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Journal of Hazardous Materials Jun 2023Harmful algal blooms (HABs) in coastal areas similarly impact both ecosystems and human health. The translocation of phytoplankton species via maritime transport can... (Review)
Review
Harmful algal blooms (HABs) in coastal areas similarly impact both ecosystems and human health. The translocation of phytoplankton species via maritime transport can potentially promote the growth of HABs in coastal systems. Accordingly, ballast water must be disinfected. The main goal of this study is to assess the effectiveness of different emerging biocides, including HO, peracetic acid (PAA), peroxymonosulfate (PMS), and peroxydisulfate (PDS). The effectiveness of these biocides is compared with that of conventional chlorination methods. Their effects on two ichthyotoxic microalgae with worldwide distribution, i.e., Prymnesium parvum and Heterosigma akashiwo, are examined. To ensure the prolonged effectiveness of the different reagents, their concentration-response curves for 14 days are constructed and examined. The results suggest a strong but shorter effect by PMS (EC50 = 0.40-1.99 mg·L) and PAA (EC50 = 0.32-2.70 mg·L), a maintained effect by HO (EC50 = 6.67-7.08 mg·L), and a negligible effect by PDS. H. akashiwo indicates higher resistance than P. parvum, except when HO is used. Based on the growth inhibition performance and consumption of the reagents as well as a review of important aspects regarding their application, using HO, PAA, or PMS can be a feasible alternative to chlorine-based reagents for inhibiting the growth of harmful phytoplankton.
Topics: Humans; Phytoplankton; Oxidants; Hydrogen Peroxide; Herbicides; Ecosystem; Harmful Algal Bloom; Disinfectants
PubMed: 36989795
DOI: 10.1016/j.jhazmat.2023.131279 -
Molecules (Basel, Switzerland) Dec 2021Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either... (Review)
Review
Covalent crosslinks within or between proteins play a key role in determining the structure and function of proteins. Some of these are formed intentionally by either enzymatic or molecular reactions and are critical to normal physiological function. Others are generated as a consequence of exposure to oxidants (radicals, excited states or two-electron species) and other endogenous or external stimuli, or as a result of the actions of a number of enzymes (e.g., oxidases and peroxidases). Increasing evidence indicates that the accumulation of unwanted crosslinks, as is seen in ageing and multiple pathologies, has adverse effects on biological function. In this article, we review the spectrum of crosslinks, both reducible and non-reducible, currently known to be formed on proteins; the mechanisms of their formation; and experimental approaches to the detection, identification and characterization of these species.
Topics: Animals; Cross-Linking Reagents; Disulfides; Enzymes; Humans; Oxidants; Oxidation-Reduction; Oxidative Stress; Peptides; Protein Aggregates; Proteins; Tandem Mass Spectrometry; Tryptophan; Tyrosine
PubMed: 35011250
DOI: 10.3390/molecules27010015 -
Journal of the American Chemical Society Oct 2022With the large number of Pd(II)-catalyzed C-H activation reactions of native substrates developed in the past decade, the development of catalysts to enable the use of...
With the large number of Pd(II)-catalyzed C-H activation reactions of native substrates developed in the past decade, the development of catalysts to enable the use of green oxidants under safe and practical conditions has become an increasingly important challenge. Notably, the compatibility of Pd(II) catalysts with sustainable aqueous HO has been a long-standing challenge in catalysis including Wacker-type oxidations. We report herein a bifunctional bidentate carboxyl-pyridone (CarboxPyridone) ligand that enables room-temperature Pd-catalyzed C-H hydroxylation of a broad range of benzoic and phenylacetic acids with an industry-compatible oxidant, aqueous hydrogen peroxide (35% HO). The scalability of this methodology is demonstrated by a 1000 mmol scale reaction of ibuprofen (206 g) using only a 1 mol % Pd catalyst loading. The utility of this protocol is further illustrated through derivatization of the products and synthesis of polyfluorinated natural product coumestan and pterocarpene from phenol intermediates prepared using this methodology.
