Preferred orientation in an angled intercalation site of a chloro-substituted lambda- [Ru(TAP)2(dppz)]2+ complex bound to d(TCGGCGCCGA)2

The crystal structure of the ruthenium DNA ‘light-switch’ complex -[Ru(TAP)2(11-Cl-dppz)]2+ (TAP = tetraazaphenanthrene, dppz = dipyrido[3,2-a':2',3'-c]phenazine)) bound to the oligonucleotide duplex d(TCGGCGCCGA)2 is reported. The synthesis of the racemic ruthenium complex is described for the first time, and the racemate was used in this study. The crystal structure, at atomic resolution (1.0 Å), shows one ligand as a wedge in the minor groove, resulting in the 51 kinking of the double helix, as with the parent lambda-[Ru(TAP)2(dppz)]2+. Each complex binds to one duplex by intercalation of the dppz ligand and also by semi-intercalation of one of the orthogonal TAP ligands into a second symmetrically equivalent duplex. The 11-Cl substituent binds with the major component (66%) oriented with the 11-chloro substituent on the purine side of the terminal step of the duplex

Reactive Interactions between the Ionic Liquid BMP‐TFSI and a Na Surface

In order to obtain atomistic insights into the initial stages of the formation of the solid electrolyte interphase (SEI) in Na ion or Na metal batteries, we employ surface chemistry experiments and DFT calculations to study the interactions and reactions between a Na surface and the ionic liquid (IL) 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP-TFSI), a candidate to be used as electrolyte in batteries. Oxygen-free Na thin films, which were grown on Ru(0001) and characterized by X-ray and ultraviolet photoelectron spectroscopy (XPS, UPS), can be understood as model of a Na-rich electrode. After deposition of submonolayer to multilayer BMP-TFSI films on the Na thin films at room temperature, XPS measurements revealed partial decomposition and the formation of a ‘contact layer’ at the Na surface, consisting of mainly TFSI-based decomposition products

Model Studies on the Formation of the Solid Electrolyte Interphase: Reaction of Li with Ultrathin Adsorbed Ionic-Liquid Films and Co3_{3}O4_{4}(111) Thin Films

In this work we aim towards the molecular understanding of the solid electrolyte interphase (SEI) formation at the electrode electrolyte interface (EEI). Herein, we investigated the interaction between the battery‐relevant ionic liquid (IL) 1‐butyl‐1‐methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP‐TFSI), Li and a Co$_{3}$O$_{4}$(111) thin film model anode grown on Ir(100) as a model study of the SEI formation in Li‐ion batteries (LIBs). We employed mostly X‐ray photoelectron spectroscopy (XPS) in combination with dispersion‐corrected density functional theory calculations (DFT‐D3). If the surface is pre‐covered by BMP‐TFSI species (model electrolyte), post‐deposition of Li (Li$^{+}$ ion shuttle) reveals thermodynamically favorable TFSI decomposition products such as LiCN, Li$_{2}$NSO$_{2}$CF$_{3}$, LiF, Li$_{2}$S, Li$_{2}$O$_{2}$, Li$_{2}$O, but also kinetic products like Li$_{2}$NCH$_{3}$C$_{4}$H$_{9}$ or LiNCH$_{3}$C$_{4}$H$_{9}$ of BMP. Simultaneously, Li adsorption and/or lithiation of Co$_{3}$O$_{4}$(111) to LinCo$_{3}$O$_{4}$ takes place due to insertion via step edges or defects; a partial transformation to CoO cannot be excluded. Formation of Co$^{0}$ could not be observed in the experiment indicating that surface reaction products and inserted/adsorbed Li at the step edges may inhibit or slow down further Li diffusion into the bulk. This study provides detailed insights of the SEI formation at the EEI, which might be crucial for the improvement of future batteries

The structural effect of Methyl substitution on the binding of Polypyridyl Ru-dppz Complexes to DNA

ABSTRACT: Polypyridyl ruthenium complexes have been intensively studied and possess photophysical properties which are both interesting and useful. They can act as probes for DNA, with a substantial enhancement in emission when bound, and can induce DNA damage upon photoirradiation and therefore, the synthesis and characterization of DNA binding of new complexes is an area of intense research activity. Whilst knowledge of how the binding of derivatives compares to the parent compound is highly desirable, this information can be difficult to obtain. Here we report the synthesis of three new methylated complexes, [Ru(TAP)2(dppz-10-Me).2Cl, [Ru(TAP)2(dppz-10,12-Me2)].2Cl and [Ru(TAP)2(dppz-11-Me)].2Cl, and examine the consequences for DNA binding through the use of atomic resolution X-ray crystallography. We find that the methyl groups are located in discrete positions with a complete directional preference. This may help to explain the quenching behavior which is found in solution for analogous [Ru(phen)2(dppz)]2+ derivatives

Delta chirality ruthenium ‘light-switch’ complexes can bind in the minor groove of DNA with five different binding modes

[Ru(phen)2(dppz)]2+ has been studied since the 1990s due to its “light-switch” properties. It can be used as a luminescent DNA probe, with emission switched on through DNA binding. The luminescence observed is dependent on the solvent accessibility of the pyrazine nitrogen atoms, and therefore is sensitive to changes in both binding site of the cation and chromophore orientation. The compound is also chiral, and there are distinct differences between the enantiomers in terms of the emission behaviour when bound to a variety of DNA sequences. Whilst a number of binary DNA-complex X-ray crystal structures is available, most include the Λ enantiomer, and there is very little structural information about binding of the Δ enantiomer. Here we present the first X-ray crystal structure of a Δ enantiomer bound to well-matched DNA, in the absence of the other, Λ, enantiomer. We show how the binding site observed here can be related to a more general pattern of motifs in the crystallographic literature and propose that the Δ enantiomer can bind with five different binding modes, offering a new hypothesis for the interpretation of solution data

Targeted PI3K/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia.

Current therapeutic approaches for chronic lymphocytic leukemia (CLL) focus on the suppression of oncogenic kinase signaling. Here, we test the hypothesis that targeted hyperactivation of the phosphatidylinositol-3-phosphate/AKT (PI3K/AKT)-signaling pathway may be leveraged to trigger CLL cell death. Though counterintuitive, our data show that genetic hyperactivation of PI3K/AKT-signaling or blocking the activity of the inhibitory phosphatase SH2-containing-inositol-5'-phosphatase-1 (SHIP1) induces acute cell death in CLL cells. Our mechanistic studies reveal that increased AKT activity upon inhibition of SHIP1 leads to increased mitochondrial respiration and causes excessive accumulation of reactive oxygen species (ROS), resulting in cell death in CLL with immunogenic features. Our results demonstrate that CLL cells critically depend on mechanisms to fine-tune PI3K/AKT activity, allowing sustained proliferation and survival but avoid ROS-induced cell death and suggest transient SHIP1-inhibition as an unexpectedly promising concept for CLL therapy

Identifying core MRI sequences for reliable automatic brain metastasis segmentation

BACKGROUND Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions