Search Results (256)

The quinazoline/quinazolinone ring is known as a unique scaffold, and its derivatives possess a broad biological activity profile, including antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, and analgesic activity, primarily focusing on anticancer activity. In this study, the synthesis of 2-[[4-oxo-3-(substituted phenyl)-3,4-dihydro-(substituted quinazolin-2-yl)]thio]-N′-(aryl/heteroaryl methylene)acetohydrazide (4a–4x) derivatives and their potential anticancer activities were investigated on the lung cancer A549 cell line, the breast cancer MCF-7 cell line, and healthy fibroblast L929 cell line. Compounds 4c, 4i, 4m, and 4u were identified as the most cytotoxic and selective molecules on the A549 cell line (IC₅₀: 44.75–78.13 µM), while 4i, 4l, 4m, and 4u were identified as the most cytotoxic and selective molecules on the MCF-7 cell line (IC₅₀: 14.43–29.39 µM). The mechanisms of action of their anticancer activities were examined and studied. It was determined that these compounds induced strong apoptosis and significantly activated caspase-3 activation in both cell types and that they interrupted the cell cycle in the pre-G (sub G0) phase. Compounds 4m and 4u exhibited EGFR inhibition (IC₅₀: 4.80 µM, IC₅₀: 5.40 µM, respectively) at a level similar to the standard drug gefitinib (IC₅₀: 1.86 ± 0.43 µM). Based on the results of the biological activity assays, molecular docking, and molecular dynamics simulation studies, the 4-quinazolinone–acetyl hydrazone scaffold can be considered a promising structural framework with potential anticancer activity. More specifically, the findings of this study indicate that the acetyl moiety may function as an important pharmacophoric group, while the trisubstituted quinazolinone core may represent a favorable structural feature for caspase-3 activation. However, the same structural framework appears to be less favorable for EGFR inhibition, possibly due to steric constraints within the EGFR binding pockets. Full article

An efficient approach to unsymmetrical 1,10-phenanthroline-2,9-dicarboxamides based on the bifunctional reactivity of 4-oxo-7-haloderivatives is reported. These substrates exhibit orthogonal reactivity, enabling selective nucleophilic aromatic substitution at the C⁷ position alongside electrophilic functionalization of the 4-oxo group under mild conditions. Reactions with a broad range of C-, N-, and O-nucleophiles afford 4-oxo-7-functionalized products in high yields, while subsequent transformations of azido- and hydroxy-substituted derivatives further demonstrate the synthetic versatility of this platform. The observed chemoselectivity is reflected in the highly selective O-functionalization of the 4-oxogroup, with alkylation proceeding under mild conditions. The developed strategy provides a general route to structurally diverse unsymmetrical derivatives and highlights the potential of 4-oxo-7-halo-systems as bifunctional building blocks. Full article

Pharmaceutical pollutants have emerged as a critical class of aquatic micropollutants due to their continuous release, persistence, and potential impacts on ecosystems and human health. Conventional wastewater treatment systems are often insufficient to achieve complete removal, necessitating the development of advanced oxidation processes (AOPs), such as Fenton and Fenton-like systems. These processes rely on the generation of reactive oxygen species (ROS), including hydroxyl radicals (•OH), superoxide species, singlet oxygen, and, in some heterogeneous systems, high-valent iron-oxo intermediates, which collectively enable the degradation of structurally diverse and recalcitrant pharmaceutical compounds. Recent advances have highlighted the pivotal role of nanomaterials as catalysts in enhancing Fenton-based processes. Nanostructured catalysts, including iron-based nanoparticles (NPs), metal oxides, carbon-based materials, and bimetallic composites, offer high surface area, tunable redox properties, and improved electron transfer, leading to enhanced catalytic efficiency and mineralization rates. Importantly, the integration of green synthesis approaches using plant extracts, microorganisms, and biopolymers provides environmentally benign routes for nanomaterial fabrication while introducing functional surface groups that improve catalytic performance. Mechanistically, pharmaceutical degradation in Fenton systems involves complex pathways driven by multiple ROS species, including •OH, superoxide radicals, and singlet oxygen, leading to the formation of intermediate products and eventual mineralization. However, challenges such as NP aggregation, metal leaching, incomplete mineralization, and potential toxicity of intermediates remain critical considerations. This review critically evaluates the occurrence of pharmaceutical pollutants, the fundamentals of Fenton and Fenton-like processes, and the design and application of green-synthesized nanomaterials as efficient catalysts. It further explores degradation mechanisms, operational parameters, and sustainability considerations, highlighting future directions for scalable, environmentally responsible water treatment technologies. Full article

