Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements.

Lipid droplet (LD) function relies on proteins partitioning between the endoplasmic reticulum (ER) phospholipid bilayer and the LD monolayer membrane to control cellular adaptation to metabolic changes. It has been proposed that these hairpin proteins integrate into both membranes in a similar monotopic topology, enabling their passive lateral diffusion during LD emergence at the ER. Here, we combine biochemical solvent-accessibility assays, electron paramagnetic resonance spectroscopy and intra-molecular crosslinking experiments with molecular dynamics simulations, and determine distinct intramembrane positionings of the ER/LD protein UBXD8 in ER bilayer and LD monolayer membranes. UBXD8 is deeply inserted into the ER bilayer with a V-shaped topology and adopts an open-shallow conformation in the LD monolayer. Major structural rearrangements are required to enable ER-to-LD partitioning. Free energy calculations suggest that such structural transition is unlikely spontaneous, indicating that ER-to-LD protein partitioning relies on more complex mechanisms than anticipated and providing regulatory means for this trans-organelle protein trafficking.

Understanding the effects of targeted modifications on the 1 : 2 Choline And GEranate structure.

1 : 2 Choline-and-geranate (CAGE) is an ionic liquid (IL) widely studied for its biomedical applications. However, both its industrial-scale preparation and its long-term storage are problematic so finding more suitable candidates which retain its advantageous properties is crucial. As a first step towards this we have conducted a targeted modification study to understand the effects of specific functional groups on the properties of CAGE. 1 : 2 Choline-and-octanoate and 1 : 2 butyltrimethylammonium-and-octanoate were synthesised and their thermal and rheological properties examined in comparison to those of CAGE. Using differential scanning calorimetry and polarising microscopy, the model compound was found to be an isotropic liquid, while the analogues were room-temperature liquid-crystals which transition to isotropic liquids upon heating. Dynamic mechanical analysis showed that the thermal behaviour of the studied systems was even more complex, with the ILs also undergoing a thermally-activated relaxation process. Furthermore, we have used electron paramagnetic resonance (EPR) spectroscopy, along with a variety of spin probes with different functional groups, in order to understand the chemical environment experienced by solutes in each system. The EPR spectra indicate that the radicals experience two distinct environments (polar and nonpolar) in the liquid-crystalline phase, but only one average environment in the isotropic phase. The liquid-crystalline phase experiments also showed that the relative populations of the two domains depend on the nature of the solutes, with polar or strongly hydrogen-bonding solutes preferring the polar domain. For charged solutes, the EPR spectra showed line-broadening, suggesting that their ionic nature leads to complex, unresolved interactions.

Room temperature ionic liquids with two symmetric ions.

Room temperature ionic liquids typically contain asymmetric organic cations. The asymmetry is thought to enhance disorder, thereby providing an entropic counter-balance to the strong, enthalpic, ionic interactions, and leading, therefore, to lower melting points. Unfortunately, the synthesis and purification of such asymmetric cations is typically more demanding. Here we introduce novel room temperature ionic liquids in which both cation and anion are formally symmetric. The chemical basis for this unprecedented behaviour is the incorporation of ether-containing side chains - which increase the configurational entropy - in the cation. Molecular dynamics simulations indicate that the ether-containing side chains transiently sample curled configurations. Our results contradict the long-standing paradigm that at least one asymmetric ion is required for ionic liquids to be molten at room temperature, and hence open up new and simpler design pathways for these remarkable materials.

Towards high performance dielectric microwave resonators for X-band EPR spectroscopy.

Microwave (MW) resonators in Electron Paramagnetic Resonance (EPR) spectroscopy concentrate the MW magnetic field (B1) at the sample and separate the MW electric field from the sample. There are numerous experimental methods in EPR spectroscopy which all impose different requirements on MW resonators (e.g. high or low quality factor, MW conversion, and B1-field homogeneity). Although commercial spectrometers offer standardized MW resonators for a broad application range, newly emerging and highly-specialized research fields push these spectrometers to or beyond their sensitivity limits. Optimizing the MW resonator offers one direct approach to improve the sensitivity. Here we present three low-cost optimization approaches for a commercially available X-band (9-10 GHz) MW resonator for three experimental purposes (continuous-wave (CW), transient and pulse EPR). We obtain enhanced MW conversion factors for all three optimized resonators and higher quality factors for two optimized resonators. The latter is important for CW and transient EPR. Furthermore, we fabricated a resonator which features an extended area of homogeneous B1-field and, hence, improved pulse EPR performance. Our results demonstrate that small changes to a commercial MW resonator can enhance its performance in general or for specific applications.

