From rust to robust disinfectants: How do iron oxides and inorganic oxidants synergize with UVA light towards bacterial inactivation?

Pathogens in drinking water remain a challenge for human health, photo-Fenton process is a promising technique for pathogen inactivation, herein, two common iron oxides, hematite and magnetite mediate persulfate (peroxymonosulfate-PMS - and peroxydisulfate-PDS) involved photo-Fenton-like processes were constructed for E. coli inactivation, and the inactivation performance was investigated and compared with the photo-Fenton process under a low intensity UVA irradiation. Results indicated that with a low dose of iron oxides (1 mg/L) and inorganic peroxides (10 mg/L), PMS-involved photo-Fenton-like process is the best substitute for the photo-Fenton one over pH range of 5-8. In addition, humic acid (HA, one of the important components of natural organic matter) incorporated iron oxide-mediated photo-Fenton-like processes for bacteria inactivation was also studied, and facilitating effect was found in UVA/hematite/PMS and UVA/magnetite/PDS systems. Reactive oxygen species (ROS) exploration experiments revealed that ·OH was the predominant radical in H2O2- and PDS-containing systems, whereas 1O2 was one of the principal reactive species in the PMS systems. In addition to the semiconductor photocatalysis of iron oxides and UVA-activated oxidants, iron-complexes (iron-oxidant complexes and iron-bacteria complexes) mediated ligand-to-metal charge transfer (LMCT) processes also made contribution to bacterial inactivation. Overall, this study demonstrates that it is feasible to replace H2O2 with PMS in a photo-Fenton-like process for water disinfection using a low dose of reagents, mediated by cheap catalysts, such as hematite and magnetite, it is also hoped to provide some insights to practical water treatment.

Dioxygen Reduction and Bioinspired Oxidations by Non-heme Iron(II)-α-Hydroxy Acid Complexes.

ConspectusAerobic organisms involve dioxygen-activating iron enzymes to perform various metabolically relevant chemical transformations. Among these enzymes, mononuclear non-heme iron enzymes reductively activate dioxygen to catalyze diverse biological oxidations, including oxygenation of C-H and C═C bonds and C-C bond cleavage with amazing selectivity. Several non-heme enzymes utilize organic cofactors as electron sources for dioxygen reduction, leading to the generation of iron-oxygen intermediates that act as active oxidants in the catalytic cycle. These unique enzymatic reactions influence the design of small molecule synthetic compounds to emulate enzyme functions and to develop bioinspired catalysts for performing selective oxidation of organic substrates with dioxygen. Selective electron transfer during dioxygen reduction on iron centers of synthetic models by a sacrificial reductant requires appropriate design strategies. Taking lessons from the role of enzyme-cofactor complexes in the selective electron transfer process, our group utilized ternary iron(II)-α-hydroxy acid complexes supported by polydentate ligands for dioxygen reduction and bioinspired oxidations. This Account focuses on the role of coordinated sacrificial reductants in the selective electron transfer for dioxygen reduction by iron complexes and highlights the versatility of iron(II)-α-hydroxy acid complexes in affecting dioxygen-dependent oxidation/oxygenation reactions. The iron(II)-coordinated α-hydroxy acid anions undergo two-electron oxidative decarboxylation concomitant with the generation of reactive iron-oxygen oxidants. A nucleophilic iron(II)-hydroperoxo species was intercepted in the decarboxylation pathway. In the presence of a Lewis acid, the O-O bond of the nucleophilic oxidant is heterolytically cleaved to generate an electrophilic iron(IV)-oxo-hydroxo oxidant. Most importantly, the oxidants generated with or without Lewis acid can carry out cis-dihydroxylation of alkenes. Furthermore, the electrophilic iron-oxygen oxidant selectively hydroxylates strong C-H bonds. Another electrophilic iron(IV)-oxo oxidant, generated from the iron(II)-α-hydroxy acid complexes in the presence of a protic acid, carries out C-H bond halogenation by using a halide anion.Thus, different metal-oxygen intermediates could be generated from dioxygen using a single reductant, and the reactivity of the ternary complexes can be tuned using external additives (Lewis/protic acid). The catalytic potential of the iron(II)-α-hydroxy complexes in performing O2-dependent oxygenations has been demonstrated. Different factors that govern the reactivity of iron-oxygen oxidants from ternary iron(II) complexes are presented. The versatile reactivity of the oxidants provides useful insights into developing catalytic methods for the selective incorporation of oxidized functionalities under environmentally benign conditions using aerial oxygen as the terminal oxidant.

