Staphylococcus aureus causes various infectious diseases, from skin impetigo to life-threatening bacteremia and sepsis, thus appearing an important target for antimicrobial therapeutics. In turn, the rapid development of antibiotic resistance and biofilm formation makes it extremely robust against treatment. Here, we unravel the molecular mechanism of the antimicrobial activity of the recently unveiled F105 consisting of three pharmacophores: chlorinated 2(5H)-furanone, sulfone, and l-menthol moieties. F105 demonstrates highly selective activity against Gram-positive bacteria and biofilm-embedded S. aureus and exhibits low risk of resistance development. We show explicitly that the fluorescent analogue of F105 rapidly penetrates into Gram-positive bacteria independently of their cell integrity and viability and accumulates there. By contrast, Gram-negative bacteria remain impermeable and, therefore, insusceptible to F105. Apparently, in bacterial cells, F105 induces reactive oxygen species (ROS) formation and nonspecifically interacts with a number of proteins, including ROS-utilizing ones. Using native and 2D PAGE, we confirm that F105 changes the charge of some proteins by either oxidation or direct interaction with them. Therefore, it seems justified to conclude that being simultaneously a ROS inducer and damaging proteins responsible for ROS utilization, F105 impairs the cellular anti-ROS defense representing a prospective ROS-inducing antibacterial agent.

According to X-ray data, homochiral pinanyl sulfone crystallizes as an asymmetric dimer formed by pairwise H-bonds involving stereochemically different oxygen atoms of sulfonyl groups of molecules A and B. Thus, a pro-R atom is invoked for the construction of a relevant H-bond in molecule A, but in the case of molecule B only a pro-S atom is involved. Newly formed chiral sulfur atoms take opposite chirality in molecules A and B, while the configuration of the pinane skeleton remains unchanged. Such a stereochemical transformation is called “crystallization-induced diastereomerization”. The stability of the asymmetric dimer found in the crystal was evaluated within the framework of DFT (B3LYP, 6-31G (d,p)) and studied via IR spectroscopy in solution.

A new procedure has been developed for the synthesis of diterpenoid (16 S)-dihydrosteviol [(16 S)-13-hydroxy- ent-kauran-19-oic acid] by acid hydrolysis (0.7% hydrochloric acid) of SWETA food sweetene

In this study, we report a counterintuitive carbonyl–carbonyl interaction explored for crystalline (2RS,3RS)-1-aryl-2-bromo-3-hydroxy-3-(2-nitrophenyl)-propan-1-ones. The mentioned β-hydroxyketones display an ability to form dimensionally different crystal formative motifs ranging from 1D to 3D. Despite the structural differences, primarily in intermolecular interactions, all the studied compounds are arranged by the same bicyclic hydrogen-bonded twelve-membered supramolecular synthon R² ₂(12), with the essential feature being an attractive interaction between two oxygen atoms of the head-to-head-arranged carbonyl groups CO⋯OC. This unusual interaction along with all the other interactions that are present in the crystal structures, for instance, H-bonds and hydrogen–hydrogen and carbonyl–halogen contacts, were investigated by means of quantum-topological analysis of the calculated electron density.

The purposeful change of crystallization conditions for rac-3-chloro-5-hydroxy-1-(4-methylbenzyl)-4-[(4-methylphenyl)sulfanyl]-1,5-dihydro-2H-pyrrol-2-one 1 leads to two different crystal modifications, namely, a racemic compound in the triclinic space group P with Z′ = 1 (α-1) and a partial solid solution based on a racemic compound in the monoclinic space group P2₁ with Z′ = 4 (β-1). The first modification, α-1, is characterized by a higher density of the molecular packing in the crystal, while the second one, β-1, by a stronger system of hydrogen bonds and the presence of positional and substitutional disorder simultaneously. The analysis of the crystal structure of modifications α and β allowed us to define some structural aspects of the partial solid solution formation. Namely, the tendency to build a stronger hydrogen bond system enables the solution of enantiomers of 1 to be formed in the crystalline phase, whereas the propensity of the molecules to adopt a more favorable transoid conformation limits the solubility of the minor enantiomer.

Over the past decades, 2(5H)-furanone derivatives have been extensively studied because of their promising ability to prevent the biofilm formation by various pathogenic bacteria. Here, we report the synthesis of a series of optically active sulfur-containing 2(5H)-furanone derivatives and characterize their biological activity. Novel thioethers were obtained by an interaction of stereochemically pure 5-(l)-menthyloxy- or 5-(l)-bornyloxy-2(5H)-furanones with aromatic thiols under basic conditions. Subsequent thioethers oxidation by an excess of hydrogen peroxide in acetic acid resulted in the formation of the corresponding chiral 2(5H)-furanone sulfones. The structure of synthesized compounds was confirmed by IR and NMR spectroscopy, HRMS, and single crystal X-ray diffraction. The leading compound, 26, possessing the sulfonyl group and l-borneol moiety, exhibited the prominent activity against Staphylococcus aureus and Bacillus subtilis with MICs of 8 μg/mL. Furthermore, at concentrations of 0.4–0.5 μg/mL, the sulfone 26 increased two-fold the efficacy of aminoglycosides gentamicin and amikacin against S. aureus. The treatment of the model-infected skin wound in the rat with a combination of gentamicin and sulfone 26 speeded up the bacterial decontamination and improved the healing of the wound. The presented results provide valuable new insights into the chemistry of 2(5H)-furanone derivatives and associated biological activities.