The electronic structure and dynamics of the excited triplet state of octaethylaluminum(III)-porphyrin investigated with advanced EPR methods.

The photoexcited triplet state of octaethylaluminum(III)-porphyrin (AlOEP) was investigated by time-resolved Electron Paramagnetic Resonance, Electron Nuclear Double Resonance and Electron Spin Echo Envelope Modulation in an organic glass at 10 and 80 K. This main group element porphyrin is unusual because the metal has a small ionic radius and is six-coordinate with axial covalent and coordination bonds. It is not known whether triplet state dynamics influence its magnetic resonance properties as has been observed for some transition metal porphyrins. Together with density functional theory modelling, the magnetic resonance data of AlOEP allow the temperature dependence of the zero-field splitting (ZFS) parameters, D and E, and the proton AZZ hyperfine coupling (hfc) tensor components of the methine protons, in the zero-field splitting frame to be determined. The results provide evidence that the ZFS, hfc and spin-lattice relaxation are indeed influenced by the presence of a dynamic process that is discussed in terms of Jahn-Teller dynamic effects. Thus, these effects should be taken into account when interpreting EPR data from larger complexes containing AlOEP.

Anion and ether group influence in protic guanidinium ionic liquids.

Ionic liquids are attractive liquid materials for many advanced applications. For targeted design, in-depth knowledge about their structure-property-relations is urgently needed. We prepared a set of novel protic ionic liquids (PILs) with a guanidinium cation with either an ether or alkyl side chain and different anions. While being a promising cation class, the available data is insufficient to guide design. We measured thermal and transport properties, nuclear magnetic resonance (NMR) spectra as well as liquid and crystalline structures supported by ab initio computations and were able to obtain a detailed insight into the influence of the anion and the ether substitution on the physical and spectroscopic properties. For the PILs, hydrogen bonding is the main interaction between cation and anion and the H-bond strength is inversely related to the proton affinity of the constituting acid and correlated to the increase of 1H and 15N chemical shifts. Using anions from acids with lower proton affinity leads to proton localization on the cation as evident from NMR spectra and self-diffusion coefficients. In contrast, proton exchange was evident in ionic liquids with triflate and trifluoroacetate anions. Using imide-type anions and ether side groups decreases glass transitions as well as fragility, and accelerated dynamics significantly. In case of the ether guanidinium ionic liquids, the conformation of the side chain adopts a curled structure as the result of dispersion interactions, while the alkyl chains prefer a linear arrangement.

Black Titania and Niobia within Ten Minutes - Mechanochemical Reduction of Metal Oxides with Alkali Metal Hydrides.

Partially or fully reduced transition metal oxides show extraordinary electronic and catalytic properties but are usually prepared by high temperature reduction reactions. This study reports the systematic investigation of the fast mechanochemical reduction of rutile-type TiO2 and H-Nb2 O5 to their partially reduced black counterparts applying NaH and LiH as reducing agents. Milling time and oxide to reducing agent ratio show a large influence on the final amount of reduced metal ions in the materials. For both oxides LiH shows a higher reducing potential than NaH. An intercalation of Li+ into the structure of the oxides was proven by PXRD and subsequent Rietveld refinements as well as 6 Li solid-state NMR spectroscopy. The products showed a decreased band gap and the presence of unpaired electrons as observed by EPR spectroscopy, proving the successful reduction of Ti4+ and Nb5+ . Furthermore, the developed material exhibits a significantly enhanced photocatalytic performance towards the degradation of methylene blue compared to the pristine oxides. The presented method is a general, time efficient and simple method to obtain reduced transition metal oxides.

Evidence of AlII Radical Addition to Benzene.

Electrophilic AlIII species have long dominated the aluminum reactivity towards arenes. Recently, nucleophilic low-valent AlI aluminyl anions have showcased oxidative additions towards arenes C-C and/or C-H bonds. Herein, we communicate compelling evidence of an AlII radical addition reaction to the benzene ring. The electron reduction of a ligand stabilized precursor with KC8 in benzene furnishes a double addition to the benzene ring instead of a C-H bond activation, producing the corresponding cyclohexa-1,3(orl,4)-dienes as Birch-type reduction product. X-ray crystallographic analysis, EPR spectroscopy, and DFT results suggest this reactivity proceeds through a stable AlII radical intermediate, whose stability is a consequence of a rigid scaffold in combination with strong steric protection.

