Molecules

This computational study investigates the thermal decomposition of 1,2,4-triazol-3(2H)-ones and their thione analogues using Density Functional Theory (DFT). The reaction proceeds via a concerted, six-membered cyclic transition state, primarily driven by the breaking of the N–N bond. A key finding is that the accuracy of the calculated activation energies (Ea) strongly depends on the choice of DFT functional. For sulfur-containing systems (thiones), the hybrid functional APFD (with 25% Hartree–Fock exchange) provides the most reliable results, effectively describing their higher polarizability. In contrast, for oxygen-containing systems (triazolones), the dispersion-corrected functional B97D-GD3BJ (with 0% Hartree–Fock exchange) delivers superior accuracy by better modeling electrostatic and dispersion interactions. The -CH₂CH₂CN group at the N-2 position acts not only as a protecting group but also stabilizes the transition state through non-covalent interactions. Electron-withdrawing substituents slightly increase the Eₐ, while electron-donating groups decrease it. Sulfur analogues consistently show significantly lower activation energies (by ~40 kJ/mol) than their oxygen counterparts, explaining their experimentally observed faster decomposition. This work establishes a dual-methodology computational framework for accurately predicting the kinetics of these reactions, providing valuable insights for the regioselective synthesis of biologically relevant triazole derivatives via controlled pyrolysis.

Kigelia africana (“sausage tree”) is an established medicinal plant in African traditional medicine, now recognized for its diverse bioactive constituents and emerging anticancer potential. This study systematically evaluates Kigelia africana fruit extract (KAE) in an in vitro model of HT-29 colorectal carcinoma cells, focusing on its cytotoxic effects, mechanistic impact on protein expression, and synergy with cisplatin chemotherapy. Across 42 oncology-related proteins, covering cell survival, apoptosis, adhesion, invasion, and signaling, KAE demonstrated extensive but typically moderate modulation, while cisplatin produced more pronounced responses in most markers. Protein changes linked to metastasis, therapy resistance, and survival were broadly suppressed, indicating significant antitumor activity. Notably, co-treatment with KAE and cisplatin in HT-29 cells resulted in marked synergistic cytotoxicity, permitting lower cisplatin doses while maintaining efficacy. LC-HRMS analyses revealed 14 metabolites in the extract, including phenolic acids naphthoquinones and iridoids, which may contribute to these effects.

Growing environmental concern over pharmaceutical contaminants in water, combined with the limited effectiveness of conventional treatment methods in removing persistent antibiotics, creates a need for advanced remediation technologies. This study investigates the degradation of the cephalosporin antibiotic cefuroxime axetil using an electrochemical advanced oxidation process with a boron-doped diamond (BDD) anode. Experiments were conducted under varying pH levels and in natural water matrices, specifically river and lake water, to evaluate the process efficiency under realistic conditions. Significant differences were observed between matrices, with the best result obtained in river water, enabling complete degradation of cefuroxime axetil within 30 min. To clarify the factors influencing process efficiency, additional experiments examined the effects of dissolved organic matter (DOM) and chlorides. Cefuroxime axetil proved highly susceptible to electrooxidation, generally following pseudo-first-order kinetics, and chloride significantly accelerated its degradation. Using high-resolution mass spectrometry, ten transformation products were identified, including six not previously reported in the literature, representing a key novelty of this work. Their potential aquatic toxicity was subsequently evaluated in silico using fish and algae models. Finally, energy consumption analysis was conducted to evaluate the impact of various factors on the process’s economic efficiency.