P NMR Study of P-Chirogenic Phosphaphenanthrenes with Molecular Flexibility tuned by Amino Acid Substituents.

Model phosphonamidates derived from 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) with molecular flexibility tuned by amino acid substituents were prepared as pairs of diastereoisomers (DSIs) differing in configuration on phosphorus atom. X-ray diffraction (XRD) determined absolute configuration on phosphorus and revealed conformational flexibility of six-membered oxa-phospha-cycle. Quantum-chemical calculations combined with machine learning provided 2-4 representative conformers from each DSI present in solution.

Chiroptical spectroscopy complemented by quantum chemical calculations accurately predicts the absolute configuration of P-chirogenic compounds.

Model P-chirogenic phosphonates derived from isopinocampheol, offering an excellent experimental system for studying chirality on the phosphorus chiral center, were studied using a set of chiroptical methods including ECD, VCD and ROA. Thanks to their rigidity, limiting the number of possible conformers, we successfully correlated the experimental UV-vis/ECD, IR/VCD and Raman/ROA results with DFT calculations. This allowed us to confidently assign the absolute configuration of our models, and our assignment is consistent with X-ray diffraction (XRD) data.

Solid-State Photoswitching of Hydrazones Based on Excited-State Intramolecular Proton Transfer.

The development of new photochromic systems is motivated by the possibility of controlling the properties and functions of materials with high spatial and temporal resolution in a reversible manner. While there are several classes of photoswitches operating in solution, the design of systems efficiently operating in the solid state remains highly challenging, mainly due to limitations related to confinement effects. Triaryl-hydrazones represent a relatively new subclass of bistable hydrazone photoswitches exhibiting efficient / photochromism in solution.

Prodrugging fungicidal amphotericin B significantly decreases its toxic effects.

Amphotericin B (AmB) is one of the most effective antifungal drugs, with a strong, dose-dependent activity against most Candida and Aspergillus species responsible for life-threatening infections. However, AmB is severely toxic, which hinders its broad use. In this proof-of-concept study, we demonstrate that prodrugging AmB considerably decreases AmB toxicity without affecting its fungicidal activity.

Discovery of highly potent SARS-CoV-2 nsp14 methyltransferase inhibitors based on adenosine 5'-carboxamides.

The emergence of SARS-CoV-2, the causative agent of COVID-19, has highlighted the need for advanced antiviral strategies. Targeting the coronaviral methyltransferase nsp14, which is essential for RNA capping, offers a promising approach for the development of small-molecule inhibitors. We designed and synthesized a series of adenosine 5'-carboxamide derivatives as potential nsp14 inhibitors and identified coumarin analogs to be particularly effective.