Formation Of Reactive Intermediates Research Articles

Insights into the transformations of Mn species for peroxymonosulfate activation by tuning the Mn3O4 shapes

The transformation among MnII, MnIII and MnIV on the surface of the manganese oxides is a critical factor for peroxymonosulfate (PMS) activation. In this work, three kinds of Mn3O4 with different shapes (plate, cube and octahedra) were prepared to tune the surface Mn valence for ciprofloxacin (CIP) degradation, and the relationship between MnIV and PMS activation was established for the first time. The octahedral Mn3O4 (Mn3O4-O) owns high catalytic activity, MnIV is the primary active site on the surface of Mn3O4 for PMS activation to generate the active radicals, while the surface –OH groups play a key role in the formation of reactive intermediates. The quenching experiments and Electron paramagnetic resonance (EPR) results suggest that the SO4− and OH radicals are the main reactive radicals in the catalytic process. The PMS activation should mainly occur in the transformation from MnIV to MnIII. This work is expected to elucidate the relationship between surface valence in manganese oxides and PMS activation by morphology-tuning.

Decomposition Pathways of Ammonium Dinitramide (ADN) and its HNO3‐Clusters Elucidated by DFT‐Calculations

AbstractAmmonium dinitramide (ADN) may serve as a ‘green’ oxidizer for rocket propellants since it provides chlorine free and minimum signature exhaust gases. However, stability issues and an erratic decomposition behaviour limit its non‐questionable general usability. Nitric acid (HNO3) is a decomposition product of ADN and is known to accelerate the decomposition autocatalytically. In this study, we investigate the effect of HNO3 on the initial decomposition steps of ADN via quantum chemical calculations based on density functional theory (DFT) in vacuo as well as in an aqueous solution. We establish and compare the reaction profiles of ADN, its anion DN− and its acid HDN as well as their HNO3‐clusters [NO3H_ADN], [NO3H_DN]− and [NO3H_HDN] towards the products NO2, HNO3 and N2O. All species exhibit various isomers with distinct decomposition pathways. We complement our study by investigating the protonated, cationic species [H_ADN]+, which may form in a low pH regime. The HNO3 clusters reveal modulated energy barriers and in part altered decomposition pathways in comparison to the free DN−, HDN, and ADN species. The altered pathways include the formation of reactive intermediates (such as H2NO3+) as well as the formation of two HNO3 molecules starting from one HNO3 molecule, hinting at accelerated decomposition of ADN due to interaction with HNO3.

Enhanced oxidation of bisphenol A by permanganate in the presence of epigallocatechin gallate: Kinetics and mechanism

Accelerated oxidation of emerging contaminants by permanganate (PM) in the presence of reducing reagents or ligands was reported in previous studies. Epigallocatechin gallate (EGCG) is a novel reagent used in water treatment, with simultaneous reducing and chelating ability. Therefore, EGCG was applied to enhance PM oxidation of bisphenol A (BPA) in this study, and showed a better performance than sulfite, hydroxylamine, EDTA, and citrate. The impacts of molar ratio of PM/EGCG, pH, dissolved oxygen, alkalinity, and natural organic matters on the performance of PM/EGCG process were investigated. The results demonstrated that optimum molar ratio of PM/EGCG was at 1:0.1, and EGCG significantly enhanced PM oxidation at pH 5–8. Dissolved oxygen and alkalinity showed inhibitory impacts on BPA degradation in PM/EGCG process, while natural organic matters have no obvious impact on the performance of PM/EGCG process. Formation of reactive Mn intermediates was confirmed using quenching experiments (with pyrophosphate) and UV–vis full scan spectra, indicating that reactive Mn intermediates were the predominant reactive species responsible for BPA degradation in PM/EGCG process. Overall, our study provides a novel and environmentally friendly alternative for enhancement of PM oxidation.

Direct kinetic measurements and theoretical predictions of an isoprene-derived Criegee intermediate

Isoprene has the highest emission into Earth's atmosphere of any nonmethane hydrocarbon. Atmospheric processing of alkenes, including isoprene, via ozonolysis leads to the formation of zwitterionic reactive intermediates, known as Criegee intermediates (CIs). Direct studies have revealed that reactions involving simple CIs can significantly impact the tropospheric oxidizing capacity, enhance particulate formation, and degrade local air quality. Methyl vinyl ketone oxide (MVK-oxide) is a four-carbon, asymmetric, resonance-stabilized CI, produced with 21 to 23% yield from isoprene ozonolysis, yet its reactivity has not been directly studied. We present direct kinetic measurements of MVK-oxide reactions with key atmospheric species using absorption spectroscopy. Direct UV-Vis absorption spectra from two independent flow cell experiments overlap with the molecular beam UV-Vis-depletion spectra reported recently [M. F. Vansco, B. Marchetti, M. I. Lester, J. Chem. Phys. 149, 44309 (2018)] but suggest different conformer distributions under jet-cooled and thermal conditions. Comparison of the experimental lifetime herein with theory indicates only the syn-conformers are observed; anti-conformers are calculated to be removed much more rapidly via unimolecular decay. We observe experimentally and predict theoretically fast reaction of syn-MVK-oxide with SO2 and formic acid, similar to smaller alkyl-substituted CIs, and by contrast, slow removal in the presence of water. We determine products through complementary multiplexed photoionization mass spectrometry, observing SO3 and identifying organic hydroperoxide formation from reaction with SO2 and formic acid, respectively. The tropospheric implications of these reactions are evaluated using a global chemistry and transport model.

Insight into Cu2O/CuO collaboration in the selective catalytic reduction of NO with NH3: Enhanced activity and synergistic mechanism

Cu-based catalysts have drawn much attention in ammonia-selective catalytic reduction (NH3-SCR) of NOx because of their outstanding low-temperature denitration (de-NOx) potential. Although satisfactory SCR performance was obtained with support from the catalytic activity of CuOx species in recent studies, the effect of the valence distribution of CuOx species on NH3-SCR reaction is still ambiguous, and elaborate exploration is necessary. Here, a series of CuAl-layered double oxide/carbon nanotubes-x (CuAl-LDO/CNTs-x) nanocatalysts with a tunable valence distribution of highly dispersed CuOx species was constructed from the topotactic transformation of CuAl-layered double hydroxide (CuAl-LDH) precursor and a controllable carbothermal reduction reaction. Multiple characterization techniques, including XRD, NH3-TPD, H2-TPR, NOx-TPD, XPS, in situ DRIFTS, and HR-TEM, were employed to elucidate the inherent relationship between the chemical properties and catalytic activity of the as-prepared catalysts. The obtained CuAl-LDO/CNTs-2 catalyst exhibited optimum catalytic performance, with NOx conversion exceeding 90% in the temperature range 180–305 °C. Such high catalytic efficiency can be attributed to the appropriate valence distribution of CuOx species, which can significantly improve the redox capacity and surface acidity of the catalysts, thereby promoting the adsorption and activation of the reactants. Combined with further theoretical calculation, a synergistic catalytic mechanism of Cu2O/CuO in the NH3-SCR reaction is tentatively proposed. Notably, the CuO active center can function as the dominant adsorption site of NO and NH3 to promote the formation of NO+ active species and the dehydrogenation activation of NH3. The Cu2O active center can act as the adsorption site for O, promoting the formation of active oxygen species O−. Consequently, the synergistic effect between Cu2O and CuO can lead to the rapid formation of reactive intermediates, proceeding via the Langmuir–Hinshelwood (reaction between adsorbed NH3 and adsorbed NOx) or Eley–Rideal (reaction between adsorbed NH3 and gaseous NO) mechanism reaction routes to complete the catalytic cycle. This work provides a fundamental understanding on Cu2O/CuO synergistic catalysis of NH3-SCR, which is propitious for the rational design and optimization of Cu-based oxide de-NOx catalysts.

Ultrasonic Enhanced Zero-Valent Iron-Based Fenton Reaction for Ciprofloxacin Removal under Aerobic Condition

The effect of aeration and ultrasonic irradiation on the performance of nano zero-valent iron (nZVI)-based Fenton reaction was investigated. The purpose of aeration was to create mixing in the system, and the mixing in the reactor was supplied only by using air bubbles without employing a mechanical mixer. The effect of four numerical variables, i.e., H2O2 amount, catalyst dose, aeration, and time, and one categorical one, i.e., ultrasonic (US) irradiation, was examined on the elimination of ciprofloxacin (CIP) from aqueous solution by response surface methodology. The accompanying the aeration and the US irradiation nZVI-based Fenton reaction could accelerate nZVI corrosion and formation of reactive intermediates, thus effectively oxidizing contaminants. A combined treatment of Fenton (nZVI/H2O2)/aeration/US resulted in higher antibiotic removal efficiency in comparison to conventional Fenton (nZVI/H2O2), Fenton (nZVI/H2O2)/aeration and Fenton (nZVI/H2O2)/US processes. A combined treatment of Fenton (nZVI/H2O2)/aeration/US achieved a 94% CIP removal within 60 min of an initial CIP concentration of 100 mg/L under neutral pH condition. Results demonstrated that ultrasonic-assisted nZVI/H2O2 process under aeration condition can be applied as an advisable choice for the treatment of organic wastewaters. Due to employing aeration instead of using mechanical stirring, this proposed process needs low energy consumption.

Structure-Activity Relationships for CYP4B1 Bioactivation of 4-Ipomeanol Congeners: Direct Correlation between Cytotoxicity and Trapped Reactive Intermediates.

Cytochrome P450 4B1 (CYP4B1) has been explored as a candidate enzyme in suicide gene systems for its ability to bioactivate the natural product 4-ipomeanol (IPO) to a reactive species that causes cytotoxicity. However, metabolic limitations of IPO necessitate discovery of new "pro-toxicant" substrates for CYP4B1. In the present study, we examined a series of synthetically facile N-alkyl-3-furancarboxamides for cytotoxicity in HepG2 cells expressing CYP4B1. This compound series maintains the furan warhead of IPO while replacing its alcohol group with alkyl chains of varying length (C1-C8). Compounds with C3-C6 carbon chain lengths showed similar potency to IPO (LD50 ≈ 5 μM). Short chain analogs (<3 carbons) and long chain analogs (>6 carbons) exhibited reduced toxicity, resulting in a parabolic relationship between alkyl chain length and cytotoxicity. A similar parabolic relationship was observed between alkyl chain length and reactive intermediate formation upon trapping of the putative enedial as a stable pyrrole adduct in incubations with purified recombinant rabbit CYP4B1 and common physiological nucleophiles. These parabolic relationships reflect the lower affinity of shorter chain compounds for CYP4B1 and increased ω-hydroxylation of the longer chain compounds by the enzyme. Furthermore, modest time-dependent inhibition of CYP4B1 by N-pentyl-3-furancarboxamide was completely abolished when trapping agents were added, demonstrating escape of reactive intermediates from the enzyme after bioactivation. An insulated CYP4B1 active site may explain the rarely observed direct correlation between adduct formation and cell toxicity reported here.

Assessment of tailor-made mesoporous metal doped TiO2 monolithic framework as fast responsive visible light photocatalysts for environmental remediation applications

The article reports on the facile one-pot synthesis of a structurally organized mesoporous crack-free monolithic network of Bi3+ doped TiO2, as a visible light workable photocatalyst materials for environmental remediation. The monolithic photocatalyst efficacy has been investigated using Acid Blue 113, an organic textile dye as the model organic pollutant, thereby rooting its decontamination potential towards dye effluents from textile and dye industries. The controlled stoichiometric surface doping of Bi3+ with the continuous framework of the TiO2 monolithic material not only ensures visible light-induced photocatalysis but also high quantum yield upon light impingement thereby leading a rapid generation of reactive radical species. The monolith structural properties and its morphology are characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), selected area electron diffraction (SAED), energy dispersive X-ray spectrometry (EDAX), diffuse reflectance spectroscopy (DRS), photoluminescence spectroscopy (PLS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and N2 adsorption-desorption isotherm analysis. The anatase phase TiO2 monolith offers a high surface area that promotes the voluminous generation of photo-induced e−/h+ pairs that proceed towards the formation of reactive radical intermediates for the fast dissipation of pollutants. To valid the efficiency and effectiveness of the Bi3+ doped TiO2 monolith photocatalyst, a comprehensive study on the physicochemical parameters such as solution pH, dopant stoichiometry, photocatalyst quantity, light intensity, photosensitizers, and reusability, proves crucial. The results reveal that under optimized conditions, the photocatalyst has an ultra-fast response time of ≤0.2 h for complete mineralization, with 0.06 g of monolithic photocatalysts that are recoverable and reusable.

Liquid chromatography-tandem mass spectrometry metabolic profiling of nazartinib reveals the formation of unexpected reactive metabolites.

Nazartinib (EGF816, NZB) is a promising third-generation human epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This novel irreversible mutant-selective EGFR inhibitor targets EGFR containing both the resistance mutation (T790M) and the activating mutations (L858R and Del19), while it does not affect wild-type EGFR. However, the metabolic pathway and bioactivation mechanisms of NZB are still unexplored. Thus, using liquid chromatography–tandem mass spectrometry, we screened for products of NZB metabolism formed in vitro by human liver microsomal preparations and investigated the formation of reactive intermediates using potassium cyanide as a nucleophile trap. Unexpectedly, the azepane ring was not bioactivated. Instead, the carbon atom between the aliphatic linear tertiary amine and electron-withdrawing system (butenoyl amide group) was bioactivated, generating iminium intermediates as reactive species. Six NZB phase I metabolites, formed by hydroxylation, oxidation and N-demethylation, were characterized. Moreover, two reactive iminium ions were characterized and their corresponding bioactivation mechanisms were proposed. Based on our results, we speculate that bioactivation of NZB can be blocked by small sterically hindering groups, isosteric replacement or a spacer. This approach might reduce the toxicity of NZB by avoiding the generation of reactive species.

The assembly of (+)-vincadifformine- and (-)-tabersonine-derived monoterpenoid indole alkaloids in Catharanthus roseus involves separate branch pathways.

The biological activity of monoterpenoid indole alkaloids (MIAs) has led to their use in cancer treatment and other medical applications. Their biosynthesis has involved the formation of reactive intermediates by responsible enzymes to elaborate several different chemical scaffolds. Modification of scaffolds through different substitution reactions has produced chemically diverse MIAs and related biological activities. The present study characterizes the three-step pathway involved in the formation of (+)-echitovenine, the major O-acetylated MIA of Catharanthus roseus roots, and differentiates it from a parallel pathway involved in the formation of hörhammericine. Separate hydrolases convert a common reactive MIA intermediate to aspidosperma skeletons of opposite specific rotations, that is (+)-vincadifformine and (-)-tabersonine, respectively. The formation of (+) minovincinine from (+) vincadifformine 19-hydroxylase (V19H) is catalyzed by a root-specific cytochrome P450 with high amino acid sequence similarity to the leaf-specific tabersonine-3-hydroxylase involved in vindoline biosynthesis. Similarly, O-acetylation of (+)-minovincinine to form (+) echitovenine involves minovincinine-O-acetytransferase. The substrate specificity of V19H and MAT for their respective (+)-enantiomers defines the separate enantiomer-specific pathway involved in (+)-echitovenine biosynthesis and differentiates it from a parallel (-)-enantiomer-specific pathway involved in the formation of hörhammericine from (-)-tabersonine.

Interfacial vs Bulk Ozonolysis of Nerolidol.

