Electron delocalization triggers nonradical Fenton-like catalysis over spinel oxides.

Nonradical Fenton-like catalysis offers opportunities to overcome the low efficiency and secondary pollution limitations of existing advanced oxidation decontamination technologies, but realizing this on transition metal spinel oxide catalysts remains challenging due to insufficient understanding of their catalytic mechanisms. Here, we explore the origins of catalytic selectivity of Fe-Mn spinel oxide and identify electron delocalization of the surface metal active site as the key driver of its nonradical catalysis. Through fine-tuning the crystal geometry to trigger Fe-Mn superexchange interaction at the spinel octahedra, ZnFeMnO4 with high-degree electron delocalization of the Mn-O unit was created to enable near 100% nonradical activation of peroxymonosulfate (PMS) at unprecedented utilization efficiency. The resulting surface-bound PMS* complex can efficiently oxidize electron-rich pollutants with extraordinary degradation activity, selectivity, and good environmental robustness to favor water decontamination applications. Our work provides a molecule-level understanding of the catalytic selectivity and bimetallic interactions of Fe-Mn spinel oxides, which may guide the design of low-cost spinel oxides for more selective and efficient decontamination applications.

Elucidation of the tyrosinase/O2/monophenol ternary intermediate that dictates the monooxygenation mechanism in melanin biosynthesis.

Melanins are highly conjugated biopolymer pigments that provide photoprotection in a wide array of organisms, from bacteria to humans. The rate-limiting step in melanin biosynthesis, which is the ortho-hydroxylation of the amino acid L-tyrosine to L-DOPA, is catalyzed by the ubiquitous enzyme tyrosinase (Ty). Ty contains a coupled binuclear copper active site that binds O2 to form a µ:η2:η2-peroxide dicopper(II) intermediate (oxy-Ty), capable of performing the regioselective monooxygenation of para-substituted monophenols to catechols. The mechanism of this critical monooxygenation reaction remains poorly understood despite extensive efforts. In this study, we have employed a combination of spectroscopic, kinetic, and computational methods to trap and characterize the elusive catalytic ternary intermediate (Ty/O2/monophenol) under single-turnover conditions and obtain molecular-level mechanistic insights into its monooxygenation reactivity. Our experimental results, coupled with quantum-mechanics/molecular-mechanics calculations, reveal that the monophenol substrate docks in the active-site pocket of oxy-Ty fully protonated, without coordination to a copper or cleavage of the µ:η2:η2-peroxide O-O bond. Formation of this ternary intermediate involves the displacement of active-site water molecules by the substrate and replacement of their H bonds to the µ:η2:η2-peroxide by a single H bond from the substrate hydroxyl group. This H-bonding interaction in the ternary intermediate enables the unprecedented monooxygenation mechanism, where the µ-η2:η2-peroxide O-O bond is cleaved to accept the phenolic proton, followed by substrate phenolate coordination to a copper site concomitant with its aromatic ortho-hydroxylation by the nonprotonated µ-oxo. This study provides insights into O2 activation and reactivity by coupled binuclear copper active sites with fundamental implications in biocatalysis.

Facilely tuning the intrinsic catalytic sites of the spinel oxide for peroxymonosulfate activation: From fundamental investigation to pilot-scale demonstration.

Heterogeneous peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) have shown a great potential for pollutant degradation, but their feasibility for large-scale water treatment application has not been demonstrated. Herein, we develop a facile coprecipitation method for the scalable production (∼10 kg) of the Cu-Fe-Mn spinel oxide (CuFeMnO). Such a catalyst has rich oxygen vacancies and symmetry-breaking sites, which endorse it with a superior PMS-catalytic capacity. We find that the working reactive species and their contributions are highly dependent on the properties of target organic pollutants. For the organics with electron-donating group (e.g., -OH), high-valent metal species are mainly responsible for the pollutant degradation, whereas for the organics with electron-withdrawing group (e.g., -COOH and -NO2), hydroxyl radical (•OH) as the secondary oxidant also plays an important role. We demonstrate that the CuFeMnO-PMS system is able to achieve efficient and stable removal of the pollutants in the secondary effluent from a municipal wastewater plant at both bench and pilot scales. Moreover, we explore the application prospect of this PMS-based AOP process for large-scale wastewater treatment. This work describes an opportunity to scalably prepare robust spinel oxide catalysts for water purification and is beneficial to the practical applications of the heterogeneous PMS-AOPs.

