Developing 1,4-Diethyl-1,2,3,4-tetrahydroquinoxalin-substituted Fluorogens Based on GFP Chromophore for Endoplasmic Reticulum and Lysosome Staining.

In the present study, we demonstrated that the introduction of a 1,4-diethyl-1,2,3,4-tetrahydroquinoxalin moiety into the arylidene part of GFP chromophore-derived compounds results in the formation of environment-sensitive fluorogens. The rationally designed and synthesized compounds exhibit remarkable solvent- and pH-dependence in fluorescence intensity. The solvent-dependent variation in fluorescence quantum yield makes it possible to use some of the proposed compounds as polarity sensors suitable for selective endoplasmic reticulum fluorescent labeling in living cells.

Photochemistry of 2-(2-formylphenyloxy)acetic acid derivatives: synthesis of hydroxychromanones and benzofuranones.

Photochemical transformations of small molecules, such as -substituted benzaldehydes, in the absence of a photocatalyst are significantly underexplored and may reveal unexpected outcomes. In the present paper, we showed that 2-(2-formylphenoxy)acetic acid and its esters undergo photocyclization into chromanone and benzofuranone derivatives under 365 nm irradiation. The reaction occurs exclusively in dimethyl sulfoxide and can be used to efficiently obtain hydroxychromanones in good yields (27-91%).

Fluorescence lifetime multiplexing with fluorogen activating protein FAST variants.

In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties.

A Combination of Library Screening and Rational Mutagenesis Expands the Available Color Palette of the Smallest Fluorogen-Activating Protein Tag nanoFAST.

NanoFAST is the smallest fluorogen-activating protein, consisting of only 98 amino acids, used as a genetically encoded fluorescent tag. Previously, only a single fluorogen with an orange color was revealed for this protein. In the present paper, using rational mutagenesis and in vitro screening of fluorogens libraries, we expanded the color palette of this tag.

Atypical cofilin signaling drives dendritic cell migration through the extracellular matrix via nuclear deformation.

To mount an adaptive immune response, dendritic cells must migrate to lymph nodes to present antigens to T cells. Critical to 3D migration is the nucleus, which is the size-limiting barrier for migration through the extracellular matrix. Here, we show that inflammatory activation of dendritic cells leads to the nucleus becoming spherically deformed and enables dendritic cells to overcome the typical 2- to 3-μm diameter limit for 3D migration through gaps in the extracellular matrix.

Two Receptor Binding Strategy of SARS-CoV-2 Is Mediated by Both the N-Terminal and Receptor-Binding Spike Domain.

It is not well understood why severe acute respiratory syndrome (SARS)-CoV-2 spreads much faster than other β-coronaviruses such as SARS-CoV and Middle East respiratory syndrome (MERS)-CoV. In a previous publication, we predicted the binding of the N-terminal domain (NTD) of SARS-CoV-2 spike to sialic acids (SAs). Here, we experimentally validate this interaction and present simulations that reveal a second possible interaction between SAs and the spike protein via a binding site located in the receptor-binding domain (RBD).

KuINins as a New Class of HIV-1 Inhibitors That Block Post-Integration DNA Repair.

Integration of HIV-1 genomic cDNA results in the formation of single-strand breaks in cellular DNA, which must be repaired for efficient viral replication. Post-integration DNA repair mainly depends on the formation of the HIV-1 integrase complex with the Ku70 protein, which promotes DNA-PK assembly at sites of integration and its activation. Here, we have developed a first-class inhibitor of the integrase-Ku70 complex formation that inhibits HIV-1 replication in cell culture by acting at the stage of post-integration DNA repair.

Latency for All: Enabling Latency of Hoveyda-Grubbs Second-Generation Catalysts by Adding Phosphite Ligands.

The Hoveyda-Grubbs catalyst (, M720 Umicore) is among the most widely used catalysts in olefin metathesis reactions. Given the usefulness of and the great interest in developing latent olefin metathesis catalysts for numerous applications, we developed a method to introduce phosphite molecules as ancillary ligands into the precatalyst framework. This modification alters the geometry of the complex from an active -dichloro form to a latent -dichloro species.

Microfluidic Vaterite Synthesis: Approaching the Nanoscale Particles.

The challenge of continuous CaCO particle synthesis is addressed using microfluidic technology. A custom microfluidic chip was used to synthesize CaCO nanoparticles in vaterite form. Our focus revolved around exploring one-phase and two-phase synthesis methods tailored for the crystallization of these nanoparticles.

PbSe/PbS Core/Shell Nanoplatelets with Enhanced Stability and Photoelectric Properties.

Lead chalcogenide nanoplatelets (NPLs) have emerged as a promising material for devices operating in the near IR and IR spectrum region. Here, we first apply the cation exchange method to PbSe/PbS core/shell NPL synthesis. The shell growth enhances NPL colloidal and environmental stability, and passivates surface trap states, preserving the main core physical properties.

Illuminating protein space with a programmable generative model.

Three billion years of evolution has produced a tremendous diversity of protein molecules, but the full potential of proteins is likely to be much greater. Accessing this potential has been challenging for both computation and experiments because the space of possible protein molecules is much larger than the space of those likely to have functions. Here we introduce Chroma, a generative model for proteins and protein complexes that can directly sample novel protein structures and sequences, and that can be conditioned to steer the generative process towards desired properties and functions.

Synthesis of chroman-annulated cyclopropanols photoinduced intramolecular [2 + 1]-cycloaddition of 2-allyloxybenzaldehydes.

