Understanding the Solid-State Structure of Riboflavin through a Multitechnique Approach.

Crystalline riboflavin (vitamin B2) performs an important biological role as an optically functional material in the tapetum lucidum of certain animals, notably lemurs and cats. The tapetum lucidum is a reflecting layer behind the retina, which serves to enhance photon capture and vision in low-light settings. Motivated by the aim of rationalizing its biological role, and given that the structure of biogenic solid-state riboflavin remains unknown, we have used a range of experimental and computational techniques to determine the solid-state structure of synthetic riboflavin. Our multitechnique approach included microcrystal XRD, powder XRD, three-dimensional electron diffraction (3D-ED), high-resolution solid-state 13C NMR spectroscopy, and dispersion-augmented density functional theory (DFT-D) calculations. Although an independent report of the crystal structure of riboflavin was published recently, our structural investigations reported herein provide a different interpretation of the intermolecular hydrogen-bonding arrangement in this material, supported by all the experimental and computational approaches utilized in our study. We also discuss, more generally, potential pitfalls that may arise in applying DFT-D geometry optimization as a bridging step between structure solution and Rietveld refinement in the structure determination of hydrogen-bonded materials from powder XRD data. Finally, we report experimental and computational values for the refractive index of riboflavin, with implications for its optical function.

Rational Design and Reticulation of Infinite qbe Rod Secondary Building Units into Metal-Organic Frameworks through a Global Desymmetrization Approach for Inverse C3 H8 /C3 H6 Separation.

The development of reticular chemistry has enabled the construction of a large array of metal-organic frameworks (MOFs) with diverse net topologies and functions. However, dominating this class of materials are those built from discrete/finite secondary building units (SBUs), yet the designed synthesis of frameworks involving infinite rod-shaped SBUs remain underdeveloped. Here, by virtue of a global linker desymmetrization approach, we successfully targeted a novel Cu-MOF (Cu-ASY) incorporating infinite Cu-carboxylate rod SBUs with its structure determined by micro electron diffraction (MicroED) crystallography. Interestingly, the rod SBU can be simplified as a unique cylindric sphere packing qbe tubule made of [43 .62 ] tiles, which further connect the tritopic linkers to give a newly discovered 3,5-connected gfc net. Cu-ASY is a permanent ultramicroporous material featuring 1D channels with highly inert surfaces and shows a preferential adsorption of propane (C3 H8 ) over propene (C3 H6 ). The efficiency of C3 H8 selective Cu-ASY is validated by multicycle breakthrough experiments, giving C3 H6 productivity of 2.2 L/kg. Density functional theory (DFT) calculations reveal that C3 H8 molecules form multiple C-H⋅⋅⋅π and atypical C-H⋅⋅⋅ H-C van der Waals interactions with the inner nonpolar surfaces. This work therefore highlights the linker desymmetrization as an encouraging and intriguing strategy for achieving unique MOF structures and properties.

Modulator-Dependent Dynamics Synergistically Enabled Record SO2 Uptake in Zr(IV) Metal-Organic Frameworks Based on Pyrene-Cored Molecular Quadripod Ligand.

Developing innovative porous solid sorbents for the capture and storage of toxic SO2 is crucial for energy-efficient transportation and subsequent processing. Nonetheless, the quest for high-performance SO2 sorbents, characterized by exceptional uptake capacity, minimal regeneration energy requirements, and outstanding recyclability under ambient conditions, remains a significant challenge. In this study, we present the design of a unique tertiary amine-embedded, pyrene-based quadripod-shaped ligand. This ligand is then assembled into a highly porous Zr-metal-organic framework (MOF) denoted as Zr-TPA, which exhibits a newly discovered 3,4,8-c woy net structure. Remarkably, our Zr-TPA MOF achieved an unprecedented SO2 sorption capacity of 22.7 mmol g-1 at 298 K and 1 bar, surpassing those of all previously reported solid sorbents. We elucidated the distinct SO2 sorption behaviors observed in isostructural Zr-TPA variants synthesized with different capping modulators (formate, acetate, benzoate, and trifluoroacetate, abbreviated as FA, HAc, BA, and TFA, respectively) through computational analyses. These analyses revealed unexpected SO2-induced modulator-node dynamics, resulting in transient chemisorption that enhanced synergistic SO2 sorption. Additionally, we conducted a proof-of-concept experiment demonstrating that the captured SO2 in Zr-TPA-FA can be converted in situ into a valuable pharmaceutical intermediate known as aryl N-aminosulfonamide, with a high yield and excellent recyclability. This highlights the potential of robust Zr-MOFs for storing SO2 in catalytic applications. In summary, this work contributes significantly to the development of efficient SO2 solid sorbents and advances our understanding of the molecular mechanisms underlying SO2 sorption in Zr-MOF materials.