Modern pyrotechnic materials are evolving from conventional fuel–oxidizer mixtures toward function-oriented energetic systems designed for controlled ignition, light emission, gas generation, pressure output and thermal response. This review analyzes recent progress in pyrotechnic materials through oxidizer chemistry, thermal and kinetic behavior, study-normalized performance comparison and bibliometric mapping. Representative oxidizer families, including nitrates, perchlorates, chlorates, metal oxides, hybrid oxide–salt systems, high-nitrogen salts, halogen-oxo oxidizers and coordination nitrate complexes, are compared in terms of chemical role and functional output. Thermal data show that decomposition temperature, heat release and activation energy must be interpreted together, since lower activation energy can indicate either enhanced reactivity or degradation during aging. A study-normalized relative performance factor (RPF) was used to compare performance changes within individual publications. The strongest relative improvements were associated with oxide selection, particle-size reduction, hybrid oxidizer design and coupling of nanothermites with gas-generating components. Bibliometric mapping confirmed a shift toward metal-based energetic materials, nanothermites, gas generators, combustion diagnostics, color systems and pyrotechnic devices. These trends show that oxidizer chemistry, particle architecture and additive function are increasingly selected for defined pressure, gas, light or thermal outputs. Full article

Mononuclear nonheme iron(IV)–oxo species supported by mixed nitrogen–sulfur (N/S) ligands remain scarce, despite the prevalence of sulfur donors in biological iron sites and their expected impact on ferryl reactivity and catalyst design. In this work, a seven-coordinate iron(II) complex, [(N₃S₂)Fe^II(ClO₄)₂], bearing a rigid 15-membered N₃S₂ macrocycle, is shown to rapidly generate a mononuclear nonheme Fe^IV=O intermediate upon reaction with m-chloroperbenzoic (m-CPBA) acid in acetonitrile. The Fe^IV=O species forms within ≤2 s and is thermally persistent (t₁/₂ = 4.3 h at 25 °C), albeit in partial yield (~39% Fe^IV=O by Mössbauer spectroscopy), placing it in an intermediate regime between highly reactive but short-lived ferryl species and more inert, long-lived analogues. The intermediate is characterized by Mössbauer spectroscopy (δ = 0.35 mm s⁻¹, ΔE_Q = 0.90 mm s⁻¹, Γ_FWHM = 0.30 mm s⁻¹, relative area = 39.4%), EPR silence, a UV–vis absorption band at 428 nm, and cryogenic high-resolution ESI–MS (m/z 223.510, (N₃S₂)Fe^IV=O²⁺). Stopped-flow kinetic studies reveal saturation behavior that is well described by a pre-equilibrium oxidant-association model and subsequent O–O bond activation, with apparent activation parameters of ΔH^‡ = 17.7 kJ mol⁻¹ and ΔS^‡ = −155 J mol⁻¹ K⁻¹, indicating a highly ordered transition state within the seven-coordinate N₃S₂ framework under the conditions employed. Functionally, the Fe^IV=O species mediates clean oxygen-atom transfer to triphenylphosphine (k₂ = 8.1 × 10⁻² M⁻¹ s⁻¹) with an effective turnover number of ~12 after correction for the Fe^IV=O yield, establishing that this mixed N/S platform is catalytically competent under mild conditions, though less reactive than state-of-the-art all-nitrogen systems. Collectively, these findings identify the seven-coordinate N₃S₂ macrocycle as a mixed-donor platform that moderately extends ferryl lifetime while retaining measurable oxo-transfer reactivity, providing mechanistic guidance for the development of nonheme iron oxidation catalysts that incorporate sulfur donors. Full article

