Leonard J. Mueller

pH-responsive nanogated ensemble based on gold-capped mesoporous silica through an acid-labile acetal linker.

A new pH-responsive hybrid nanogated ensemble has been developed by using acetal group linked gold nanoparticle capped mesoporous silica. The hydrolysis of acetal linker at acidic environment makes the gold nanoparticles work as a gatekeeper to control the release of guest molecules from mesoporous silica under different pHs.

Mechanism of Photoinduced Bending and Twisting in Crystalline Microneedles and Microribbons Composed of 9-Methylanthracene

The solid-state photodimerization of 9-methylanthracene is used as a model system to investigate how crystal morphology and reaction dynamics affect photomechanical deformations of single microcrystals. By varying the crystallization conditions, two different crystal shapes, microneedles and microribbons, are grown on a clean water surface. The microribbons twist under irradiation, while the microneedles bend. In both shapes, the maximum deformation occurs at roughly the midpoint of the reaction, while further dimerization causes the crystals return to their original shapes. Powder X-ray diffraction patterns establish that the needles and ribbons have the same crystal orientation and that the photoreaction proceeds in a crystal-to-crystal manner. NMR spin-lattice relaxation measurements are consistent with the rapid formation of large (>100 nm) dimer crystal domains. Simultaneous measurement of the needle bending and monomer fluorescence signal allows us to correlate the bending with the reaction progress. The behavior is qualitatively reproduced by a model in which the motion is driven by strain between spatially distinct reactant and product domains, also called heterometry. We consider several different mechanisms that could give rise to these spatially distinct domains. The ability to control the photoinduced crystal deformation by manipulating crystal shape and solid-state reaction kinetics suggests that photoreactive molecular crystals may be useful for generating well-defined motions on small length scales.

Anion Stripping as a General Method to Create Cationic Porous Framework with Mobile Anions

Metal-organic frameworks (MOFs) with cationic frameworks and mobile anions have many applications from sensing, anion exchange and separation, to fast ion conductivity. Despite recent progress, the vast majority of MOFs have neutral frameworks. A common mechanism for the formation of neutral frameworks is the attachment of anionic species such as F(-) or OH(-) to the framework metal sites, neutralizing an otherwise cationic scaffolding. Here, we report a general method capable of converting such neutral frameworks directly into cationic ones with concurrent generation of mobile anions. Our method is based on the differential affinity between distinct metal ions with framework anionic species. Specifically, Al(3+) is used to strip F(-) anions away from framework Cr(3+) sites, leading to cationic frameworks with mobile Cl(-) anions. The subsequent anion exchange with OH(-) further leads to a porous network with mobile OH(-) anions. New materials prepared by anion stripping can undergo ion exchange with anionic organic dyes and also exhibit much improved ionic conductivity compared to the original unmodified MOFs.

Solid-state photochemical and photomechanical properties of molecular crystal nanorods composed of anthracene ester derivatives

A series of 9-anthroate esters that can form photoresponsive molecular crystal nanorods is prepared and their properties are investigated. All crystal structures that can support a [4 + 4] photodimerization reaction lead to nanorods that undergo photomechanical deformations without fragmentation. In order to determine the molecular-level motions that give rise to the nanorod photomechanical response, the reaction of anthracene-9-carboxylic acid tert-butyl ester is studied in detail using X-ray diffraction and solid-state NMR techniques. The monomer crystal is well-aligned within the nanorod and reacts to form the photodimer crystal according to first-order kinetics. The solid-state reacted dimer crystal is a metastable intermediate that slowly converts into the low energy dimer crystal structure over the course of weeks. Based on single crystal X-ray diffraction studies and solid-state NMR data, this intermediate structure is likely composed of the [4 + 4] photodimer that has not yet undergone the ester group rotations and repacking is necessary to form the lower energy crystal polymorph that is produced directly by crystallization from solution. Our results show that the photomechanical response of these molecular crystal nanostructures is determined by nonequilibrium intermediate states and cannot be predicted based solely on knowledge of the equilibrium reactant and product crystal structures.

Influence of Peripheral Groups on the Physical and Chemical Behavior of Cinchona Alkaloids

While cinchona alkaloids play a key role in many applications, from medicine to catalysis, there is not yet a complete understanding of the reasons for their unique chemical behavior. Past studies have identified the chiral pocket formed by the two main constituting moieties of the cinchona, the quinoline and quinuclidine rings, as the main factor determining their physiological and enatioselective reactivity. That explanation, however, does not account for the differences observed among similar cinchona alkaloids. Here we show that subtle changes in the position of the substituent groups outside the central chiral pocket explain the disparities observed in basic physicochemical properties between pairs of near-enantiomers (quinine vs quinidine, cinchonidine vs cinchonine) such as crystal structure, solubility, and adsorption equilibrium. Both energetic and entropic factors need to be considered to fully account for the trends observed.

J-based 2D homonuclear and heteronuclear correlation in solid-state proteins.

