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Technologies for quantifying circulating tumour DNA (ctDNA) in liquid biopsies could enable real-time measurements of cancer progression, profoundly impacting patient care. Sequencing methods can be too complex and time-consuming for regular point-of-care monitoring, but nanotechnology offers an alternative, harnessing the unique properties of objects tens to hundreds of nanometres in size. This systematic review was performed to identify all examples of nanotechnology-based ctDNA detection and assess their potential for clinical use. Google Scholar, PubMed, Web of Science, Google Patents, Espacenet and Embase/MEDLINE were searched up to 23rd March 2021. The review identified nanotechnology-based methods for ctDNA detection for which quantitative measures (e.g., limit of detection, LOD) were reported and biologically relevant samples were used. The pre-defined inclusion criteria were met by 66 records. LODs ranged from 10 zM to 50nM. 25 records presented an LOD of 10fM or below. Nanotechnology-based approaches could provide the basis for the next wave of advances in ctDNA diagnostics, enabling analysis at the point-of-care, but none are currently used clinically. Further work is needed in development and validation; trade-offs are expected between different performance measures e.g., number of sequences detected and time to result.

Avadomide is a cereblon E3 ligase modulator and a potent antitumor and immunomodulatory agent. Avadomide trials are challenged by neutropenia as a major adverse event and a dose-limiting toxicity. Intermittent dosing schedules supported by preclinical data provide a strategy to reduce frequency and severity of neutropenia; however, the identification of optimal dosing schedules remains a clinical challenge. Quantitative systems pharmacology (QSP) modeling offers opportunities for virtual screening of efficacy and toxicity levels produced by alternative dose and schedule regimens, thereby supporting decision-making in translational drug development. We formulated a QSP model to capture the mechanism of avadomide-induced neutropenia, which involves cereblon-mediated degradation of transcription factor Ikaros, resulting in a maturation block of the neutrophil lineage. The neutropenia model was integrated with avadomide-specific pharmacokinetic and pharmacodynamic models to capture dose-dependent effects. Additionally, we generated a disease-specific virtual patient population to represent the variability in patient characteristics and response to treatment observed for a diffuse large B-cell lymphoma trial cohort. Model utility was demonstrated by simulating the avadomide effect in the virtual population for various dosing schedules and determining the incidence of high-grade neutropenia, its duration, and the probability of recovery to low-grade neutropenia., (© 2021. The Author(s).)

Porous ionic liquids combining alkylphosphonium halides with ZIF-8 absorb large amounts of carbon dioxide that can be catalytically coupled with epoxides to form cyclic carbonates. High activity and selectivity under mild reaction conditions points towards a new promising, high-performing, sustainable family of sorbents for simultaneous carbon capture and transformation.

Porous ionic liquids are non-volatile, versatile materials that associate porosity and fluidity. New porous ionic liquids, based on the ZIF-8 metal-organic framework and on phosphonium acetate or levulinate salts, were prepared and show an increased capacity to absorb carbon dioxide at low pressures. Porous suspensions based on phosphonium levulinate ionic liquid absorb reversibly 103 % more carbon dioxide per mass than pure ZIF-8 at 1 bar and 303 K. We show how the rational combination of MOFs with ionic liquids can greatly enhance low pressure CO 2 absorption, paving the way towards a new generation of high-performance, readily available liquid materials for effective low pressure carbon capture., (© 2021 Wiley-VCH GmbH.)

The coupling protocols combining photoemission spectroscopy and other characterization methods such as electrochemical, electrical, optical, thermal, or magnetic paved the way to considerable progress in the field of materials science. Access to complementary data on the same object is relevant, but in the vast majority of cases, it is carried out sequentially and separately. This raises the complex question of the equivalence of the analyzed surfaces subjected to these different characterizations. In the frame of lithium ion battery technology (LIB), several techniques have been developed to follow in operando condition the reactivity of electro-active materials toward liquid or solid electrolytes. Besides the knowledge of the redox processes obtained using operando protocols, especially at the interfaces, some limitations associated with material sensitivity and/or the characterization techniques are still a breakdown to widen our understanding of the origin of the LIB performance degradation processes. Herein, we propose a new design of an operando cell adapted to perform X-ray photoemission spectroscopy (XPS) at the interface between electrode and electrolyte under electrochemical solicitations. To illustrate its performance, the crucial issues associated with the lithium metal interface have been scrutinized using Li/Li symmetrical cells and two types of ionic liquids, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (C 1 C 6 ImTFSI) and 1-hexyl-3-methylimidazolium bis(fluorosulfonyl)imide (C 1 C 6 ImFSI) laden with LiTFSI salt. Our original setup allowed us to follow-up the lithium surface reactivity toward these ionic liquid based electrolytes in open circuit voltage condition and under polarization. Beside the gain of time and the matter saving, we highlighted and optimized the blocking issues to perform accurate OXPS measurement for probing the evolution of the chemical structure and the surface potential change at the interface lithium/electrolyte in dynamic mode.

