Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP.

Protein function hinges on small shifts of three-dimensional structure. Elevating temperature or pressure may provide experimentally accessible insights into such shifts, but the effects of these distinct perturbations on protein structures have not been compared in atomic detail. To quantitatively explore these two axes, we report the first pair of structures at physiological temperature versus.

Pushed to extremes: distinct effects of high temperature vs. pressure on the structure of an atypical phosphatase.

Protein function hinges on small shifts of three-dimensional structure. Elevating temperature or pressure may provide experimentally accessible insights into such shifts, but the effects of these distinct perturbations on protein structures have not been compared in atomic detail. To quantitatively explore these two axes, we report the first pair of structures at physiological temperature vs.

New insights into the molecular mechanisms of glutaminase C inhibitors in cancer cells using serial room temperature crystallography.

Cancer cells frequently exhibit uncoupling of the glycolytic pathway from the TCA cycle (i.e., the "Warburg effect") and as a result, often become dependent on their ability to increase glutamine catabolism.

Crystal structure of the pheromone Er-13 from the ciliate Euplotes raikovi, with implications for a protein-protein association model in pheromone/receptor interactions.

In the ciliate Euplotes raikovi, water-borne protein pheromones promote the vegetative cell growth and mating by competitively binding as autocrine and heterologous signals to putative cell receptors represented by membrane-bound pheromone isoforms. A previously determined crystal structure of pheromone Er-1 supported a pheromone/receptor binding model in which strong protein-protein interactions result from the cooperative utilization of two distinct types of contact interfaces that arrange molecules into linear chains, and these into two-dimensional layers. We have now determined the crystal structure of a new pheromone, Er-13, isolated from cultures that are strongly mating reactive withculturessource of pheromone Er-1.

Integrated sample-handling and mounting system for fixed-target serial synchrotron crystallography.

Serial synchrotron crystallography (SSX) is enabling the efficient use of small crystals for structure-function studies of biomolecules and for drug discovery. An integrated SSX system has been developed comprising ultralow background-scatter sample holders suitable for room and cryogenic temperature crystallographic data collection, a sample-loading station and a humid `gloveless' glovebox. The sample holders incorporate thin-film supports with a variety of designs optimized for different crystal-loading challenges.

Making routine native SAD a reality: lessons from beamline X06DA at the Swiss Light Source.

Native single-wavelength anomalous dispersion (SAD) is the most attractive de novo phasing method in macromolecular crystallography, as it directly utilizes intrinsic anomalous scattering from native crystals. However, the success of such an experiment depends on accurate measurements of the reflection intensities and therefore on careful data-collection protocols. Here, the low-dose, multiple-orientation data-collection protocol for native SAD phasing developed at beamline X06DA (PXIII) at the Swiss Light Source is reviewed, and its usage over the last four years on conventional crystals (>50 µm) is reported.

Fixed-target serial oscillation crystallography at room temperature.

A fixed-target approach to high-throughput room-temperature serial synchrotron crystallography with oscillation is described. Patterned silicon chips with microwells provide high crystal-loading density with an extremely high hit rate. The microfocus, undulator-fed beamline at CHESS, which has compound refractive optics and a fast-framing detector, was built and optimized for this experiment.

Charge-Transfer Salts of 6,6-Dicyanopentafulvenes: From Topology to Charge Separation in Solution.

6,6-Dicyanopentafulvene derivatives and metallocenes with redox potentials appropriate for forming their radical anions form highly persistent donor-acceptor salts. The charge-transfer salts of 2,3,4,5-tetraphenyl-6,6-dicyanofulvene with cobaltocene (1⋅Cp Co) and 2,3,4,5-tetrakis(triisopropylsilyl)-6,6-dicyanofulvene with decamethylferrocene (2⋅Fc*) have been prepared. The X-ray structures of the two salts, formed as black plates, were obtained and are discussed herein.

Unconventional Synthesis of a Cu Rotaxane with a Superacceptor Stopper: Ultrafast Excited-State Dynamics and Near-Infrared Luminescence.

A Cu bis-phenanthroline rotaxane was prepared by using the [2+2] cycloaddition-retroelectrocyclization (CA-RE) reaction to graft a bulky dicyanoquinodimethane (DCNQ) stopper. The electronic properties were investigated with electrochemical and photophysical techniques, in parallel with three reference compounds, namely, the DCNQ derivative alone, the DCNQ-based phenanthroline ligand, and an analogue Cu complex lacking the DCNQ moiety. In all the systems containing the DCNQ unit, the lowest electronic excited states are centered thereon, with the singlet level (S ) located at about 1.