Herein, a novel insensitive diazonium inner salt of 2-nitro-5-oxo[1,2,4]triazolo[1,5-c]pyrimidin-8-diazonium-7-olate (NTPD) was synthesized through a concise three-step route. The structure and performance of this material were comprehensively studied. Single-crystal X-ray diffraction analysis revealed that NTPD possesses a distinctive fused-ring framework featuring an inner salt (zwitterionic) structure, wherein the diazonium and phenolate functionalities are intramolecularly integrated within a compact, highly conjugated heterocyclic system. Furthermore, in comparison with previously reported diazonium compounds, NTPD exhibits a superior combination of enhanced thermal stability and significantly reduced mechanical sensitivity. Specifically, its onset decomposition temperature reaches 206 °C, representing a substantial improvement over conventional diazo derivatives, while its impact sensitivity of 7 J positions it among the least sensitive diazonium-based energetic materials reported to date. The exceptional performance of NTPD is strongly attributed to its nearly planar molecular geometry and the extensive hydrogen-bonding network present within its crystal lattice, which collectively reinforce structural rigidity, enhance packing stability, and effectively dissipate external mechanical stimuli. Full article

Asthma is a heterogeneous chronic airway disease in which oxidative stress (OS) plays a central mechanistic role beyond classical immune-mediated inflammation. Reactive oxygen and nitrogen species (ROS/RNS), generated by recruited inflammatory cells and activated airway structural cells, drive epithelial injury, mucus hypersecretion, airway remodeling, and modulate key transcription factors including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. This review synthesizes current evidence on the multilevel redox-based determinants of asthma severity, spanning from genetic polymorphisms to circulating biomarkers. We examine serum antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxiredoxins (PRDXs), and the thioredoxin (Trx) system as dynamic indicators of systemic redox status and disease severity, alongside oxidative enzymes including NADPH oxidases and dual oxidases (NOX/DUOX), xanthine oxidase (XO), and myeloperoxidase (MPO) that serve as upstream sources of airway oxidant burden. Functional genetic polymorphisms in antioxidant genes (SOD2, CAT, glutathione S-transferase mu 1/glutathione S-transferase theta 1 (GSTM1/GSTT1), heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/KEAP1)) and oxidative enzyme genes including nitric oxide synthase 1/2/3 (NOS1/2/3), MPO, cytochrome b-245 alpha chain (CYBA), and xanthine dehydrogenase (XDH) are reviewed as modulators of individual redox capacity and asthma susceptibility, with particular attention to gene–environment interactions. We further discuss oxidative damage biomarkers, including malondialdehyde (MDA), 8-isoprostanes, 4-hydroxynonenal, 8-oxo-7, 8-dihydro-2′-deoxyguanosine, protein carbonyls, 3-nitrotyrosine, and advanced oxidation protein products as indicators of lipid, DNA, and protein oxidation that correlate with disease activity and control. The roles of micronutrient cofactors in modulating antioxidant enzyme function and their potential as contextual biomarkers are also addressed. Additionally, emerging evidence on microRNAs (miRNAs) linked to OS biology in asthma is presented. Finally, we critically evaluate the challenges limiting clinical translation, including biomarker non-specificity, analytical variability, gene–environment complexity, and the absence of standardized reference ranges. This integrated framework supports the development of multilevel redox prognostic panels combining genetic, enzymatic, and oxidative damage readouts for improved asthma phenotyping, severity stratification, and personalized therapeutic approaches. Full article