Ozone readily reacts with olefins with the formation of more reactive Criegee intermediates (CIs). The transient CIs impact HO x cycles, and they play a role in new particle formation in the troposphere. Oxidation by O3 occurs both in the gas-phase, in the liquid phase, and at air-water and air-aerosol interfaces. In light of the importance of O3 in environmental and engineered chemical transformations, we have investigated the ozonolysis mechanisms of a triolefin C15-alcohol, nerolidol (Nero, a biogenic sesquiterpene), at the air-water interface in the presence of acetonitrile. Surface-sensitive pneumatic ionization mass spectrometric detection of α-hydroxy-hydroperoxides and functionalized carboxylates, generated by the hydration and isomerization of CIs, respectively, enables us to evaluate the relative reactivity of each C=C toward O3. In addition, we compare bulk-phase ozonolysis chemistry to similar reactions taking place at the air-water interface. Our experimental results show that O3 reacts primarily with the (CH3)2C=CH- and -(CH3)C=CH- moieties (>∼98%), while the O3 attack on the terminal -HC=CH2 site (<∼2%) is a minor pathway during both interfacial and bulk ozonolysis. The presence of functionalized-carboxylates on interfaces but not in bulk-phase reactions with O3 indicates that the isomerization of the CIs is not hindered at the air-water interface due to the lower availability of water .

Application of in vitro Drug Metabolism Studies in Chemical Structure Optimization for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP).

Currently no approved treatment exists for fibrodysplasia ossificans progressiva (FOP) patients, and disease progression results in severe restriction of joint function and premature mortality. LDN-193189 has been demonstrated to be efficacious in a mouse FOP disease model after oral administration. To support species selection for drug safety evaluation and to guide structure optimization for back-up compounds, in vitro metabolism of LDN-193189 was investigated in liver microsome and cytosol fractions of mouse, rat, dog, rabbit, monkey and human. Metabolism studies included analysis of reactive intermediate formation using glutathione and potassium cyanide (KCN) and analysis of non-P450 mediated metabolites in cytosol fractions of various species. Metabolite profiles and metabolic soft spots of LDN-193189 were elucidated using LC/UV and mass spectral techniques. The in vitro metabolism of LDN-193189 was significantly dependent on aldehyde oxidase, with formation of the major NIH-Q55 metabolite. The piperazinyl moiety of LDN-193189 was liable to NADPH-dependent metabolism which generated reactive iminium intermediates, as confirmed through KCN trapping experiments, and aniline metabolites (M337 and M380), which brought up potential drug safety concerns. Subsequently, strategies were employed to avoid metabolic liabilities leading to the synthesis of Compounds 1, 2, and 3. This study demonstrated the importance of metabolite identification for the discovery of novel and safe drug candidates for the treatment of FOP and helped medicinal chemists steer away from potential metabolic liabilities.

Mechanistic Role of Cytochrome P450 (CYP) 1 Enzymes in Polycyclic Aromatic Hydrocarbon (PAH)‐Mediated Carcinogenesis

Lung cancer is the leading cause of cancer‐related deaths in the United States. Polycyclic aromatic hydrocarbons (PAHs) are a group of chemicals that increase the risk of lung cancer in humans. PAHs induce phase I and II metabolism enzymes through aryl hydrocarbon receptor (AhR)‐ dependent and independent pathways. Cytochrome P450 (CYPs) enzymes are among these phase I enzymes and promote detoxification of PAHs. However, CYP1A1, 1A2, and 1B1, which belong to the CYP1A1 family of enzymes, are also involved in the bioactivation of PAHs, leading to the formation of reactive intermediates that can form mutagenic DNA adducts. In this study, we hypothesized that mice lacking all the genes of the Cyp1 family will be resistant to PAH‐mediated pulmonary carcinogenesis. To test this hypothesis, A/J (WT) and Cyp1a1/1a2/1b1‐triple knockout (Cyp1‐3ko) mice were exposed to 3‐methylcholanthrene (MC; 100 μmol/kg), benzo(a)pyrene (BP; 200 μmol/kg), or corn oil (vehicle) via a single intraperitoneal injection. Liver and lung tissues were harvested at 1, 8, and 15 days post PAH exposure for our short‐term studies. Mice in our tumor study were harvested 36 weeks post PAH exposure for tumor incidence and multiplicity analysis. We found that MC caused significant induction of hepatic CYP1A1/1A2 gene expression in WT but not CYP1‐3KO mice at each time point. MC treatment caused formation of DNA adducts in liver and lung for up to 15 days post MC treatment in both genotypes. However, compared to WT animals, Cyp1‐3ko mice had significantly reduced hepatic DNA adducts on day 15 and up to 95% less pulmonary DNA adducts at 1, 8 and 15 days post MC treatment. In addition to the DNA adduct inhibition, Cyp1‐3ko mice formed 93% less pulmonary tumors compared to their MC treated WT counterparts. The significant reduction in DNA adducts and pulmonary tumors in Cyp1‐3ko mice provide strong evidence of the mechanistic role these enzymes play in PAH‐mediated carcinogenesis. Future studies on the specific role of each of the enzymes of the CYP1A family will be important for the identification of specific targets that could be used in the prevention and/or treatment of lung carcinogenesis in humans exposed to PAHs and other environmental carcinogens.Support or Funding Information1R01ES029382‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Benzyne Cascade Reactions via Benzoxetenonium Ions and Their Rearrangements to o-Quinone Methides.

