Strain-Induced Ferromagnetic to Antiferromagnetic Crossover in d⁹‑Ion (Cu²⁺ and Ag²⁺)‑Layered Perovskites

A characteristic aspect of undoped high-temperature layered copper oxide superconductors is their strong in-plane antiferromagnetic coupling. This state is markedly different from that found in other chemically similar copper- or silver-layered fluorides, which display a ferromagnetic ground state. The latter has been connected in the literature with the presence of an orthorhombic deformation of the lattice that shifts the intermediate ligand between two metal ions to be closer to one and further from the other. This distortion is completely absent in the oxides, which are essentially tetragonal. However, no quantitative information exists about how this distortion influences the antiferromagnetic state and its relative stability with respect to the ferromagnetic state. Here, we carry out first-principles simulations to show that the fluorides in the parent tetragonal phase are also antiferromagnetic and that the antiferromagnetic-to-ferromagnetic transition is only triggered for a large enough distortion, with a typical ligand shift of 0.1 Å. Moreover, we employ a valence-bond model and second-principles simulations to show that the factor in superexchange that favors the antiferromagnetic state reduces as the ligand moves away from the symmetric metal–metal position. Importantly, we find that this distortion is sensitive to the application of an epitaxial strain which, in turn, allows controlling the difference of energy between ferromagnetic and antiferromagnetic states and thus the Curie or Néel temperatures. In fact, for compressive strains larger than 5.1%, this piezomagnetic effect makes K2CuF4 and Cs2AgF4 antiferromagnetic, making these two lattices close chemical analogs of oxide superconductors

Studies of Volumetric and Transport Properties of Ionic Liquid–Water Mixtures and Its Viability To Be Used in Absorption Systems

Binary systems of two ionic liquids (ILs), 1-ethylpyridinium methanesulfonate [C₂Py]­[MeSO₃] and choline dihydrogen phosphate [Chol]­[H₂PO₄], and water have been experimentally studied. Density, viscosity, electrical conductivity and proton activity have been measured at several temperatures covering all the miscibility range. From density data, isobaric coefficient of thermal expansion was calculated to study the volumetric behavior of the mixtures. All volumetric data were fit using polynomial equations. The Vogel–Fulcher–Tamman (VFT) equation accurately describes the temperature dependence of viscosity for all systems. Systems based on [C₂Py]­[MeSO₃] are less dense and viscous than those involving [Chol]­[H₂PO₄], making [C₂Py]­[MeSO₃] more suitable for absorption systems where pumping cost has a significant importance. Electrical conductivity data were adjusted using the Casteel–Amis equation. Similar trends were found for both systems, although ionic conductivity is higher for [C₂Py]­[MeSO₃] + H₂O mixtures. The relation between viscosity and electrical conductivity was also explored. According to Walden plots, ILs present low ionicity; however, internal friction and ionic concentration does not seem to be enough to explain the behavior of ionic conductivity and IL concentration. Proton activity measurements show different tendencies with molar fraction of each IL, [C₂Py]­[MeSO₃] leads to lower p<i>a</i>_H+ values than [Chol]­[H₂PO₄] in the binary mixtures. Results of ionic conductivity and proton activity suggest a higher corrosive potential of [C₂Py]­[MeSO₃] + H₂O; however, a further analysis needs to be done to evaluate this risk in absorption systems. Finally, a composition analysis based on ionic chromatography (IC) was carried out to obtain insight about its effect on their physicochemical properties

Alternating Current Electrokinetic Properties of Gold-Coated Microspheres

We present dielectrophoresis (DEP) and electrorotation (ROT) measurements of gold-coated polystyrene microspheres as a function of frequency and for several electrolyte conductivities. Particle rotation was counterfield with a maximum rotation rate observed at a single characteristic frequency. Negative DEP was observed for frequencies lower than this characteristic frequency and positive DEP for signal frequencies higher than this. These experimental observations are in agreement with predictions for the force and torque on the induced dipole of a perfectly polarizable metal sphere. We present a theoretical model for this case, and good agreement is found for both ROT and DEP measurements if we take into account the viscous friction for a spherical particle near a wall. From the characteristic frequency for rotation, we obtain the capacitance of the electrical double layer at the electrolyte–particle interface. Remarkably, no effect of induced charge electroosmosis around the particles can be inferred from DEP measurements

