Identification of a novel spirocyclic Nek2 inhibitor using high throughput virtual screening.

NIMA Related Kinase 2 (Nek2) kinase is an attractive target for the development of therapeutic agents for several types of highly invasive cancers. Despite this, no small molecule inhibitor has advanced to the late clinical stages thus far. In this work, we have identified a novel spirocyclic inhibitor (V8) of Nek2 kinase, utilizing a high-throughput virtual screening (HTVS) approach.

Wastewater surveillance of SARS-CoV-2 genomic populations on a country-wide scale through targeted sequencing.

SARS-CoV-2 surveillance of viral populations in wastewater samples is recognized as a useful tool for monitoring epidemic waves and boosting health preparedness. Next generation sequencing of viral RNA isolated from wastewater is a convenient and cost-effective strategy to understand the molecular epidemiology of SARS-CoV-2 and provide insights on the population dynamics of viral variants at the community level. However, in low- and middle-income countries, isolated groups have performed wastewater monitoring and data has not been extensively shared in the scientific community.

Genetic diversity and evolutionary convergence of cryptic SARS- CoV-2 lineages detected via wastewater sequencing.

Wastewater-based epidemiology (WBE) is an effective way of tracking the appearance and spread of SARS-COV-2 lineages through communities. Beginning in early 2021, we implemented a targeted approach to amplify and sequence the receptor binding domain (RBD) of SARS-COV-2 to characterize viral lineages present in sewersheds. Over the course of 2021, we reproducibly detected multiple SARS-COV-2 RBD lineages that have never been observed in patient samples in 9 sewersheds located in 3 states in the USA.

Interplay between Magnetoresistance and Kondo Resonance in Radical Single-Molecule Junctions.

We report transport measurements on tunable single-molecule junctions of the organic perchlorotrityl radical molecule, contacted with gold electrodes at low temperature. The current-voltage characteristics of a subset of junctions shows zero-bias anomalies due to the Kondo effect and in addition elevated magnetoresistance (MR). Junctions without Kondo resonance reveal a much stronger MR.

Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater.

Tracking SARS-CoV-2 genetic diversity is strongly indicated because diversifying selection may lead to the emergence of novel variants resistant to naturally acquired or vaccine-induced immunity. To monitor New York City (NYC) for the presence of novel variants, we deep sequence most of the receptor binding domain coding sequence of the S protein of SARS-CoV-2 isolated from the New York City wastewater. Here we report detecting increasing frequencies of novel cryptic SARS-CoV-2 lineages not recognized in GISAID's EpiCoV database.

Functional Analysis of Actin-Binding Proteins in the Central Nervous System of Drosophila.

Using Drosophila actin-binding protein Dunc-115 as an example, this chapter describes a MARCM (mosaic analysis with a repressible cell marker)-based method for analyzing cytoskeletal components for their functions in the nervous system. Following a concise description about the principle, a step-by-step protocol is provided for generating the needed stocks and for histological analysis. Additional details and explanations have been given in the accompanying notes.

Enhanced coupling through π-stacking in imidazole-based molecular junctions.

We demonstrate that imidazole based π-π stacked dimers form strong and efficient conductance pathways in single-molecule junctions using the scanning-tunneling microscope-break junction (STM-BJ) technique and density functional theory-based calculations. We first characterize an imidazole-gold contact by measuring the conductance of imidazolyl-terminated alkanes (, = 3-6). We show that the conductance of these alkanes decays exponentially with increasing length, indicating that the mechanism for electron transport is through tunneling or super-exchange.

Structural analysis of ionic liquids with symmetric and asymmetric fluorinated anions.

Ionic liquids (ILs) with relatively low viscosities and broad windows of electrochemical stability are often constructed by pairing asymmetric cations with bisfluorosulfonylimide (FSI) or bistriflimide (NTf ) anions. In this work, we systematically studied the structures of ILs with these anions and related perfluorobis-sulfonylimide anions with asymmetry and/or longer chains: (fluorosulfonyl)(trifluoromethylsulfonyl)imide (BSI ), bis(pentafluoroethylsulfonyl)imide (BETI), and (trifluoromethylsulfonyl) (nonafluorobutylsulfonyl)imide (BSI ) using high energy X-ray scattering and molecular dynamics simulation methods. 1-alkyl-3-methylimidazolium cations with shorter (ethyl, Im ) and longer (octyl, Im ) hydrocarbon chains were selected to examine how the sizes of nonpolar hydrocarbon and fluorous chains affect IL structures and properties.

Spectroscopic Assessment of Intra- and Intermolecular Hydrogen Bonding in Ether-Functionalized Imidazolium Ionic Liquids.

Functionalization of the imidazolium (Im) cationic component of ionic liquids (ILs) with ether chains affords the possibility of tuning their properties through manipulation of the resulting interion and intramolecular interactions. Herein, we quantify these interactions at the molecular level through analysis of the vibrational spectra displayed by size-selected and cryogenically cooled ions. These spectra are obtained using the "tagging" approach carried out with photofragmentation tandem mass spectrometry.

Porous microspheres of polyaniline, poly(o-toluidine), and poly(m-toluidine) prepared from double emulsions stabilized by toluidine isomers as the single surfactant.

Hypothesis: Porous spheres of the conducting polymer polyaniline (PANI) and its derivatives are promising materials for use as functional encapsulants for payload delivery and catalyst supports. Stable water-in-oil-in water (W/O/W) double emulsions can be used to obtain this morphology, but typically require multiple surfactants and stabilizers. A single surfactant system that uses a small amphiphilic molecule is desirable, as it can simplify the method, improve its efficiency, and reduce its cost.

Interplay of Nitrogen-Atom Inversion and Conformational Inversion in Enantiomerization of 1H-1-Benzazepines.

A series of 2,4-disubstituted 1H-1-benzazepines, 2a-d, 4, and 6, were studied, varying both the substituents at C2 and C4 and at the nitrogen atom. The conformational inversion (ring-flip) and nitrogen-atom inversion (N-inversion) energetics were studied by variable-temperature NMR spectroscopy and computations. The steric bulk of the nitrogen-atom substituent was found to affect both the conformation of the azepine ring and the geometry around the nitrogen atom.

Cyclic phosphonium ionic liquids.

Ionic liquids (ILs) incorporating cyclic phosphonium cations are a novel category of materials. We report here on the synthesis and characterization of four new cyclic phosphonium bis(trifluoromethylsulfonyl)amide ILs with aliphatic and aromatic pendant groups. In addition to the syntheses of these novel materials, we report on a comparison of their properties with their ammonium congeners.

pKa of acetate in water: a computational study.

Several computational methods including the conductor-like polarizable continuum model, CPCM with both UAKS and UAHF cavities, Cramer and Truhlar's generalized Born solvation model, SM5.4(AM1), SM5.4(PM3), and SM5.