Scalar‐based two‐dimensional heteronuclear experiments are reported for NCO and NCA chemical shift correlation in the solid state. In conjunction with homonuclear CACO correlation, these experiments form a useful set for tracing connectivities and assigning backbone resonances in solid‐state proteins. The applicability of this approach is demonstrated on two proteins, the β 1 immunoglobulin binding domain of protein G at 9.4 T and reassembled thioredoxin at 14.1 T, using different decoupling conditions and MAS frequencies. These constant‐time J‐based correlation experiments exhibit increased resolution in the indirect dimension owing to homonuclear and heteronuclear decoupling, and because the indirect evolution and transfer periods are combined into a single constant time interval, this increased resolution is not obtained at the cost of sensitivity. These experiments are also shown to be compatible with in‐phase anti‐phase (IPAP) selection, giving increased resolution in the directly detected dimension. Copyright

Sulfamate proton solvent exchange in heparin oligosaccharides: Evidence for a persistent hydrogen bond in the antithrombin-binding pentasaccharide Arixtra

Sulfamate groups (NHSO(3)(-)) are important structural elements in the glycosaminoglycans (GAGs) heparin and heparan sulfate (HS). In this work, proton nuclear magnetic resonance (NMR) line-shape analysis is used to explore the solvent exchange properties of the sulfamate NH groups within heparin-related mono-, di-, tetra- and pentasaccharides as a function of pH and temperature. The results of these experiments identified a persistent hydrogen bond within the Arixtra (fondaparinux sodium) pentasaccharide between the internal glucosamine sulfamate NH and the adjacent 3-O-sulfo group. This discovery provides new insights into the solution structure of the Arixtra pentasaccharide and suggests that 3-O-sulfation of the heparin N-sulfoglucosamine (GlcNS) residues pre-organize the secondary structure in a way that facilitates binding to antithrombin-III. NMR studies of the GlcNS NH groups can provide important information about heparin structure complementary to that available from NMR spectral analysis of the carbon-bound protons.

Dependence of the solid-state photomechanical response of 4-chlorocinnamic acid on crystal shape and size

The photochemical dynamics of crystals composed of 4-chlorocinnamic acid (4Cl-CA), whose photochemistry is dominated by an irreversible [2+2] photodimerization reaction, are studied using 13C solid-state NMR, powder X-ray diffraction, and optical and electron microscopy. We find that photoreaction leads to a new crystal phase, but prolonged irradiation leads to an amorphous solid. To investigate effect of crystal morphology on the photoresponsive behavior, molecular crystals with different shapes and sizes are prepared and compared under the same irradiation conditions. Microribbons with submicron thicknesses twist under irradiation, but no response is observed in larger crystals with thicknesses of 5–10 microns. Possible mechanisms to explain these differences are discussed, including differences in defect densities, optical properties, and heat dissipation. We posit that the dominant effect is the dependence of the torsion constant on crystal thickness, which leads to the thinner microribbons being more susceptible to deformation by an internal energy density. This work shows that photo-induced twisting can be observed in photoreactive systems different from the anthracene [4+4] photodimerization studied previously. Our results also suggest that shrinking crystal dimensions to the nanoscale can give rise to new types of photomechanical motion.

31P NMR Investigation of Backbone Dynamics in DNA Binding Sites

The backbone conformation of DNA plays an important role in the indirect readout mechanisms for protein--DNA recognition events. Thus, investigating the backbone dynamics of each step in DNA binding sequences provides useful information necessary for the characterization of these interactions. Here, we use 31P dynamic NMR to characterize the backbone conformation and dynamics in the Dickerson dodecamer, a sequence containing the EcoRI binding site, and confirm solid-state 2H NMR results showing that the C3pG4 and C9pG10 steps experience unique dynamics and that these dynamics are quenched upon cytosine methylation. In addition, we show that cytosine methylation affects the conformation and dynamics of neighboring nucleotide steps, but this effect is localized to only near neighbors and base-pairing partners. Last, we have been able to characterize the percent BII in each backbone step and illustrate that the C3pG4 and C9pG10 favor the noncanonical BII conformation, even at low temperatures. Our results demonstrate that 31P dynamic NMR provides a robust and efficient method for characterizing the backbone dynamics in DNA. This allows simple, rapid determination of sequence-dependent dynamical information, providing a useful method for studying trends in protein-DNA recognition events.

J-Based 3D sidechain correlation in solid-state proteins

Scalar-based three-dimensional homonuclear correlation experiments are reported for (13)C sidechain correlation in solid-state proteins. These experiments are based on a sensitive constant-time format, in which homonuclear scalar couplings are utilized for polarization transfer, but decoupled during chemical shift evolution, to yield highly resolved indirect dimensions and band selectivity as desired. The methods therefore yield spectra of high quality that give unique sets of sidechain correlations for small proteins even at 9.4 Tesla (400 MHz (1)H frequency). We demonstrate versions of the pulse sequence that enable correlation from the sidechain to the backbone carbonyl as well as purely sidechain correlation sets; together these two data sets provide the majority of (13)C-(13)C correlations for assignment. The polarization transfer efficiency is approximately 30% over two bonds. In the protein GB1 (56 residues), we find essentially all cross peaks uniquely resolved. We find similar efficiency of transfer (approximately 30%) in the 140 kDa tryptophan synthase (TS), since the relaxation rates of immobilized solid proteins are not sensitive to global molecular tumbling, as long as the correlation time is much longer than the magic-angle spinning rotor period. In 3D data sets of TS at 400 MHz, some peaks are resolved and, in combination with higher field data sets, we anticipate that assignments will be possible; in this vein, we demonstrate 2D (13)C-(13)C spectra of TS at 900 MHz that are well resolved. These results together provide optimism about the prospects for assigning the spectra of such large enzymes in the solid state.