PlatinER: A Highly Potent Anticancer Platinum(II) Complex that Induces Endoplasmic Reticulum Stress Driven Immunogenic Cell Death

Immunogenic cell death (ICD) is a rare immunostimulatory form of cell death that can improve the clinical outcomes of chemo-immunotherapeutic combination regimens through the establishment of a long-term cancer immunity. None of the clinically used DNA-binding Pt^II complexes is considered a Type II ICD inducer. We generated a series of Pt^II-carbene complexes by applying minor structural alterations to the scaffold of a Type II ICD inducer Pt-NHC and compared their efficiency in triggering ICD-related cellular responses and phagocytosis. We successfully identified PlatinER, a novel highly potent Pt^II candidate with superior ICD properties. Crucially, the magnitude of ICD-associated phagocytosis induced upon exposure of cancer cells to Pt complexes was dependent on the levels of ER-localized reactive oxygen species (ROS) generation, which underpins their mechanisms of action and provides a feasible approach for the design of more effective Type II ICD inducers.     

Measure preserving homomorphisms and independent sets in tensor graph powers

In this note, we study the behavior of independent sets of maximum probability measure in tensor graph powers. To do this, we introduce an upper bound using measure preserving homomorphisms. This work extends some previous results concerning independence ratios of tensor graph powers.     

Polymerization Compounding on the Surface of Zirconia Nanoparticles

Zirconia nanoparticles were encapsulated by polyethylene via a polymerization compounding method using a Ziegler-Natta catalyst. The chemical reaction was carried out in an organic solvent under moderate pressure of ethylene monomer. Transmission electron microscopy (TEM) indicated the presence of a thin layer of polymer, about 6 nm, uniformly applied around the particles. However, the thickness of coating layer can be controlled as a function of time and operating conditions of the process. The morphology study using scanning electron microscopy (SEM) as well as TEM revealed that although the nanoparticles seem to be coated individually, some agglomerates, encapsulated by a polymer film, could be observed. The grafting of the catalyst to the original surface of particles was further confirmed by X-ray photoelectron spectroscopy (XPS).     

Zirconium-catalyzed asymmetric Kabachnik–Fields reactions of aromatic and aliphatic aldehydes

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates. A catalyst was sought that would give high asymmetric inductions for aromatic and, and more particularly, for aliphatic aldehydes since there has not previously been an effective catalyst developed for this class of aldehydes. The optimal catalyst is prepared from three equivalents of the 7,7′-di-t-butylVANOL ligand, one equivalent of N-methylimidazole and one equivalent of zirconium tetraisopropoxide. This catalyst was most efficient in the presence of 10 mol% benzoic acid. Optimal conditions for aryl aldehydes required the use of 3,5-diisopropyl-2-hydroxyaniline and gave the aryl α-aminophosphonates in up to 96% yield and 98% ee over 11 different aryl aldehydes. The best aniline for aliphatic aldehydes was found to be 3-t-butyl-2-hydroxyaniline and gave the corresponding phosphonates in up to 83% yield and 97% ee over 18 examples. The asymmetric inductions for aliphatic aldehydes were comparable with those for aromatic aldehydes with a mean induction of 90% ee for the former and 91% ee for the latter. The best method for the liberation of the free amine from the aniline substituted α-aminophosphonates involved oxidation with N-iodosuccinimide.

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik–Fields reaction to give α-aminophosphonates.     

Adsorption of Hexavalent Chromium Using Activated Carbon Produced from Sargassum ssp.: Comparison between Lab Experiments and Molecular Dynamics Simulations

Adsorption is one of the most successful physicochemical approaches for removing heavy metal contaminants from polluted water. The use of residual biomass for the production of adsorbents has attracted a lot of attention due to its cheap price and environmentally friendly approach. The transformation of Sargassum—an invasive brown macroalga—into activated carbon (AC) via phosphoric acid thermochemical activation was explored in an effort to increase the value of Sargassum seaweed biomass. Several techniques (nitrogen adsorption, pH_PZC, Boehm titration, FTIR and XPS) were used to characterize the physicochemical properties of the activated carbons. The SAC600 3/1 was predominantly microporous and mesoporous (39.6% and 60.4%, respectively) and revealed a high specific surface area (1695 m²·g⁻¹). To serve as a comparison element, a commercial reference activated carbon with a large specific surface area (1900 m²·g⁻¹) was also investigated. The influence of several parameters on the adsorption capacity of AC was studied: solution pH, solution temperature, contact time and Cr(VI) concentration. The best adsorption capacities were found at very acid (pH 2) solution pH and at lower temperatures. The adsorption kinetics of SAC600 3/1 fitted well a pseudo-second-order type 1 model and the adsorption isotherm was better described by a Jovanovic-Freundlich isotherm model. Molecular dynamics (MD) simulations confirmed the experimental results and determined that hydroxyl and carboxylate groups are the most influential functional groups in the adsorption process of chromium anions. MD simulations also showed that the addition of MgCl₂ to the activated carbon surface before adsorption experiments, slightly increases the adsorption of HCrO₄⁻ and CrO₄²⁻ anions. Finally, this theoretical study was experimentally validated obtaining an increase of 5.6% in chromium uptake.     

Dual‐Targeting Dual‐Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity

A novel and highly efficient dual‐targeting platform was designed to ensure targeted in vivo delivery of dual‐action Pt^IV prodrugs. The dual targeting was established by liposomal encapsulation of Pt^IV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first stage of targeting to attain a high accumulation of the drug‐loaded liposomes in the tumor. After the release of the Pt^IV prodrug inside cancer cells, a second stage of targeting directed a portion of the Pt^IV prodrugs to the mitochondria. Upon intracellular reduction, these Pt^IV prodrugs released two bioactive molecules, acting both on the mitochondrial and on the nuclear DNA. Our Pt^IV system showed excellent activity in vitro and in vivo, characterized by a cytotoxicity in a low micromolar range and complete tumor remission, respectively. Notably, marked in vivo activity was accompanied by reduced kidney toxicity, highlighting the unique therapeutic potential of our novel dual‐targeting dual‐action platform.     

Athermal performance in high-Q polymer-clad silicon microdisk resonators

We present a method for eliminating the temperature dependence of the resonance wavelength in high-Q silicon-based microdisk resonators by using a polymer cladding with a negative thermo-optic coefficient. Design requirements for athermal performance are derived based on theory and simulation, and their validity is experimentally verified.     

Permanent confinement in the compact QED3 with fermionic matter

We argue that the compact three dimensional electrodynamics with massless relativistic fermions is always in the confined phase, in spite of the bare interaction between the magnetic monopoles being rendered logarithmic by fermions. The effect is caused by screening by other dipoles, which transforms the logarithmic back into the Coulomb interaction at large distances. Possible implications for the chiral symmetry breaking for fermions are discussed, and the global phase diagram of the theory is proposed.