A new thermal isomerization of polyynes is described. Benzyne intermediates substituted by a C(RR')OR'' substituent adjacent to one of the benzyne sp-hybridized carbons give rise to products in which the OR' moiety has migrated to the proximal benzyne carbon. This process likely proceeds via sequential formation of multiple reactive intermediates: an initial thermally generated benzyne, a strained benzoxetenonium ion, and an o-quinone methide. As some examples demonstrate, the overall transformation can be quite efficient. The mechanism of this novel reaction is further supported by experiments and DFT calculations.

First oxidation products from the reaction of hydroxyl radicals with isoprene for pristine environmental conditions

Isoprene, C5H8, inserts about half of the non-methane carbon flux of biogenic origin into the atmosphere. Its degradation is primarily initiated by the reaction with hydroxyl radicals. Here we show experimentally the formation of reactive intermediates and corresponding closed-shell products from the reaction of hydroxyl radicals with isoprene for low nitric oxide and low hydroperoxy radical conditions. Detailed product analysis is achieved by mass spectrometric techniques. Quantum chemical calculations support the usefulness of applied ionization schemes. Observed peroxy radicals are the isomeric HO-C5H8O2 radicals and their isomerization products HO-C5H8(O2)O2, bearing most likely an additional hydroperoxy group, and in traces HO-C5H8(O2)2O2 with two hydroperoxy groups. Main closed-shell products from unimolecular peroxy radical reactions are hydroperoxy aldehydes, C5H8O3, and smaller yield products with the composition C5H8O4 and C4H8O5. Detected signals of C10H18O4, C10H18O6, and C5H10O2 stand for products arising from peroxy radical self- and cross-reactions.

Indirect Photodegradation of Sulfamethoxazole in Water

Indirect photodegradation is one of the primary approaches for the removal of pharmaceutical contaminants from water. This degradation process is dominated by chromophoric dissolved organic matter (CDOM). After illumination, CDOM produces many reactive intermediates, which can react with drug pollutants to achieve indirect photodegradation. In this article, we focused on four different sources of CDOM and factors affecting indirect sulfamethoxazole (SMZ) photolysis. The results show that the indirect photodegradation effect of SMZ is significantly influenced by CDOM. This indirect photodegradation has a dual nature. It promotes the indirect photodegradation of SMZ through the formation of various reactive intermediates and at the same time inhibits the photodegradation of SMZ through light shielding and masking of reactive intermediates. The indirect photodegradation of SMZ is mainly controlled by active intermediates such as 3CDOM*, HO·, and 1O2 produced by CDOM; 3CDOM* is the main participant in indirect photodegradation of SMZ. In addition, the pH, salinity, and nitrate ions have a significant effect on the indirect photodegradation of SMZ, while bicarbonate ions have no significant effect on the indirect photodegradation of SMZ.

Identification of reactive intermediate formation and bioactivation pathways in Abemaciclib metabolism by LC-MS/MS: in vitro metabolic investigation.