1,2,4,5-Tetraoxane derivatives/hybrids as potent antimalarial endoperoxides: Chronological advancements, structure-activity relationship (SAR) studies and future perspectives.

Malaria is a life-threatening disease that affects tropical and subtropical regions worldwide. Various drugs were used to treat malaria, including artemisinin and derivatives, antibiotics (tetracycline, doxycycline), quinolines (chloroquine, amodiaquine), and folate antagonists (sulfadoxine and pyrimethamine). Since the malarial parasites developed drug resistance, there is a need to develop new chemical entities with high efficacy and low toxicity. In this context, 1,2,4,5-tetraoxanes emerged as an essential scaffold and have shown promising antimalarial activity. To improve activity and overcome resistance to various antimalarial drugs; 1,2,4,5-tetraoxanes were fused with various aryl/heteroaryl/alicyclic/spiro moieties (steroid-based 1,2,4,5-tetraoxanes, triazine-based 1,2,4,5-tetraoxanes, aminoquinoline-based 1,2,4,5-tetraoxanes, dispiro-based 1,2,4,5-tetraoxanes, piperidine-based 1,2,4,5-tetraoxanes and diaryl-based 1,2,4,5-tetraoxanes). The present review aims to focus on covering the relevant literature published during the past 30 years (1992-2022). We summarize the most significant in vitro, in vivo results and structure-activity relationship studies of 1,2,4,5-tetraoxane-based hybrids as antimalarial agents. The structural evolution of different hybrids can provide the framework for the future development of 1,2,4,5-tetraoxane-based hybrids to treat malaria.

Mediated Peroxymonosulfate Activation at the Single Atom Fe-N3O1 Sites: Synergistic Degradation of Antibiotics by Two Non-Radical Pathways.

The activation of persulfates to degrade refractory organic pollutants is a hot issue in advanced oxidation right now. Here, it is reported that single-atom Fe-incorporated carbon nitride (Fe-CN-650) can effectively activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. Through some characterization techniques and DFT calculation, it is proved that Fe single atoms in Fe-CN-650 exist mainly in the form of Fe-N3O1 coordination, and Fe-N3O1 exhibited better affinity for PMS than the traditional Fe-N4 structure. The degradation rate constant of SMX in the Fe-CN-650/PMS system reached 0.472 min-1, and 90.80% of SMX can still be effectively degraded within 10 min after five consecutive recovery cycles. The radical quenching experiment and electrochemical analysis confirm that the pollutants are mainly degraded by two non-radical pathways through 1O2 and Fe(IV)═O induced at the Fe-N3O1 sites. In addition, the intermediate products of SMX degradation in the Fe-CN-650/PMS system show toxicity attenuation or non-toxicity. This study offers valuable insights into the design of carbon-based single-atom catalysts and provides a potential remediation technology for the optimum activation of PMS to disintegrate organic pollutants.

Targeted Endoperoxides Delivering Singlet Oxygen to Cancer Cell Mitochondria: Exploration of the Therapeutic Potential.

The clinical practice of photodynamic therapy of cancer (PDT) is mostly limited to superficial types of cancer. The major reason behind this limited applicability is the need for light in the photogeneration of ROS, and in particular singlet oxygen. In order to circumvent this major roadblock, we designed and synthesized naphthalene-derived endoperoxides with mitochondria targeting triphenylphosphonium moieties. Here, we show that these compounds release singlet oxygen by thermal cycloreversion, and initiate cell death with IC50<10 µM in cancer cell cultures. The mouse 4T1 breast tumor model study, where the endoperoxide compound was introduced intraperitoneally, also showed highly promising results, with negligible systemic toxicity. Targeted delivery of singlet oxygen to cancer cell mitochondria could be the breakthrough needed to transform Photodynamic Therapy into a broadly applicable methodology for cancer treatment by keeping the central tenet and discarding problematic dependencies on oxygen or external light.

Facet-Dependent Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 Dual S-Scheme Photocatalyst as an Efficient Visible-Light-Driven Peroxymonosulfate Activator for Norfloxacin Degradation.