The reductive aromatization of tridecacyclene.

The radical anion and dianion of tridecacyclene (CH, 1) have been prepared by reduction with potassium metal. Analysis of the solid-state structure of the dipotassium salt of the dianion (3) reveals evidence of increased aromatic character within the structure's central 8-membered ring despite preservation of the tub-like shape inherent to its neutral parent.

Pentaindenocorannulene: Properties, Assemblies, and C Complex.

Pentaindenocorannulene (C H  , 1), a deep bowl polynuclear aromatic hydrocarbon, accepts 4 electrons, crystallizes in columnar bowl-in-bowl assemblies and forms a nested C @1 complex. Spectra, structures and computations are presented.

EIGER detector: application in macromolecular crystallography.

The development of single-photon-counting detectors, such as the PILATUS, has been a major recent breakthrough in macromolecular crystallography, enabling noise-free detection and novel data-acquisition modes. The new EIGER detector features a pixel size of 75 × 75 µm, frame rates of up to 3000 Hz and a dead time as low as 3.8 µs.

Design and Synthesis of Aviram-Ratner-Type Dyads and Rectification Studies in Langmuir-Blodgett (LB) Films.

The design and synthesis of Aviram-Ratner-type molecular rectifiers, featuring an anilino-substituted extended tetracyanoquinodimethane (exTCNQ) acceptor, covalently linked by the σ-spacer bicyclo[2.2.2]octane (BCO) to a tetrathiafulvalene (TTF) donor moiety, are described.

Data-collection strategy for challenging native SAD phasing.

Recent improvements in data-collection strategies have pushed the limits of native SAD (single-wavelength anomalous diffraction) phasing, a method that uses the weak anomalous signal of light elements naturally present in macromolecules. These involve the merging of multiple data sets from either multiple crystals or from a single crystal collected in multiple orientations at a low X-ray dose. Both approaches yield data of high multiplicity while minimizing radiation damage and systematic error, thus ensuring accurate measurements of the anomalous differences.

Crystal structures of three complexes of zinc chloride with tri-tert-butyl-phosphane.

Under anhydrous conditions and in the absence of a Lewis-base solvent, a zinc chloride complex with tri-tert-butyl-phosphane as the μ-bridged dimer is formed, viz. di-μ-chlorido-bis-[chlorido-bis-(tri-tert-butyl-phosphane)zinc], [ZnCl4(C12H27P)2], (1), which features a nearly square-shaped (ZnCl)2 cyclic core and whose Cl atoms inter-act weakly with C-H groups on the phosphane ligand. In the presence of THF, monomeric di-chlorido-(tetra-hydro-furan-κO)(tri-tert-butyl-phosphane-κP)zinc, [ZnCl2(C4H8O)(C12H27P)] or [P(tBu3)(THF)ZnCl2], (2), is formed.

Tridecacyclene: A Cyclic Tetramer of Acenaphthylene.

In this manuscript, we describe the single-step preparation of a cyclic tetramer of acenaphthylene through a Lewis acid-catalyzed aldol cyclization of 1-acenaphthenone. The previously unexplored cyclic tetramer material differs from the better-known cyclic trimer, decacyclene, due to the presence of a central eight-membered ring. This ring not only forces the molecule to distort significantly from planarity, but is also responsible for its unique electronic properties, including a decrease in the reduction potential (by about 0.

Stabilizing Pentacene By Cyclopentannulation.

A new class of stabilized pentacene derivatives with externally fused five-membered rings are prepared by means of a key palladium-catalyzed cyclopentannulation step. The target compounds are synthesized by chemical manipulation of a partially saturated 6,13-dibromopentacene precursor that can be fully aromatized in a final step through a DDQ-mediated dehydrogenation reaction (DDQ=2,3-dichloro-5,6-dicyano-1,4-benzoquinone). The new 1,2,8,9-tetraaryldicyclopenta[fg,qr]pentacene derivatives have narrow energy gaps of circa 1.

An enantioselective artificial Suzukiase based on the biotin-streptavidin technology.

Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee.

Anilino-Substituted Multicyanobuta-1,3-diene Electron Acceptors: TICT Molecules with Accessible Conical Intersections.