Selective photoinduced charge separation in perylenediimide-pillar[5]arene rotaxanes.

The ability to control photoinduced charge transfer within molecules represents a major challenge requiring precise control of the relative positioning and orientation of donor and acceptor groups. Here we show that such photoinduced charge transfer processes within homo- and hetero-rotaxanes can be controlled through organisation of the components of the mechanically interlocked molecules, introducing alternative pathways for electron donation. Specifically, studies of two rotaxanes are described: a homo[3]rotaxane, built from a perylenediimide diimidazolium rod that threads two pillar[5]arene macrocycles, and a hetero[4]rotaxane in which an additional bis(1,5-naphtho)-38-crown-10 (BN38C10) macrocycle encircles the central perylenediimide. The two rotaxanes are characterised by a combination of techniques including electron diffraction crystallography in the case of the hetero[4]rotaxane. Cyclic voltammetry, spectroelectrochemistry, and EPR spectroscopy are employed to establish the behaviour of the redox states of both rotaxanes and these data are used to inform photophysical studies using time-resolved infra-red (TRIR) and transient absorption (TA) spectroscopies. The latter studies illustrate the formation of a symmetry-breaking charge-separated state in the case of the homo[3]rotaxane in which charge transfer between the pillar[5]arene and perylenediimide is observed involving only one of the two macrocyclic components. In the case of the hetero[4]rotaxane charge separation is observed involving only the BN38C10 macrocycle and the perylenediimide leaving the pillar[5]arene components unperturbed.

Single crystal X-ray structure determination and temperature-dependent structural studies of the smectogenic compound 7OS5.

Structural characteristics of solid and liquid crystalline phases of 7OS5 (4-n-pentylphenyl-4'-n-heptyloxythiobenzoate), the achiral smectogenic mesogen with the shortest terminal carbon chain in the nOS5 homologous series, are studied by complementary methods. Simultaneously perfomed X-ray diffraction and differential scanning calorimetry occur to be a powerful tool to study metastable phases. The single crystal structure of a high-temperature phase, supercooled from the room temperature down to -183°C [orthorhombic crystal system; space group Pca21; a = 54.285 (5) Å, b = 5.5843 (3) Å, c = 14.841 (1) Å, Z = 8] is determined. Lamellar ordering of elongated molecules is stabilized by hydrogen bonds . Temperature dependence of unit-cell parameters in two crystal phases as well as structural parameters of liquid crystalline phases (smectic layer spacing, tilt angle, average distance between the long axes of molecules and correlation lengths) are determined by X-ray diffraction. The obtained results are compared with the data available for other compounds in the nOS5 homologous series.

Coherent Electron Transport in Air-Stable, Printed Single-Crystal Organic Semiconductor and Application to Megahertz Transistors.

Organic semiconductors (OSCs) have attracted growing attention for optoelectronic applications such as field-effect transistors (FETs), and coherent (or band-like) carrier transport properties in OSC single crystals (SCs) have been of interest as they can lead to high carrier mobilities. Recently, such p-type OSC SCs compatible with a printing technology have been used to achieve high-speed FETs; therefore, developments of n-type counterparts may be promising for realizing high-speed complementary organic circuits. Herein, coherent electron transport properties in a printed SC of a state-of-the-art, air-stable n-type OSC, PhC2 -BQQDI, by means of variable-temperature gated Hall effect measurements and X-ray single-crystal diffraction analyses in conjunction with band structure calculations, are reported. Furthermore, the SC FET is tested for high-speed operations, which obtains a cutoff frequency of 4.3 MHz at an operation voltage of 20 V in air. Thus, PhC2 -BQQDI is shown as a new candidate for practical applications of SC-based, organic complementary devices.