A lack of eco-friendly, highly active photocatalyst for peroxymonosulfate (PMS) activation and unclear environmental risks are significant challenges. Herein, we developed a double S-scheme Fe2O3/BiVO4(110)/BiVO4(010)/Fe2O3 photocatalyst to activate PMS and investigated its impact on wheat seed germination. We observed an improvement in charge separation by depositing Fe2O3 on the (010) and (110) surfaces of BiVO4. This enhancement is attributed to the formation of a dual S-scheme charge transfer mechanism at the interfaces of Fe2O3/BiVO4(110) and BiVO4(010)/Fe2O3. By introducing PMS into the system, photogenerated electrons effectively activate PMS, generating reactive oxygen species (ROS) such as hydroxyl radicals (·OH) and sulfate radicals (SO4·-). Among the tested systems, the 20% Fe2O3/BiVO4/Vis/PMS system exhibits the highest catalytic efficiency for norfloxacin (NOR) removal, reaching 95% in 40 min. This is twice the catalytic efficiency of the Fe2O3/BiVO4/PMS system, 1.8 times that of the Fe2O3/BiVO4 system, and 5 times that of the BiVO4 system. Seed germination experiments revealed that Fe2O3/BiVO4 heterojunction was beneficial for wheat seed germination, while PMS had a significant negative effect. This study provides valuable insights into the development of efficient and sustainable photocatalytic systems for the removal of organic pollutants from wastewater.

Equipping Uridine with Three Dipeptide Motifs for the Inhibition of Radical-Induced DNA Oxidation.

We report the discovery and characterization of antioxidative effects of uridine linked with three dipeptide motifs against DNA oxidation induced by peroxyl radicals. First, the dipeptide motifs are constructed by using the Ugi four-component reaction (Ugi 4CR), in which caffeic, ferulic, sinapic, and syringic acids are used as the carboxylic acid resources, vanillin, benzaldehyde, and p-hydroxybenzaldehyde are used as the aldehyde resources, tyramine- and dopamine-related isocyanides as well as ethyl isocyanoacetate are used as the isocyanide resources, and 2-(p-aminophenyl)ethanol is used as the amine component. We found that the antioxidative effects of the Ugi 4CR products are 1.3-2.8 times higher than those of caffeic, ferulic, sinapic, and syringic acids in the protection of DNA against peroxyl radical-induced oxidation. Moreover, when three Ugi 4CR products are linked with three hydroxyl groups of uridine by using three succinic anhydrides as the linkage, the inhibitory effects of the afforded uridine-dipeptide hybrids against the DNA oxidation increase 4.4-8.9 times (>3 times) compared to that of the Ugi 4CR product. This is due to the hybrid structure consisting of uridine and three motifs of the Ugi 4CR product enabling binding with the DNA strand more efficiently and quenching free radicals more rapidly. Therefore, the hybrid structure constructed by the nucleoside with antioxidative dipeptides offers an additional advantage for protecting DNA against radical-induced oxidation.

Structure elucidation, absolute configuration, and biological evaluation of cyclic peroxides from the sponge Plakinastrella sp.

Two cyclic peroxides, plakortides V (1) and W (2) were purified from the organic extract of the sponge Plakinastrella sp. Their planar structures were established based on extensive NMR and MS analysis and the absolute configurations of the three stereogenic centers of the 1,2-dioxane moiety were determined to be 3R,4S,6S by comparative analysis of the 1H NMR spectral data of the R- or S-MTPA Mosher esters. Compounds 1 and 2 exhibited potent cytotoxic activity against LOX IMVI (melanoma), UO-31 (renal), and HL-60 (TB) (leukemia) cell lines in the NCI-60 cytotoxicity assay.

Silver peroxide-incorporated carbon dots with high photothermal performance for combating bacteria.

The widespread use of antibiotics often increases bacterial resistance. Herein, we reported a silver peroxide-incorporated carbon dots (defined as Ag2O2-CDs) with high photothermal conversion efficiency viain situoxidation process. The prepared Ag2O2-CDs exhibited ultra-small size of 2.0 nm and hybrid phase structure. Meanwhile, the Ag2O2-CDs were of a similar optical performance comparing with traditional carbon dots (CDs). Importantly, the incorporation of Ag2O2into CDs significantly enhanced photothermal conversion efficiency from 3.8% to 28.5%. By combining silver ion toxicity and photothermal ablation, the Ag2O2-CDs were capable of destroying gram-positive and gram-negative bacterium effectively. These findings demonstrated that the Ag2O2-CDs could be served as a potential antibacterial agent for clinical applications.