2-Allyloxybenzaldehydes undergo [2 + 1] cycloadditions under 365 nm LED irradiation to form the corresponding chroman-fused cyclopropanols. The reaction proceeds easily without any catalysts or additives in dimethyl sulfoxide.

Structural Characterization of Fluorescent Proteins Using Tunable Femtosecond Stimulated Raman Spectroscopy.

The versatile functions of fluorescent proteins (FPs) as fluorescence biomarkers depend on their intrinsic chromophores interacting with the protein environment. Besides X-ray crystallography, vibrational spectroscopy represents a highly valuable tool for characterizing the chromophore structure and revealing the roles of chromophore-environment interactions. In this work, we aim to benchmark the ground-state vibrational signatures of a series of FPs with emission colors spanning from green, yellow, orange, to red, as well as the solvated model chromophores for some of these FPs, using wavelength-tunable femtosecond stimulated Raman spectroscopy (FSRS) in conjunction with quantum calculations.

Merging Johnson-Claisen and Aromatic Claisen [3,3]-Sigmatropic Rearrangements: Ytterbium Triflate/2,6-Di--butylpyridine Catalytic System.

General synthetic approach toward phenols with a polyfunctional side-chain is described. It is based on two subsequent [3,3]-sigmatropic rearrangements, in particular, Johnson-Claisen and aromatic Claisen. Facilitation of the reaction sequence is achieved by the separation of steps and discovery of the efficient catalysts for aromatic Claisen rearrangement.

Meta-CF-Substituted Analogues of the GFP Chromophore with Remarkable Solvatochromism.

In this work, we have shown that the introduction of a trifluoromethyl group into the me-ta-position of arylidene imidazolones (GFP chromophore core) leads to a dramatic increase in their fluorescence in nonpolar and aprotic media. The presence of a pronounced solvent-dependent gradation of fluorescence intensity makes it possible to use these substances as fluorescent polarity sensors. In particular, we showed that one of the created compounds could be used for selective labeling of the endoplasmic reticulum of living cells.

Total Synthesis of Racemic Thieno[3,2-]thiochromene Tricarboxylate, a Luciferin from Marine Polychaeta .

We report the first total synthesis of racemic luciferin, a thieno[3,2-]thiochromene tricarboxylate comprising a 6-6-5-fused tricyclic skeleton with three sulfur atoms in different electronic states. The key transformation is based on tandem condensation of bifunctional thiol-phosphonate, obtained from dimethyl acetylene dicarboxylate, with benzothiophene-6,7-quinone. The presented convergent approach provides the synthesis of the target compound with a previously unreported fused heterocyclic core in 11 steps, thus allowing for unambiguous confirmation of the chemical structure of luciferin by 2D-NMR spectroscopy.

Giant worm-shaped ESCRT scaffolds surround actin-independent integrin clusters.

Endosomal Sorting Complex Required for Transport (ESCRT) proteins can be transiently recruited to the plasma membrane for membrane repair and formation of extracellular vesicles. Here, we discovered micrometer-sized worm-shaped ESCRT structures that stably persist for multiple hours at the plasma membrane of macrophages, dendritic cells, and fibroblasts. These structures surround clusters of integrins and known cargoes of extracellular vesicles.

NanoLuc Luciferase as a Fluorogen-Activating Protein for GFP Chromophore Based Fluorogens.

In this work, we showed that the well-known NanoLuc luciferase can act as a fluorogen activating protein for various arylidene-imidazolones structurally similar to the Kaede protein chromophore. We showed that such compounds can be used as fluorescent sensors for this protein and can also be used in pairs with it in fluorescent microscopy as a genetically encoded tag.

Entrapment of metastable nanocrystals by polyoxometalates.

Entirely inorganic polyoxometalate cluster-anion ligands are herein used to entrap and impart heat resistance to metastable metal-oxide based NCs. This is demonstrated by trapping 6-line ferrihydrite NCs that form as intermediates in the spontaneous conversion of β-FeOOH to hematite (α-FeO). The results suggest that polyoxometalate ligation may prove to be a general method for stabilizing metastable phases as the cores of entirely inorganic macro-anion like complexes.

[Insomnia in neurological patients with disabilities].

Sleep is the most important factor reflecting the level of psychophysical well-being of a person and influencing him/her to the same extent. The greater susceptibility to sleep disturbances in patients with disabilities is associated with numerous factors. In the existing literature, there are few studies of insomnia in people with neurological disabilities.

Emergence of Visible-Light Water Oxidation Upon Hexaniobate-Ligand Entrapment of Quantum-Confined Copper-Oxide Cores.

The formation of small 1 to 3 nm organic-ligand free metal-oxide nanocrystals (NCs) is essential to utilization of their attractive size-dependent properties in electronic devices and catalysis. We now report that hexaniobate cluster-anions, [Nb O ] , can arrest the growth of metal-oxide NCs and stabilize them as water-soluble complexes. This is exemplified by formation of hexaniobate-complexed 2.

Near-Infrared Emission of HgTe Nanoplatelets Tuned by Pb-Doping.

Doping the semiconductor nanocrystals is one of the most effective ways to obtain unique materials suitable for high-performance next-generation optoelectronic devices. In this study, we demonstrate a novel nanomaterial for the near-infrared spectral region. To do this, we developed a partial cation exchange reaction on the HgTe nanoplatelets, substituting Hg cations with Pb cations.