Ensemble structural analyses depict the regulatory mechanism of non-phosphorylated human MAP2K4.

Mitogen-activated protein kinase kinase 4 (MAP2K4) plays a critical role in regulating the stress-activated protein kinase signaling cascade. A small angle X-ray scattering experiment, a powerful technique for analyzing a solution structure cleared from the structural artifacts due to crystal packing, provided the ensemble structures of human non-phosphorylated MAP2K4 in three states involving the apo form, the binary complex with an ATP analogue, and the ternary complex with the ATP analogue and substrate peptide. These ensemble structures provided more detailed mechanisms for regulating MAP2K4 in addition to those delineated only by the crystal structures in three states.

Development of a structure determination method using a multidrug-resistance regulator protein as a framework.

The structure determination of organic compounds is desirable for the development of medicines, aroma chemicals, and agricultural chemicals. However, the crystallization of organic compounds is often troublesome, because crystallization requires a relatively large quantity of high purity compounds and crystallization trials often need to be performed repetitively using different conditions. Some proteins are known to be able to bind to various organic compounds. The multidrug-resistance regulator protein RamR is one such protein. We have developed a structure determination method for organic compounds using RamR. RamR bound to organic compounds, including one compound that was not a known ligand for RamR, and the structures of the complexes were successfully determined. Because the RamR crystal is hydrophilic, this method may be useful for compounds that cannot be handled by the crystalline sponge method.

Zigzag-Elongated Fused π-Electronic Core: A Molecular Design Strategy to Maximize Charge-Carrier Mobility.

Printed and flexible electronics requires solution-processable organic semiconductors with a carrier mobility (µ) of ≈10 cm2 V-1 s-1 as well as high chemical and thermal durability. In this study, chryseno[2,1-b:8,7-b']dithiophene (ChDT) and its derivatives, which have a zigzag-elongated fused π-electronic core (π-core) and a peculiar highest occupied molecular orbital (HOMO) configuration, are reported as materials with conceptually new semiconducting π-cores. ChDT and its derivatives are prepared by a versatile synthetic procedure. A comprehensive investigation reveals that the ChDT π-core exhibits increasing structural stability in the bulk crystal phase, and that it is unaffected by a variation of the transfer integral, induced by the perpetual molecular motion of organic materials owing to the combination of its molecular shape and its particular HOMO configuration. Notably, ChDT derivatives exhibit excellent chemical and thermal stability, high charge-carrier mobility under ambient conditions (µ ≤ 10 cm2 V-1 s-1), and a crystal phase that is highly stable, even at temperatures above 250 °C.

Building-block architecture of botulinum toxin complex: Conformational changes provide insights into the hemagglutination ability of the complex.

Clostridium botulinum produces the botulinum neurotoxin (BoNT). Previously, we provided evidence for the "building-block" model of botulinum toxin complex (TC). In this model, a single BoNT is associated with a single nontoxic nonhemagglutinin (NTNHA), yielding M-TC; three HA-70 molecules are attached and form M-TC/HA-70, and one to three "arms" of the HA-33/HA-17 trimer (two HA-33 and one HA-17) further bind to M-TC/HA-70 via HA-17 and HA-70 binding, yielding one-, two-, and three-arm L-TC. Of all TCs, only the three-arm L-TC caused hemagglutination. In this study, we determined the solution structures for the botulinum TCs using small-angle X-ray scattering (SAXS). The mature three-arm L-TC exhibited the shape of a "bird spreading its wings", in contrast to the model having three "arms", as revealed by transmission electron microscopy. SAXS images indicated that one of the three arms of the HA-33/HA-17 trimer bound to both HA-70 and BoNT. Taken together, these findings regarding the conformational changes in the building-block architecture of TC may explain why only three-arm L-TC exhibited hemagglutination.

