Development of Polyhydroxybutyrate-Based Packaging Films and Methods to Their Ultrasonic Welding.

This study developed a technical task associated with the formation of welded joints based on biodegradable polymers and their subsequent physicochemical characterization. The primary objective was to establish the effect of the welding process and modification of natural poly(3-hydroxybutyrate) (PHB) with N,N-dibutylundecenoylamide (DBUA) as a plasticizing agent on the structure and properties of PHB-based biopolymer materials as well as the process and structure of welded joints formation using ultrasonic welding technique. The weldability of biodegradable layers based on PHB and PHB/DBUA mixture was ultrasonically welded and optimized using a standard Branson press-type installation.

Recyclization of 5-Amino- oxazoles as a Route to new Functionalized Heterocycles (Developments of V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine).

The recyclizations of 5-amino- and 5-hydrazine-1,3-oxazoles mainly with electron-withdrawing group in 4 position are considered. The chemical behavior of these heterocycles is due to the presence of two hidden amide fragments; therefore, the recyclization processes include a stage of nucleophile attack on 2 or 5 position of the oxazole cycle. When the nitrile group is present in 4 position, it is often involved in the recyclization forming α-aminoazoles.

Synthesis and Cycloaddition Reactions of 1-Azido-1,1,2,2-tetrafluoroethane.

A new fluorinated azidoethane─1-azido-1,1,2,2-tetrafluoroethane─was prepared in quantitative yield by the addition of an azide anion to tetrafluoroethylene in a protic medium. The title azide was shown to be thermally stable and insensitive to impact. Copper(I)-catalyzed [3 + 2] cycloaddition with alkynes afforded 4-substituted -tetrafluoroethyl-1,2,3-triazoles which underwent rhodium(II)-catalyzed transannulation with nitriles to novel -tetrafluoroethylimidazoles or the reaction with triflic acid to enamido triflates.

Concentrated ionic liquids for proteomics: Caveat emptor!

The use of concentrated ionic liquids (ILs) in the bioanalytical chemistry of proteins is sparse; typically, dilute aqueous IL solutions are used. Concentrated ILs have unique properties that may allow researchers to dissolve previously insoluble protein analytes, to increase the depth and robustness of sample preparation and the analysis of proteins. Previous research using concentrated ILs for this purpose is sparse and there is a need to systematically investigate the structure-activity relationship between the IL structure and its capacity to solubilise proteins.

1-Azaspiro[3.3]heptane as a Bioisostere of Piperidine.

1-Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO S-NCO, to give spirocyclic β-lactams.

Quinoline Hydrazone Derivatives as New Antibacterials against Multidrug Resistant Strains.

To develop novel antimicrobial agents a series of 2(4)-hydrazone derivatives of quinoline were designed, synthesized and tested. QSAR models of the antibacterial activity of quinoline derivatives were developed by the OCHEM web platform using different machine learning methods. A virtual set of quinoline derivatives was verified with a previously published classification model of anti-E.

Structure-Activity Relationship Prediction-Based Synthesis and Cytotoxicity Evaluation against the HEp-2 Laryngeal Carcinoma Cell of Isoflavone-Cytisine Mannich Bases.

QSAR analysis of previously synthesized and nature-inspired virtual isoflavone-cytisine hybrids against the HEp-2 laryngeal carcinoma cell lines was performed using the OCHEM web platform. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds such as 8-cytisinylmethyl derivatives of 5,7- and 6,7-dihydroxyisoflavones. The synthetic procedure for selective aminomethylation of 5,7-dihydroxyisoflavones with cytisine was developed.

Design and experimental validation of the oxazole and thiazole derivatives as potential antivirals against of human cytomegalovirus.

QSAR studies of a set of previously synthesized azole derivatives tested against human cytomegalovirus (HCMV) were performed using the OCHEM web platform. The predictive ability of the classification models has a balanced accuracy (BA) of 73-79%. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with a reasonable accuracy within the applicability domain (BA = 76-83%).

Mechanochemistry-Amended Barbier Reaction as an Expedient Alternative to Grignard Synthesis.

Organomagnesium halides (Grignard reagents) are essential carbanionic building blocks widely used in carbon-carbon and carbon-heteroatom bond-forming reactions with various electrophiles. In the Barbier variant of the Grignard synthesis, the generation of air- and moisture-sensitive Grignard reagents occurs concurrently with their reaction with an electrophile. Although operationally simpler, the classic Barbier approach suffers from low yields due to multiple side reactions, thereby limiting the scope of its application.

Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors.

Antiviral therapeutics to treat SARS-CoV-2 are needed to diminish the morbidity of the ongoing COVID-19 pandemic. A well-precedented drug target is the main viral protease (M ), which is targeted by an approved drug and by several investigational drugs. Emerging viral resistance has made new inhibitor chemotypes more pressing.

New Prospective Phosphodiesterase Inhibitors: Phosphorylated Oxazole Derivatives in Treatment of Hypertension.

One of the promising chemical groups for the development of new antihypertensive medicines, the action of which is associated with the inhibition of phosphodiesterase III (PDE3) activity, are phosphorylated oxazole derivatives (OVPs). This study aimed to prove experimentally the presence of the OVPs antihypertensive effect associated with decreasing of PDE activity and to justify its molecular mechanism. An experimental study of the effect of OVPs on phosphodiesterase activity was performed on Wistar rats.

Synthesis, Characterization and in vitro Anticancer Evaluation of 5-Sulfinyl(sulfonyl)-4-arylsulfonyl-Substituted 1,3-Oxazoles.

A novel series of 5-sulfinyl(sulfonyl)-4-arylsulfonyl-substituted 1,3-oxazoles has been synthesized, characterized and subjected to NCI in vitro assessment. Cancer cell lines of all subpanels were most sensitive to 2-{[4-[(4-fluorophenyl)sulfonyl]-2-(2-furyl)-1,3-oxazol-5-yl]sulfinyl}acetamide (3 l). Its antiproliferative and cytotoxic activity averaged over each subpanel was manifested in a very narrow range of concentrations (GI : 1.

Design, synthesis and evaluation of the anti-breast cancer activity of 1,3-oxazolo[4,5-]pyrimidine and 1,3-oxazolo[5,4-]pyrimidine derivatives.

A series of 1,3-oxazolo[4,5-]pyrimidine and 1,3-oxazolo[5,4-]pyrimidine derivatives were synthesized and functionalized in this study. The obtained compounds were tested against breast cancer cell lines of the NCI subpanel, followed by further analysis using the COMPARE algorithm from the Therapeutics Development Program, NCI. All synthesized derivatives displayed activity against most cell lines in the range of micromolar concentrations in terms of all parameters studied.

Thermal transport properties of porous silicon filled by ionic liquid nanocomposite system.

This paper investigates thermal transport in a nanocomposite system consisting of a porous silicon matrix filled with ionic liquid. Firstly, the thermal conductivity and heat capacity of two imidazolium and one ammonium ionic liquids were evaluated using the photoacoustic approach in piezoelectric configuration and differential scanning calorimetry, respectively. Then, the thermal transport properties of the composite system "ionic liquid confined inside porous silicon matrix" were investigated with the photoacoustic approach in gas-microphone configuration.

Nature of Linear Spectral Properties and Fast Relaxations in the Excited States and Two-Photon Absorption Efficiency of 3-Thiazolyl and 3-Phenyltiazolyl Coumarin Derivatives.

Coumarin-based fluorescent agents play an important role in the manifold fundamental scientific and technological areas and need to be carefully studied. In this research, linear photophysics, photochemistry, fast vibronic relaxations, and two-photon absorption (2PA) of the coumarin derivatives, methyl 4-[2-(7-methoxy-2-oxo-chromen-3-yl)thiazol-4-yl]butanoate () and methyl 4-[4-[2-(7-methoxy-2-oxo-chromen-3-yl)thiazol-4-yl]phenoxy]butanoate (), were comprehensively analyzed using stationary and time-resolved spectroscopic techniques, along with quantum-chemical calculations. The steady-state one-photon absorption, fluorescence emission, and excitation anisotropy spectra, as well as 3D fluorescence maps of 3-hetarylcoumarins and were obtained at room temperature in solvents of different polarities.

General and Scalable Approach to Trifluoromethyl-Substituted Cyclopropanes.

CF-cyclopropanes with aliphatic, aromatic, and even heteroaromatic substituents were prepared on a multigram scale by deoxyfluorination of cyclopropane carboxylic acids or their salts with sulfur tetrafluoride. For labile α-pyridine acetic acids, only the use of their potassium salts allowed to obtain the needed products. Derivatization of CF-cyclopropanes into building blocks ready for direct use in medicinal chemistry was performed.