We reported a new perspective on the correlation between the electronic structure of an ionic liquid (IL)-based electrolyte probed by X-ray photoelectron spectroscopy and the transport properties analyzed by impedance spectroscopy. We highlighted the core level chemical shifts of 1-hexyl-3-methylimidazolium (bis(trifluoromethanesulfonyl)imide) (C 1 C 6 ImTFSI), 1-hexyl-3-methylimidazolium bis(fluorosulfonyl)imide (C 1 C 6 ImFSI), and 1-hexyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide (C 1 C 1 C 6 ImTFSI) laden with LiTFSI salt and vinylene carbonate (VC) or fluoroethylene carbonate (FEC) with regard to the transport properties of cations and anions. We pointed out based on detailed binding energy shift analyses a clear effect of the anion on the local organization of Li + ions. The significant peak shift in the case of C 1 C 6 ImTFSI laden with LiTFSI corroborates the formation of [Li(TFSI) 2 ] - complexes. On the contrary, the lower amplitude of the binding energy shift of C 1 C 6 ImFSI for both anion- and cation-related peaks indicates that the electronic distribution around the cation and the anion is not affected when the LiTFSI salt is added, which plays a strong role in the ion dynamics (lower viscosity) of the electrolyte. The X-ray photoelectron spectroscopy (XPS) result supports the preponderant role of imidazolium ionic liquid based on FSI anion to form an electrolyte less prone to form ionic complexes. The methylation of the imidazolium cation contributes to the reduction of the interaction between the C 1 C 1 C 6 Im cation and TFSI anion, while additives VC and FEC contribute to the change of the alkyl configuration in C 1 C 6 Im cation, leading to the modification of the macroscopic properties of the ILs.

Electrophoretic nuclear magnetic resonance (eNMR) is a powerful tool in studies of nonaqueous electrolytes, such as ionic liquids. It delivers electrophoretic mobilities of the ionic constituents and thus sheds light on ion correlations. In applications of liquid electrolytes, uncharged additives are often employed, detectable via 1 H NMR. Characterizing their mobility and coordination to charged entities is desirable; however, it is often hampered by small intensities and 1 H signals overlapping with major constituents of the electrolyte. In this work, we evaluate methods of phase analysis of overlapping resonances to yield electrophoretic mobilities even for minor constituents. We use phase-sensitive spectral deconvolution via a set of Lorentz distributions for the investigation of the migration behavior of additives in two different ionic liquid-based lithium salt electrolytes. For vinylene carbonate as an additive, no field-induced drift is observed; thus, its coordination to the Li + ion does not induce a correlated drift with Li + . On the other hand, in a solvate ionic liquid with tetraglyme (G4) as an additive, a correlated migration of tetraglyme with lithium as a complex solvate cation is directly proven by eNMR. The phase evaluation procedure of superimposed resonances thus broadens the applicability of eNMR to application-relevant complex electrolyte mixtures containing neutral additives with superimposed resonances., (© 2019 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.)

Failure to clear antigens causes CD8 + T cells to become increasingly hypo-functional, a state known as exhaustion. We combined manually extracted information from published literature with gene expression data from diverse model systems to infer a set of molecular regulatory interactions that underpin exhaustion. Topological analysis and simulation modeling of the network suggests CD8 + T cells undergo 2 major transitions in state following stimulation. The time cells spend in the earlier pro-memory/proliferative (PP) state is a fixed and inherent property of the network structure. Transition to the second state is necessary for exhaustion. Combining insights from network topology analysis and simulation modeling, we predict the extent to which each node in our network drives cells towards an exhausted state. We demonstrate the utility of our approach by experimentally testing the prediction that drug-induced interference with EZH2 function increases the proportion of pro-memory/proliferative cells in the early days post-activation.

Small molecule inhibitors of BRAF and MEK have proven effective at inhibiting tumor growth in melanoma patients, however this efficacy is limited due to the almost universal development of drug resistance. To provide advanced insight into the signaling responses that occur following kinase inhibition we have performed quantitative (phospho)-proteomics of human melanoma cells treated with either dabrafenib, a BRAF inhibitor; trametinib, a MEK inhibitor or SCH772984, an ERK inhibitor. Over nine experiments we identified 7827 class I phosphorylation sites on 4960 proteins. This included 54 phosphorylation sites that were significantly down-modulated after exposure to all three inhibitors, 34 of which have not been previously reported. Functional analysis of these novel ERK targets identified roles for them in GTPase activity and regulation, apoptosis and cell-cell adhesion. Comparison of the results presented here with previously reported phosphorylation sites downstream of ERK showed a limited degree of overlap suggesting that ERK signaling responses may be highly cell line and cue specific. In addition we identified 26 phosphorylation sites that were only responsive to dabrafenib. We provide further orthogonal experimental evidence for 3 of these sites in human embryonic kidney cells over-expressing BRAF as well as further computational insights using KinomeXplorer. The validated phosphorylation sites were found to be involved in actin regulation, which has been proposed as a novel mechanism for inhibiting resistance development. These results would suggest that the linearity of the BRAF-MEK-ERK module is at least context dependent.