In this study, a new series of (E)-4-((2-(2-(4-amino-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetyl)hydrazono)methyl)phenyl 4-halogenobenzenesulfonates (3a–3d), where 3a = F, 3b = Cl, 3c = Br, and 3d = I, were successfully synthesized via a straightforward synthetic route. The structures of the obtained compounds were fully characterized and confirmed by spectroscopic techniques, including FT-IR, ¹H NMR, and ¹³C NMR, as well as LC-MS/MS analysis. 1,2,4-triazole-based hydrazone derivatives (3a–3d) were investigated using IR and NMR spectroscopy and DFT calculations. Intermolecular interactions, HOMO-LUMO, dipole moment, polarization, first-order hyperpolarizability, and molecular electrostatic potential studies on the molecules were examined. The HOMO and LUMO energy gap study supports the charge transfer probability in the molecules. These were conducted to investigate the reactivity and stability of heterocyclic molecules in bioactivity analysis. Electron density mapping within the molecular electrostatic potential plot and electrostatic potential representation within the iso-surface plot evaluated the concept of charge distribution in the molecule as nucleophilic reactions and electrophilic regions. The predicted nonlinear optical (NLO) properties of the molecules are much greater than those of urea. The results obtained from these investigations collectively provide evidence that the molecules possess nonlinear optical applications. Novel triazole–hydrazone-functionalized aryl sulfonate derivatives (3a–3d) were evaluated for their anticancer potential against a panel of brain and non-brain cancer cell lines. Compound 3b exhibited the most favorable overall biological profile, displaying potent activity against SH-SY5Y neuroblastoma (GI = 7.59 μM) and U87MG glioblastoma cells (GI = 13.85 μM), together with the lowest toxicity toward normal FL fibroblasts (GI = 62.02 μM). Compounds 3c and 3d demonstrated remarkable potency against IDHmut-U87 glioma cells (GI = 3.87 and 3.27 μM, respectively), although their selectivity toward cancer cells was limited. DNA degradation studies revealed substantial fragmentation, particularly in C6 and SH-SY5Y cells, while migration assays indicated reduced cellular motility. Molecular docking studies identified compound 3b as the strongest PI3Kα binder, supporting a possible. In addition, the antimicrobial activities of compounds 3a–3d were evaluated against selected Gram-positive and Gram-negative bacteria as well as Candida species using the broth microdilution method. The compounds exhibited measurable antimicrobial effects with MIC values ranging from 156 to 625 µg/mL, showing moderate growth inhibition against the tested microorganisms. Although the observed activity was lower than that of the reference antimicrobial agents, the results indicate that these triazole–hydrazone derivatives possess a detectable level of antimicrobial activity and provide a basis for further structural optimization. Collectively, the results suggest that compound 3b represents the most promising lead structure due to its balanced combination of potency, selectivity, and predicted target engagement. Molecular docking was performed to evaluate the binding potential of newly synthesized triazole derivatives (3a–3d) against PI3Kα. The docking protocol was validated by re-docking alpelisib, yielding an RMSD of 0.64 Å. Among the tested compounds, 3b showed the most favorable binding energy (−9.94 kcal/mol) and estimated Ki value (52.13 nM), consistent with its superior in vitro activity. Its interactions with key PI3Kα residues, including Val851, Ser854, Met922, and Asp933, support a stable binding mode within the ATP-binding pocket. In silico ADME and toxicity analyses suggested acceptable drug-likeness characteristics, absence of major hepatotoxic, mutagenic, and carcinogenic liabilities, and moderate predicted acute toxicity profiles. These findings suggest that 3b is the most promising derivative for further validation. Full article

The structure, relative stability, spin-state preference, and preliminary oxygen-release behavior of small nickel–oxygen clusters, (NiO₂)_n (n = 1–4), were investigated using density functional theory at the M06-2X/def2-TZVP level of theory. Several initial topologies and spin multiplicities were explored to distinguish between dissociated Ni···O₂ solutions, bonded dioxo-like arrangements, and side-on metal–dioxygen motifs. For the monomer, the lowest-energy solution of the fully explored set corresponds to a non-bonded Ni···O₂ arrangement; however, when the analysis is restricted to chemically bonded NiO₂ minima, the linear high-spin O–Ni–O structure is the most stable configuration. The side-on η²-O₂ motif was found as a higher-energy bonded minimum, retaining an elongated O–O bond and therefore representing an activated dioxygen-like species. ELF and LOL analyses were used as complementary localization descriptors to distinguish between the electronically separated oxo-like domains of the linear structure and the more coupled localization pattern of the side-on dioxygen adduct. Aggregation from n = 2 to n = 4 suggests a transition from compact bridged motifs to more open Ni–O frameworks. However, the size-dependent trend is discussed only within the explicitly explored conformational space. Preliminary analysis of O₂ release from the tetramer indicates that oxygen evolution is not a simple dissociation event but involves substantial structural reorganization. Overall, the results support the view that small (NiO₂)_n clusters may behave as metastable oxygen-rich intermediates, while also highlighting the strong sensitivity of their energetic ordering to spin state, topology, and structural relaxation. Full article

