Ru(II)‐based antineoplastic: A “wingtip” N‐heterocyclic carbene facilitates access to a new class of organometallics that are cytotoxic to common cancer cell lines

The syntheses, structures, and chemotherapeutic activities of Ag(I)‐, Au(I)‐, and Ru(II)‐complexes ligated to a novel N‐heterocyclic carbene ligand, 2‐(4‐nitrophenyl)imidazo[1,5‐a]pyridin‐2‐ylidene ( 1 ), are described. The corresponding complexes, [Ag( 1 )₂][PF₆], [Au( 1 )₂][PF₆] ( 3 ), and [Ru( 1 )(p‐cymene)Cl][PF₆] ( 4 ), were prepared using convenient transmetallation chemistry and characterized using a range of spectroscopic and analytical techniques. X‐ray crystallography revealed that complexes 2 and 3 adopted linear structures whereas 4 exhibited a prototypical “piano‐stool”‐like geometry; the structural assignments were further supported by DFT calculations. A series of in vitro studies revealed that while the aforementioned Ag(I), Au(I) and Ru(II) complexes exhibited significant cytotoxicities against the human colon adenocarcinoma (HCT 116), lung cancer (A549), and breast cancer (MCF7) cell lines, the Ru derivative was most prominent.     

Substituent effects on the Lewis acidity of 4,6-di-tert-butylchatechol boronate esters

In studying the factors which contribute to the Lewis acidity of organoboron compounds we investigated approaches to the design of robust, novel Lewis acids purposed for metal-free catalysis. Based on a sterically encumbered catechol motif, a series of boronate esters are shown to demonstrate modest Lewis acidities for the conventional Gutmann-Beckett test as an inquisitive investigation.     

Metal-Free Synthesis of Functional 1-Substituted-1,2,3-Triazoles from Ethenesulfonyl Fluoride and Organic Azides

The boom in growth of 1,4-disubstituted triazole products, in particular, since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the Cu^I-catalyzed azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1-substituted-1,2,3-triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click-inspired protocol for the synthesis of 1-substituted-1,2,3-triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal-free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1-substituted-1,2,3-triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1-substituted triazolium sulfonyl fluoride salts.     

Understanding the Origin of Highly Selective CO2 Electroreduction to CO on Ni,N-doped Carbon Catalysts

Ni,N-doped carbon catalysts have shown promising catalytic performance for CO₂ electroreduction (CO₂R) to CO; this activity has often been attributed to the presence of nitrogen-coordinated, single Ni atom active sites. However, experimentally confirming Ni−N bonding and correlating CO₂ reduction (CO₂R) activity to these species has remained a fundamental challenge. We synthesized polyacrylonitrile-derived Ni,N-doped carbon electrocatalysts (Ni-PACN) with a range of pyrolysis temperatures and Ni loadings and correlated their electrochemical activity with extensive physiochemical characterization to rigorously address the origin of activity in these materials. We found that the CO₂R to CO partial current density increased with increased Ni content before plateauing at 2 wt % which suggests a dispersed Ni active site. These dispersed active sites were investigated by hard and soft X-ray spectroscopy, which revealed that pyrrolic nitrogen ligands selectively bind Ni atoms in a distorted square-planar geometry that strongly resembles the active sites of molecular metal–porphyrin catalysts.     

Zwitterionic Block Copolymers for the Synthesis and Stabilization of Perovskite Nanocrystals

Traditional hot injection methods for the preparation of cesium lead halide perovskite nanocrystals (CsPbX₃ PNCs, where X=Cl, Br, or I) rely on small molecule surfactants to produce PNCs with cube, plate, or rod-like morphologies. Here, we describe a new method whereby zwitterionic block copolymers are employed as macromolecular ligands in PNC synthesis, affording PNCs with excellent colloidal stability, high photoluminescence quantum yield, and in some cases distinctly non-cubic shapes. The block copolymers used in this study – composed of a poly(n-butyl methacrylate) hydrophobic block and zwitterionic methacrylate hydrophilic blocks – dissolve in useful solvents for PNC growth despite containing large mole percentages of zwitterionic groups. PNCs prepared with block copolymer ligands were found to disperse and retain their fluorescence in a range of polar organic solvents and were amenable to direct integration into optically transparent nanocomposite thin films with high PNC content.     

Modeling receptor flexibility in the structure-based design of KRASG12C inhibitors

Journal of Computer-Aided Molecular Design - KRAS has long been referred to as an ‘undruggable’ target due to its high affinity for its cognate ligands (GDP and GTP) and its lack of...     

A velocity program using the Kanade–Lucas–Tomasi feature-tracking algorithm with demonstration for pressure and electroosmosis conditions

Investigating microfluidic flow profiles is of interest in the microfluidics field for the determination of various characteristics of a lab-on-a-chip system. Microparticle tracking velocimetry uses computational methods upon recording video footage of microfluidic flow to ultimately visualize motion within a microfluidic system across all frames of a video. Current methods are computationally expensive or require extensive instrumentation. A computational method suited to microparticle tracking applications is the robust Kanade–Lucas–Tomasi (KLT) feature-tracking algorithm. This work explores a microparticle tracking velocimetry program using the KLT feature-tracking algorithm. The developed program is demonstrated using pressure-driven and EOF and compared with the respective mathematical fluid flow models. An electrostatics analysis of EOF conditions is performed in the development of the mathematical using a Poisson's Equation solver. This analysis is used to quantify the zeta potential of the electroosmotic system. Overall, the KLT feature-tracking algorithm presented in this work proved to be highly reliable and computationally efficient for investigations of pressure-driven and EOF in a microfluidic system.     

Increased Stress Resistance and Lifespan in Chaenorhabditis elegans Wildtype and Knockout Mutants—Implications for Depression Treatment by Medicinal Herbs

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withania somnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.