Lithium reactivity toward an electrolytic media and dendrite growth phenomenon constitutes the main drawback for its use as an anode material for the lithium battery technology. Ionic liquids (ILs) were pointed out as promising electrolyte solvent candidates to prevent thermal runaway in a lithium battery system. However, the reactivity of lithium toward such a kind of an electrolyte is still under debate. In this study, the interaction between lithium metal and imidazolium-based ILs, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (C 1 C 6 ImTFSI) and 1-hexyl-3-methylimidazolium bis(fluorosulfonyl)imide (C 1 C 6 ImFSI), has been investigated based on the nondestructive methodology coupling electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) in coin cells aged several days at open-circuit voltage. The main components detected by XPS in the bulk separator and at the surface of the lithium metal are the byproducts of cation and anion degradation. Similarities and differences were noticed depending on the anion nature of bis(trifluoromethylsulfonyl)imide versus bis(fluorosulfonyl)imide. The role of lithium salt addition (LiTFSI) was also pointed, giving rise to the stability improvement of the electrolytic solution toward the lithium anode. A direct correlation between the resistance of the bulk electrolyte and of the interface electrolyte/lithium and chemical composition changes were established based on a detailed EIS and XPS combined study.

The liquid-phase exfoliation of graphite is one of the most promising methods to increase production and commercial availability of graphene. Because ionic liquids can be easily obtained with chosen molecular structures and tuneable physicochemical properties, they can be use as media to optimize the exfoliation of graphite. The understanding of the interactions involved between graphite and various chemical functions in the solvent ions will be helpful to find liquids capable of dissociating and stabilizing important quantities of large graphene layers. After a step of sonication, as a mechanical precursor, samples of suspended exfoliated graphene in different ionic liquids have been characterized experimentally in terms of flake size, number of layers, total concentration and purity of the exfoliated material. Nine different ionic liquids based on imidazolium, pyrrolidinium and ammonium cations and on bis(trifluoromethylsulfonyl)imide, triflate, dicyanamide, tricyanomethanide, and methyl sulfate anions have been tested. UV-vis, Raman and X-ray photoelectron in addition to high resolution transmission electron and atomic force microscopy have been selected to characterize suspended exfoliated graphene in ionic liquids. The number of layers in the flakes exfoliated, the size and concentration depend of the structure of the ionic liquid selected. In order to obtain large flake sizes, ionic liquids with bis(trifluoromethylsulfonyl)imide anions and a cation with an alkyl chain of medium length should be selected. Smaller cation and anion favors the exfoliation of graphene. The exfoliation caused the formation of C-H bonds and the oxidation of the graphitic surface.

To increase the safety and stability of lithium-ion batteries, the development of electrolytes based on ionic liquids (ILs) has gained a lot of attention in recent years. However, with graphite electrodes, neat ILs afford weak cycling performance in the absence of organic additives (e.g., vinylene carbonate, VC). The potential formation of a [Li + ]-O VC interaction/coordination could have a major influence on the observed electrochemical behavior of Li-ion batteries. On a specific electrolyte, 1-hexyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide [C 1 C 6 Im][NTf 2 ] in association with Li[NTf 2 ] (1 mol L -1 ) and VC, we performed NOESY, { 1 H- 7 Li} HOESY correlations, and pulsed field gradient spin-echo NMR measurements, combined with molecular dynamics simulations to determine whether such an interaction/coordination between VC and Li + ions is noticeable. { 7 Li- 1 H} HOESY experiment shows the vicinity of VC with [Li + ] cation, and strong correlations and association between [Li + ] and VC are observed in intense first peaks in radial distribution functions and quantified by the coordination numbers in the first solvation shell between [Li + ] and the carbonyl oxygen atom of VC.

Cobalt nanoparticles (CoNPs) exhibit quite unique magnetic, catalytic, and optical properties. In this work, imidazolium-based ionic liquids (ILs) are successfully used to elaborate magnetically responsive suspensions of quite monodisperse CoNPs with diameters below 5 nm. The as-synthesized CoNPs adopt the noncompact and metastable structure of ϵ-Co that progressively evolves at room temperature toward the stable hexagonal close-packed allotrope of Co. Accordingly, magnetization curves are consistent with zero-valent Co. As expected in this size range, the CoNPs are superparamagnetic at room temperature. Their blocking temperature is found to depend on the size of the IL cation. The CoNPs produced in an IL with a large cation exhibit a very high anisotropy, attributed to an enhanced dipolar coupling of the NPs, even though a larger interparticle distance is observed in this IL. Finally, the presence of surface hydrides on the CoNPs is assessed and paves the way toward the synthesis for Co-based bimetallic NPs.

The metallization of porous silicon (PSi) is generally realized through physical vapor deposition (PVD) or electrochemical processes using aqueous solutions. The former uses a strong vacuum and does not allow for a conformal deposition into the pores. In the latter, the water used as solvent causes oxidation of the silicon during the reduction of the salt precursors. Moreover, as PSi is hydrophobic, the metal penetration into the pores is restricted to the near-surface region. Using a solution of organometallic (OM) precursors in ionic liquid (IL), we have developed an easy and efficient way to fully metallize the pores throughout the several-µm-thick porous Si. This process affords supported metallic nanoparticles characterized by a narrow size distribution. This process is demonstrated for different metals (Pt, Pd, Cu, and Ru) and can probably be extended to other metals. Moreover, as no reducing agent is necessary (the decomposition in an argon atmosphere at 50 °C is fostered by surface silicon hydride groups borne by PSi), the safety and the cost of the process are improved.