Deep Oxidation of Chlorinated VOCs by Efficient Catalytic Peroxide Activation over Nanoconfined Co@NCNT Catalysts.

The catalytic removal of chlorinated VOCs (CVOCs) in gas-solid reactions usually suffers from chlorine-containing byproduct formation and catalyst deactivation. AOP wet scrubber has recently attracted ever-increasing interest in VOC treatment due to its advantages of high efficiency and no gaseous byproduct emission. Herein, the low-valence Co nanoparticles (NPs) confined in a N-doped carbon nanotube (Co@NCNT) were studied to activate peroxymonosulfate (PMS) for efficient CVOC removal in a wet scrubber. Co@NCNT exhibited unprecedented catalytic activity, recyclability, and low Co ion leakage (0.19 mg L-1) for chlorobenzene degradation in a very wide pH range (3-11). The chlorobenzene removal efficiency was kept stable above 90% over Co@NCNT, much higher than that of nonconfined Co@NCNS (45%). The low-valence Co NPs achieved a continuous electron redox cycling (Co0/Co2+ → Co3+ → Co0/Co2+) and greatly promoted the O-O bond dissociation of PMS with the least energy (0.83 eV) inside the channel of Co@NCNT to form abundant HO• and SO4•-. Thus, the deep oxidation of chlorobenzene was achieved without any biphenyl byproducts from the coupling reaction. This study provided a new avenue for designing novel nanoconfined catalysts with outstanding activity, paving the way for the deep oxidation of CVOC waste gas via AOP wet scrubber.

Reactive Oxygen Species Formation and Peroxide and Carbonyl Decomposition in Aqueous Photolysis of Secondary Organic Aerosols.

The mechanism and kinetics of reactive oxygen species (ROS) formation when atmospheric secondary organic aerosol (SOA) is exposed to solar radiation are poorly understood. In this study, we combined an in situ UV-vis irradiation system with electron paramagnetic resonance (EPR) spectroscopy to characterize the photolytic formation of ROS in aqueous extracts of SOA formed by the oxidation of isoprene, α-pinene, α-terpineol, and toluene. We observed substantial formation of free radicals, including •OH, superoxide (HO2•), and organic radicals (R•/RO•) upon irradiation. Compared to dark conditions, the radical yield was enhanced by a factor of ∼30 for •OH and by a factor of 2-10 for superoxide radicals, and we observed the emergence of organic radicals. Total peroxide measurements showed substantial decreases of peroxide contents after photoirradiation, indicating that organic peroxides can be an important source of the observed radicals. A liquid chromatography interfaced with high-resolution mass spectrometry was used to detect a number of organic radicals in the form of adducts with a spin trap, BMPO. The types of detected radicals and aqueous photolysis of model compounds indicated that photolysis of carbonyls by Norrish type I mechanisms plays an important role in the organic radical formation. The photolytic ROS formation serves as the driving force for cloud and fog processing of SOA.

Discerning the Relevance of Singlet Oxygen in Pollutant Degradation in Peroxymonosulfate Activation Processes.

Significant efforts have recently been exerted toward construction of singlet oxygen (1O2)-dominated catalytic oxidation systems for selective removal of organic contaminants from wastewater, with peroxides serving as the chemical source. However, the relevance of 1O2 in the removal of pollutants remains ambiguous and requires elucidation. In this study, we scrupulously exclude the significant role of 1O2 in contaminant degradation in various peroxymonosulfate (PMS) activation systems. Multiple experimental results indicate that the activation of PMS catalyzed by CuO, MnO2, Fe-doped g-C3N4 (Fe-CN), or N-doped graphite does not predominantly follow the 1O2 pathway. More importantly, the reactivity of 1O2 is remarkably overestimated in the literature, given its inferior capacity in degradation of a range of heterocyclic contaminants and aromatic compounds possessing electron-withdrawing groups. In addition, the strong physical quenching effect of water, coupled with the low oxidizing ability of 1O2, would notably reduce the utilization efficiency of peroxide, which is particularly apparent in the degradation of micropollutants. We reckon that this study is expected to end the long-running dispute associated with the relevance of 1O2 in pollutant removal.

Synthesis and Characterization of Organic Peroxides from Monoterpene-Derived Criegee Intermediates in Secondary Organic Aerosol.