Topics: Biological Products; Catalysis; Hydrogen Peroxide; Hydroxylation; Ibuprofen; Ligands; Oxidants; Palladium; Phenols; Phenylacetates; Pyridones; Temperature; Water
PubMed: 36137252
DOI: 10.1021/jacs.2c08332 -
Organic Letters May 2020For decades, oxidative dearomatization has been employed as a key step in the synthesis of complex molecules. Challenges in controlling the chemo- and site-selectivity...
For decades, oxidative dearomatization has been employed as a key step in the synthesis of complex molecules. Challenges in controlling the chemo- and site-selectivity of this transformation have sparked the development of a variety of specialized oxidants; however, these result in stoichiometric amounts of organic byproducts. Herein, we describe a photocatalytic method for oxidative dearomatization using molecular oxygen as the stoichiometric oxidant. This provides environmentally benign entry to highly substituted -quinols, reactive intermediates which can be elaborated to a number of natural product families.
Topics: Benzaldehydes; Catalysis; Hydroquinones; Oxidants, Photochemical; Oxidation-Reduction; Photochemical Processes
PubMed: 32293185
DOI: 10.1021/acs.orglett.0c01207 -
International Journal of Molecular... Oct 2021Interest in the use of pharmacological ascorbate as a treatment for cancer has increased considerably since it was introduced by Cameron and Pauling in the 1970s.... (Review)
Review
Interest in the use of pharmacological ascorbate as a treatment for cancer has increased considerably since it was introduced by Cameron and Pauling in the 1970s. Recently, pharmacological ascorbate has been used in preclinical and early-phase clinical trials as a selective radiation sensitizer in cancer. The results of these studies are promising. This review summarizes data on pharmacological ascorbate (1) as a safe and efficacious adjuvant to cancer therapy; (2) as a selective radiosensitizer of cancer via a mechanism involving hydrogen peroxide; and (3) as a radioprotector in normal tissues. Additionally, we present new data demonstrating the ability of pharmacological ascorbate to enhance radiation-induced DNA damage in glioblastoma cells, facilitating cancer cell death. We propose that pharmacological ascorbate may be a general radiosensitizer in cancer therapy and simultaneously a radioprotector of normal tissue.
Topics: Animals; Antioxidants; Ascorbic Acid; Humans; Hydrogen Peroxide; Neoplasms; Oxidants; Oxidative Stress; Radiation Tolerance; Radiation-Sensitizing Agents; Reactive Oxygen Species
PubMed: 34639220
DOI: 10.3390/ijms221910880 -
Proceedings of the National Academy of... Aug 2022Tetrahydropapaverine (THP) and papaverine are plant natural products with clinically significant roles. THP is a precursor in the production of the drugs atracurium and...
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 -methylcoclaurine hydroxylase with activity on coclaurine, enabling de novo norreticuline biosynthesis. Similarly, we developed a variant of scoulerine 9--methyltransferase capable of -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.
Topics: Biological Products; Cytochrome P-450 Enzyme System; Hydrogen Peroxide; Oxidants; Papaverine; Plant Proteins; Protein Engineering; Saccharomyces cerevisiae
PubMed: 35939674
DOI: 10.1073/pnas.2205848119 -
Oxidative Medicine and Cellular... 2020The nuclear transcription factor p53, discovered in 1979, has a broad range of biological functions, primarily the regulation of apoptosis, the cell cycle, and DNA... (Review)
Review
The nuclear transcription factor p53, discovered in 1979, has a broad range of biological functions, primarily the regulation of apoptosis, the cell cycle, and DNA repair. In addition to these canonical functions, a growing body of evidence suggests that p53 plays an important role in regulating intracellular redox homeostasis through transcriptional and nontranscriptional mechanisms. Oxidative stress induction and p53 activation are common responses to chemical exposure and are suggested to play critical roles in chemical-induced toxicity. The activation of p53 can exert either prooxidant or antioxidant activity, depending on the context. In this review, we discuss the functional role of p53 in regulating chemical-induced oxidative stress, summarize the potential signaling pathways involved in p53's regulation of chemically mediated oxidative stress, and propose issues that should be addressed in future studies to improve understanding of the relationship between p53 and chemical-induced oxidative stress.
