling identification of multiple molecular contacts and overlapping pixatimod and ACE2 binding sites. Assays with multiple clinical isolates of SARS-CoV-2 virus show that pixatimod potently inhibits the infection of monkey Vero E6 cells and physiologically relevant human bronchial epithelial cells at safe therapeutic concentrations. Pixatimod also retained broad potency against variants of concern (VOC) including B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Furthermore, in a K18-hACE2 mouse model, pixatimod significantly reduced SARS-CoV-2 viral titers in the upper respiratory tract and virus-induced weight loss. This demonstration of potent anti-SARS-CoV-2 activity tolerant to emerging mutations establishes proof-of-concept for targeting the HS-Spike protein-ACE2 axis with synthetic HS mimetics and provides a strong rationale for clinical investigation of pixatimod as a potential multimodal therapeutic for COVID-19.
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| 8. |
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| 9. |
- Huang, Xiaofeng, et al.
(författare)
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Solvent Gaming Chemistry to Control the Quality of Halide Perovskite Thin Films for Photovoltaics
- 2022
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Ingår i: ACS CENTRAL SCIENCE. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 8:7, s. 1008-1016
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Tidskriftsartikel (refereegranskat)abstract
- Research on solvent chemistry, particularly for halide perovskite intermediates, has been advancing the development of perovskite solar cells (PSCs) toward commercial applications. A predictive understanding of solvent effects on the perovskite formation is thus essential. This work systematically discloses the relationship among the basicity of solvents, solvent-contained intermediate structures, and intermediate-to-perovskite alpha-FAPbI(3) evolutions. Depending on their basicity, solvents exhibit their own favorite bonding selection with FA(+) or Pb2+ cations by forming either hydrogen bonds or coordination bonds, resulting in two different kinds of intermediate structures. While both intermediates can be evolved into alpha-FAPbI(3) below the delta-to-alpha thermodynamic temperature, the hydrogen-bond-favorable kind could form defect-less alpha-FAPbI(3) via sidestepping the break of strong coordination bonds. The disclosed solvent gaming mechanism guides the solvent selection for fabricating high-quality perovskite films and thus high-performance PSCs and modules.
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| 10. |
- Huang, Xiaoli, et al.
(författare)
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The Molecular Basis for Inhibition of Stemlike Cancer Cells by Salinomycin
- 2018
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:6, s. 760-767
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are phenotypically heterogeneous and include subpopulations of cancer cells with stemlike properties. The natural product salinomycin, a K+-selective ionophore, was recently found to exert selectivity against such cancer stem cells. This selective effect is thought to be due to inhibition of the Wnt signaling pathway, but the mechanistic basis remains unclear. Here, we develop a functionally competent fluorescent conjugate of salinomycin to investigate the molecular mechanism of this compound. By subcellular imaging, we demonstrate a rapid cellular uptake of the conjugate and accumulation in the endoplasmic reticulum (ER). This localization is connected to induction of Ca2+ release from the ER into the cytosol. Depletion of Ca2+ from the ER induces the unfolded protein response as shown by global mRNA analysis and Western blot analysis of proteins in the pathway. In particular, salinomycin-induced ER Ca2+ depletion up-regulates C/EBP homologous protein (CHOP), which inhibits Wnt signaling by down-regulating β-catenin. The increased cytosolic Ca2+ also activates protein kinase C, which has been shown to inhibit Wnt signaling. These results reveal that salinomycin acts in the ER membrane of breast cancer cells to cause enhanced Ca2+ release into the cytosol, presumably by mediating a counter-flux of K+ ions. The clarified mechanistic picture highlights the importance of ion fluxes in the ER as an entry to inducing phenotypic effects and should facilitate rational development of cancer treatments.
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| 11. |
- Ibrahim, MX, et al.
(författare)
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Toward a New Therapy for Rapidly Aging Children
- 2021
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Ingår i: ACS central science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 7:8, s. 1292-1294
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 12. |
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| 13. |
- Lv, Hao, et al.
(författare)
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Synthesis and Crystal-Phase Engineering of Mesoporous Palladium-Boron Alloy Nanoparticles
- 2020
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Ingår i: ACS central science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 6:12, s. 2347-2353
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Tidskriftsartikel (refereegranskat)abstract
- Rational design and synthesis of noble metal nanomaterials with desired crystal phases (atomic level) and controllable structures/morphologies (mesoscopic level) are paramount for modulating their physiochemical properties. However, it is challenging to simultaneously explore atomic crystal-phase structures and ordered mesoscopic morphologies. Here, we report a simple synergistic templating strategy for the preparation of palladium-boron (Pd-B) nanoparticles with precisely controllable crystal-phases and highly ordered mesostructures. The engineering of crystal-phase structures at atomic levels is achieved by interstitially inserting metallic B atoms into face-centered cubic mesoporous Pd (fcc-mesoPd) confined in a mesoporous silica template. With the gradual insertion of B atoms, fcc-mesoPd is transformed into fcc-mesoPd(5)B, hcp-mesoPd(2)B with randomly distributed B atoms (hcp-mesoPd(2)B-r), and hcp-mesoPd(2)B with an atomically ordered B sequence (hcp-mesoPd(2)B-o) while preserving well-defined mesostructures. This synergistic templating strategy can be extended to engineer crystal-phase structures with various mesostructures/morphologies, including nanoparticles, nanobundles, and nanorods. Moreover, we investigate the crystal-phase-dependent catalytic performance toward the reduction reaction of p-nitrophenol and find that hcp-mesoPd(2)B-o displays much better catalytic activity. This work thus paves a new way for the synthesis of hcp-Pd2B nanomaterials with mesoscopically ordered structure/morphology and offers new insights of fcc-to-hcp evolution mechanisms which could be applied on other noble metal-based nanomaterials for various targeted applications.
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| 14. |
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| 15. |
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| 16. |
- Rawle, Robert J., et al.
(författare)
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pH Dependence of Zika Membrane Fusion Kinetics Reveals an Off-Pathway State
- 2018
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Ingår i: ACS CENTRAL SCIENCE. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:11, s. 1503-1510
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Tidskriftsartikel (refereegranskat)abstract
- The recent spread of Zika virus stimulated extensive research on its structure, pathogenesis, and immunology, but mechanistic study of entry has lagged behind, in part due to the lack of a defined reconstituted system. Here, we report Zika membrane fusion measured using a platform that bypasses these barriers, enabling observation of single-virus fusion kinetics without receptor reconstitution. Surprisingly, target membrane binding and low pH are sufficient to trigger viral hemifusion to liposomes containing only neutral lipids. Second, although the extent of hemifusion strongly depends on pH, hemifusion rates are relatively insensitive to pH. Kinetic analysis shows that an off-pathway state is required to capture this pH-dependence and suggests this may be related to viral inactivation. Our surrogate-receptor approach thus yields new understanding of flaviviral entry mechanisms and should be applicable to many emerging viruses.
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| 17. |
- Simonetti, Leandro, et al.
(författare)
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Genetically Encoded Cyclic Peptide Phage Display Libraries
- 2020
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Ingår i: ACS CENTRAL SCIENCE. - : AMER CHEMICAL SOC. - 2374-7943 .- 2374-7951. ; 6:3, s. 336-338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Phage display of self-cycling peptides as an efficient and scalable approach to discover macrocyclic inhibitors of protein-protein interactions.
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| 18. |
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| 19. |
- Spicer, Christopher D., et al.
(författare)
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Synthesis of Phospho-Amino Acid Analogues as Tissue Adhesive Cement Additives
- 2020
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Ingår i: ACS CENTRAL SCIENCE. - : AMER CHEMICAL SOC. - 2374-7943 .- 2374-7951. ; 6:2, s. 226-231
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report the synthesis of a library of phospho-amino acid analogues, via a novel single-step allyl-phosphoester protection/Pd-mediated deprotection strategy. These phosphoserine and phosphotyrosine analogues were then applied as additives to create adhesive calcium phosphate cements, allowing us to probe the chemical origins of the increased surface binding strength. We demonstrate the importance of multiple calcium binding motifs in mediating adhesion, as well as highlighting the crucial role played by substrate hydrophobicity and orientation in controlling binding strength.
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| 20. |
- Tamayo-Mendoza, Teresa, et al.
(författare)
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Automatic Differentiation in Quantum Chemistry with Applications to Fully Variational Hartree-Fock
- 2018
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Ingår i: ACS CENTRAL SCIENCE. - : AMER CHEMICAL SOC. - 2374-7943 .- 2374-7951. ; 4:5, s. 559-566
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Tidskriftsartikel (refereegranskat)abstract
- Automatic differentiation (AD) is a powerful tool that allows calculating derivatives of implemented algorithms with respect to all of their parameters up to machine precision, without the need to explicitly add any additional functions. Thus, AD has great potential in quantum chemistry, where gradients are omnipresent but also difficult to obtain, and researchers typically spend a considerable amount of time finding suitable analytical forms when implementing derivatives. Here, we demonstrate that AD can be used to compute gradients with respect to any parameter throughout a complete quantum chemistry method. We present DiffiQult, a Hartree-Fock implementation, entirely differentiated with the use of AD tools. DiffiQult is a software package written in plain Python with minimal deviation from standard code which illustrates the capability of AD to save human effort and time in implementations of exact gradients in quantum chemistry. We leverage the obtained gradients to optimize the parameters of one-particle basis sets in the context of the floating Gaussian framework.