Abemaciclib (Verzenio®) is approved as a tyrosine kinase inhibitor (TKI) for breast cancer treatment. In this study, in vitro phase I metabolic profiling of Abemaciclib (ABC) was done using rat liver microsomes (RLMs). We checked the formation of reactive intermediates in ABC metabolism using RLMs in the presence of potassium cyanide (KCN) that was used as a capturing agent for iminium reactive intermediates forming a stable complex that can be characterized by LC–MS/MS. Nine in vitro phase I metabolites and three cyano adducts were identified. The metabolic reactions involved in the formation of these metabolites and adducts are reduction, oxidation, hydroxylation and cyanide addition. The bioactivation pathway was also proposed. Knowing the electrodeficient bioactive centre in ABC structure helped in making targeted modifications to improve its safety and retain its efficacy. Blocking or isosteric replacement of α-carbon to the tertiary nitrogen atoms of piperazine ring can aid in reducing toxic side effects of ABC. No previous articles were found about in vitro metabolic profiling for ABC or structural identification of the formed reactive metabolites for ABC.

Bifunctional Phenol Quinone Methide Precursors: Synthesis and Biological Activity

New bifunctional quinone methide (QM) precursors, bisphenols 2a–2e, and monofunctional QM precursor 7 were synthesized. Upon treatment with fluoride, desilylation triggers formation of reactive intermediates, QMs, which was demonstrated by trapping QM with azide or methanol. The ability of QMs to alkylate and cross-link DNA was assayed by investigation of the effects of QMs to DNA denaturing, but without conclusive evidence. Furthermore, treatment of a plasmid DNA with compounds 2a–2e and KF, followed by the analysis by alkaline denaturing gel electrophoresis, did not provide evidence for the DNA cross-linking. MTT test performed on two human cancer cell lines (MCF7 breast adenocarcinoma and SUM159 pleomorphic breast carcinoma), with and without fluoride, indicated that 2a–2e or the corresponding QMs did not exhibit cytotoxic activity, in line with the lack of ability to cross-link DNA. The lack of reactivity with DNA and biological activity were explained by sequential formation of QMs where bifunctional cytotoxic reagent is probably never produced. Instead, the sequential generation of monofunctional QM followed by a faster hydrolysis leads to the destruction of biologically active reagent. The findings described here are particularly important for the rational design of new generation of QM precursor molecules that will attain desirable DNA reactivity and cytotoxicity.

Photocatalytic Oxyamination of Alkenes: Copper(II) Salts as Terminal Oxidants in Photoredox Catalysis

A photocatalytic method for the oxyamination of alkenes using simple nucleophilic nitrogen atom sources in place of prefunctionalized electrophilic nitrogen atom donors is reported. Copper(II) is an inexpensive, practical, and uniquely effective terminal oxidant for this process. In contrast to oxygen, peroxides, and similar oxidants commonly utilized in non-photochemical oxidative methods, the use of copper(II) as a terminal oxidant in photoredox reactions avoids the formation of reactive heteroatom-centered radical intermediates that can be incompatible with electron-rich functional groups. As a demonstration of the generality of this concept, it has been shown that diamination and deoxygenation reactions can also be accomplished using similar photooxidative conditions.

Oxygen-Incorporated NiMoP2 Nanowire Arrays for Enhanced Hydrogen Evolution Activity in Alkaline Solution

Catalytic water splitting for commercial hydrogen production demands efficient and robust earth-abundant catalysts. However, sluggish kinetics of water dissociation in alkaline electrolyte impedes the formation of reactive intermediates by discharge of water. Here, oxygen-incorporated NiMoP2 nanowire arrays are engineered on Ni foam substrate (denoted as O-NiMoP2/Ni) by controllable partial phosphorization of metal oxide precursors to boost HER activity under alkaline environment. The incorporation of oxygen can significantly modify the electronic structure of NiMoP2 and optimize both HER Gibbs free-energy change (ΔGH*) and water adsorption energy change (ΔGH2O*). Results demonstrate that the O-NiMoP2/Ni nanowire arrays require quite low HER overpotentials of 31 and 134 mV to drive the geometrical catalytic current densities of 10 and 100 mA cm–2, respectively. The activity and stability in 1 M KOH are also superior to those of the state-of-the-art transition-metal phosphides (TMPs).