Acoustically Induced Flashback in a Staged Swirl-Stabilized Combustor

This paper describes a joint experimental and numerical investigation of the interaction between thermoacoustics and flashback mechanisms in a swirled turbulent burner. An academic air/propane combustor terminated by a choked nozzle is operated up to 2.5 bars. Experiments show that the flame can stabilize either within the combustion chamber or flashback inside the injection duct, intermittently or permanently. The present study focuses on the mechanisms leading to flashback: this phenomenon can occur naturally, depending on the swirl level which can be adjusted in the experiment by introducing axial flow through the upstream inlet. It can also be triggered by acoustic waves, either through acoustic forcing or self-excited thermoacoustic instability. Flashback is difficult to study experimentally, but it can be investigated numerically using LES: in a first configuration, the outlet of the chamber is treated as a non-reflecting surface through which harmonic waves can be introduced. In this case, a 20 kPa acoustic forcing is sufficient to trigger permanent flashback after a few cycles. When the LES computational domain includes the choked nozzle used experimentally, no forcing is needed for flashback to occur. Self-excited oscillations reach high levels rapidly, leading to flame flashback, as observed experimentally. These results also suggest a simple method to avoid flashback by using fuel staging, which is then tested successfully in both LES and experiments.     

Synthesis and Biological Activity of a Cytostatic Inhibitor of MLLr Leukemia Targeting the DOT1L Protein

Histone methyltransferase DOT1L catalyzes mono-, di- and trimethylation of histone 3 at lysine residue 79 (H3K79) and hypermethylation of H3K79 has been linked to the development of acute leukemias characterized by the MLL (mixed-lineage leukemia) rearrangements (MLLr cells). The inhibition of H3K79 methylation inhibits MLLr cells proliferation, and an inhibitor specific for DOT1L, pinometostat, was in clinical trials (Phase Ib/II). However, the compound showed poor pharmacological properties. Thus, there is a need to find new potent inhibitors of DOT1L for the treatment of rearranged leukemias. Here we present the design, synthesis, and biological evaluation of a small molecule that inhibits in the nM level the enzymatic activity of hDOT1L, H3K79 methylation in MLLr cells with comparable potency to pinometostat, associated with improved metabolic stability and a characteristic cytostatic effect.     

Specific Versus Non-specific Response in Exponential Molecular Amplification from Cross-Catalysis: Modeling the Influence of Background Amplifications on the Analytical Performances

Molecule based signal amplifications relying on an autocatalytic process may represent an ideal strategy for the development of ultrasensitive analytical or bioanalytical assays, the main reason being the exponential nature of the amplification. However, to take full advantage of such amplification rates, high stability of the starting co-reactants is required in order to avoid any undesirable background amplification. Here, on the basis of a simple kinetic model of cross-catalysis including a certain degree of intrinsic instability of co-reactants, we highlight the key parameters governing the analytical response of the system and discuss the analytical performances that are expected from a given kinetic set. In particular, we show how the detection limit is directly related to the relative instability of reactants within each catalytic loop. The model is validated with an experimental dataset and is intended to serve as a guide in the design and optimization of autocatalytic molecular-based amplification systems with improved analytical performances.     

Exponential amplification by redox cross-catalysis and unmasking of doubly protected molecular probes

The strength of autocatalytic reactions lies in their ability to provide a powerful means of molecular amplification, which can be very useful for improving the analytical performances of a multitude of analytical and bioanalytical methods. However, one of the major difficulties in designing an efficient autocatalytic amplification system is the requirement for reactants that are both highly reactive and chemically stable in order to avoid limitations imposed by undesirable background amplifications. In the present work, we devised a reaction network based on a redox cross-catalysis principle, in which two catalytic loops activate each other. The first loop, catalyzed by H₂O₂, involves the oxidative deprotection of a naphthylboronate ester probe into a redox-active naphthohydroquinone, which in turn catalyzes the production of H₂O₂ by redox cycling in the presence of a reducing enzyme/substrate couple. We present here a set of new molecular probes with improved reactivity and stability, resulting in particularly steep sigmoidal kinetic traces and enhanced discrimination between specific and nonspecific responses. This translates into the sensitive detection of H₂O₂ down to a few nM in less than 10 minutes or a redox cycling compound such as the 2-amino-3-chloro-1,4-naphthoquinone down to 50 pM in less than 30 minutes. The critical reason leading to these remarkably good performances is the extended stability stemming from the double masking of the naphthohydroquinone core by two boronate groups, a counterintuitive strategy if we consider the need for two equivalents of H₂O₂ for full deprotection. An in-depth study of the mechanism and dynamics of this complex reaction network is conducted in order to better understand, predict and optimize its functioning. From this investigation, the time response as well as detection limit are found to be highly dependent on pH, nature of the buffer, and concentration of the reducing enzyme.

Reduction of the non-specific background in autocatalytic molecular amplifications by a double masking strategy.     