Background/Objectives: Cardiovascular diseases (CVDs) and cancer remain major global health challenges and are among the leading causes of mortality worldwide, including in Kuwait. Medicinal plants are important sources of bioactive compounds with therapeutic potential. This study aimed to identify the phytochemical constituents of Curcuma longa L. root extract and evaluate their potential cardioprotective and anticancer activities using integrated computational approaches. Methods: Phytochemical profiling of Curcuma longa root extract was performed using gas chromatography–mass spectrometry (GC–MS). The identified compounds were evaluated through molecular docking against selected cardiovascular- and cancer-related targets, including HMG-CoA reductase, phosphoinositide 3-kinase (PI3K), cyclin-dependent kinase 6 (CDK6), and HER2 kinase receptors. Protein–ligand interactions were analyzed to determine binding stability. Biological activity prediction and pharmacokinetic properties were assessed using PASS prediction and SwissADME tools, while density functional theory (DFT) calculations were conducted to investigate electronic and quantum chemical characteristics associated with ligand reactivity. Results: GC–MS analysis identified seventeen phytochemical constituents with retention times ranging from 7.57 to 32.70 min. The major compounds detected were 2-oxo-cyclooctaneacetic acid (30.88%), curlone (20.99%), and tumerone (13.85%). Molecular docking revealed favorable binding affinities for α-curcumene, caryophyllene, bergamotene, cyclohexene derivatives, tumerone, curlone, and (6R,7R)-bisabolone against the selected targets, with interaction profiles comparable to reference drugs. PASS and SwissADME analyses indicated promising biological activities, acceptable drug-likeness, and favorable pharmacokinetic properties. DFT analysis demonstrated that curlone and tumerone possessed stable electronic configurations and favorable reactivity profiles. Conclusions: The findings suggest that bioactive compounds from Curcuma longa may serve as promising lead candidates for the development of cardioprotective and anticancer agents. However, further experimental validation through in vitro and in vivo studies is required to confirm these computational predictions. Full article

Tributyrin, a short-chain fatty acid derivative, has been shown to hold potential in improving intestinal health in livestock and poultry. However, its multidimensional effects on the health of meat pigeons, particularly during the young pigeon stage, remain unclear. This study aimed to investigate the comprehensive effects of dietary tributyrin supplementation on the growth, health status, intestinal function, and metabolic profile of young pigeons. A total of 100 healthy 29-day-old White King pigeons, with half male and half female, were randomly divided into a control group (fed a basal diet) and a treatment group (fed a basal diet supplemented with 1500 mg/kg tributyrin) for a 35-day trial. The results showed that compared with the control group, young pigeons in the treatment group had significantly reduced serum triglyceride levels, alanine aminotransferase activity, and concentrations of pro-inflammatory cytokines (TNF-α, IL-6), along with significantly increased levels of high-density lipoprotein, immunoglobulin G, total antioxidant capacity, and glutathione peroxidase activity. Concurrently, the villus height-to-crypt depth ratio in the jejunum and ileum was significantly elevated, indicating improved intestinal morphological structure. Untargeted metabolomics analysis further revealed significant changes in the relative abundances of 13 key differential metabolites (e.g., L-carnitine, pyridoxamine, indoleacetic acid) in the small intestinal contents of the treatment group. These metabolites were mainly enriched in metabolic pathways such as 2-oxoCarboxylic acid metabolism, tryptophan metabolism, and vitamin B6 metabolism. In conclusion, dietary supplementation with 1500 mg/kg tributyrin can exert multifaceted beneficial effects on young pigeon health by improving lipid metabolism, enhancing immune and antioxidant functions, optimizing intestinal structure, and regulating the local metabolic network. This study provides a theoretical basis for the application of tributyrin as a functional additive in the green and healthy production of meat pigeons. Full article