A theoretical investigation based on DFT, TD-DFT, and CASSCF/CASPT2 methods has been carried out to elucidate the photophysics of two anilino-substituted pentacyano- and tetracyanobuta-1,3-dienes (PCBD and TCBD, respectively). These molecules exhibit exceptional electron-accepting properties, but their effective use in multicomponent systems for photoinduced electron transfer is limited because they undergo ultrafast (∼1 ps) radiationless deactivation. We show that the lowest-energy excited states of these molecules have a twisted intramolecular charge-transfer character and deactivate to the ground state through energetically accessible conical intersections (CIs).

Advanced Crystallographic Data Collection Protocols for Experimental Phasing.

Experimental phasing by single- or multi-wavelength anomalous dispersion (SAD or MAD) has become the most popular method of de novo macromolecular structure determination. Continuous advances at third-generation synchrotron sources have enabled the deployment of rapid data collection protocols that are capable of recording SAD or MAD data sets. However, procedural simplifications driven by the pursuit of high throughput have led to a loss of sophistication in data collection strategies, adversely affecting measurement accuracy from the viewpoint of anomalous phasing.

The [2 + 2] Cycloaddition-Retroelectrocyclization and [4 + 2] Hetero-Diels-Alder Reactions of 2-(Dicyanomethylene)indan-1,3-dione with Electron-Rich Alkynes: Influence of Lewis Acids on Reactivity.

The reaction of electrophilic 2-(dicyanomethylene)indan-1,3-dione (DCID) with substituted, electron-rich alkynes provides two classes of push-pull chromophores with interesting optoelectronic properties. The formal [2 + 2] cycloaddition-retroelectrocyclization reaction at the exocyclic double bond of DCID gives cyanobuta-1,3-dienes, and the formal [4 + 2] hetero-Diels-Alder (HDA) reaction at an enone moiety of DCID generates fused 4H-pyran heterocycles. Both products can be obtained in good yield and excellent selectivity by carefully tuning the reaction conditions; in particular, the use of Lewis acids dramatically enhances formation of the HDA adduct.

The 6,6-dicyanopentafulvene core: a template for the design of electron-acceptor compounds.

The electron-accepting ability of 6,6-dicyanopentafulvenes (DCFs) can be varied extensively through substitution on the five-membered ring. The reduction potentials for a set of 2,3,4,5-tetraphenyl-substituted DCFs, with varying substituents at the para-position of the phenyl rings, strongly correlate with their Hammett σp-parameters. By combining cyclic voltammetry with DFT calculations ((U)B3LYP/6-311+G(d)), using the conductor-like polarizable continuum model (CPCM) for implicit solvation, the absolute reduction potentials of a set of twenty DCFs were reproduced with a mean absolute deviation of 0.

Push-Pull Buta-1,2,3-trienes: exceptionally low rotational barriers of cumulenic C=C bonds and proacetylenic reactivity.

A variety of asymmetrically donor-acceptor-substituted [3]cumulenes (buta-1,2,3-trienes) were synthesized by developed procedures. The activation barriers to rotation ΔG(≠) were measured by variable temperature NMR spectroscopy and found to be as low as 11.8 kcal mol(-1) , in the range of the barriers for rotation around sterically hindered single bonds.

All-optical switching with 1-ps response time in a DDMEBT enabled silicon grating coupler/resonator hybrid device.

An amorphous film of the third-order nonlinear optical material DDMEBT was spun onto silicon chips for the first time, filling 80 nm lithographic features. A 710 μm² device was designed, fabricated, and tested that acts both as a nonlinear resonator switch and as an input/output grating coupler to a perfectly vertical single mode fiber. Autocorrelation and spectral measurements indicate the device has <1 ps response time, 4 nm of switching bandwidth, and 4 dB of on/off contrast.

6,6-Dicyanopentafulvenes: teaching an old dog new tricks.

6,6-Dicyanopentafulvene (DCF) is a fascinating molecular entity that consists of a cyclopentadiene ring conjugated to an exocyclic double bond bearing two cyano groups on its periphery. Herein, we give a brief history of the chemistry of DCFs prior to our arrival to the field in 2011, followed by a summary of our work. We show how substitution on the ring and the exocyclic bond affects the HOMO and LUMO energies of pentafulvenes and how the design of DCFs was exploited computationally for the first time.