Protein kinases control cellular responses to environmental cues by swift and accurate signal processing. Breakdowns in this high-fidelity capability are a driving force in cancer and other diseases. Thus, our limited understanding of which amino acids in the kinase domain encode substrate specificity, the so-called determinants of specificity (DoS), constitutes a major obstacle in cancer signaling. Here, we systematically discover several DoS and experimentally validate three of them, named the αC1, αC3, and APE-7 residues. We demonstrate that DoS form sparse networks of non-conserved residues spanning distant regions. Our results reveal a likely role for inter-residue allostery in specificity and an evolutionary decoupling of kinase activity and specificity, which appear loaded on independent groups of residues. Finally, we uncover similar properties driving SH2 domain specificity and demonstrate how the identification of DoS can be utilized to elucidate a greater understanding of the role of signaling networks in cancer (Creixell et al., 2015 [this issue of Cell])., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Suspensions of bimetallic nanoparticles (NPs) of Ru and Cu have been synthesized by simultaneous decomposition of two organometallic compounds in an ionic liquid. These suspensions have been characterized by Anomalous Small-Angle X-ray Scattering (ASAXS) at energies slightly below the Ru K-edge. It is found that the NPs adopt a Ru-core, a Cu-shell structure, with a constant Ru core diameter of 1.9 nm for all Ru : Cu compositions, while the Cu shell thickness increases with Cu content up to 0.9 nm. The formation of RuCuNPs thus proceeds through rapid decomposition of the Ru precursor into RuNPs of constant size followed by the reaction of the Cu precursor and agglomeration as a Cu shell. Thus, the different decomposition kinetics of precursors make possible the elaboration of core-shell NPs composed of two metals without chemical affinity.

A series of six long chain alkyl mono- and bi-cationic imidazolium based salts with bis(trifluoromethylsulfonyl)imide (NTf2(-)) as the anion were synthesized and characterized. The single crystal structure of 1-methyl-3-octadecylimidazolium bis(trifluoromethylsulfonyl)imide could be obtained by X-ray analysis. All these long chain alkyl imidazolium based ILs were applied in the synthesis of nickel nanoparticles via chemical decomposition of an organometallic precursor of nickel. In these media, spontaneous decomposition of Ni(COD)2 (COD = 1,5-cyclooctadiene) in the absence of H2 occurred giving small NPs (≤4 nm) with narrow size distributions. Interestingly, formation of regularly interspaced NP arrays was also observed in long chain ILs. Such array formation could be interesting for potential applications such as carbon nanotube growth.

The energy storage market relating to lithium based systems regularly grows in size and expands in terms of a portfolio of energy and power demanding applications. Thus safety focused research must more than ever accompany related technological breakthroughs regarding performance of cells, resulting in intensive research on the chemistry and materials science to design more reliable batteries. Formulating electrolyte solutions with nonvolatile and hardly flammable ionic liquids instead of actual carbonate mixtures could be safer. However, few definitions of thermal stability of electrolytes based on ionic liquids have been reported in the case of abuse conditions (fire, shortcut, overcharge or overdischarge). This work investigates thermal stability up to combustion of 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C1C4Im][NTf2]) and 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide ([PYR14][NTf2]) ionic liquids, and their corresponding electrolytes containing lithium bis(trifluoromethanesulfonyl)imide LiNTf2. Their possible routes of degradation during thermal abuse testings were investigated by thermodynamic studies under several experimental conditions. Their behaviours under fire were also tested, including the analysis of emitted compounds.

Transformation of lignocellulosic biomass to biofuels involves multiple processes, in which thermal decomposition, hydrotreatment are the most central steps. Current work focuses on the impact of several solid acids and Keggin-type heteropolyacids on the decomposition temperature (Td) of pine wood and the characterization of the resulted products. It has been observed that a mechanical mixture of solid acids with pine wood has no influence on Td, while the use of heteropolyacids lower the Td by 100°C. Moreover, the treatment of biomass with a catalytic amount of H3PW12O40 leads to formation of three fractions: solid, liquid and gas, which have been investigated by elemental analysis, TGA, FTIR, GC-MS and NMR. The use of heteropolyacid leads, at 300°C, to a selective transformation of more than 50 wt.% of the holocellulose part of the lignocellulosic biomass. Moreover, 60 wt.% of the catalyst H3PW12O40 are recovered., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The influence of the presence of imidazolium side chain unsaturation on the solubility of ethane and ethylene was studied in three ionic liquids: 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide-saturated alkyl side-chain in the cation; 1-methyl-3-(buten-3-yl)imidazolium bis(trifluorosulfonyl)imide-double bond in the side-chain of the cation; and 1-methyl-3-benzylimidazolium bis(trifluorosulfonyl)imide-benzyl group in the side-chain of the cation. The solubility of both gases decreases when the side-chain of the cations is functionalized with an unsaturated group. This can be explained by a less favorable enthalpy of solvation. The difference of solubility between ethane and ethylene can be explained from a balance of enthalpic and entropic factors: for the ionic liquid with the saturated alkyl side-chain and the benzyl-substituted side-chain, it is the favorable entropy of solvation that explains the larger ethylene solubility, whereas in the case of the saturated side-chain, it is the more favorable enthalpy of solvation. Molecular simulation allowed the identification of the mechanisms of solvation and the preferential solvation sites for each gas in the different ionic liquids. Simulations have shown that the entropy of solvation is more favorable when the presence of the gas weakens the cation-anion interactions or when the gas can be solvated near different sites of the ionic liquid.