Expanding the Chemical Space of 1,2-Difunctionalized Cyclobutanes.

An efficient approach to the synthesis of previously unavailable or hardly accessible 1,2-difunctionalized cyclobutanes (mostly with NH/NHBoc, OH, SH, or SOF groups attached to the carbocycle either directly or via a CH unit) relying on the divergent strategy is described. This class of compounds provides -enriched and conformationally restricted building blocks that are of special demand for medicinal chemistry. The target compounds were prepared not only as pure racemic (±)-- and (±)--diastereomers but in some cases also as single enantiomers.

In Silico Design and Experimental Validation of Novel Oxazole Derivatives Against Varicella zoster virus.

Varicella zoster virus (VZV) infection causes severe disease such as chickenpox, shingles, and postherpetic neuralgia, often leading to disability. Reactivation of latent VZV is associated with a decrease in specific cellular immunity in the elderly and in patients with immunodeficiency. However, due to the limited efficacy of existing therapy and the emergence of antiviral resistance, it has become necessary to develop new and effective antiviral drugs for the treatment of diseases caused by VZV, particularly in the setting of opportunistic infections.

C-C Coupling through Nitrogen Deletion: Application to Library Synthesis.

Invited for the cover of this issue are Oleksandr Grygorenko and his Ukrainian colleagues at Enamine Ltd., Taras Shevchenko National University of Kyiv, National Academy of Sciences of Ukraine, and ChemSpace, as well as Mark Levin at the University of Chicago. The image depicts application of a nitrogen-deleting anomeric amide to parallel C(sp )-C(sp ) coupling.

C-C Coupling through Nitrogen Deletion: Application to Library Synthesis.

A protocol for parallel C(sp )-C(sp ) coupling of (hetero)aromatic aldehydes and (hetero)arylmethyl amines based on a reductive amination - "nitrogen deletion" reaction sequence has been developed. After preliminary validation experiments, an illustrative compound library of 25 members was prepared with 76 % synthetic efficiency. The estimated chemical space accessible by the proposed approach covers almost 600 000 representatives that are scarcely represented in current compound databases.

Fluorinated Aliphatic Diazirines: Preparation, Characterization, and Model Photolabeling Studies.

The previously unknown difluoromethyl diazirines and the previously neglected trifluoromethyl-aliphatic diazirines were synthesized and characterized. Model photolabeling experiments and biological studies showed that these compounds could indeed be used as photoaffinity labels.

Inhibition of glutathione S-transferases by photoactive calix[4]arene α-ketophosphonic acids.

Calix[4]arenes bearing photoactive α-ketophosphonic acid groups at the upper rim of the macrocycle were synthesized and evaluated as inhibitors of glutathione S-transferases. Irradiation at 365 nm increased the inhibition effects of some macrocyclic compounds on GSTP1-1 by more than two orders of magnitude. Calix[4]arene bis-α-ketophosphonic acids substituted at the lower rim by n-propyl or n-butyl groups showed IC values in the low micromolar range.

Correlation between Nonlinear Optical Effects and Structural Features of Aurone-Based Methacrylic Polymeric Thin Films.

In this study, new photonics architectures and aurone-based methacrylic polymers were designed and synthesized for their optical and nonlinear optical properties. The studied polymeric thin films were deposited by spin coating method. SHG and THG effects were measured via Maker fringe technique in transmission mode and determined using theoretical models.

Evaluation of Anticancer Activity of 1,3-Oxazol-4-ylphosphonium Salts in Vitro.

A novel series of 1,3-oxazol-4-yltriphenylphosphonium salts has been synthesized and functionalized. Oxazole derivatives were subjected to NCI in vitro assessment. Seven most active derivatives have been selected for five-dose assay.

The Latest FDA-Approved Pharmaceuticals Containing Fragments of Tailor-Made Amino Acids and Fluorine.

Nowadays, the selective introduction of fluorine into bioactive compounds is a mature strategy in the design of drugs allowing to increase efficiency, biological half-life and bio-absorption. On the other hand, amino acids (AAs) represent one of the most ubiquitious classes of naturally occurring organic compounds, which are found in over 40% of newly marked small-molecule pharmaceutical drugs and medical formulations. The primary goal of this work is to underscore two major trends in the design of modern pharmaceuticals.