The Influence of Chemical Modification on Linker Rotational Dynamics in Metal–Organic Frameworks

The robust synthetic flexibility of metal–organic frameworks (MOFs) offers a promising class of tailorable materials, for which the ability to tune specific physicochemical properties is highly desired. This is achievable only through a thorough description of the consequences for chemical manipulations both in structure and dynamics. Magic angle spinning solid‐state NMR spectroscopy offers many modalities in this pursuit, particularly for dynamic studies. Herein, we employ a separated‐local‐field NMR approach to show how specific intraframework chemical modifications to MOF UiO‐66 heavily modulate the dynamic evolution of the organic ring moiety over several orders of magnitude.Intraframework ring rotations in metal–organic frameworks have been sensitively detected by dipolar dephasing over the rotor period in magic angle spinning solid‐state NMR experiments. Information on the dynamics within MOFs is important, because the rate of rotational motions of linkers affects sorption and separation properties of MOFs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144616/1/anie201805004.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144616/2/anie201805004-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144616/3/anie201805004_am.pd

Role of Anomalous Water Constraints in the Efficacy of Pharmaceuticals Probed by 1H Solid‐State NMR

Water plays a complex and central role in determining the structural and reactive properties in numerous chemical systems. In crystalline materials with structural water, the primary focus is often to relate hydrogen bonding motifs to functional properties such as solubility, which is highly relevant in pharmaceutical applications. Nevertheless, understanding the full electrostatic landscape is necessary for a complete structure‐function picture. Herein, a combination of tools including 1H magic angle spinning NMR and X‐ray crystallography are employed to evaluate the local landscape of water in crystalline hydrates. Two hydrates of an anti‐leukemia drug mercaptopurine, which exhibit dramatically different dehydration temperatures (by 90 °C) and a three‐fold difference in the in vivo bioavailability, are compared. The results identify an electrosteric caging mechanism for a kinetically trapped water in the hemihydrate form, which is responsible for the dramatic differences in properties.1H chemical shift tensors are valuable in the structural and dynamical studies of a variety of materials, and are directly measurable with fast MAS spinning experiments. The use of these novel techniques to reveal the structural differences water can adopt in pharmaceutical hydrates is demonstrated.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138433/1/slct201701547_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138433/2/slct201701547-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138433/3/slct201701547.pd

Analysis of the In Vivo Transcriptome of Bordetella pertussis during Infection of Mice

Bordetella pertussis causes the disease whooping cough through coordinated control of virulence factors by the Bordetella virulence gene system. Microarrays and, more recently, RNA sequencing (RNA-seq) have been used to describe in vitro gene expression profiles of B. pertussis and other pathogens. In previous studies, we have analyzed the in vitro gene expression profiles of B. pertussis, and we hypothesize that the infection transcriptome profile in vivo is significantly different from that under laboratory growth conditions. To study the infection transcriptome of B. pertussis, we developed a simple filtration technique for isolation of bacteria from infected lungs. The work flow involves filtering the bacteria out of the lung homogenate using a 5-μm-pore-size syringe filter. The captured bacteria are then lysed to isolate RNA for Illumina library preparation and RNA-seq analysis. Upon comparing the in vitro and in vivo gene expression profiles, we identified 351 and 255 genes as activated and repressed, respectively, during murine lung infection. As expected, numerous genes associated with virulent-phase growth were activated in the murine host, including pertussis toxin (PT), the PT secretion apparatus, and the type III secretion system. A significant number of genes encoding iron acquisition and heme uptake proteins were highly expressed during infection, supporting iron acquisition as critical for B. pertussis survival in vivo. Numerous metabolic genes were repressed during infection. Overall, these data shed light on the gene expression profile of B. pertussisduring infection, and this method will facilitate efforts to understand how this pathogen causes infection

The Influence of Chemical Modification on Linker Rotational Dynamics in Metal–Organic Frameworks