Suspensions of small sized (1-2.5 nm) ruthenium nanoparticles (RuNPs) have been obtained by decomposition, under H(2), of (η(4)-1,5-cyclooctadiene)(η(6)-1,3,5-cyclooctatriene)ruthenium(0), [Ru(COD)(COT)], in the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(1)C(4)Im][NTf(2)], and in the presence of different compounds acting as ligands: C(8)H(17)NH(2), PPhH(2), PPh(2)H and H(2)O. Previous and new liquid NMR experiments showed that the ligands are coordinated or in the proximity to the surface of the RuNPs. Herein is reported how the ligand affects the catalytic performance (activity and selectivity) compared to a ligand-free system of RuNPs, when RuNPs in [C(1)C(4)Im][NTf(2)] are used as catalysts for the hydrogenation of various unsaturated compounds (1,3-cyclohexadiene, limonene and styrene). It has been observed that σ-donor ligands increase the activity of the nanoparticles, contrarily to π-acceptor ones.

Biomolecular systems that can process information are sought for computational applications, because of their potential for parallelism and miniaturization and because their biocompatibility also makes them suitable for future biomedical applications. DNA has been used to design machines, motors, finite automata, logic gates, reaction networks and logic programs, amongst many other structures and dynamic behaviours. Here we design and program a synthetic DNA network to implement computational paradigms abstracted from cellular regulatory networks. These show information processing properties that are desirable in artificial, engineered molecular systems, including robustness of the output in relation to different sources of variation. We show the results of numerical simulations of the dynamic behaviour of the network and preliminary experimental analysis of its main components.

The influence of the nature of two different ionic liquids, namely 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(1)C(4)Im][NTf(2)], and 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide, [C(1)C(1)C(4)Im][NTf(2)], on the catalytic hydrogenation of 1,3-cyclohexadiene with [Rh(COD)(PPh(3))(2)][NTf(2)] (COD = 1,5-cyclooctadiene) was studied. Initially, the effect of different concentrations of 1,3-cyclohexadiene on the molecular interactions and on the structure in two ionic liquids was investigated by NMR and by molecular dynamic simulations. It was found that in both ionic liquids 1,3-cyclohexadiene is solvated preferentially in the lipophilic regions. Furthermore, the higher solubility of 1,3-cyclohexadiene in [C(1)C(4)Im][NTf(2)] and the smaller positive values of the excess molar enthalpy of mixing for the 1,3-cyclohexadiene + [C(1)C(4)Im][NTf(2)] system in comparison with 1,3-cyclohexadiene + [C(1)C(1)C(4)Im][NTf(2)] indicate more favorable interactions between 1,3-cyclohexadiene and the C(1)C(4)Im(+) cation than with the C(1)C(1)C(4)Im(+) cation. Subsequently, diffusivity and conductivity measurements of the 1,3-cyclohexadiene + ionic liquid mixtures at different compositions allowed a characterization of mass and charge transport in the media and access to the ionicity of ionic liquids in the mixture. From the dependence of the ratio between molar conductivity and the conductivity inferred from NMR diffusion measurements, Λ(imp)/Λ(NMR), on concentration of 1,3-cyclohexadiene in the ionic liquid mixture, it was found that increasing the amount of 1,3-cyclohexadiene leads to a decrease in the ionicity of the medium. Finally, the reactivity of the catalytic hydrogenation of 1,3-cyclohexadiene using [Rh(COD)(PPh(3))(2)][NTf(2)] performed in [C(1)C(4)Im][NTf(2)] at different compositions of 1,3-cyclohexadiene and in [C(1)C(1)C(4)Im][NTf(2)] at one composition was related linearly to the viscosity, hence the reaction rate is determined by the mass transport properties of the media.

Ionic liquids are a stabilizing medium for the in situ synthesis of ruthenium nanoparticles. Herein we show that the addition of molecular polar solutes to the ionic liquid, even in low concentrations, eliminates the role of the ionic liquid 3D structure in controlling the size of ruthenium nanoparticles, and can induce their aggregation. We have performed the synthesis of ruthenium nanoparticles by decomposition of [Ru(COD)(COT)] in 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(1)C(4)Im][NTf(2)], under H(2) in the presence of varying amounts of water or 1-octylamine. For water added during the synthesis of metallic nanoparticles, a decrease of the solubility in the ionic liquid was observed, showed by nanoparticles located at the interface between aqueous and ionic phases. When 1-octylamine is present during the synthesis, stable nanoparticles of a constant size are obtained. When 1-octylamine is added after the synthesis, aggregation of the ruthenium nanoparticles is observed. In order to explain these phenomena, we have explored the molecular interactions between the different species using (13)C-NMR and DOSY (Diffusional Order Spectroscopy) experiments, mixing calorimetry, surface tension measurements and molecular simulations. We conclude that the behaviour of the ruthenium nanoparticles in [C(1)C(4)Im][NTf(2)] in the presence of 1-octylamine depends on the interaction between the ligand and the nanoparticles in terms of the energetics but also of the structural arrangement of the amine at the nanoparticle's surface.