Unveiling the treatment-driven secondary risks of pharmaceuticals: New lessons from calcium channel blocker transformation by multiple oxidants.

The worldwide detection of numerous pharmaceuticals and their transformation products (TPs) in different environmental matrices has gained considerable concern about their potential ecological hazards. Increasing evidence suggested that calcium channel blockers (CCBs) are ubiquitous pharmaceutical pollutants in natural waters. However, their TPs, reaction pathways, and secondary risks have been limitedly known during oxidative water treatment. This study systematically assessed the TP formation and transformation mechanisms of two typical CCBs (i.e., amlodipine, AML; verapamil, VER) oxidized by ferrate(VI), permanganate, and ozone, as well as the in silico prediction on the TPs' properties. The high-resolution mass spectrometer analysis suggested a total of 16 TPs of AML and 8 TPs of VER identified for these reaction systems. Transformation of AML mainly proceeded through hydroxylation of the aromatic ring, ether bond cleavage, NH2 substitution by a hydroxyl group, and H-abstraction, while VER was oxidized via hydroxylation/opening of the aromatic ring and cleavage of the CN bond. Notably, certain TPs of both CCBs were estimated with low biodegradation, multi-endpoint toxicity, and high persistence and bioaccumulation, suggesting their severe risks to aquatic ecosystems. This study has implications for understanding the environmental behaviors, fate, and secondary risks of the globally prevalent and concerned CCBs under oxidative water treatment scenarios.

Methylmercury Degradation by Trivalent Manganese.

Methylmercury (MeHg) is a potent neurotoxin and has great adverse health impacts on humans. Organisms and sunlight-mediated demethylation are well-known detoxification pathways of MeHg, yet whether abiotic environmental components contribute to MeHg degradation remains poorly known. Here, we report that MeHg can be degraded by trivalent manganese (Mn(III)), a naturally occurring and widespread oxidant. We found that 28 ± 4% MeHg could be degraded by Mn(III) located on synthesized Mn dioxide (MnO2-x) surfaces during the reaction of 0.91 µg·L-1 MeHg and 5 g·L-1 mineral at an initial pH of 6.0 for 12 h in 10 mM NaNO3 at 25 °C. The presence of low-molecular-weight organic acids (e.g., oxalate and citrate) substantially enhances MeHg degradation by MnO2-x via the formation of soluble Mn(III)-ligand complexes, leading to the cleavage of the carbon-Hg bond. MeHg can also be degraded by reactions with Mn(III)-pyrophosphate complexes, with apparent degradation rate constants comparable to those by biotic and photolytic degradation. Thiol ligands (cysteine and glutathione) show negligible effects on MeHg demethylation by Mn(III). This research demonstrates potential roles of Mn(III) in degrading MeHg in natural environments, which may be further explored for remediating heavily polluted soils and engineered systems containing MeHg.

Reactivities of iron(IV)-oxido compounds with pentadentate bispidine ligands.

The FeIVO complexes of bispidines (3,7-diazabicyclo[3.3.1]nonane derivatives) are known to be highly reactive oxidants - with the tetradentate bispidine, the so far most reactive ferryl complex has been reported and two isomeric pentadentate ligands also lead to very reactive high-valent oxidants. With a series of 4 new bispidine derivatives we now try to address the question why the bispidine scaffold in general leads to very reactive oxidants and how this can be tuned by ligand modifications. The study is based on a full structural, spectroscopic and electrochemical analysis of the iron(II) precursors, spectroscopic data of the iron(IV)-oxido complexes, a kinetic analysis of the stoichiometric oxidation of thioanisole by five different bispidine­iron(IV)-oxido complexes and on product analyses of reactions by the five ferryl oxidants with thioanisole, ß-methylstyrene and cis-stilbene as substrates.