The robust synthetic flexibility of metal–organic frameworks (MOFs) offers a promising class of tailorable materials, for which the ability to tune specific physicochemical properties is highly desired. This is achievable only through a thorough description of the consequences for chemical manipulations both in structure and dynamics. Magic angle spinning solid‐state NMR spectroscopy offers many modalities in this pursuit, particularly for dynamic studies. Herein, we employ a separated‐local‐field NMR approach to show how specific intraframework chemical modifications to MOF UiO‐66 heavily modulate the dynamic evolution of the organic ring moiety over several orders of magnitude.Ringrotationen in MOFs wurden in Festkörper‐NMR‐Experimenten unter Probenrotation um den magischen Winkel durch dipolare Dephasierung über die Rotorperiode detektiert. Informationen zur Dynamik in Metall‐organischen Gerüsten sind wichtig, weil die Geschwindigkeit der Rotationsbewegung des Linkers die Sorptions‐ und Trenneigenschaften von MOFs beeinflusst.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144665/1/ange201805004_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144665/2/ange201805004-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144665/3/ange201805004.pd

Simple Monomers for Precise Polymer Functionalization During Ring-Opening Metathesis Polymerization

Controlling the monomer sequence of synthetic polymers is a grand challenge in polymer science. Conventional sequence control has been achieved in dispersed polymers by exploiting the kinetic tendencies of monomers and their order of addition. While the sequence of blocks in multiblock copolymers can be readily tuned using sequential addition of monomers (SAM), control over the sequence distribution is eroded as the targeted block size approaches a single monomer unit (i.e., Xn ∼ 1) due to the stochastic nature of chain-growth reactions. Thus, unique monomers are needed to ensure precise single additions. Herein, we investigate common classes of cyclic olefin monomers for ring-opening metathesis polymerization (ROMP) to identify monomers for single unit addition during sequential monomer addition synthesis. Through careful analysis of polymerization kinetics, we find that easily synthesized oxanorbornene imide monomers are suitable for single-addition reactions. With the identified monomers, we demonstrate the synthesis of multiblock copolymers containing up to three precise functionalization sites and singly cross-linked four-armed star copolymers. We envision that expanded kinetic analyses of monomer reactivities in ROMP reactions will enable novel polymer synthesis capabilities such as the autonomous synthesis of sequence-defined polymers or one-shot multiblock copolymer syntheses

Room‐Temperature Ferroelectricity in an Organic Cocrystal

Ferroelectric materials exhibit switchable remanent polarization due to reversible symmetry breaking under an applied electric field. Previous research has leveraged temperature‐induced neutral‐ionic transitions in charge‐transfer (CT) cocrystals to access ferroelectrics that operate through displacement of molecules under an applied field. However, displacive ferroelectric behavior is rare in organic CT cocrystals and achieving a Curie temperature (TC) above ambient has been elusive. Here a cocrystal between acenaphthene and 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane is presented that shows switchable remanent polarization at room temperature (TC=68 °C). Raman spectroscopy, X‐ray diffraction, and solid‐state NMR spectroscopy indicate the ferroelectric behavior is facilitated by acenaphthene (AN) rotation, deviating from conventional design strategies for CT ferroelectrics. These findings highlight the relevance of non‐CT interactions in the design of displacive ferroelectric cocrystals.Switchable remanent polarization at room temperature is displayed by the organic charge‐transfer cocrystal AN‐F4TCNQ. The ferroelectric Curie temperature was measured at 68 °C by differential scanning calorimetry, prompting further electronic and structural characterization of AN‐F4TCNQ which revealed that dynamic motion of acenaphthene (AN) contributes to the high‐temperature polarization switching.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145367/1/anie201805071.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145367/2/anie201805071-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145367/3/anie201805071_am.pd

