A solvent-free two-step synthesis of polyfunctionalized pyrazoles under ball-milling mechanochemical conditions was developed. The protocol comprises (3 + 2)-cycloaddition of in situ generated nitrile imines and chalcones, followed by oxidation of the initially formed 5-acylpyrazolines with activated MnO₂. The second step proceeds via an exclusive deacylative pathway, to give a series of 1,4-diarylpyrazoles functionalized with a fluorinated (CF₃) or non-fluorinated (Ph, COOEt, Ac) substituent at C(3) of the heterocyclic ring. In contrast, MnO₂-mediated oxidation of a model isomeric 4-acylpyrazoline proceeded with low chemoselectivity, leading to fully substituted pyrazole as a major product formed via dehydrogenative aromatization. The presented approach extends the scope of the known methods carried out in organic solvents and enables the preparation of polyfunctionalized pyrazoles, which are of general interest in medicine and material sciences.

Background: Despite the extensive use of antibiotics and the growing challenge of antimicrobial resistance, there has been a lack of substantial initiatives aimed at diminishing the prevalence of infections in nursing homes and enhancing the detection of urinary tract infections (UTIs). Objective: This study aims to systematize and enhance efforts to prevent health care–associated infections, mainly UTIs and reduce antibiotic inappropriateness by implementing a multifaceted intervention targeting health care professionals in nursing homes. Methods: A before-and-after intervention study carried out in a minimum of 10 nursing homes in each of the 8 European participating countries (Denmark, Greece, Hungary, Lithuania, Poland, Slovakia, Slovenia, and Spain). A team of 4 professionals consisting of nurses, doctors, health care assistants, or health care helpers are actively involved in each nursing home. Over the initial 3-month period, professionals in each nursing home are registering information on UTIs as well as infection and prevention control measures by means of the Audit Project Odense method. The audit will be repeated after implementing a multifaceted intervention. The intervention will consist of feedback and discussion of the results from the first registration, training on the implementation of infection and prevention control techniques provided by experts, appropriateness of the diagnostic approach and antibiotic prescribing for UTIs, and provision of information materials on infection control and antimicrobial stewardship targeted to staff, residents, and relatives. We will compare the pre- and postintervention audit results using chi-square test for prescription appropriateness and Student t test for implemented hygiene elements. Results: A total of 109 nursing homes have participated in the pilot study and the first registration audit. The results of the first audit registration are expected to be published in autumn of 2024. The final results will be published by the end of 2025. Conclusions: This is a European Union–funded project aimed at contributing to the battle against antimicrobial resistance through improvement of the quality of management of common infections based on evidence-based interventions tailored to the nursing home setting and a diverse range of professionals. We expect the intervention to result in a significant increase in the number of hygiene activities implemented by health care providers and residents. Additionally, we anticipate a marked reduction in the number of inappropriately managed UTIs, as well as a substantial decrease in the overall incidence of infections following the intervention. International Registered Report Identifier (IRRID): DERR1-10.2196/60099

The synthesis of two series of monocyclic and bicyclic trifluoromethylated 4,5-dihydro-1,2,4-triazin-6(1H)-one derivatives based on (3+3)-annulation of methyl esters derived from natural α-amino acids with in situ generated trifluoroacetonitrile imines has been described. The devised protocol is characterized by a wide scope, easily accessible substrates, remarkable functional group tolerance, and high chemical yield. In reactions with chiral starting materials, no racemization at the stereogenic centers was observed and the respective enantiomerically pure products were obtained. Selected functional group interconversions carried out under catalytic hydrogenation and mild PTC oxidation conditions were also demonstrated.

The aim of this work was to evaluate the impact of the thiophene-derived aminophosphonates 1–6 on seedling emergence and growth of monocotyledonous oat (Avena sativa) and dicotyledonous radish (Raphanus sativus L.), and phytotoxicity against three persistent and resistant weeds (Galinsoga parviflora Cav., Rumex acetosa L., and Chenopodium album). Aminophosphonates 1–6 have never been described in the literature. The phytotoxicity of tested aminophosphonates toward their potential application as soil-applied herbicides was evaluated according to the OECD (Organization for Economic and Cooperation Development Publishing) 208 Guideline. In addition, their ecotoxicological impact on crustaceans Heterocypris incongruens and bacteria Aliivibrio fischeri was measured using the OSTRACODTOXKIT^TM and Microtox^® tests. Obtained results showed that none of the tested compounds were found sufficiently phytotoxic and none of them have any herbicidal potential. None of the tested compounds showed important toxicity against Aliivibrio fischeri but they should be considered as slightly harmful. Harmful impacts of compounds 1–6 on Heterocypris incongruens were found to be significant.

The emergence of antifungal resistance highlights the need for new chemotypes with improved biological activity. In this study, a series of new 3-CF₃-1,2,4-triazin-6(1H)-ones was synthesized via a (3+3)-cycloaddition of in situ-generated CF₃-nitrile imines with amino acid esters, followed by DDQ-mediated chemoselective oxidation of the corresponding 4,5-dihydro intermediates. The compounds were evaluated for antifungal, antibacterial, and cytotoxic activities. The synthesized derivatives displayed selective antifungal activity, whereas only weak antibacterial and cytotoxic effects were observed. The highest potency was observed for C(5)-unsubstituted derivatives, which exhibited the broadest antimicrobial spectrum and inhibited the growth of Candida albicans, Trichophyton rubrum, and Epidermophyton floccosum with MIC₅₀ values below 4 mg/L. In addition, the dermatophytes showed a biphasic dose-dependent response, characterized by growth stimulation at low concentrations and inhibition at higher concentrations, consistent with hormesis. These findings identify trifluoromethylated 1,2,4-triazin-6(1H)-ones, particularly C(5)-unsubstituted derivatives, as promising scaffolds for the development of new antifungal agents.