Difluorenyl carbo‐Benzenes: Synthesis,Electronic Structure,and Two‐Photon Absorption Properties of Hydrocarbon Quadrupolar Chromophores

The synthesis, crystal and electronic structures, and one‐ and two‐photon absorption properties of two quadrupolar fluorenyl‐substituted tetraphenyl carbo‐benzenes are described. These all‐hydrocarbon chromophores, differing in the nature of the linkers between the fluorenyl substituents and the carbo‐benzene core (C?C bonds for 3 a , C?C?C?C expanders for 3 b ), exhibit quasi–superimposable one‐photon absorption (1PA) spectra but different two‐photon absorption (2PA) cross‐sections σ_2PA. Z‐scan measurements (under NIR femtosecond excitation) indeed showed that the C?C expansion results in an approximately twofold increase in the σ_2PA value, from 336 to 656 GM (1 GM=10^?50 cm⁴ s molecule^?1 photon^?1) at λ=800 nm. The first excited states of A_u and A_g symmetry accounting for 1PA and 2PA, respectively, were calculated at the TDDFT level of theory and used for sum‐over‐state estimations of σ_2PA(λ_i), in which λ_i=2 hc/E_i, h is Planck’s constant, c is the speed of light, and E_i is the energy of the 2PA‐allowed transition. The calculated σ_2PA values of 227 GM at 687 nm for 3 a and 349 GM at 708 nm for 3 b are in agreement with the Z‐scan results.     

A Redox‐Active Binder for Electrochemical Capacitor Electrodes

A promising strategy for increasing the performance of supercapacitors is proposed. Until now, a popular strategy for increasing the specific capacity of the electrode consists of grafting redox molecules onto a high surface area carbon structure to add a faradaic contribution to the charge storage. Unfortunately, the grafting of molecules to the carbon surface leads to a dramatic decrease of the electrochemical performances of the composite material. Herein, we used the organic binder as an active material in the charge/discharge process. Redox molecules were attached onto its polymeric skeleton to obtain a redox binder with the dual functionalities of both the binder and the active material. In this way, the electrochemical performance was improved without detrimentally affecting the properties of the porous carbon. Results showed that the use of a redox binder is promising for enhancing both energy and power densities.     

carbo‐Naphthalene: A Polycyclic carbo‐Benzenoid Fragment of α‐Graphyne

A ring carbo‐mer of naphthalene, C₃₂Ar₈ (Ar=p‐n‐pentylphenyl), has been obtained as a stable blue chromophore, after a 19‐step synthetic route involving methods inspired from those used in the synthesis of carbo‐benzenes, or specifically devised for the present target, like a double Sonogashira‐type coupling reaction. The last step is a SnCl₂/HCl‐mediated reduction of a decaoxy‐carbo‐decalin, which is prepared through successive [8+10] macrocyclization steps. Two carbo‐benzene references are also described, C₁₈Ar₆ and o‐C₁₈Ar₄(C≡C‐SiiPr₃)₂. The carbo‐naphthalene bicycle is locally aromatic according to structural and magnetic criteria, as revealed by strong diatropic ring current effects on the deshielding of ¹H nuclei of the Ar groups and on the negative value of the DFT‐calculated NICS at the center of the C₁₈ rings (?12.8 ppm). The stability and aromaticity of this smallest fused molecular fragment of α‐graphyne allows prediction of the same properties for the carbon allotrope itself.     

Morphological Profiling Identifies the Motor Protein Eg5 as Cellular Target of Spirooxindoles

Oxindoles and iso-oxindoles are natural product-derived scaffolds that provide inspiration for the design and synthesis of novel biologically relevant compound classes. Notably, the spirocyclic connection of oxindoles with iso-oxindoles has not been explored by nature but promises to provide structurally related compounds endowed with novel bioactivity. Therefore, methods for their efficient synthesis and the conclusive discovery of their cellular targets are highly desirable. We describe a selective Rh^III-catalyzed scaffold-divergent synthesis of spirooxindole–isooxindoles and spirooxindole–oxindoles from differently protected diazooxindoles and N-pivaloyloxy aryl amides which includes a functional group-controlled Lossen rearrangement as key step. Unbiased morphological profiling of a corresponding compound collection in the Cell Painting assay efficiently identified the mitotic kinesin Eg5 as the cellular target of the spirooxindoles, defining a unique Eg5 inhibitor chemotype.     

Structural Elucidation of C6H4+. Using Chemical Reaction Monitoring: Charge Transfer Versus Bond Forming Reactions

Mass spectrometry is a powerful tool but when used on its own, without specific activation of ions, the ion mass is the single observable and the structural information is absent. One way of retrieving this information is by using ion–molecule reactions. We propose a general method to disentangle isomeric structures by combining mass spectrometry, tunable synchrotron light source, and quantum-chemistry calculations. We use reactive chemical monitoring technique, which consists in tracking reactivity changes as a function of photoionization energy i. e. the ionic structure. We illustrate the power of this technique with charge transfer reactions of C₆H₄^+. isomers with allene and propyne and discuss its universal applicability. Furthermore, we emphasize the special reactivity characteristics of distonic ions, where strong charge transfer reactivity but very limited reactivity involving bond formation and following cleavages were observed and attributed to the unconventional ortho-benzyne distonic cation.