Room‐Temperature Ferroelectricity in an Organic Cocrystal

Ferroelectric materials exhibit switchable remanent polarization due to reversible symmetry breaking under an applied electric field. Previous research has leveraged temperature‐induced neutral‐ionic transitions in charge‐transfer (CT) cocrystals to access ferroelectrics that operate through displacement of molecules under an applied field. However, displacive ferroelectric behavior is rare in organic CT cocrystals and achieving a Curie temperature (TC) above ambient has been elusive. Here a cocrystal between acenaphthene and 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane is presented that shows switchable remanent polarization at room temperature (TC=68 °C). Raman spectroscopy, X‐ray diffraction, and solid‐state NMR spectroscopy indicate the ferroelectric behavior is facilitated by acenaphthene (AN) rotation, deviating from conventional design strategies for CT ferroelectrics. These findings highlight the relevance of non‐CT interactions in the design of displacive ferroelectric cocrystals.Schaltbare Restpolarisierung bei Raumtemperatur wird für den organischen Ladungstransferkokristall AN‐F4TCNQ beobachtet. Die Curie‐Temperatur für den ferroelektrischen Übergang wurde mit dynamischer Differenzkalorimetrie zu 68 °C bestimmt. Die anschließende elektronische und strukturelle Charakterisierung von AN‐F4TCNQ ergab, dass dynamische Bewegungen von Acenaphthen (AN) zu der hohen Wechseltemperatur der Polarisierung beitragen.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145232/1/ange201805071.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145232/2/ange201805071-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145232/3/ange201805071_am.pd

Analysis of the In Vivo Transcriptome of Bordetella pertussis during Infection of Mice

In vitro growth conditions for bacteria do not fully recapitulate the host environment. RNA sequencing transcriptome analysis allows for the characterization of the infection gene expression profiles of pathogens in complex environments. Isolation of the pathogen from infected tissues is critical because of the large amounts of host RNA present in crude lysates of infected organs. A filtration method was developed that enabled enrichment of the pathogen RNA for RNA-seq analysis. The resulting data describe the “infection transcriptome” of B. pertussis in the murine lung. This strategy can be utilized for pathogens in other hosts and, thus, expand our knowledge of what bacteria express during infection.Bordetella pertussis causes the disease whooping cough through coordinated control of virulence factors by the Bordetella virulence gene system. Microarrays and, more recently, RNA sequencing (RNA-seq) have been used to describe in vitro gene expression profiles of B. pertussis and other pathogens. In previous studies, we have analyzed the in vitro gene expression profiles of B. pertussis, and we hypothesize that the infection transcriptome profile in vivo is significantly different from that under laboratory growth conditions. To study the infection transcriptome of B. pertussis, we developed a simple filtration technique for isolation of bacteria from infected lungs. The work flow involves filtering the bacteria out of the lung homogenate using a 5-μm-pore-size syringe filter. The captured bacteria are then lysed to isolate RNA for Illumina library preparation and RNA-seq analysis. Upon comparing the in vitro and in vivo gene expression profiles, we identified 351 and 255 genes as activated and repressed, respectively, during murine lung infection. As expected, numerous genes associated with virulent-phase growth were activated in the murine host, including pertussis toxin (PT), the PT secretion apparatus, and the type III secretion system. A significant number of genes encoding iron acquisition and heme uptake proteins were highly expressed during infection, supporting iron acquisition as critical for B. pertussis survival in vivo. Numerous metabolic genes were repressed during infection. Overall, these data shed light on the gene expression profile of B. pertussis during infection, and this method will facilitate efforts to understand how this pathogen causes infection

C₆₀ Oxide as a Key Component of Aqueous C₆₀ Colloidal Suspensions

Stable aqueous fullerene colloidal suspensions (<i>n</i>C₆₀) are demonstrated to rely on the [6,6]-closed epoxide derivative of the fullerene (C₆₀O) for stability. This derivative is present, though often unrecognized, in small quantities in nearly all C₆₀ starting materials due to a reaction with air. The low-yield formation of <i>n</i>C₆₀ from organic solvent solutions results from a preferential partitioning and thus enrichment of C₆₀O in the colloidal particles. This partitioning is significantly retarded in the <i>n</i>C₆₀ synthesis method that does not involve organic solvent solutions: long-term stirring in water. Instead, this method relies on trace levels of ozone in the ambient atmosphere to produce sufficient C₆₀O at the surfaces of the <i>n</i>C₆₀ particles to allow stable suspension in water. Controlled-atmosphere syntheses, deliberate C₆₀O enrichment, light scattering measurements, and extraction followed by HPLC analysis and UV–visible absorption spectroscopy support the above model of <i>n</i>C₆₀ formation and stabilization