Pleurocins A and B: Unusual 11(9 → 7)-abeo-Ergostanes and Eringiacetal B: A 13,14-seco-13,14-Epoxyergostane from Fruiting Bodies of Pleurotus eryngii and Their Inhibitory Effects on Nitric Oxide Production.

Two novel 11(9 → 7)-abeo-ergostane-type steroids, named pleurocins A (1) and B (2), a 13,14-seco-13,14-epoxy ergostane, named eringiacetal B (3), and an ergostane steroid (4) were isolated from the fruiting bodies of Pleurotus eryngii (Pleurotaceae). Their structures were determined by spectroscopic data and X-ray crystallography. A possible biogenesis pathway for 1-3 was also described. Compounds 1-3 exhibited inhibitory activities against NO production with almost no cytotoxicity at concentrations lower than 30 µM.

Crystal structure of the solute-binding protein BxlE from Streptomyces thermoviolaceus OPC-520 complexed with xylobiose.

BxlE from Streptomyces thermoviolaceus OPC-520 is a xylo-oligosaccharide (mainly xylobiose)-binding protein that serves as the initial receptor for the bacterial ABC-type xylo-oligosaccharide transport system. To determine the ligand-binding mechanism of BxlE, X-ray structures of ligand-free (open form) and ligand (xylobiose)-bound (closed form) BxlE were determined at 1.85 Å resolution. BxlE consists of two globular domains that are linked by two ß-strands, with the cleft at the interface of the two domains creating the ligand-binding pocket. In the ligand-free open form, this pocket consists of a U-shaped and negatively charged groove located between the two domains. In the xylobiose-bound closed form of BxlE, both the N and C domains move to fold the ligand without conformational changes in either domain. Xylobiose is buried in the groove and wrapped by the N-domain mainly via hydrogen bond interactions and by the C-domain primarily via non-polar interactions with Trp side chains. In addition to the concave shape matching the binding of xylobiose, an inter-domain salt bridge between Asp-47 and Lys-294 limits the space in the ligand-binding site. This domain-stabilized mechanism of ligand binding to BxlE is a unique feature that is not observed with other solute-binding proteins.

Cyclopropane-Based Peptidomimetics Mimicking Wide-Ranging Secondary Structures of Peptides: Conformational Analysis and Their Use in Rational Ligand Optimization.

Detailed conformational analyses of our previously reported cyclopropane-based peptidomimetics and conformational analysis-driven ligand optimization are described. Computational calculations and X-ray crystallography showed that the characteristic features of cyclopropane function effectively to constrain the molecular conformation in a three-dimensionally diverse manner. Subsequent principal component analysis revealed that the diversity covers the broad chemical space filled by peptide secondary structures in terms of both main-chain and side-chain conformations. Based on these analyses, a lead stereoisomer targeting melanocortin receptors was identified, and its potency and subtype selectivity were improved by further derivatization. The presented strategy is effective not only for designing non-peptidic ligands from a peptide ligand but also for the rational optimization of these ligands based on the plausible target-binding conformation without requiring the three- dimensional structural information of the target and its peptide ligands.

Conformational divergence in the HA-33/HA-17 trimer of serotype C and D botulinum toxin complex.

Clostridium botulinum produces a large toxin complex (L-TC) comprising botulinum neurotoxin associated with auxiliary nontoxic proteins. A complex of 33- and 17-kDa hemagglutinins (an HA-33/HA-17 trimer) enhances L-TC transport across the intestinal epithelial cell layer via binding HA-33 to a sugar on the cell surface. At least two subtypes of serotype C/D HA-33 exhibit differing preferences for the sugars sialic acid and galactose. Here, we compared the three-dimensional structures of the galactose-binding HA-33 and HA-33/HA-17 trimers produced by the C-Yoichi strain. Comparisons of serotype C/D HA-33 sequences reveal a variable region with relatively low sequence similarity across the C. botulinum strains; the variability of this region may influence the manner of sugar-recognition by HA-33. Crystal structures of sialic acid- and galactose-binding HA-33 are broadly similar in appearance. However, small-angle X-ray scattering revealed distinct solution structures for HA-33/HA-17 trimers. A structural change in the C-terminal variable region of HA-33 might cause a dramatic shift in the conformation and sugar-recognition mode of HA-33/HA-17 trimer.