Oxidative potential of two Brazilian endophytic fungi from Handroanthus impetiginosus towards progesterone.

Biotransformation has been successfully employed to conduct uncommon reactions, which would hardly be carried out by chemical synthesis. A wide diversity of compounds may be metabolized by fungi, leading to chemical derivatives through selective reactions that work under ecofriendly conditions. Endophytic fungi live inside vegetal tissues without causing damage to the host plant, making available unique enzymes for interesting chemical derivatization. Biotransformation of steroids by endophytic fungi may provide new derivatives as these microorganisms came from uncommon and underexplored habitats. In this study, endophytic strains isolated from Handroanthus impetiginosus leaves were assayed for biotransformation of progesterone, and its derivatives were identified through GC-EI-MS analysis. The endophyte Talaromyces sp. H4 was capable of transforming the steroidal nucleus selectively into four products through selective ene-reduction of the C4-C5 double bond and C-17 oxidation. The best conversion rate of progesterone (>90 %) was reached with Penicillium citrinum H7 endophytic strain that transformed the substrate into one derivative. The results highlight endophytic fungi's potential to obtain new and interesting steroidal derivatizations.

Nano- and micro-scale zerovalent iron-activated peroxydisulfate for methyl phenyl sulfoxide probe transformation in aerobic water: Quantifying the relative roles of SO4·-, Fe(IV), and ·OH.

Multiple reactive intermediates have been proposed to be involved in peroxydisulfate (PDS) activation by zerovalent iron (ZVI), including sulfate radical (SO4·-) produced via iron-oxide shell mediated electron transfer, ferryl ion species (Fe(IV)) formed from Fe(II)-PDS interaction, and hydroxyl radical (·OH) generated by ZVI aerobic oxygenation. In this study, evolution of the relative role of these intermediates in microscale and nanoscale ZVI (mZVI vs. nZVI) activated PDS processes is comparatively investigated by using a methyl phenyl sulfoxide (PMSO) probe that selectively reacts with Fe(IV) to produce methyl phenyl sulfone (PMSO2). Interestingly, during PMSO transformation by mZVI/PDS process, yields of PMSO2 (η(PMSO2)) exhibit three-stage behavior that they first increase to a maximum (∼80% but lower than 100%) (Stage I) and then plateau for a period (Stage II) followed by a decrease phase (Stage III). Accordingly, the relative role of Fe(IV) in PMSO transformation is unceasingly improved in Stage I and subsequently reaches equilibrium with that of free radicals in Stage II, while it finally decreases in Stage III. Similar η(PMSO2) evolution trends are obtained in nZVI/PDS process, except that the η(PMSO2) increase in Stage I is negligible, possibly due to the exceptional fast nZVI dissolution. It was further clarified by tert-butyl alcohol scavenging assay that, in addition to Fe(IV), the free radical involved in Stages I and II is SO4·-, while ·OH was dominant in Stage III. Moreover, studies on O2 effect reveal that ZVI aerobic oxygenation participates in mZVI corrosion during the entire process, while it is only involved in nZVI corrosion when PDS content is reduced to a low concentration, indicating that the reactivities of PDS and O2 are similar in mZVI corrosion, but differ greatly in nZVI corrosion. Additionally, effects of reactant dose and pH on η(PMSO2) evolution are also explored. Dynamics of the relative role of different reactive oxidants should be taken into account in further applications of ZVI/PDS in situ chemical remediation technology considering their different chemistries.

Biosynthesis of tetrahydropapaverine and semisynthesis of papaverine in yeast.

Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and cisatracurium, and papaverine is used as an antispasmodic during vascular surgery. In recent years, metabolic engineering advances have enabled the production of natural products through heterologous expression of pathway enzymes in yeast. Heterologous biosynthesis of THP and papaverine could play a role in ensuring a stable supply of these clinically significant products. Biosynthesis of THP and papaverine has not been achieved to date, in part because multiple pathway enzymes have not been elucidated. Here, we describe the development of an engineered yeast strain for de novo biosynthesis of THP. The production of THP is achieved through heterologous expression of two enzyme variants with activity on nonnative substrates. Through protein engineering, we developed a variant of N-methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9-O-methyltransferase capable of O-methylating 1-benzylisoquinoline alkaloids at the 3' position, enabling de novo THP biosynthesis. Flux through the heterologous pathway was improved by knocking out yeast multidrug resistance transporters and optimization of media conditions. Overall, strain engineering increased the concentration of biosynthesized THP 600-fold to 121 µg/L. Finally, we demonstrate a strategy for papaverine semisynthesis using hydrogen peroxide as an oxidizing agent. Through optimizing pH, temperature, reaction time, and oxidizing agent concentration, we demonstrated the ability to produce semisynthesized papaverine through oxidation of biosynthesized THP.

Which is the real oxidant in competitive ligand self-hydroxylation and substrate oxidation-a biomimetic iron(II)-hydroperoxo species or an oxo-iron(IV)-hydroxy one?

Nonheme iron(II)-hydroperoxo species (FeII-(η2-OOH)) 1 and the concomitant oxo-iron(IV)-hydroxyl one 2 are proposed as the key intermediates of a large class of 2-oxoglutarate dependent dioxygenases (e.g., isopenicillin N synthase). Extensive biomimetic experiments have been exerted to identify which one is the real oxidant and to reveal the structure-function relationship of them, whereas the mechanistic picture is still elusive. To this end, density functional theory (DFT) calculations were performed to systematically study the mechanistic details of ligand self-hydroxylation and competitive substrate oxidation by these two species supported by a tridentate ligand Fe(TpPh2)(benzilate) (TpPh2 = hydrotris(3,5-diphenylpyrazole-1-yl)borate). The calculated results revealed that the structure and the conversion of the FeII-(η2-OOH) complex 1 are obviously different from the ferric FeIII-OOH one. The orientation of the Fe-OOH moiety of 1 is side-on, while that of the ferric FeIII-OOH species is end-on. The conversion of 1 to the high-valent iron-oxo species is exothermic, while the conversion of the ferric FeIII-OOH species to the high-valent species is endothermic. Thus, the sluggish 1 does not act as the oxidant and readily decays to the robust 2. The activation energy of intramolecular ligand self-hydroxylation in 2 is 14.8 kcal mol-1 and intermolecular substrate oxidations (e.g., thioanisole sulfoxidation) with a lower barrier show a strong inhibiting ability toward ligand self-hydroxylation, while those with a higher barrier (e.g., cyclohexane hydroxylation) have no effect. Our theoretical results fit nicely with the experimental observations and will enrich the knowledge of the metal-oxygen intermediate and play a positive role in the rational design of new biomimetic catalysts.

Dehydromethionine is a common product of methionine oxidation by singlet molecular oxygen and hypohalous acids.

Methionine is one of the main targets for biological oxidants. Its reaction with the majority of oxidants generates only methionine sulfoxide. However, when N-terminal methionine reacts with hypohalous acids (HOCl and HOBr) or singlet molecular oxygen (1O2), it can also generate a cyclic product called dehydromethionine (DHM). Previously, DHM was suggested as a biomarker of oxidative stress induced by hypohalous acids. However, DHM can also be generated by 1O2 -oxidation of methionine, and the contribution of this pathway of DHM formation in a context of a site-specific redox imbalance in an organism is unknown. In this work, a through comparison of the reactions of hypohalous acids and 1O2 with methionine, either free or inserted in peptides and proteins was undertaken. In addition, we performed methionine photooxidation in heavy water (H218O) to determine the influence of the pH in the mechanism of DHM formation. We showed that for free methionine, or methionine-containing peptides, the yields of DHM formation in the reactions with 1O2 were close to those achieved by HOBr oxidation, but much higher than the yields obtained with HOCl as the oxidant. This was true for all pH tested (5, 7.4, and 9). Interestingly, for the protein ubiquitin, DHM yields after reaction with 1O2 were higher than those obtained with both hypohalous acids. Our results indicate that 1O2 may also be an important source of DHM in biological systems.