Efficient Lignin Fractionation from Scots Pine (Pinus sylvestris) Using Ammonium-Based Protic Ionic Liquid: Process Optimization and Characterization of Recovered Lignin.

Lignin-based chemicals and biomaterials will be feasible alternatives to their fossil-fuel-based counterparts once their breakdown into constituents is economically viable. The existing commercial market for lignin remains limited due to its complex heterogenous structure and lack of extraction/depolymerization techniques. Hence, in the present study, a novel low-cost ammonium-based protic ionic liquid (PIL), 2-hydroxyethyl ammonium lactate [N11H(2OH)][LAC], is used for the selective fractionation and improved extraction of lignin from Scots pine (Pinus sylvestris) softwood biomass (PWB). The optimization of three process parameters, viz., the incubation time, temperature, and biomass:PIL (BM:PIL) ratio, was performed to determine the best pretreatment conditions for lignin extraction. Under the optimal pretreatment conditions (180 °C, 3 h, and 1:3 BM:PIL ratio), [N11H(2OH)][LAC] yielded 61% delignification with a lignin recovery of 56%; the cellulose content of the recovered pulp was approximately 45%. Further, the biochemical composition of the recovered lignin and pulp was determined and the recovered lignin was characterized using 1H-13C heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy, quantitative 31P NMR, gel permeation chromatography (GPC), attenuated total reflectance (ATF)-Fourier transform infrared spectroscopy (ATR-FTIR), and thermal gravimetric analysis (TGA) analysis. Our results reveal that [N11H(2OH)][LAC] is significantly involved in the cleavage of predominant ß-O-4' linkages for the generation of aromatic monomers followed by the in situ depolymerization of PWB lignin. The simultaneous extraction and depolymerization of PWB lignin favors the utilization of recalcitrant pine biomass as feedstock for biorefinery schemes.

Molecular Dynamics of Ionic Liquids from Fast-Field Cycling NMR and Molecular Dynamics Simulations.

Understanding the connection between the molecular structure of ionic liquids and their properties is of paramount importance for practical applications. However, this connection can only be established if a broad range of physicochemical properties on different length and time scales is already available. Even then, the interpretation of the results often remains ambiguous due to the natural limits of experimental approaches. Here we use fast-field cycling (FFC) to access both translational and rotational dynamics of ionic liquids. These combined with a comprehensive physicochemical characterization and MD simulations provide a toolkit to give insight into the mechanisms of molecular mechanics. The FFC results are consistent with the computer simulation and conventional physicochemical approaches. We show that curling of the side chains around the positively charged cationic core is essential for the properties of ether-functionalized ionic liquids, and we demonstrate that neither geometry nor polarity alone are sufficient to explain the macroscopic properties.

Flexibility is the key to tuning the transport properties of fluorinated imide-based ionic liquids.

Ionic liquids are becoming increasingly popular for practical applications such as biomass processing and lithium-ion batteries. However, identifying ionic liquids with optimal properties for specific applications by trial and error is extremely inefficient since there are a vast number of potential candidate ions. Here we combine experimental and computational techniques to determine how the interplay of fluorination, flexibility and mass affects the transport properties of ionic liquids with the popular imide anion. We observe that fluorination and flexibility have a large impact on properties such as viscosity, whereas the influence of mass is negligible. Using targeted modifications, we show that conformational flexibility provides a significant contribution to the success of fluorination as a design element. Contrary to conventional wisdom, fluorination by itself is thus not a guarantor for beneficial properties such as low viscosity.

Novel Phosphonium-Based Ionic Liquid Electrolytes for Battery Applications.

In this study, we address the fundamental question of the physicochemical and electrochemical properties of phosphonium-based ionic liquids containing the counter-ions bis(trifluoromethanesulfonyl)imide ([TFSI]-) and bis(fluorosulfonyl)imide ([FSI]-). To clarify these structure-property as well as structure-activity relationships, trimethyl-based alkyl- and ether-containing phosphonium ILs were systematically synthesized, and their properties, namely density, flow characteristics, alkali metal compatibility, oxidative stability, aluminum corrosivity as well as their use in Li-ion cells were examined comprehensively. The variable moiety on the phosphonium cation exhibited a chain length of four and five, respectively. The properties were discussed as a function of the side chain, counter-ion and salt addition ([Li][TFSI] or [Li][FSI]). High stability coupled with good flow characteristics were found for the phosphonium IL [P1114][TFSI] and the mixture [P1114][TFSI] + [Li][TFSI], respectively.

Palladium Terminal Imido Complexes with Nitrene Character.

