10 research outputs found
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Alternative Donor--Acceptor Stacks from Crown Ethers and Naphthalene Diimide Derivatives: Rapid, Selective Formation from Solution and Solid State Grinding
Self assembling {pi}-conjugated molecules into ordered structures are of increasing interest in the field of organic electronics. One particular example is charge transfer complexes containing columnar alternative donor-acceptor (ADA) stacks, where neutral and ionic ground states can be readily tuned to modulate electrical, optical, and ferroelectrical properties. Aromatic-aromatic and charge transfer interactions have been the leading driving forces in assisting the self-assembly of ADA stacks. Various folding structures containing ADA stacks were assembled in solution with the aid of solvophobic or ion-binding interactions. Meanwhile, examples of solid ADA stacks, which are more appealing for practical use in devices, were obtained from cocrystalization of binary components or mesophase assembly of liquid crystals in bulk blends. Regardless of these examples, faster and more controllable approaches towards precise supramolecular order in the solid state are still highly desirable
Multidimensional Solid-State Nuclear Magnetic Resonance of a Functional Multiprotein Chemoreceptor Array
The bacterial chemoreceptor complex
governs signal detection and
the upstream elements of chemotactic behavior, but the detailed molecular
mechanism is still unclear. We have assembled nativelike functional
arrays of an aspartate receptor cytoplasmic fragment (CF) with its
two cytoplasmic protein partners (CheA and CheW) for solid-state nuclear
magnetic resonance (NMR) studies of structural changes involved in
signaling. In this initial study of the uniformly <sup>13</sup>C-
and <sup>15</sup>N-enriched CF in these >13.8 MDa size arrays,
residue-type
assignments are made for amino acids that together make up 90% of
the protein. We demonstrate that homo- and heteronuclear two-dimensional
spectra are consistent with structure-based chemical shift predictions:
a number of major assignable correlations are consistent with the
predominantly α-helical secondary structure, and minor correlations
are consistent with the disordered C-terminal tail. Sub-parts per
million line widths and spectral changes upon freezing of samples
suggest these arrays are structurally homogeneous and sufficiently
immobilized for efficient solid-state NMR
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Effects of Composition and Structure of Mg/Al Oxides on Their Activity and Selectivity for the Condensation of Methyl Ketones
The effects of chemical
composition and pretreatment on Mg–Al
hydrotalcites and alumina-supported MgO were evaluated for the gas-phase,
self-condensation reaction of C<sub>3</sub>–C<sub>5</sub> biomass-derived
methyl ketones. We show that the selectivity toward the acyclic dimer
enone and the cyclic enone trimer can be tuned by controlling the
temperature of hydrotalcite calcination. Methyl ketone cyclization
is promoted by Lewis acidic sites present on the hydrotalcite catalysts.
XRD and thermal decomposition analysis reveal that the formation of
periclase MgO starts above 623 K accompanied by complete disappearance
of the hydrotalcite structure and is accompanied by an increase in
hydroxyl condensation as the formation of well-crystallized periclase. <sup>27</sup>Al MQMAS and <sup>25</sup>Mg MAS NMR show that at progressively
higher temperatures, Al<sup>3+</sup> cations diffuses out of the octahedral
brucite layers and incorporate into the tetrahedral and octahedral
sites of the MgO matrix thereby creating defects to compensate the
excess positive charge generated. The oxygen anions adjacent to the
Mg<sup>2+</sup>/Al<sup>3+</sup> defects become coordinatively unsaturated,
leading to the formation of new basic sites. A kinetic isotope effect, <i>k</i><sub>H</sub>/<i>k</i><sub>D</sub> = 0.96, is
observed at 473 K for the reaction of (CH<sub>3</sub>)<sub>2</sub>CO versus (CD<sub>3</sub>)<sub>2</sub>CO, which suggests that carbon–carbon
bond formation leading to the dimer aldol product is the rate-determining
step in the condensation reaction of methyl ketones. We also show
that acid–base catalysts having similar reactivity and higher
hydrothermal stability to that of calcined hydrotalcites can be achieved
by creating defects in MgO crystallites supported alumina as a consequence
of the diffusion of Al<sup>3+</sup> cations into MgO. The physical
properties of these materials are shown to be very similar to those
of hydrotalcite calcined at 823 K
Human Cannabinoid 1 GPCR C-Terminal Domain Interacts with Bilayer Phospholipids to Modulate the Structure of its Membrane Environment
G protein-coupled receptors (GPCRs) play critical physiological and therapeutic roles. The human cannabinoid 1 GPCR (hCB1) is a prime pharmacotherapeutic target for addiction and cardiometabolic disease. Our prior biophysical studies on the structural biology of a synthetic peptide representing the functionally significant hCB1 transmembrane helix 7 (TMH7) and its cytoplasmic extension, helix 8 (H8), [hCB1(TMH7/H8)] demonstrated that the helices are oriented virtually perpendicular to each other in membrane-mimetic environments. We identified several hCB1(TMH7/H8) structure-function determinants, including multiple electrostatic amino-acid interactions and a proline kink involving the highly conserved NPXXY motif. In phospholipid bicelles, TMH7 structure, orientation, and topology relative to H8 are dynamically modulated by the surrounding membrane phospholipid bilayer. These data provide a contextual basis for the present solid-state NMR study to investigate whether intermolecular interactions between hCB1(TMH7/H8) and its phospholipid environment may affect membrane-bilayer structure. For this purpose, we measured 1H–13C heteronuclear dipolar couplings for the choline, glycerol, and acyl-chain regions of dimyristoylphosphocholine in a magnetically aligned hCB1(TMH7/H8) bicelle sample. The results identify discrete regional interactions between hCB1(TMH7/H8) and membrane lipid molecules that increase phospholipid motion and decrease phospholipid order, indicating that the peptide’s partial traversal of the bilayer alters membrane structure. These data offer new insight into hCB1(TMH7/H8) properties and support the concept that the membrane bilayer itself may serve as a mechanochemical mediator of hCB1/GPCR signal transduction. Since interaction with its membrane environment has been implicated in hCB1 function and its modulation by small-molecule therapeutics, our work should help inform hCB1 pharmacology and the design of hCB1-targeted drugs