Stepwise Synthetic Approach for MOFs with Site Specific Heterolinkers and Hollow MOF Superstructure

Department of ChemistryMetal???organic frameworks (MOFs), a new class of porous crystalline materials, have received significant attention due to their great potential applications in various areas such as gas storage, separation, heterogeneous catalysis, and chemical sensing. The framework modifications can be often achieved by introduction of organic ligands with variable functional groups via direct solvothermal one-pot reactions. This one-pot synthesis is difficult to locate organic ligands into specific positions, resulting in hybrid MOFs with random distribution of the ligands in the frameworks. Thus, many researchers have attempted to position ligands with specific functional groups into predetermined sites in the framework. Hollow structures with cavities at the center of the particles are of great importance because of their fascinating characteristics such as low density, high surface-to-volume ratio, low thermal expansion coefficient and high loading capacity. Several hollow MOF structures have been prepared via synthetic strategies similar to those employed for the preparation of the hollow metal/metal oxide nano-/microstructures. The resulting products are generally in the form of agglomerates with weak binding force. It is thus still a big task to synthesize well-defined single crystalline hollow MOF superstructures. The first part of this thesis describes the rational syntheses of a series of new 12-c fcu Zr-MOFs (ZRN-XB) with two different linkers through the stepwise postsynthetic linker insertion into a flexible 8-c bcu Zr-MOF (ZRN-bcu). Postsynthetic linker insertions of a series of length-mismatching but symmetry-matching BDC derivatives (XBDC) were attempted. Even though the XBDC linkers are shorter than the distance between potential linkage sites in ZRNbcu, the XBDC linkers are well inserted into the remaining potential linkage sites to form a new framework with 12-c fcu topology. These results indicate that symmetry-matching between the inserted ligands and the potential linkage sites plays a critical role in postsynthetic ligand insertion processes. The second part of the thesis discusses the syntheses of single crystalline hollow MOFs with cavity dimensions of several micrometers and hundreds of micrometers by a sacrificial hard template strategy. Conventional one-pot synthetic approach in presence of Cu2+, 5- hydroxylisophthalic acid (H2hip) and various linkers only produced the metal-organic polyhedron (MOP),. A series of isostructural and isoreticular Cu-MOFs could be obtained via stepwise reactions using the cuboctahedral MOP as a molecular precursor. When a methanol solution of a ditopic neutral ligand is directly added to the MOP crystals, the reaction between the MOP crystals and linkers occur on the out surface of the MOP crystals. The difference between the rate of linker diffusion into MOP crystals and the rate of the MOP building units diffusion makes hollow superstructure.clos

Mouse Homologue of the Schizophrenia Susceptibility Gene ZNF804A as a Target of Hoxc8

Using a ChIP-cloning technique, we identified a Zinc finger protein 804a (Zfp804a) as one of the putative Hoxc8 downstream target genes. We confirmed binding of Hoxc8 to an intronic region of Zfp804a by ChIP-PCR in F9 cells as well as in mouse embryos. Hoxc8 upregulated Zfp804a mRNA levels and augmented minimal promoter activity in vitro. In E11.5 mouse embryos, Zfp804a and Hoxc8 were coexpressed. Recent genome-wide studies identified Zfp804a (or ZNF804A in humans) as a plausible marker for schizophrenia, leading us to hypothesize that this embryogenic regulatory control might also exert influence in development of complex traits such as psychosis

Single crystalline hollow metal-organic frameworks: a metal-organic polyhedron single crystal as a sacrificial template

Single crystalline hollow metal-organic frameworks (MOFs) with cavity dimensions on the order of several micrometers and hundreds of micrometers were prepared using a metal-organic polyhedron single crystal as a sacrificial hard template. The hollow nature of the MOF crystal was confirmed by scanning electron microscopy of the crystal sliced using a focused ion beam.open2

Rat primary cortical cell tri-culture to study effects of amyloid-beta on microglia function

INTRODUCTION: The etiology and progression of sporadic Alzheimer's Disease (AD) have been studied for decades. One proposed mechanism is that amyloid-beta (Aβ) proteins induce neuroinflammation, synapse loss, and neuronal cell death. Microglia play an especially important role in Aβ clearance, and alterations in microglial function due to aging or disease may result in Aβ accumulation and deleterious effects on neuronal function. However, studying these complex factors in vivo , where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of microglia, astrocytes and neurons in the same culture. Here, we employ a tri-culture model of rat primary neurons, astrocytes, and microglia and compare it to co-culture (neurons and astrocytes) and mono-culture enriched for microglia to study microglial function (i.e., motility and Aβ clearance) and proteomic response to exogenous Aβ. METHODS: We established cortical co-culture (neurons and astrocytes), tri-culture (neurons, astrocytes, and microglia), and mono-culture (microglia) from perinatal rat pups. On days in vitro (DIV) 7 - 14, the cultures were exposed to fluorescently-labeled Aβ (FITC-Aβ) particles for varying durations. Images were analyzed to determine the number of FITC-Aβ particles after specific lengths of exposure. A group of cells were stained for βIII-tubulin, GFAP, and Iba1 for morphological analysis via quantitative fluorescence microscopy. Cytokine profiles from conditioned media were obtained. Live-cell imaging with images acquired every 5 minutes for 4 hours was employed to extract microglia motility parameters (e.g., Euclidean distance, migration speed, directionality ratio). RESULTS AND DISCUSSION: FITC-Aβ particles were more effectively cleared in the tri-culture compared to the co-culture. This was attributed to microglia engulfing FITC-Aβ particles, as confirmed via epifluorescence and confocal microscopy. Adding FITC-Aβ significantly increased the size of microglia, but had no significant effect on neuronal surface coverage or astrocyte size. Analysis of the cytokine profile upon FITC-Aβ addition revealed a significant increase in proinflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6) in tri-culture, but not co-culture. In addition, Aβ addition altered microglia motility marked by swarming-like motion with decreased Euclidean distance yet unaltered speed. These results highlight the importance of cell-cell communication in microglia function (e.g., motility and Aβ clearance) and the utility of the tri-culture model to further investigate microglia dysfunction in AD