Oxidative stress generates oxidized phospholipids (OxPLs) that alter membrane structure and inflammatory lipid signaling, yet the underlying biophysical mechanisms remain poorly understood. Here, we examine how two structurally distinct truncated oxidized phosphatidylcholines (OxPCs), 1-palmitoyl-2-(5′-oxo-valeroyl)-sn-glycero-3-phosphocholine (POVPC) and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC), remodel membrane lateral organization and regulate secretory phospholipase A₂ (sPLA₂) activity. Large unilamellar vesicles composed of sphingomyelin, cholesterol, and either monounsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or polyunsaturated 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC) were used to reconstitute the liquid-ordered/liquid-disordered (L_o/L_d) phase coexistence characteristic of eukaryotic plasma membranes. Fluorescence spectroscopy revealed that OxPLs modulate lipid packing and nanodomain organization in a structure- and composition-dependent manner. POVPC promoted pronounced membrane ordering and L_o domain stabilization compared with PGPC, particularly in monounsaturated membranes with low cholesterol content. In contrast, PDPC-containing membranes, especially at elevated cholesterol, exhibited enhanced structural resilience to OxPL-induced perturbations. These biophysical changes were associated with distinct functional outcomes. Notably, the relationship between membrane structural parameters and sPLA₂ activity was not linear, indicating a decoupling between bulk membrane properties and enzymatic response. sPLA₂ activity was linked to membrane lateral organization: the size of L_o domains modulate hydrolysis by influencing the physicochemical properties of L_o/L_d interfaces, which may represent preferential sites for enzyme activation. Consistent with this, POVPC reduced sPLA₂ activity through stabilization of ordered domains at both low and high cholesterol, while PGPC enhanced hydrolysis at high cholesterol. Importantly, PDPC-containing membranes attenuated sPLA₂ activity and exhibited a protective effect against OxPC-induced enzymatic activation. Together, these findings identify membrane lateral organization as a key regulator of sPLA₂ function and provide mechanistic insight into how oxidative stress can differentially modulate inflammatory lipid signaling depending on membrane composition. This work highlights membrane organization as an active determinant of enzyme activity and a potential target in pathologies associated with oxidative stress, including atherosclerosis, neuroinflammation, and metabolic disease. Full article

Arsenic contamination, mainly in the arsenate (As(V)) form, continues to pose a serious threat to groundwater quality worldwide due to its long-term stability and toxicity at very low levels. Herein, we demonstrate, for the first time, a three-dimensional graphene oxide-based nanocomposite composed of Cu nanoparticle-doped, amino-functionalized UiO-66 (Cu/UiO-66-NH₂) anchored on a graphene oxide framework (Cu/UiO-66-NH₂@GO) as a novel and efficient nanosorbent for the rapid removal of As(V) in groundwater-like solutions. The nanocomposite was characterized by SEM and HRTEM to confirm the hybrid structure and by XRD, N₂ adsorption–desorption isotherms, and XPS to investigate crystallinity, porosity, and surface chemistry. The derived material exhibited a highly dispersed morphology and performed rapid arsenate solid-phase extraction to attain equilibration within 10 min and was effective for a wide pH range of 2–11. The best fit for the kinetic profiles was provided by the pseudo-second-order model. Interestingly, the maximum adsorption capacity of 747.9 mg g⁻¹ at pH 6.8 was achieved, demonstrating the benefits of the complementary pairing of dispersive GO sheets and Zr-MOF adsorption domains with Cu-derived active sites. Mechanistically, the enhanced uptake is ascribed to a combination of effects, including electrostatic pre-concentration, ligand exchange, and inner-sphere complexation at metal-oxo nodes; spectroscopic analysis (XPS and FTIR) suggests that the majority of arsenate is immobilized via a strong Zr-O-As bond at coordinatively unsaturated Zr centers, which is in line with t-ZrO₂-like surface domains formed within the nanocomposite. The embedded GO support inhibits further framework interpenetration and enhances active site availability and mass transport, leading to fast and high-capacity arsenate capture in groundwater samples with related conditions. Taken together, this work presents a powerful design concept that integrates unique GO-supported, Cu-modified UiO-66-NH₂ with Zr-O binding motifs to afford high-rate remediation nanocomposites, providing an excellent platform for next-generation arsenate remediation materials. Full article