Very stable suspensions of small sized (c.a. 1.2 nm) and homogeneously dispersed ruthenium nanoparticles (RuNPs) were obtained by decomposition, under H(2), of (η(4)-1,5-cyclooctadiene)(η(6)-1,3,5-cyclooctatriene)ruthenium(0), [Ru(COD)(COT)], in various imidazolium derived ionic liquids (ILs: [RMIm][NTf(2)] (R = C(n)H(2n+1) where n = 2; 4; 6; 8; 10) and in the presence of amines as ligands (1-octylamine, 1-hexadecylamine). These nanoparticles were compared to others stabilized either in pure ILs or by the same ligands in THF. NMR experiments ((13)C solution and DOSY) demonstrate that the amines are coordinated to the surface of the RuNPs. These RuNPs were investigated for the hydrogenation of aromatics and have shown a high level of recyclability (up to 10 cycles) with neither loss of activity nor significant agglomeration.

The organometallic complexes ([Ru(COD)(2-methylallyl)2] and [Ni(COD)2] (COD=1,5-cyclooctadiene) dissolved in imidazolium ionic liquids (ILs) undergo reduction and decomposition, respectively, to afford stable ruthenium and nickel metal(0) nanoparticles (Ru(0)-NPs and Ni(0)-NPs) in the absence of classical reducing agents. Depending on the case, the reduction/auto-decomposition is promoted by either the cation and/or anion of the neat imidazolium ILs.

A supported ionic liquid phase (SILP) catalyst prepared from [PrMIM][Ph(2)P(3-C(6)H(4)SO(3))] (PrMIM = 1-propyl-3-methylimidazolium), [Rh(CO)(2)(acac)] (acacH = 2,4-pentanedione) [OctMIM]NTf(2) (OctMIM = 1-n-octyl-3-methylimidazolium, Tf = CF(3)SO(2)) and microporous silica has been used for the continuous flow hydroformylation of 1-octene in the presence of compressed CO(2). Statistical experimental design was used to show that the reaction rate is neither much affected by the film thickness (IL loading) nor by the syngas:substrate ratio. However, a factor-dependent interaction between the syngas:substrate ratio and film thickness on the reaction rate was revealed. Increasing the substrate flow led to increased reaction rates but lower overall yields. One of the most important parameters proved to be the phase behaviour of the mobile phase, which was studied by varying the reaction pressure. At low CO(2) pressures or when N(2) was used instead of CO(2) rates were low because of poor gas diffusion to the catalytic sites in the SILP. Furthermore, leaching of IL and Rh was high because the substrate is liquid and the IL had been designed to dissolve in it. As the CO(2) pressure was increased, the reaction rate increased and the IL and Rh leaching were reduced, because an expanded liquid phase developed. Due to its lower viscosity the expanded liquid allows better transport of gases to the catalyst and is a poorer solvent for the IL and the catalyst because of its reduced polarity. Above 100 bar (close to the transition to a single phase at 106 bar), the rate of reaction dropped again with increasing pressure because the flowing phase becomes a better and better solvent for the alkene, reducing its partitioning into the IL film. Under optimised conditions, the catalyst was shown to be stable over at least 40 h of continuous catalysis with a steady state turnover frequency (TOF, mol product (mol Rh)(-1)) of 500 h(-1) at low Rh leaching (0.2 ppm). The selectivity of the catalyst was not much affected by the variation of process parameters. The linear:branched (l:b) ratios were ca. 3, similar to that obtained using the very same catalyst in conventional organic solvents.

The catalytic hydrogenation of 1,3-cyclohexadiene using [Rh(COD)(PPh(3))(2)]NTf(2) (COD = 1,5-cyclooctadiene) was performed in two ionic liquids: 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [C(1)C(4)Im][NTf(2)], and 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide, [C(1)C(1)C(4)Im][NTf(2)]. It is observed that the reaction is twice as fast in [C(1)C(4)Im][NTf(2)] than in [C(1)C(1)C(4)Im][NTf(2)]. To explain the difference in reactivity, molecular interactions and the microscopic structure of ionic liquid +1,3-cyclohexadiene mixtures were studied by NMR and titration calorimetry experiments, and by molecular simulation in the liquid phase. Diffusivity and viscosity measurements allowed the characterization of mass transport in the reaction media. We could conclude that the diffusivity of 1,3-cyclohexadiene is 1.9 times higher in [C(1)C(4)Im][NTf(2)] than in [C(1)C(1)C(4)Im][NTf(2)] and that this difference could explain the lower reactivity observed in [C(1)C(1)C(4)Im][NTf(2)].