The Reference Phase Correction for the Fluctuated Scanning Lines and the Slope of the Stage in Tissue Characterization by Scanning Acoustic Microscope

In this study, a new approach was investigated to extract reference phases from the scanning acoustic microscope to calculate the speed of sound when dealing with the slope of the stage and fluctuation of the scanning lines. To capture the slope and the fluctuation pattern, data of the first lines along the horizontal and vertical axes on the stage were used. A corrective function was then utilized to improve the accuracy of reference phase extraction. The method was then corroborated by demonstrating tumor discrimination in mice skin by means of scanning acoustic microscopy (SAM). B16-F10 melanoma cells were used to grow the tumor. Hematoxylin and eosin (H&E) staining was applied for histology characterization of the sample. A comparison of both acoustics and histology was conducted. Phase analysis was performed to examine the effects of both slope and fluctuation. The results showed that our approach significantly improved the tumor detection and accuracy of scanning acoustic microscopy

Operation of national coordinating service for interhospital transfer from emergency departments: experience and implications from Korea

Background Since 2014, Korea has been operating the National Emergency Medical Situation Room (NEMSR) to provide regional emergency departments (EDs) with coordination services for the interhospital transfer of critically ill patients. The present study aimed to describe the NEMSRs experience and interhospital transfer pattern from EDs nationwide, and investigate the factors related to delayed transfers or transfers that could not be arranged by the NEMSR. Methods This study was a retrospective cross-sectional analysis of the NEMSRs coordination registry from 2017 to 2019. The demographic and hospital characteristics related to emergency transfers were analyzed with hierarchical logistic models. Results The NEMSR received a total of 14,003 requests for the arrangement of the interhospital transfers of critically ill patients from 2017 to 2019. Of 10,222 requests included in the analysis, 8297 (81.17%) successful transfers were coordinated by the NEMSR. Transfers were requested mainly due to a shortage of medical staff (59.79%) and ICU beds (30.80%). Delayed transfers were significantly associated with insufficient hospital resources. The larger the bed capacity of the sending hospital, the more difficult it was to coordinate the transfer (odds ratio [OR] for transfer not arranged = 2.04; 95% confidence interval [CI]: 1.48–2.82, ≥ 1000 beds vs. < 300 beds) and the longer the transfer was delayed (OR for delays of more than 44 minutes = 2.08; 95% CI: 1.57–2.76, ≥ 1000 beds vs. < 300 beds). Conclusions The operation of the NEMSR has clinical importance in that it could efficiently coordinate interhospital transfers through a protocolized process and resource information system. The coordination role is significant as information technology in emergency care develops while regional gaps in the distribution of medical resources widen

Templated and template-free fabrication strategies for zero-dimensional hollow MOF superstructures

Various fabrication strategies for hollow metal-organic framework (MOF) superstructures are reviewed and classified using various types of external templates and their properties. Hollow MOF superstructures have also been prepared without external templates, wherein unstable intermediates obtained during reactions convert to the final hollow MOF superstructures. Many hollow MOF superstructures have been fabricated using hard templates. After the core-shell core@ MOF structure was prepared using a hard template, the core was selectively etched to generate a hollow MOF superstructure. Another approach for generating hollow superstructures is to use a solid reactant as a sacrificial template; this method requires no additional etching process. Soft templates such as discontinuous liquid/emulsion droplets and gas bubbles in a continuous soft phase have also been employed to prepare hollow MOF superstructures

The process of Linker insertion into a Zirconium based MOF with bcu topology

The synthesis of metal-organic frameworks (MOFs) that contain mixed heterolinker ligands of different lengths is very important for the modulation and the tune of the framework properties. Despite tremendous endeavor, it is still very difficult to synthesize a new Zr-based MOF with mixed heterolinker ligands. Recently, preparations of a series of new Zr-MOFs of 10-, 11- and 12-connectivity that contain mixed heterolinker ligands are reported via sequential insertions of additional linkers into a Zr-MOF of 8-connectivity composed of relatively flexible ligand, dimethyl 2,2&apos;-dimethylbiphenyl-4,4&apos;-dicarboxylic acid (H2Me2-BPDC) having dihedral angle of biphenyl rings.1 Here we report the preparation of a new Zr-MOF of 8-connectivity with rigid 2,6-naphthalene dicarboxylic acid (H2NDC) and preparations of a series of new Zr-based MOF of 12-connectivity that contain NDC and functionalized 1,4-benzenedicarboxylate via additional linker insertion. Through single crystal X-ray diffraction, the processes of additional insertion of ligands can be confirmed