Whereas triplet-nitrene complexes of the late transition metals are isolable and key intermediates in catalysis, singlet-nitrene ligands remain elusive. Herein we communicate three such palladium terminal imido complexes with singlet ground states. UV-vis-NIR electronic spectroscopy with broad bands up to 1400 nm as well as high-level computations (DFT, STEOM-CCSD, CASSCF/NEVPT2, EOS analysis) and reactivity studies suggest significant palladium(0) singlet-nitrene character. Although the aliphatic nitrene complexes proved to be too reactive for isolation in analytically pure form as a result of elimination of isobutylene, the aryl congener could be characterized by SC-XRD, elemental analysis, IR-, NMR spectroscopy, and HRMS. The complexes' distinguished ambiphilicity allows them to activate hexafluorobenzene, triphenylphosphine, and pinacol borane, catalytically dehydrogenate cyclohexene, and aminate ethylene via nitrene transfer at or below room temperature.

Effect of the cation structure on the properties of homobaric imidazolium ionic liquids.

In this work we investigate the structure-property relationships in a series of alkylimidazolium ionic liquids with almost identical molecular weight. Using a combination of theoretical calculations and experimental measurements, we have shown that re-arranging the alkyl side chain or adding functional groups results in quite distinct features in the resultant ILs. The synthesised ILs, although structurally very similar, cover a wide spectrum of properties ranging from highly fluid, glass forming liquids to high melting point crystalline salts. Theoretical ab initio calculations provide insight on minimum energy orientations for the cations, which then are compared to experimental X-ray crystallography measurements to extract information on hydrogen bonding and to verify our understanding of the studied structures. Molecular dynamics simulations of the simplest (core) ionic liquids are used in order to help us interpret our experimental results and understand better why methylation of C2 position of the imidazolium ring results in ILs with such different properties compared to their non-methylated analogues.

Pressing matter: why are ionic liquids so viscous?

Room temperature ionic liquids are considered to have huge potential for practical applications such as batteries. However, their high viscosity presents a significant challenge to their use changing from niche to ubiquitous. The modelling and prediction of viscosity in ionic liquids is the subject of an ongoing debate involving two competing hypotheses: molecular and local mechanisms versus collective and long-range mechanisms. To distinguish between these two theories, we compared an ionic liquid with its uncharged, isoelectronic, isostructural molecular mimic. We measured the viscosity of the molecular mimic at high pressure to emulate the high densities in ionic liquids, which result from the Coulomb interactions in the latter. We were thus able to reveal that the relative contributions of coulombic compaction and the charge network interactions are of similar magnitude. We therefore suggest that the optimisation of the viscosity in room temperature ionic liquids must follow a dual approach.

Curled cation structures accelerate the dynamics of ionic liquids.

Ionic liquids are modern liquid materials with potential and actual implementation in many advanced technologies. They combine many favourable and modifiable properties but have a major inherent drawback compared to molecular liquids - slower dynamics. In previous studies we found that the dynamics of ionic liquids are significantly accelerated by the introduction of multiple ether side chains into the cations. However, the origin of the improved transport properties, whether as a result of the altered cation conformation or due to the absence of nanostructuring within the liquid as a result of the higher polarity of the ether chains, remained to be clarified. Therefore, we prepared two novel sets of methylammonium based ionic liquids; one set with three ether substituents and another set with three butyl side chains, in order to compare their dynamic properties and liquid structures. Using a range of anions, we show that the dynamics of the ether-substituted cations are systematically and distinctly accelerated. Liquefaction temperatures are lowered and fragilities increased, while at the same time cation-anion distances are slightly larger for the alkylated samples. Furthermore, pronounced liquid nanostructures were not observed. Molecular dynamics simulations demonstrate that the origin of the altered properties of the ether substituted ionic liquids is primarily due to a curled ether chain conformation, in contrast to the alkylated cations where the alkyl chains retain a linear conformation. Thus, the observed structure-property relations can be explained by changes in the geometric shape of the cations, rather than by the absence of a liquid nanostructure. Application of quantum chemical calculations to a simplified model system revealed that intramolecular hydrogen-bonding is responsible for approximately half of the stabilisation of the curled ether-cations, whereas the other half stems from non-specific long-range interactions. These findings give more detailed insights into the structure-property relations of ionic liquids and will guide the development of ionic liquids that do not suffer from slow dynamics.

Ether functionalisation, ion conformation and the optimisation of macroscopic properties in ionic liquids.