Ozonolysis of alkenes is known to produce reactive intermediates─stabilized Criegee intermediates (SCIs), and their subsequent bimolecular reactions with various carboxylic acids can form α-acyloxyalkyl hydroperoxides (AAHPs), which is considered a major class of organic peroxides in secondary organic aerosol (SOA). Despite their atmospheric and health importance, the molecular-level identification of organic peroxides in atmospheric aerosols is highly challenging, preventing further assessment of their environmental fate. Here, we synthesize 20 atmospherically relevant AAHPs through liquid-phase ozonolysis, in which two types of monoterpene-derived SCIs from either α-pinene or 3-carene are scavenged by 10 different carboxylic acids to form AAHPs with diverse structures. These AAHPs are identified individually by liquid chromatography coupled with high-resolution mass spectrometry. AAHPs were previously thought to decompose quickly in an aqueous environment such as cloud droplets, but we demonstrate here that AAHPs hydrolysis rates are highly compound-dependent with rate constants differing by 2 orders of magnitude. In contrast, the aqueous-phase formation rate constants between SCI and various carboxylic acids vary only within a factor of 2-3. Finally, we identified two of the 20 synthesized AAHPs in α-pinene SOA and two in 3-carene SOA, contributing ∼0.3% to the total SOA mass. Our results improve the current molecular-level understanding of organic peroxides and are useful for a more accurate assessment of their environmental fate and health impact.

Oxyanion-Sensitive Catalytic Activity of Ni(II)/Oxyanion Systems for Heterogeneous Organic Degradation: Differential Oxidizing Capacity of Ni(III) and Ni(IV) as High-Valent Intermediates.

This study demonstrated that NiO and Ni(OH)2 as Ni(II) catalysts exhibited significant activity for organic oxidation in the presence of various oxyanions, such as hypochlorous acid (HOCl), peroxymonosulfate (PMS), and peroxydisulfate (PDS), which markedly contrasted with Co-based counterparts exclusively activating PMS to yield sulfate radicals. The oxidizing capacity of the Ni catalyst/oxyanion varied depending on the oxyanion type. Ni catalyst/PMS (or HOCl) degraded a broad spectrum of organics, whereas PDS enabled selective phenol oxidation. This stemmed from the differential reactivity of two high-valent Ni intermediates, Ni(III) and Ni(IV). A high similarity with Ni(III)OOH in a substrate-specific reactivity indicated the role of Ni(III) as the primary oxidant of Ni-activated PDS. With the minor progress of redox reactions with radical probes and multiple spectroscopic evidence on moderate Ni(III) accumulation, the significant elimination of non-phenolic contaminants by NiOOH/PMS (or HOCl) suggested the involvement of Ni(IV) in the substrate-insensitive treatment capability of Ni catalyst/PMS (or HOCl). Since the electron-transfer oxidation of organics by high-valent Ni species involved Ni(II) regeneration, the loss of the treatment efficiency of Ni/oxyanion was marginal over multiple catalytic cycles.

Highly Reactive Peroxide Species Promoted Soot Oxidation over an Ordered Macroporous Ce0.8Zr0.2O2 Integrated Catalyzed Diesel Particulate Filter.

Particulate matter, represented by soot particles, poses a significant global environmental threat, necessitating efficient control technology. Here, we innovatively designed and elaborately fabricated ordered hierarchical macroporous catalysts of Ce0.8Zr0.2O2 (OM CZO) integrated on a catalyzed diesel particulate filter (CDPF) using the self-assembly method. An oxygen-vacancy-enriched ordered macroporous Ce0.8Zr0.2O2 catalyst (VO-OM CZO) integrated CDPF was synthesized by subsequent NaBH4 reduction. The VO-OM CZO integrated CDPF exhibited a markedly enhanced soot oxidation activity compared to OM CZO and powder CZO coated CDPFs (T50: 430 vs 490 and 545 °C, respectively). The well-defined OM structure of the VO-OM CZO catalysts effectively improves the contact efficiency between soot and the catalysts. Meanwhile, oxygen vacancies trigger the formation of a large amount of highly reactive peroxide species (O22-) from molecular oxygen (O2) through electron abstraction from the three adjacent Ce3+ (3Ce3+ + Vö + O2 → 3Ce4+ + O22-), contributing to the efficient soot oxidation. This work demonstrates the fabrication of the ordered macroporous CZO integrated CDPF and reveals the importance of structure and surface engineering in soot oxidation, which sheds light on the design of highly efficient PM capture and removal devices.