In Silico simulation of Cytochrome P450-Mediated metabolism of aromatic amines: A case study of N-Hydroxylation.

Aromatic amines, the widely used raw materials in industry, cause long-term exposure to human bodies. They can be metabolized by cytochrome P450 enzymes to form active electrophilic compounds, which will potentially react with nucleophilic DNA to exert carcinogenesis. The short lifetime and versatility of the oxidant (a high-valent iron (IV)-oxo species, compound I) of P450 enzymes prompts us to use theoretical methods to investigate the metabolism of aromatic amines. In this work, the density functional theory (DFT) has been employed to simulate the hydroxylation metabolism through H-abstraction and to calculate the activation energy of this reaction for 28 aromatic amines. The results indicate that the steric effects, inductive effects and conjugative effects greatly contribute to the metabolism activity of the chemicals. The further correlation reveals that the dissociation energy of -NH2 (BDEN-H) can successfully predict the time-consuming calculated activation energy (R2 for aromatic and heteroaromatic amines are 0.93 and 0.86, respectively), so BDEN-H can be taken as a key parameter to characterize the relative stability of aromatic amines in P450 enzymes and further to quickly assess their potential toxicity. The validation results prove such relationship has good statistical performance (qcv2 for aromatic and heteroaromatic amines are 0.95 and 0.90, respectively) and can be used to other aromatic amines in the application domain, greatly reducing computational cost and providing useful support for experimental research.

Density Functional Theory Investigation of the Biocatalytic Mechanisms of pH-Driven Biomimetic Behavior in CeO2.

There is considerable interest in the pH-dependent, switchable, biocatalytic properties of cerium oxide (CeO2) nanoparticles in biomedicine, where these materials exhibit beneficial antioxidant activity against reactive oxygen species (ROS) at a basic physiological pH but cytotoxic prooxidant activity in an acidic cancer cell pH microenvironment. While the general characteristics of the role of oxygen vacancies are known, the mechanism of their action at the atomic scale under different pH conditions has yet to be elucidated. The present work applies density functional theory (DFT) calculations to interpret, at the atomic scale, the pH-induced behavior of the stable {111} surface of CeO2 containing oxygen vacancies. Analysis of the surface-adsorbed media species reveals the critical role of pH on the interaction between ROS (•O2- and H2O2) and the defective CeO2 {111} surface. Under basic conditions, the superoxide dismutase (SOD) and catalase (CAT) biomimetic reactions can be performed cyclically, scavenging and decomposing ROS to harmless products, making CeO2 an excellent antioxidant. However, under acidic conditions, the CAT biomimetic reaction is hindered owing to the limited reversibility of Ce3+ ↔ Ce4+ and formation ↔ annihilation of oxygen vacancies. A Fenton biomimetic reaction (H2O2 + Ce3+ → Ce4+ + OH- + •OH) is predicted to occur simultaneously with the SOD and CAT biomimetic reactions, resulting in the formation of hydroxyl radicals, making CeO2 a cytotoxic prooxidant.

Molecular Mechanisms of Action of Selected Substances Involved in the Reduction of Benzo[a]pyrene-Induced Oxidative Stress.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) primarily formed by burning of fossil fuels, wood and other organic materials. BaP as group I carcinogen shows mutagenic and carcinogenic effects. One of the important mechanisms of action of (BaP) is its free radical activity, the effect of which is the induction of oxidative stress in cells. BaP induces oxidative stress through the production of reactive oxygen species (ROS), disturbances of the activity of antioxidant enzymes, and the reduction of the level of non-enzymatic antioxidants as well as of cytokine production. Chemical compounds, such as vitamin E, curcumin, quercetin, catechin, cyanidin, kuromanin, berberine, resveratrol, baicalein, myricetin, catechin hydrate, hesperetin, rhaponticin, as well as taurine, atorvastatin, diallyl sulfide, and those contained in green and white tea, lower the oxidative stress induced by BaP. They regulate the expression of genes involved in oxidative stress and inflammation, and therefore can reduce the level of ROS. These substances remove ROS and reduce the level of lipid and protein peroxidation, reduce formation of adducts with DNA, increase the level of enzymatic and non-enzymatic antioxidants and reduce the level of pro-inflammatory cytokines. BaP can undergo chemical modification in the living cells, which results in more reactive metabolites formation. Some of protective substances have the ability to reduce BaP metabolism, and in particular reduce the induction of cytochrome (CYP P450), which reduces the formation of oxidative metabolites, and therefore decreases ROS production. The aim of this review is to discuss the oxidative properties of BaP, and describe protective activities of selected chemicals against BaP activity based on of the latest publications.