Characterization of a Rh(III) porphyrin-CO complex: its structure and reactivity with an electron acceptor.

To analyse the electrocatalytic oxidation of carbon monoxide by Rh porphyrins, we isolated a CO-adduct of Rh octaethylporphyrin, and examined its properties and reactivity by IR, NMR, and X-ray crystallographic analyses. The results indicate that the CO adduct of Rh octaethylporphyrin is vulnerable to nucleophilic attack by H2O. The CO-adduct was easily oxidized by an electron acceptor (1,4-naphthoquinone) to generate CO2. This indicates that CO is sufficiently activated in the CO complex of Rh octaethylporphyrin to reduce an electron acceptor. This mechanism is in contrast to that for the CO oxidation by Pt-based electrocatalysts.

Spectroscopic tracking of Schiff base compounds' hydrogen bonding reorganization associated with solid-to-solid phase transition.

A series of 2,6-dihydroxynaphthalene-1-methylidene alkylamines whose alkyl chain lengths ranged from 9 to 12 was spectroscopically examined. Transmission ultraviolet-visible absorption microspectroscopy revealed that the spectra of solid thin-films of the crystalline samples showed two distinct profiles depending on polymorphs as well as on alkyl chain length. We concluded that these spectral changes occurred not because of conventional intramolecular proton transfer but because of the molecules' interactions with an external proton source, that is, the intermolecular proton transfer. The spectral changes were accompanied by changes in the intermolecular hydrogen bonding network. When a crystal of a sample compound was heated, its spectrum changed dramatically before the crystal underwent a solid-to-solid phase transition to another polymorph. We concluded that these spectral changes indicated strengthening of intermolecular hydrogen bonding or intermolecular proton transfer, which would have triggered a drastic change in the hydrogen bonding network structure.

High-performance solution-processable N-shaped organic semiconducting materials with stabilized crystal phase.

N-shaped organic semiconductors are synthesized via four steps from a readily available starting material. Such semiconductors exhibit preferable ionization potential for p-type operation, thermally stable crystalline phase over 200 °C, and high carrier mobility up to 16 cm(2) V(-1) s(-1) (12.1 cm(2) V(-1) s(-1) on average) with small threshold voltages in solution-crystallized field-effect transistors.

Kinetic resolution of allyl fluorides by enantioselective allylic trifluoromethylation based on silicon-assisted C-F bond cleavage.

Two birds, one stone! The first kinetic resolution of allyl fluorides was achieved by the development of an organocatalyzed enantioselective allylic trifluoromethylation. Two kinds of chiral fluorinated compounds, which incorporate C*F and C*CF3 units, respectively, can thus be accessed by a single transformation.

Furan fused V-shaped organic semiconducting materials with high emission and high mobility.

We report a facile synthetic protocol for preparation of dinaphtho[2,3-b:2',3'-d]furan (DNF-V) derivatives. DNF-V derivatives showed high emissive behaviour in solid. A solution-crystallized transistor based on alkylated DNF-V derivatives showed an excellent carrier mobility of up to 1.3 cm(2) V(-1) s(-1), thereby proving to be a new solution-processable active organic semiconductor with high emission and high mobility.

V-shaped organic semiconductors with solution processability, high mobility, and high thermal durability.

V-shaped organic semiconductors have been designed and synthesized via a large-scale applicable synthetic route. Solution-crystallized films based on such molecules have demonstrated high-performance transistor properties with maximum mobilities of up to 9.5 cm(2) V(-1) s(-1) as well as pronounced thermal durability of up to 150 °C inherent in the V-shaped cores.