In situ labelling and spectroscopic experiments are used to explain the key points in the stabilisation of ruthenium nanoparticles (RuNPs) generated in imidazolium-based ionic liquids (ILs) by decomposition of (eta(4)-1,5-cyclooctadiene)(eta(6)-1,3,5-cyclooctatriene)ruthenium(0), Ru(COD)(COT), under dihydrogen. These are found to be: (1) the presence of hydrides at the RuNP surface and, (2) the confinement of RuNPs in the non-polar domains of the structured IL, induced by the rigid 3-D organisation. These results lead to a novel stabilisation model for NPs in ionic liquids.

Dialkylimidazolium chlorometallate molten salts resulting from the combination of zirconium or hafnium tetrachloride and 1-butyl-3-methylimidazolium chloride, [C(1)C(4)Im][Cl], have been prepared with a molar fraction of MCl(4), R = n(MCl4)/n(MCl4) + n([C1C4IM][Cl]) equal to 0, 0.1, 0.2, 0.33, 0.5, 0.67. The structure and composition were studied by Differential Scanning Calorimetry (DSC), (35)Cl (263 to 333 K), (1)H and (13)C solid state and solution NMR spectroscopy, and electrospray ionisation (ESI) mass spectrometry. The primary anions of the MCl(4)-based ILs were [MCl(5)], [MCl(6)] and [M(2)Cl(9)], whose relative abundances varied with R. For R = 0.33, pure solid [C(1)C(4)Im](2)[MCl(6)], for both M = Zr and Hf are formed (m.p. = 366 and 385 K, respectively). For R = 0.67 pure ionic liquids [C(1)C(4)Im][M(2)Cl(9)] for both M = Zr and Hf are formed (T(g) = 224 and 220 K, respectively). The thermal dissociation has been attempted of [C(1)C(4)Im](2)[HfCl(6)], and [C(1)C(4)Im](2)[ZrCl(6)] monitored by (35)Cl and (91)Zr solid NMR (high temperature up to 551 K).

Nonlinear cooperative behavior appears naturally in many systems, such as cardiac cell oscillations; cellular calcium oscillations; oscillatory chemical reactions, and fireflies. Such systems have been studied in detail due to their inherent properties of robustness, adaptability, scalability, and emergence. In this paper, such nonlinear cooperative behaviors are considered within the domain of electronic system design. We investigate these desirable properties in a system composed of electronic oscillators. The paper presents a series of circuit simulation results showing that self-organizing principles, which can be emulated in an electronic circuit, enable the systems to show a phase transition to synchronization, in a manner similar to those of natural systems. Circuit simulation results presented here show that the circuits are robust to the unreliable performance of the electronic oscillators and tolerant to their run-time faults. These are important findings for future engineering applications in which the system's elements are likely to be unreliable and faulty, such as in molecular- and nanoelectronic systems.

The solute-solvent interactions and the site-site distances between toluene and ionic liquids (ILs) 1-butyl-2,3-dimethylimidazolium bis(trifluoromethylsulfonyl)imide [BMMIm][NTf2] and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [BMIm][NTf2] at various molar ratios were determined by NMR experiments (1D NMR, rotating-frame Overhauser effect spectroscopy (ROESY)) and by molecular simulation using an atomistic force field. The difference in behavior of toluene in these ILs has been related to the presence of H-bonding between the C2-H and the anion in [BMIm][NTf2] generating a stronger association (>20 kJ.mol-1) than in the case of [BMMIm][NTf2]. Consequently, toluene cannot cleave this H-bond in [BMIm][NTf2] which remains in large aggregates of ionic pairs. However, toluene penetrates the less strongly bonded network of [BMMIm][NTf2] and interacts with [BMMIm] cations.

This paper investigates how self-organisation might be harnessed for the manipulation and control of calcium oscillations. Calcium signalling mechanisms are responsible for a number of important functions within biological systems, such as fertilization, secretion, contraction, neuronal signalling and learning. In this paper, calcium oscillations are investigated as a biological periodic process. Within biological systems such periodic behaviour is one of the outcomes from self-organisation. The understanding of periodic processes in living systems can enable more accurate diagnosis and physiologically suitable clinical therapies to be proposed, for diseases such as cancer, epilepsy, cardiac diseases and other dynamic diseases. In this paper these ideas are investigated by means of the calcium-induced calcium release (CICR) model and a number of representative simulations of intra and inter-cellular calcium oscillations are used to illustrate the manipulation and control of these oscillations in normal and pathological situations.

A new family of hydroxytris(pentafluorophenyl)borate anions [B(C6F5)3OH](-) associated with organic and aprotic cations c+ (imidazolium, pyrrolidinium and phosphonium) has been prepared by a general one-pot synthesis that implies the chloride borate analogues [B(C6F5)3Cl](-)[c]+. The [c]+[B(C6F5)3OH](-) salts have been isolated and fully characterized. The borate anion [B(C6F5)3OH](-) has been shown to protonate the Zr-Me bond in the Cp2ZrMe2 complex forming CH4 and the first published example of anionic [Cp2Zr(Me)OB(C6F5)3](-) species. Standard spectroscopic methods demonstrate the covalent character of the Zr metal center and the anionic character of the boron atom. This protonolysis methodology using [B(C6F5)3OH](-) anion affords a new route for the incorporation of a covalently bonded anionic functionality on organometallic complexes. This provides a new way to immobilize transition metal complexes in ionic liquids.