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production.

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H2O2. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.

Aqueous Iron(IV)-Oxo Complex: An Emerging Powerful Reactive Oxidant Formed by Iron(II)-Based Advanced Oxidation Processes for Oxidative Water Treatment.

High-valent iron(IV)-oxo complexes are of great significance as reactive intermediates implicated in diverse chemical and biological systems. The aqueous iron(IV)-oxo complex (FeaqIVO2+) is the simplest but one of the most powerful ferryl ion species, which possesses a high-spin state, high reduction potential, and long lifetime. It has been well documented that FeaqIVO2+ reacts with organic compounds through various pathways (hydrogen-atom, hydride, oxygen-atom, and electron transfer as well as electrophilic addition) at moderate reaction rates and show selective reactivity toward inorganic ions prevailing in natural water, which single out FeaqIVO2+ as a superior candidate for oxidative water treatment. This review provides state-of-the-art knowledge on the chemical properties and oxidation mechanism and kinetics of FeaqIVO2+, with special attention to the similarities and differences to two representative free radicals (hydroxyl radical and sulfate radical). Moreover, the prospective role of FeaqIVO2+ in Feaq2+ activation-initiated advanced oxidation processes (AOPs) has been intensively investigated over the past 20 years, which has significantly challenged the conventional recognition that free radicals dominated in these AOPs. The latest progress in identifying the contribution of FeaqIVO2+ in Feaq2+-based AOPs is thereby reviewed, highlighting controversies on the nature of the reactive oxidants formed in several Feaq2+ activated peroxide and oxyacid processes. Finally, future perspectives for advancing the evaluation of FeaqIVO2+ reactivity from an engineering viewpoint are proposed.

The Peroxymonocarbonate Anion HCO4- as an Effective Oxidant in the Gas Phase: A Mass Spectrometric and Theoretical Study on the Reaction with SO2.

The peroxymonocarbonate anion, HCO4-, the covalent adduct between the carbon dioxide and hydrogen peroxide anion, effectively reacts with SO2 in the gas phase following three oxidative routes. Mass spectrometric and electronic structure calculations show that sulphur dioxide is oxidised through a common intermediate to the hydrogen sulphate anion, sulphur trioxide, and sulphur trioxide anion as primary products through formal HO2-, oxygen atom, and oxygen ion transfers. The hydrogen sulphite anion is also formed as a secondary product from the oxygen atom transfer path. The uncommon nucleophilic behaviour of HCO4- is disclosed by the Lewis acidic properties of SO2, an amphiphilic molecule that forms intermediates with characteristic and diagnostic geometries with peroxymonocarbonate.

Comparative Study of Antioxidant and Pro-Oxidant Properties of Homoleptic and Heteroleptic Copper Complexes with Amino Acids, Dipeptides and 1,10-Phenanthroline: The Quest for Antitumor Compounds.