Cyanide-Isolated Cobalt Catalyst for Ultraefficient Advanced Oxidation Treatment.

Catalyst design with a "Co-N-C" structure at the atomic level has shown great interest for peroxymonosulfate (PMS) activation toward advanced oxidation water treatment. Here, we present an innovative way of producing cobalt hexacyanocobaltate (Co-HCC) with an abundance of atomically isolated CoII-NC sites at the outer surface. This material allows ultraefficient PMS activation to generate plenty of sulfate and hydroxyl radicals, with a turnover frequency much higher than those of most cobalt-based catalysts reported so far and even the homogeneous catalysis by Co2+ ions. We gained fundamental insights on its unprecedently high catalytic performance based on experimental results and computational study. Then, we controlled the growth of Co-HCC on a ceramic membrane to form a confined oxidation environment that utilizes the extended surface area and maximal exposure of short-lived radicals for a fast removal of organic pollutants that enter the pores. As a result, this catalytic membrane achieves complete disruption of micropollutants under a water flux up to 10,000 LMH (merely 0.2 s retention time) and further >90% mineralization of organic pollutants in complex industrial wastewater matrices (<100 s retention time), together with the merits of operational simplicity and great longevity (2 weeks continuous run). Our study elicits a new milestone in "Co-N-C" catalyst structure design for PMS activation and highlights the great interest of producing catalytic membranes for a confined treatment of organic pollutants from partial oxidation to complete mineralization as a new benchmark.

Revisiting the Iron(II)/Cobalt(II)-Based Homogenous Fenton-like Processes from the Standpoint of Diverse Metal-Oxygen Complexes.

The aqueous FeIV-oxo complex and FeIII-peroxy complex (e.g., ligand-assisted or interfacial FeIII-hydroperoxo intermediates) have been recognized as crucial reactive intermediates for decontamination in iron-based Fenton-like processes. Intermediates with terminal oxo ligands can undergo the oxygen atom exchange process with water molecules, whereas peroxides are unable to induce such exchanges. Therefore, these distinct metal-oxygen complexes can be distinguished based on the above feature. In this study, we identified previously unknown intermediates with a peroxy moiety and cobalt center that were generated during peroxymonosulfate (PMS) activation via aqueous CoII ions under acidic conditions. Results of theoretical calculations and tip-enhanced Raman spectroscopy revealed that the CoII ion tended to coordinate with the PMS anion to form a bidentate complex with a tetrahedral structure. These reactive cobalt intermediates were collectively named the CoII-PMS* complex. Depending on the inherent characteristics of the target contaminants, the CoII-PMS* complex can directly oxidize organic compounds or trigger PMS disproportionation to release hydroxyl radicals and sulfate radicals for collaborative decontamination. This work provides a comparative study between iron- and cobalt-based Fenton-like processes and proposes novel insights from the standpoint of diverse metal-oxygen complexes.

Design and synthesis of visible light-activatable photocaged peroxides for optical control of ROS-mediated cellular signaling.

We designed and synthesized two novel photocaged peroxide compounds, N5TBHP and N6TBHP, featuring nitrogen-containing fused ring coumarin skeletons. Notably, a tetrahydroquinoline fused coumarin derivative, N6TBHP demonstrated significantly higher photocleavage efficiency under visible light at 455 nm compared to N5TBHP, which contains an indoline fused coumarin. This process effectively releases the oxidative stress inducer tert-butylhydroperoxide (TBHP). Additionally, N6TBHP exhibits high resistance to glutathione (GSH), and its UV spectral analysis suggests enhanced intracellular stability due to reduced reactivity with GSH through self-assembly. Furthermore, N6TBHP can release an optimal amount of TBHP into cells under visible light irradiation with minimal cell damage. These properties position N6TBHP as a promising tool for advancing research in intracellular redox signaling.

Norterpene Cyclic Peroxides from the Marine Sponge Diacarnus spinipoculum, Inhibitors of Transient Receptor Potential Ankyrin 1.

Bioassay-guided isolation of the extract from the marine sponge Diacarnus spinipoculum showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides (1-12) and eight norsesterterpene cyclic peroxides (13-20). Among these, 10 (5-7, 11, 12, 16-20) are unprecedented analogs. Compounds with either a hydroxy (5, 11) or a methoxy (6, 12) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds 4, 6, 10, and 12 are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds 17-20. The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid 19 displaying the most potent activity (IC50 2.0 µM).