Rapid hydroformylation of 1-octene (rates up to 800 h(-1)) with the catalyst remaining stable for at least 40 h and with very low rhodium leaching levels (0.5 ppm) is demonstrated when using a system involving flowing the substrate, reacting gases and products dissolved in supercritical CO(2) (scCO(2)) over a fixed bed supported ionic liquid phase catalyst.

Cp*ZrMe3 reacts with silica pretreated at 800 degrees C, SiO(2-(800)) through two pathways: (a) protolysis of a Zr-Me group by surface silanols and (b) transfer of a methyl group to the surface by opening of strained siloxane bridges, in a relative proportion of ca. 9/1, respectively, affording a well-defined surface species [([triple bond]SiO)ZrCp*(Me)2], 3, but with two different local environments 3a, [([triple bond]SiO)ZrCp*(Me)2][[triple bond]Si-O-Si[triple bond]], and the other with 3b, [structure: see text]. The reaction of the species 3 with B(C6F5)3 is controlled by this local environment and gives three surface species [([triple bond]SiO)ZrCp*(Me)](+)[MeB(C6F5)3]- [[triple bond]Si-O-Si[triple bond]], 4a (20%), [([triple bond]SiO)ZrCp*(Me)](+)[(Me)B(C6F5)3]- [[triple bond]Si-Me], 4b (10%), and [([triple bond]SiO)2ZrCp*](+)[(Me)B(C6F5)(3)](-)[[triple bond]Si-O-Si[triple bond]], 5 (70%). On the contrary, the reaction of Cp*Zr(Me)3, Cp2Zr(Me)2 with [[triple bond]SiO-B(C6F5)3](-)[HNEt2Ph]+, 6, leads to a unique species [([triple bond]SiO)B(C6F5)3](-)[Cp*Zr(Me)2.NEt2Ph]+, 7, and [([triple bond]SiO)ZrCp2](+)[(Me)B(C6F5)3]-, 9 respectively. The complexes 4 and 7 are active catalysts in ethylene polymerization at room temperature, 93 and 67 kg PE mol Zr1- atm(-1) bar(-1), respectively, indicating that covalently bounded Zr catalyst 4 is slightly more active than the "floating" cationic catalyst 7.

The reaction of Cp*ZrMe3, 1, with the heterogeneous activator [[triple bond]SiO-B(C6F5)3]- [HNEt2Ph]+, 2, has been investigated to generate, by an irreversible process of methane elimination, the well-defined cationic silica-supported metallocenium species [[triple bond]SiO-B(C6F5)3]- [Cp*ZrMe2(NEt2Ph)]+, 3, as an active olefin polymerisation catalyst.

The reaction of the Lewis acid B(C(6)F(5))(3) with silanol groups of silica surfaces, dehydroxylated at different temperatures (300, 500, 700, and 800 degrees C), has been investigated in presence of the Brønsted base NEt(2)Ph. The structure of the resulting modified silica supports [triple bond Si-OB(C(6)F(5))(3)](-)[HNEt(2)Ph](+) (1) has been carefully identified by IR and multinuclear solid-state NMR spectroscopies, isotopic (2)H and (18)O labeling, elemental analysis, molecular modeling, and comparison with synthesized molecular models. Highly dehydroxylated silica surfaces were required to transform selectively each silanol group into unique [triple bond Si-OB(C(6)F(5))(3)](-)[HNEt(2)Ph](+) fragments. For lower dehydroxylation temperatures, two sorts of surface sites were coexisting on silica: the free silanol groups [triple bond SiOH] and the ionic species 1.

The reaction of Rh(eta(3)-C(3)H(5))(3) with the surface hydroxyl groups of partially dehydroxylated silica leads to the formation of the surface organometallic complex (&tbd1;SiO)(&tbd1;SiOX)Rh(eta(3)-C(3)H(5))(2), 1 (where X is H or Si&tbd1;), with evolution of propene. The reaction of 1 with PMe(3) was examined, and two major pathways were discovered. Reductive elimination of two allyl ligands as 1,5-hexadiene and coordination of PMe(3) give the surface product (&tbd1;SiO)Rh(PMe(3))(3), 2, which was characterized by elemental analysis, IR and (31)P MAS NMR spectroscopy. We also prepared 2 independently from CH(3)Rh(PMe(3))(3) and partially dehydroxylated silica. The second major reaction pathway is the elimination of propene to give (&tbd1;SiO)(2)Rh(eta(1)-C(3)H(5))(PMe(3))(3), 3. The presence of the sigma-bound allyl ligand was inferred from its characteristic IR spectrum. The reactivity of 3 toward CO was examined: insertion of CO into the Rh-C bond followed by reductive elimination of the silyl ester &tbd1;SiOC(O)C(3)H(5) produces (&tbd1;SiO)Rh(CO)(PMe(3))(2), 4. In static vacuum, 3 decomposes to give allyl alcohol, which is slowly decarbonylated by 2.