The Relation Between Position and Chemical Composition of Bis-Indole Substituents Determines Their Interactions with G-Quadruplex DNA

G-quadruplex (G4) DNA structures are linked to fundamental biological processes and human diseases, which has triggered the development of compounds that affect these DNA structures. However, more knowledge is needed about how small molecules interact with G4 DNA structures. This study describes the development of a new class of bis-indoles (3,3-diindolyl-methyl derivatives) and detailed studies of how they interact with G4 DNA using orthogonal assays, biophysical techniques, and computational studies. This revealed compounds that strongly bind and stabilize G4 DNA structures, and detailed binding interactions which for example, show that charge variance can play a key role in G4 DNA binding. Furthermore, the structure–activity relationships generated opened the possibilities to replace or introduce new substituents on the core structure, which is of key importance to optimize compound properties or introduce probes to further expand the possibilities of these compounds as tailored research tools to study G4 biology.     

Switchable ionic liquids enable efficient nanofibrillation of wood pulp

Use of switchable ionic liquid (SIL) pulp offers an efficient and greener technology to produce nanofibers via ultrafine grinding. In this study, we demonstrate that SIL pulp opens up a mechanically efficient route to the nanofibrillation of wood pulp, thus providing both a low cost and chemically benign route to the production of cellulose nanofibers. The degree of fibrillation during the process was evaluated by viscosity and optical microscopy of SIL treated, bleached SIL treated and a reference pulp. Furthermore, films were prepared from the fibrillated material for characterization and tensile testing. It was observed that substantially improved mechanical properties were attained as a result of the grinding process, thus signifying nanofibrillation. Both SIL treated and bleached SIL treated pulps were fibrillated into nanofibers with fiber diameters below 15 nm thus forming networks of hydrophilic nature with an intact crystalline structure. Notably, it was found that the SIL pulp could be fibrillated more efficiently than traditional pulp since nanofibers could be produced with more than 30% less energy when compared to the reference pulp. Additionally, bleaching reduced the energy demand by further 16%. The study demonstrated that this switchable ionic liquid treatment has considerable potential in the commercial production of nanofibers due to the increased efficiency in fibrillation.     

Investigation of chloromethane complexes of cryptophane‐A analogue with butoxy groups using 13C NMR in the solid state and solution along with single crystal X‐ray diffraction

Host‐guest complexes between cryptophane‐A analogue with butoxy groups (cryptophane‐But) and chloromethanes (chloroform, dichloromethane) were investigated in the solid state by means of magic‐angle spinning ¹³C NMR spectroscopy. The separated local fields method with ¹³C‐¹H dipolar recoupling was used to determine the residual dipolar coupling for the guest molecules encaged in the host cavity. In the case of chloroform guest, the residual dipolar interaction was estimated to be about 19 kHz, consistent with a strongly restricted mobility of the guest in the cavity, while no residual interaction was observed for encaged dichloromethane. In order to rationalize this unexpected result, we performed single crystal X‐ray diffraction studies, which confirmed that both guest molecules indeed were present inside the cryptophane cavity, with a certain level of disorder. To improve the insight in the dynamics, we performed a ¹³C NMR spin‐lattice relaxation study for the dichloromethane guest in solution. The system was characterized by chemical exchange, which was slow on the chemical shift time scale but fast with respect to the relaxation rates. Despite these disadvantageous conditions, we demonstrated that the data could be analyzed and that the results were consistent with an isotropic reorientation of dichloromethane within the cryptophane cavity. Copyright © 2015 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd.     

A stiff and compact impact-force transducer based on strain measurement

A stiff and compact transducer for both static and impact compressive forces has been developed. The principle of the transducer is based on measurement of tangential strain around the periphery of an axially loaded short and axixymmetric body. It is shown that for an appropriate choice of transducer geometry the output is nearly insensitive to the distribution of the force over the loaded surface. In an experimental investigation, a prototype of the transducer was subjected to both static and impact loads of different distributions. The results show only a few percent variation in transducer sensitivity for the load distributions used. The transducer consists essentially of a homogeneous body and is simple to male. The size and material can be chosen to fit special applications.     

Optical characterization of methanol compression-ignition combustion in a heavy-duty engine

In the search for renewable fuels, there are very few candidates as compelling as methanol. It can be derived from refuse material and industrial waste, while the infrastructure exists worldwide to support broad and fast adoption, potentially even as a “drop-in” fuel for existing vehicles with only minor modifications. The most efficient engines currently available are compression-ignition engines, however they often come with high emissions or compromises like the soot-NO_x trade-off. Methanol however, is a low sooting fuel that can potentially be used in such engines despite its high resistance to auto-ignition and reduce emissions while maintaining high engine efficiency. Due to the auto-ignition resistance, few studies of methanol compression-ignition exist and even fewer are conducted in an optically accessible engine. Here, two cases of premixed combustion and two of spray-driven combustion of methanol are studied in a Heavy-Duty optically accessible engine. Ignition and combustion propagation are characterized with a combination of time-resolved natural flame luminosity measurements and single-shot, acetone fuel-tracer, laser induced fluorescence. Additionally, Mie-scattering is used to identify the interaction between liquid spray and ignition sites in spray-driven methanol combustion. Results show that methanol combusts drastically different compared to conventional fuels, especially in spray-driven combustion. The evaporative cooling effect of methanol appears to play a major role in the auto-ignition characteristics of the delivered fuel. Ignition sites appear right at the end of injection when the evaporative cooling effect is withdrawn or at liquid length oscillations where, again the effect is momentarily retracted. To the authors’ knowledge, this has not been documented before.     

Numerical simulation of a mixed-mode reaction front in a PPC engine

The ignition process, mode of combustion and reaction front propagation in a partially premixed combustion (PPC) engine running with a primary reference fuel (87% iso-octane, 13% n-heptane by volume) is studied numerically in a large eddy simulation. Different combustion modes, ignition front propagation, premixed flame and non-premixed flame, are observed simultaneously. Displacement speed of CO iso-surface propagation describes the transition of premixed auto-ignition to non-premixed flame. High temporal resolution optical data of CH₂O and chemiluminescence are compared with simulated results. A high speed ignition front is seen to expand through fuel-rich mixture and stabilize around stoichiometry in a non-premixed flame while lean premixed combustion occurs in the spray wake at a much slower pace. A good qualitative agreement of the distribution of chemiluminescence and CH₂O formation and destruction shows that the simulation approach sufficiently captures the driving physics of mixed-mode combustion in PPC engines. The study shows that the transition from auto-ignition to flame occurs over a period of several crank angles and the reaction front propagation can be captured using the described model.     

Dirac Eigenvalues for Generic Metrics on Three-Manifolds

We show that for generic Riemannian metrics on a closed spin manifold of dimension three the Dirac operator has only simple eigenvalues.