Modifications of Microvascular EC Surface Modulate Phototoxicity of a Porphycene anti-ICAM‑1 Immunoconjugate; Therapeutic Implications

Inflammation and shear stress can upregulate expression of cellular adhesion molecules in endothelial cells (EC). The modified EC surface becomes a mediating interface between the circulating blood elements and the endothelium, and grants opportunity for immunotherapy. In photodynamic therapy (PDT), immunotargeting might overcome the lack of selectivity of currently used sensitizers. In this study, we hypothesized that differential ICAM-1 expression modulates the effects of a drug targeted to surface ICAM-1. A novel porphycene–anti-ICAM-1 conjugate was synthesized and applied to treat endothelial cells from macro and microvasculature. Results show that the conjugate induces phototoxicity in inflamed, but not in healthy, microvascular EC. Conversely, macrovascular EC exhibited phototoxicity regardless of their state. These findings have two major implications; the relevance of ICAM-1 as a modulator of drug effects in microvasculature, and the potential of the porphycene bioconjugate as a promising novel PDT agent

Discovery of Reversible DNA Methyltransferase and Lysine Methyltransferase G9a Inhibitors with Antitumoral in Vivo Efficacy

Using knowledge- and structure-based approaches, we designed and synthesized reversible chemical probes that simultaneously inhibit the activity of two epigenetic targets, histone 3 lysine 9 methyltransferase (G9a) and DNA methyltransferases (DNMT), at nanomolar ranges. Enzymatic competition assays confirmed our design strategy: substrate competitive inhibitors. Next, an initial exploration around our hit <b>11</b> was pursued to identify an adequate tool compound for in vivo testing. In vitro treatment of different hematological neoplasia cell lines led to the identification of molecules with clear antiproliferative efficacies (GI₅₀ values in the nanomolar range). On the basis of epigenetic functional cellular responses (levels of lysine 9 methylation and 5-methylcytosine), an acceptable therapeutic window (around 1 log unit) and a suitable pharmacokinetic profile, <b>12</b> was selected for in vivo proof-of-concept (Nat. Commun. 2017, 8, 15424). Herein, <b>12</b> achieved a significant in vivo efficacy: 70% overall tumor growth inhibition of a human acute myeloid leukemia (AML) xenograft in a mouse model

Discovery of Reversible DNA Methyltransferase and Lysine Methyltransferase G9a Inhibitors with Antitumoral in Vivo Efficacy

Using knowledge- and structure-based approaches, we designed and synthesized reversible chemical probes that simultaneously inhibit the activity of two epigenetic targets, histone 3 lysine 9 methyltransferase (G9a) and DNA methyltransferases (DNMT), at nanomolar ranges. Enzymatic competition assays confirmed our design strategy: substrate competitive inhibitors. Next, an initial exploration around our hit <b>11</b> was pursued to identify an adequate tool compound for in vivo testing. In vitro treatment of different hematological neoplasia cell lines led to the identification of molecules with clear antiproliferative efficacies (GI₅₀ values in the nanomolar range). On the basis of epigenetic functional cellular responses (levels of lysine 9 methylation and 5-methylcytosine), an acceptable therapeutic window (around 1 log unit) and a suitable pharmacokinetic profile, <b>12</b> was selected for in vivo proof-of-concept (Nat. Commun. 2017, 8, 15424). Herein, <b>12</b> achieved a significant in vivo efficacy: 70% overall tumor growth inhibition of a human acute myeloid leukemia (AML) xenograft in a mouse model