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| 21. |
- Yang, Dong, et al.
(författare)
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The Surface Chemistry of Metal Oxide Clusters : From Metal–Organic Frameworks to Minerals
- 2020
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 6:9, s. 1523-1533
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Tidskriftsartikel (refereegranskat)abstract
- Many metal–organic frameworks (MOFs) incorporate nodes that are small metal oxide clusters. Some of these MOFs are stable at high temperatures, offering good prospects as catalysts—prospects that focus attention on their defect sites and reactivities—all part of a broader subject: the surface chemistry of metal oxide clusters, illustrated here for MOF nodes and for polyoxocations and polyoxoanions. Ligands on MOF defect sites form during synthesis and are central to the understanding and control of MOF reactivity. Reactions of alcohols are illustrative probes of Zr6O8 node defects in UiO-66, characterized by the interconversions of formate, methoxy, hydroxy, and linker carboxylate ligands and by catalysis of alcohol dehydration reactions. We posit that new reactivities of MOF nodes will emerge from incorporation of a wide range of groups on their surfaces and from targeted substitutions of metals within them.
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| 22. |
- Yeung, Sing Yee, et al.
(författare)
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Reversible Self-Assembled Monolayers (rSAMs) : Adaptable Surfaces for Enhanced Multivalent Interactions and Ultrasensitive Virus Detection
- 2017
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7951 .- 2374-7943. ; 3:11, s. 1198-1207
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Tidskriftsartikel (refereegranskat)abstract
- We report on the design of pH-switchable monolayers allowing a reversible and ordered introduction of affinity reagents on sensor surfaces. The principal layer building blocks consist of α-(4-amidinophenoxy)alkanes decorated at the ω-position with affinity ligands. These spontaneously self-assemble on top of carboxylic acid terminated SAMs to form reversible homo or mixed monolayers (rSAMs) that are tunable with respect to the nature of the head group, layer order and stability while featuring pH responsiveness and the dynamic nature of noncovalent build assemblies. We show that this results in a range of unique biosensor features. As a first example a sialic acid rSAM featuring strong lectin affinity is here used to sense hemagglutinin and influenza virus (H5N1) at the pM and fM level by in situ ellipsometry in a fully reversible fashion. We believe that the rSAM concept will find widespread use in surface chemistry and overall for boosting sensitivity in affinity biosensors.
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| 23. |
- Yuan, Shuai, et al.
(författare)
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[Ti8Zr2O12(COO)(16)] Cluster : An Ideal Inorganic Building Unit for Photoactive Metal-Organic Frameworks
- 2018
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Ingår i: Acs Central Science. - : American Chemical Society (ACS). - 2374-7943 .- 2374-7951. ; 4:1, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- Metal-organic frameworks (MOFs) based on Ti-oxo clusters (Ti-MOFs) represent a naturally self-assembled superlattice of TiO2 nanoparticles separated by designable organic linkers as antenna chromophores, epitomizing a promising platform for solar energy conversion. However, despite the vast, diverse, and well-developed Ti-cluster chemistry, only a scarce number of Ti-MOFs have been documented. The synthetic conditions of most Ti-based clusters are incompatible with those required for MOF crystallization, which has severely limited the development of Ti-MOFs. This challenge has been met herein by the discovery of the [Ti8Zr2O12(COO)(16)] cluster as a nearly ideal building unit for photoactive MOFs. A family of isoreticular photoactive MOFs were assembled, and their orbital alignments were fine-tuned by rational functionalization of organic linkers under computational guidance. These MOFs demonstrate high porosity, excellent chemical stability, tunable photoresponse, and good activity toward photocatalytic hydrogen evolution reactions. The discovery of the [Ti8Zr2O12(COO)(16)] cluster and the facile construction of photoactive MOFs from this cluster shall pave the way for the development of future Ti-MOF-based photocatalysts. GRAPHICS
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| 24. |
- Öhrström, Lars, 1963
(författare)
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Framework Chemistry Transforming our Perception of the Solid State
- 2017
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Ingår i: ACS Central Science. - : American Chemical Society (ACS). - 2374-7951 .- 2374-7943. ; 3:6, s. 528-530
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 American Chemical Society. "Retrofitting" metal?organic frameworks challenges our perceptions about the properties of crystalline materials.
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| 25. |
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| 26. |
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