In a search for new antitumoral agents, a series of homoleptic copper(II) complexes with amino acids and dipeptides, as well as heteroleptic complexes containing both dipeptides and 1,10-phenanthroline, were studied. Furthermore, a single-crystal structure containing alanyl-leucinato ([Cu3(AlaLeu)3(H2O)3(CO3)]·PF6·H2O), which is the first homotrinuclear carbonato-bridged copper(II) complex with a dipeptide moiety, is presented. To assess possible antitumor action mechanisms, we focused on the comparative analysis of pro- and antioxidant behaviors. Pro-oxidant activity, in which the reactive oxygen species (ROS) formed by the reaction of the complexes with H2O2 produce oxidative damage to 2-deoxy-d-ribose, was evaluated using the TBARS method. Additionally, the antioxidant action was quantified through the superoxide dismutase (SOD)-like activity, using a protocol based on the inhibitory effect of SOD on the reduction of nitrobluetetrazolium (NBT) by the superoxide anion generated by the xanthine/xanthine oxidase system. Our findings show that Cu-amino acid complexes are strong ROS producers and moderate SOD mimics. Conversely, Cu-dipeptide-phen complexes are good SOD mimics but poor ROS producers. The activity of Cu-dipeptide complexes was strongly dependent on the dipeptide. A DFT computational analysis revealed that complexes with high SOD-like activity tend to display a large dipole moment and condensed-to-copper charge, softness and LUMO contribution. Moreover, good ROS producers have higher global hardness and copper electrophilicity, lower copper softness and flexible and freely accessible coordination polyhedra.

Examining cellular responses to reconstituted antibody protein liquids.

Protein ionic liquids (PIL) are a new class of biologic stabilizers designed to protect the functionality and extend the shelf-life of biotechnological and therapeutic agents making them more readily available, and resistant to austere environments. Protein biorecognition elements such as monoclonal antibodies are commonly utilized therapeutics that require the robust stabilization offered by PILs, but biocompatibility remains an important issue. This study has focused on characterizing the biocompatibility of an antibody based PIL by exposing multiple cells types to a cationized immunoglobulin suspended in an anionic liquid (IgG-IL). The IgG-IL caused no significant alterations in cellular health for all three cell types with treatments < 12.5 µg/mL. Concentrations ≥ 12.5 µg/mL resulted in significant necrotic cell death in A549 and HaCaT cells, and caspase associated cell death in HepG2 cells. In addition, all cells displayed evidence of oxidative stress and IL-8 induction in response to IgG-IL exposures. Therapeutic Ig can be utilized with a wide dose range that extends into concentrations we have found to exhibit cytotoxicity raising a toxicity concern and a need for more extensive understanding of the biocompatibility of IgG-ILs.

Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion.

OBJECTIVE: Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. METHODS: Thirty healthy male Wistar rats (220 ± 20 g, 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. RESULTS: We found that the levels of adhesion scores and interleukin- (IL-) 1ß, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) ß 1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1ß, IL-6, and TNF-α), fibrosis (TGF-ß 1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. CONCLUSION: Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.

Adenine Radical Cation Formation by a Ligand-Centered Excited State of an Intercalated Chromium Polypyridyl Complex Leads to Enhanced DNA Photo-oxidation.

Assessment of the DNA photo-oxidation and synthetic photocatalytic activity of chromium polypyridyl complexes is dominated by consideration of their long-lived metal-centered excited states. Here we report the participation of the excited states of [Cr(TMP)2dppz]3+ (1) (TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) in DNA photoreactions. The interactions of enantiomers of 1 with natural DNA or with oligodeoxynucleotides with varying AT content (0-100%) have been studied by steady state UV/visible absorption and luminescence spectroscopic methods, and the emission of 1 is found to be quenched in all systems. The time-resolved infrared (TRIR) and visible absorption spectra (TA) of 1 following excitation in the region between 350 to 400 nm reveal the presence of relatively long-lived dppz-centered states which eventually yield the emissive metal-centered state. The dppz-localized states are fully quenched when bound by GC base pairs and partially so in the presence of an AT base-pair system to generate purine radical cations. The sensitized formation of the adenine radical cation species (A•+T) is identified by assigning the TRIR spectra with help of DFT calculations. In natural DNA and oligodeoxynucleotides containing a mixture of AT and GC of base pairs, the observed time-resolved spectra are consistent with eventual photo-oxidation occurring predominantly at guanine through hole migration between base pairs. The combined targeting of purines leads to enhanced photo-oxidation of guanine. These results show that DNA photo-oxidation by the intercalated 1, which locates the dppz in contact with the target purines, is dominated by the LC centered excited state. This work has implications for future phototherapeutics and photocatalysis.