| 1. |
- Fu, Y., et al.
(author)
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Defect-Assisted Loading and Docking Conformations of Pharmaceuticals in Metal–Organic Frameworks
- 2021
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:14, s. 7719-7727
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Journal article (peer-reviewed)abstract
- Understanding of drug–carrier interactions is essential for the design and application of metal–organic framework (MOF)-based drug-delivery systems, and such drug–carrier interactions can be fundamentally different for MOFs with or without defects. Herein, we reveal that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host–guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites, and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOFs without defects, the loading capacity is greatly reduced. We employed solid-state NMR spectroscopy and molecular simulations to elucidate the drug–carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects were revealed.
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| 2. |
- Fu, Yao, et al.
(author)
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Duet of Acetate and Water at the Defects of Metal-Organic Frameworks
- 2019
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In: Nano letters (Print). - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 19:3, s. 1618-1624
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Journal article (peer-reviewed)abstract
- Metal-organic frameworks (MOFs) are porous crystalline materials with promising applications in molecular adsorption, separation, and catalysis. It has been discovered recently that structural defects introduced unintentionally or by design could have a significant impact on their properties. However, the exact chemical composition and structural evolution under different conditions at the defects are still under debate. In this study, we performed multidimensional solid-state nuclear magnetic resonance (SSNMR) coupled with computer simulations to elucidate an important scenario of MOF defects, uncovering the dynamic interplay between residual acetate and water. Acetate, as a defect modulator, and water, as a byproduct, are prevalent defect-associated species, which are among the key factors determining the reactivity and stability of defects. We discovered that acetate molecules coordinate to a single metal site monodentately and pair with water at the neighboring position. The acetates are highly flexible, which undergo fast libration as well as a slow kinetic exchange with water through dynamic hydrogen bonds. The dynamic processes under variable temperatures and different hydration levels have been quantitatively analyzed across a broad time scale from microseconds to seconds. The integration of SSNMR and computer simulations allows a precision probe into defective MOF structures with intrinsic dynamics and disorder.
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| 3. |
- Kang, Zhengzhong, 1990-, et al.
(author)
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Adsorption and folding of single strand DNA on metal-organic frameworks: a molecular simulation study
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Other publication (other academic/artistic)abstract
- DNA-MOF nanoparticles based on the loading, release, and conformational change of DNA on MOFs have been frequently explored in gene therapy, drug delivery, and biosensor design. Nevertheless, the mechanism of DNA-MOF interactions, which is a fundamental issue behind these applications, remains largely unclear. Here, we applied molecular simulation methods to study systematically the adsorption and folding of ssDNA with different sequences on ideal and defective UiO-66-NH2 MOFs. We find that the ssDNA prefers to be adsorbed on the surfaces rather than inside the cages due to the size limitation of the cages. It is difficult for the ssDNA to be adsorbed on the ideal MOF surface through van der Waals interactions but it can be stably loaded on the defective MOF surface through electrostatic interactions. The whole process of the ssDNA adsorption onto the defective MOFs includes three stages: fast adsorption, conformational reconfiguration, and lock-down adsorption. The loading state of the ssDNA on UiO-66-NH2 is the coexistence of the adsorbed and dangling nucleotides. The binding of the ssDNA on the MOFs is dominated by the multiple point anchoring of the phosphate groups of the ssDNA on the clusters of UiO-66-NH2. Water layers with complex hydrogen-bond network function as a gate, preventing the ssDNA from approaching to UiO-66-NH2 before adsorption and inhibiting it from leaving UiO-66-NH2 after anchoring. Unlike the circular folding structure in the solution, the adsorbed ssDNA displays a slender conformation or duplex like structure. Our results thus provide a deep understanding of DNA-MOF interactions.
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| 4. |
- Li, Jiachen, et al.
(author)
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A combined computational and experimental approach predicts thrombin adsorption to zeolites
- 2023
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In: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 221, s. 113007-
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Journal article (peer-reviewed)abstract
- Robust protein-nanomaterial surface analysis is important, but also a challenge. Thrombin plays an important role in the coagulant activity of protein corona mediated by Ca2+ ion exchanged zeolites. However, the mech-anism for this modulation remains unresolved. In this study, we proposed a combined computational and experimental approach to determine the adsorbed sites and orientations of thrombin binding to Ca2+-exchanged LTA-type (CaA) zeolite. Specifically, fourteen ensembles of simulated annealing molecular dynamics (SAMD) simulations and experimental surface residues microenvironment analysis were used to reduce the starting orientations needed for further molecular dynamics (MD) simulations. The combined MD simulations and pro -coagulant activity characterization also reveal the consequent corresponding deactivation of thrombin on CaA zeolite. It is mainly caused by two aspects: (1) the secondary structure of thrombin can change after its adsorption on the CaA zeolite. (2) The positively charged area of thrombin mediates the preferential interaction between thrombin and CaA zeolite. Some thrombin substrate sites are thus blocked by zeolite after its adsorption. This study not only provides a promising method for characterizing the protein-nanoparticle interaction, but also gives an insight into the design and application of zeolite with high procoagulant activity.
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| 5. |
- Liang, Lijun, et al.