Oxidation of RNA has gained interest from the community due, in part, to a link in the progression/development of disease as well as other biological processes such as apoptosis, ageing, hibernation, and signalling, amongst others. Different types of RNA with varying functions and size have been shown to be oxidized in vivo, including ribosomal RNA (rRNA), transfer RNA (tRNA), microRNA (miRNA), messenger RNA (mRNA), and mitochondrial RNA (mtRNA). This process occurs from reactions between reactive oxygen species (ROS) and all biopolymers, including RNA, from endogenous as well as exogenous sources. As a consequence, mechanisms that handle oxidized RNA are important, and enzymatic degradation is the most commonly studied process to date. This review focuses on the ribonucleases that have been shown to play a role in the degradation of oxidized RNA. While emphasis is placed on, arguably, the most common oxidatively generated chemical modification, 8-oxo-7,8-dihydroguanosine (8-oxoG), the products that arise from the oxidation of other canonical nucleosides as well as naturally occurring modifications are also discussed in the context of RNA oxidation. Processing of oxidized RNA via its enzymatic degradation is likely the main route, but a potential role of other proteins involved in the handling of oxidized RNA is hypothesized, e.g., helicases, export proteins, and extracellular environments. We postulate that this is an area with great potential for discovery. Full article

Emerging pharmaceutical contaminants, including sulfonamide antibiotics such as sulfamethoxazole (SMX), persist in natural water bodies at ng L⁻¹ to µg L⁻¹ concentrations and are inadequately removed by conventional wastewater treatment technologies, posing significant ecological and public health risks. Porphyrin-based quantum catalysts activated by peroxymonosulfate (PMS) represent a promising advanced oxidation strategy for the remediation of such recalcitrant micro-pollutants. However, the precise molecular mechanisms governing their catalytic activity remain incompletely understood. In this study, we present a comprehensive mechanistic investigation of SMX oxidation catalyzed by Mn (III) meso-tetraphenylporphyrin (Mn-TPP) in the presence of PMS, employing spin-unrestricted density functional theory (DFT) at the Becke, 3-parameter, Lee–Yang–Parr (B3LYP-D3BJ) level of theory with dispersion corrections. Full Gibbs free energy profiles for the catalytic cycle were constructed through geometry optimizations using the LACVP basis set on Mn and 6-31G(d,p) on all non-metal atoms, followed by single-point energy calculation at the 6-311+G(d,p) level, incorporating the SMD implicit solvation model to stimulate aqueous environment conditions. The results demonstrate that the oxidation of Mn TPP by PMS to generate the key high-valent intermediate Mn(V)=O(TPP)⁺ is thermodynamically and kinetically favorable. The activation barrier for Mn(V)=O(TPP)⁺ formation via PMS activation is ΔG† = 17.2 kcal mol⁻¹ (SMD water, 298 K), confirming that this step is kinetically accessible under ambient environmental conditions. Subsequent SMX oxidation processes proceed via concerted radical and non-radical mechanistic pathways, with the most thermodynamically favorable route exhibiting a strongly exergonic reaction-free energy (ΔGr), indicating that significant mineralization of the target pollutant is thermodynamically accessible. The transition state analysis reveals spin density localization characteristic of the Mn-Oxo species, establishing a direct correlation between quantum confinement effects, electronic structure and the observed catalytic selectivity and oxidation stability of the Mn-TPP system. These mechanistic insights provide quantitative molecular-level design parameters, including activation barriers, spin state requirements, and electronic structure descriptors for the rational optimization of next-generation porphyrin-based quantum catalysts capable of efficiently degrading persistent pharmaceutical contaminants in complex aqueous matrices. Full article