Topics: Animals; Antioxidants; Humans; Oxidants; Oxidative Stress; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 32190175
DOI: 10.1155/2020/6039769 -
Free Radical Biology & Medicine Apr 2021Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from the competing...
Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from the competing substrates chloride and thiocyanate. MPO and the overproduction of HOCl are strongly linked with vascular cell dysfunction and inflammation in atherosclerosis. HOCl is highly reactive and causes marked cell dysfunction and death, whereas data with HOSCN are conflicting, and highly dependent on the nature of the cell type. In this study we have examined the reactivity of HOCl and HOSCN with human coronary artery smooth muscle cells (HCASMC), given the key role of this cell type in maintaining vascular function. HOCl reacts rapidly with the cells, resulting in extensive cell death by both necrosis and apoptosis, and increased levels of intracellular calcium. In contrast, HOSCN reacts more slowly, with cell death occurring only after prolonged incubation, and in the absence of the accumulation of intracellular calcium. Exposure of HCASMC to HOCl also influences mitochondrial respiration, decreases glycolysis, lactate release, the production of ATP, cellular thiols and glutathione levels. These changes occurred to varying extents on exposure of the cells to HOSCN, where evidence was also obtained for the reversible modification of cellular thiols. HOCl also induced alterations in the mRNA expression of multiple inflammatory and phenotypic genes. Interestingly, the extent and nature of these changes was highly dependent on the specific cell donor used, with more marked effects observed in cells isolated from diseased compared to healthy vessels. Overall, these data provide new insight into pathways promoting vascular dysfunction during chronic inflammation, support the use of thiocyanate as a means to modulate MPO-induced cellular damage in atherosclerosis.
Topics: Cell Line; Humans; Hypochlorous Acid; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Oxidants; Peroxidase
PubMed: 33631301
DOI: 10.1016/j.freeradbiomed.2021.02.021 -
Nature Mar 2022Biaryl compounds, with two connected aromatic rings, are found across medicine, materials science and asymmetric catalysis. The necessity of joining arene building...
Biaryl compounds, with two connected aromatic rings, are found across medicine, materials science and asymmetric catalysis. The necessity of joining arene building blocks to access these valuable compounds has inspired several approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task. Oxidative coupling of two C-H bonds offers an efficient strategy for the formation of a biaryl C-C bond; however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to numerous small-molecule-mediated methods by providing a paradigm with catalyst-controlled selectivity. Here we disclose a strategy for biocatalytic cross-coupling through oxidative C-C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyse cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site selectivity and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.
Topics: Biocatalysis; Carbon; Chemistry Techniques, Synthetic; Coumarins; Cytochrome P-450 Enzyme System; Hydrogen; Oxidants; Oxidation-Reduction; Substrate Specificity
PubMed: 35236972
DOI: 10.1038/s41586-021-04365-7 -
Biomolecules Jun 2023Numerous chemical probes have been used to measure or image oxidative, nitrosative and related stress induced by free radicals in biology and biochemistry. In many... (Review)
Review
Numerous chemical probes have been used to measure or image oxidative, nitrosative and related stress induced by free radicals in biology and biochemistry. In many instances, the chemical pathways involved are reasonably well understood. However, the rate constants for key reactions involved are often not yet characterized, and thus it is difficult to ensure the measurements reflect the flux of oxidant/radical species and are not influenced by competing factors. Key questions frequently unanswered are whether the reagents are used under 'saturating' conditions, how specific probes are for particular radicals or oxidants and the extent of the involvement of competing reactions (e.g., with thiols, ascorbate and other antioxidants). The commonest-used probe for 'reactive oxygen species' in biology actually generates superoxide radicals in producing the measured product in aerobic systems. This review emphasizes the need to understand reaction pathways and in particular to quantify the kinetic parameters of key reactions, as well as measure the intracellular levels and localization of probes, if such reagents are to be used with confidence.
Topics: Reactive Oxygen Species; Oxidation-Reduction; Free Radicals; Superoxides; Oxidants; Antioxidants; Coloring Agents; Oxidative Stress
PubMed: 37509077
DOI: 10.3390/biom13071041