Ionic liquids are an attractive material class due to their wide liquid range, intrinsic ionic conductivity, and high chemical as well as electrochemical stability. However, the widespread use of ionic liquids is hindered by significantly higher viscosities compared to conventional molecular solvents. In this work, we show how the transport properties of ionic liquids can be altered significantly, even for isostructural ions that have the same backbone. To this end, structure-property relationships have been determined for a set of 16 systematically varied representative ionic liquids. Variations in molecular structure include ammonium vs. phosphonium, ether vs. alkyl side chains, and rigid vs. flexible anions. Ab initio calculations are used to relate molecular structures to the thermal, structural and transport properties of the ionic liquids. We find that the differences in properties of ether and alkyl functionalised ionic liquids are primarily dependent on minimum energy geometries, with the conformational flexibility of ether side chains appearing to be of secondary importance. We also show unprecedented correlations between anion conformational flexibility and transport properties. Critically, increasing fluidity upon consecutive introduction of ether side chains and phosphonium centres into the cation is found to be dependent on whether the anion is flexible or rigid. We demonstrate that targeted design of functional groups based on structure-property relationships can yield ionic liquids of exceptionally high fluidity.

Adsorption and activation of molecular oxygen over atomic copper(I/II) site on ceria.

Supported atomic metal sites have discrete molecular orbitals. Precise control over the energies of these sites is key to achieving novel reaction pathways with superior selectivity. Here, we achieve selective oxygen (O2) activation by utilising a framework of cerium (Ce) cations to reduce the energy of 3d orbitals of isolated copper (Cu) sites. Operando X-ray absorption spectroscopy, electron paramagnetic resonance and density-functional theory simulations are used to demonstrate that a [Cu(I)O2]3- site selectively adsorbs molecular O2, forming a rarely reported electrophilic η2-O2 species at 298 K. Assisted by neighbouring Ce(III) cations, η2-O2 is finally reduced to two O2-, that create two Cu-O-Ce oxo-bridges at 453 K. The isolated Cu(I)/(II) sites are ten times more active in CO oxidation than CuO clusters, showing a turnover frequency of 0.028 ± 0.003 s-1 at 373 K and 0.01 bar PCO. The unique electronic structure of [Cu(I)O2]3- site suggests its potential in selective oxidation.

Equilibrium Formation of Stable All-Silicon Versions of 1,3-Cyclobutanediyl.

Main group analogues of cyclobutane-1,3-diyls are fascinating due to their unique reactivity and electronic properties. So far only heteronuclear examples have been isolated. Here we report the isolation and characterization of all-silicon 1,3-cyclobutanediyls as stable closed-shell singlet species from the reversible reactions of cyclotrisilene c-Si3 Tip4 (Tip=2,4,6-triisopropylphenyl) with the N-heterocyclic silylenes c-[(CR2 CH2 )(NtBu)2 ]Si: (R=H or methyl) with saturated backbones. At elevated temperatures, tetrasilacyclobutenes are obtained from these equilibrium mixtures. The corresponding reaction with the unsaturated N-heterocyclic silylene c-(CH)2 (NtBu)2 Si: proceeds directly to the corresponding tetrasilacyclobutene without detection of the assumed 1,3-cyclobutanediyl intermediate.

Exploiting Excited-State Aromaticity To Design Highly Stable Singlet Fission Materials.

Singlet fission, the process of forming two triplet excitons from one singlet exciton, is a characteristic reserved for only a handful of organic molecules due to the atypical energetic requirement for low energy excited triplet states. The predominant strategy for achieving such a trait is by increasing ground state diradical character; however, this greatly reduces ambient stability. Herein, we exploit Baird's rule of excited state aromaticity to manipulate the singlet-triplet energy gap and create novel singlet fission candidates. We achieve this through the inclusion of a [4n] 5-membered heterocycle, whose electronic resonance promotes aromaticity in the triplet state, stabilizing its energy relative to the singlet excited state. Using this theory, we design a family of derivatives of indolonaphthyridine thiophene (INDT) with highly tunable excited state energies. Not only do we access novel singlet fission materials, they also exhibit excellent ambient stability, imparted due to the delocalized nature of the triplet excited state. Spin-coated films retained up to 85% activity after several weeks of exposure to oxygen and light, while analogous films of TIPS-pentacene showed full degradation after 4 days, showcasing the excellent stability of this class of singlet fission scaffold. Extension of our theoretical analysis to almost ten thousand candidates reveals an unprecedented degree of tunability and several thousand potential fission-capable candidates, while clearly demonstrating the relationship between triplet aromaticity and singlet-triplet energy gap, confirming this novel strategy for manipulating the exchange energy in organic materials.