(author)
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Theoretical Evaluation on Potential Cytotoxicity of Graphene Quantum Dots
- 2016
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In: ACS Biomaterials Science & Engineering. - : AMER CHEMICAL SOC. - 2373-9878. ; 2:11, s. 1983-1991
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Journal article (peer-reviewed)abstract
- Owing to unique morphology, ultrasmall lateral sizes, and exceptional properties, graphene quantum dots (GQDs) hold great potential in many applications, especially in the field of electrochemical biosensors, bioimaging, drug delivery, et cetera. Its biosafety and potential cytotoxicity to human and animal cells has been a growing concern in recent years. In this work, the potential cytotoxicity of GQDs was evaluated by molecular dynamics simulations. Our simulation demonstrates that small size GQDs could easily permeate into the lipid membrane in a vertical way. It is relatively difficult to permeate into the lipid membrane for GQDs that are larger than GQD61 on the nanosecond time-scale. The thickness of the POPC membrane could even be affected by the small size of GQDs. Free energy calculations revealed that the free energy barrier of GQD permeation through the lipid membrane could greatly change with the change of GQD size. Under high GQD concentration, the GQD molecules could rapidly aggregate in water but disaggregate after entering into the membrane interior. Moreover, high concentrations of GQDs could induce changes in the structure properties and diffusion properties of the lipid bilayer, and it may affect the cell signal transduction. However, GQDs with relatively small size are not large enough to mechanically damage the lipid membrane. Our results suggest that the cytotoxicity of GQDs with small size is low and may be appropriate for biomedical application.
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| 6. |
- Liang, Lijun, et al.
(author)
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Translocation mechanism of C-60 and C-60 derivations across a cell membrane
- 2016
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In: Journal of nanoparticle research. - : Springer. - 1388-0764 .- 1572-896X. ; 18:11
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Journal article (peer-reviewed)abstract
- Carbon-based nanoparticles (NPs) such as fullerenes and nanotubes have been extensively studied for drug delivery in recent years. The permeation process of fullerene and its derivative molecules through membrane is essential to the utilization of fullerene-based drug delivery system, but the mechanism and the dynamics of permeation through cell membrane are still unclear. In this study, coarse-grained molecular dynamics simulations were performed to investigate the permeation process of functionalized fullerene molecules (ca. 0.72 nm) through the membrane. Our results show that single functionalized fullerene molecule in such nanoscale could permeate the lipid membrane in micro-second time scale. Pristine C-60 molecules prefer to aggregate into several small clusters while C60OH15 molecules could aggregate into one big cluster to permeate through the lipid membrane. After permeation of C-60 or its derivatives into membrane, all C-60 and C60OH15 molecules disaggregated and monodispersed in the lipid membrane.
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| 7. |
- Shi, C., et al.
(author)
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Molecular dynamics simulations indicate that DNA bases using graphene nanopores can be identified by their translocation times
- 2015
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In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:13, s. 9389-9395
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Journal article (peer-reviewed)abstract
- The improvement of the resolution of DNA sequencing by nanopore technology is very important for its real-life application. In this paper, we report our work on using molecular dynamics simulation to study the dependence of DNA sequencing on the translocation time of DNA through a graphene nanopore, using the single-strand DNA fragment translocation through graphene nanopores with diameters down to ∼2 nm as examples. We found that A, T, C, and G could be identified by the difference in the translocation time between different types of nucleotides through 2 nm graphene nanopores. In particular, the recognition of the graphene nanopore for different nucleotides can be greatly enhanced in a low electric field. Our study suggests that the recognition of a graphene nanopore by different nucleotides is the key factor for sequencing DNA by translocation time. Our study also indicates that the surface of a graphene nanopore can be modified to increase the recognition of nucleotides and to improve the resolution of DNA sequencing based on the DNA translocation time with a suitable electric field.
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| 8. |
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| 9. |
- Wang, Z., et al.
(author)
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Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA-Metal-Organic Frameworks with Soluble Exoskeleton
- 2017
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In: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 139:44, s. 15784-15791
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Journal article (peer-reviewed)abstract
- DNA has proven of high utility to modulate the surface functionality of metal-organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for preparing DNA-MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (∼2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA-MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA-MOFs (isMOFs) by intrinsically coordinating cytosine-phosphate-guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was further armed by a protection shell of calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG-MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential "protect-release" program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.
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| 10. |
- Zhang, Lin, et al.
(author)
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Ultradeep Removal of Moisture in Gases to Parts-per-Billion Levels : The Exploration of Adsorbents
- 2018
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In: The Journal of Physical Chemistry C. - : AMER CHEMICAL SOC. - 1932-7447 .- 1932-7455. ; 122:5, s. 2840-2847
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Journal article (peer-reviewed)abstract
- Owing to the rigid standards of manufacturing semiconductor components, decrease of the moisture to parts-per-billion (ppb), at a global level, is always vital but extremely nerve-racking in the production of high-purity gases. Herein, typical adsorbents including oxides (SiO2 and gamma-Al2O3), zeolites (4A and NaX), and metal-organic frameworks (MOFs; HKUST-1, UiO-66, and ZIF-8) are investigated with respect to the abilities of ultradeep dewatering from N-2. Compared with other adsorbents, NaX performs much better on both dewatering efficiency (DE, from 2750 to 66 ppb) and the adsorption capacity (AC, 1.55 x 10(4) L N-2.g(-1)). Moreover, it is for the first time experimentally and theoretically proved that the dewatering ability of X zeolite mainly depends on its cation species (Na+, Li+, K+, Cs+, Mg2+, Ca2+, Sr2+, or Ba2+), the forces between the zeolite and H2O, and the number of H2O molecules per cell of the zeolite. CaX thus shows a fascinating DE from 2750 to 33 ppb, a huge AC of 9.08 x 10(4) L N-2.g(-1), and an ideal reusability, compared with results of the scarce contributions reported to date.
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