Presently, the most effective way to transport drugs specifically to mitochondria inside the cells is of pharmacophoric interest as mitochondria are recognized as one of the most important targets for new drug design in cancer diagnosis. To date, there are many reviews covering the photophysical, photochemical, and anticancer properties of ruthenium(II) based metallodrugs owing to their high interest in biological applications. There are, however, no reviews specifically covering the mitochondria-localized luminescent Ru(II) complexes and their subsequent mitochondria-mediated anticancer activities. Therefore, this mini-review will describe the physicochemical basis for the mitochondrial accumulation of ruthenium complexes, their synthetic strategies to localize and monitor the mitochondria in living cells, and their related underlying anticancer results. Finally, we review the related areas from previous works describing the mitochondria-localized ruthenium complexes for the treatment of cancer-related diseases. Along with this, we also deliberate the perspectives and future directions for emerging more bifunctional Ru(II) complexes that can target, image, and kill tumors more efficiently in comparison with the existing mitochondria-targeted cancer therapeutics.
Photo‐Enhanced Oil Toxicity to Alcid Immune Function
Abstract
Oil spills are devastating to seabirds, causing high levels of mortality and toxic physiological effects, especially to immune function. Sunlight exposure can further enhance the toxicity of oil to marine species by generating photodegradation products. Photo-enhanced oil toxicity to marine birds has not been studied. Therefore, the goal of the present study was to investigate the toxicity and photo-enhanced toxicity of oil to lymphocyte proliferation, macrophage phagocytosis, and reactive oxygen species production in three alcid species, common murres (Uria aalge), tufted puffins (Fratercula cirrhata), and horned puffins (Fratercula corniculata). Intrinsic factors (species, age, and sex) had a more significant effect on lymphocyte proliferation than exposure to oil or photoactivated oil. Macrophage phagocytosis was significantly reduced in oil and photoactivated oil treatments, whereas hydrogen peroxide production was significantly increased. Interestingly, nonphotoactivated oil stimulated significantly more hydrogen peroxide than photoactivated oil. The results suggest that alcid immune function could be variably influenced during an oil spill depending on the species, sex, and age of the bird as well as the season and level of sunlight exposure. Environ Toxicol Chem 2023;00:1–11. © 2023 SETAC
Copper(I)‐Catalyzed Interrupted Click Reaction: Synthesis of 1,4,5‐Trisubstituted 5‐Chloro‐1,2,3‐Triazoles
A Cu(I)-catalyzed interrupted click reaction, using N-chlorophthalimide as electrophilic chlorine source, enabling the facile synthesis of 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles in one step from readily available terminal alkynes and azides is reported. This approach allowed complete control of regioselectivities with a broad substrate scope. Furthermore, a novel epoxidation was developed using 5-chloro-triazole as substrate, which could be further applied in various organic transformations.
Abstract
5-Halo-1,2,3-triazoles are important scaffolds in organic chemistry, but current click reactions cannot produce 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles in a simple way. Herein, we disclosed a Cu(I)-catalyzed interrupted click reaction, using N-chlorophthalimide as an electrophilic chlorine source, enabling the facile synthesis of 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles in one step from readily available terminal alkynes and azides. Complete control of regioselectivities with a broad substrate scope was accomplished by this approach. Furthermore, a novel epoxidation was developed using 5-chloro-triazole as substrate, which could be further applied in various organic transformations.
Metal‐Free and Visible Light‐Induced Difunctionalizations of α‐CF3 Styrenes with Aryl Diazonium Salts and Hetero Nucleophiles
This concise protocol provided easy access to the α-CF3 tertiary alkyl ethers, alcohol and fluorides with good yields and excellent functional group tolerance. In addition, the four-component “SO2” insertion reaction also worked efficiently to produce the α-CF3, β-sulfonyl ethers in moderate to good yields. A radical-polar crossover coupling pathway was proposed for the C−O bond formation.
Abstract
Metal-free, visible light-induced difunctionalizations of α-CF3 styrenes with aryl diazonium salts and various hetero nucleophiles (ROH, H2O, N3 − and F−) are described. This concise protocol provided easy access to the α-CF3 tertiary alkyl ethers, alcohol and fluorides with good yields and excellent functional group tolerance. In addition, the four-component “SO2” insertion reaction also worked efficiently to produce the α-CF3, β-sulfonyl ethers in moderate to good yields. A radical-polar crossover coupling pathway was proposed for the C−O bond formation.
Generation of Cannabigerolic Acid Derivatives and Their Precursors by Using the Promiscuity of the Aromatic Prenyltransferase NphB
The conversion of novel olivetolic acid derivatives with the highly promiscuous prenyltransferase NphB is analyzed as a tool for the creation of synthetic cannabinoid libraries. By using in silico and in vitro experiments CBGA derivatives were synthesized and characterized as products of enzyme catalysis.
Abstract
NphB is an aromatic prenyltransferase with high promiscuity for phenolics including flavonoids, isoflavonoids, and plant polyketides. It has been demonstrated that cannabigerolic acid is successfully formed by the reaction catalysed by NphB using geranyl diphosphate and olivetolic acid as substrates. In this study, the substrate specificity of NphB was further determined by using olivetolic acid derivatives as potential substrates for the formation of new synthetic cannabinoids. The derivatives differ in the hydrocarbon chain attached to C6 of the core structure. We performed in silico experiments, including docking of olivetolic acid derivatives, to identify differences in their binding modes. Substrate acceptance was predicted. Based on these results, a library of olivetolic acid derivatives was constructed and synthesized by using different organic synthetic routes. Conversion was monitored in in vitro assays with purified NphB versions. For the substrates leading to a high conversion olivetolic acid-C8, olivetolic acid-C2 and 2-benzyl-4,6-dihydroxybenzoic acid, the products were further elucidated and identified as cannbigerolic acid derivatives. Therefore, these substrates show potential to be adapted in cannabinoid biosynthesis.
Attachment of Hydrogen Molecules to Atomic Ions (Na+, Cl−): Examination of an Adiabatic Separation of the H2 Rotational Motion
In this computational work it is shown that hydrogen clusters doped with ions, formed by molecules in the first excited rotational state (ortho-H2), are more stable and tend to have larger coordination numbers than clusters composed by molecules in the ground rotational state (para-H2).
Abstract
Interactions between molecular hydrogen and ions are of interest in cluster science, astrochemistry and hydrogen storage. In dynamical simulations, H2 molecules are usually modelled as point particles, an approximation that can fail for anisotropic interactions. Here, we apply an adiabatic separation of the H2 rotational motion to build effective pseudoatom-ion potentials and in turn study the properties of (H2) n Na+/Cl− clusters. These interaction potentials are based on high-level ab initio calculations and Improved Lennard-Jones parametrizations, while the subsequent dynamics has been performed by quantum Monte Carlo calculations. By comparisons with simulations explicitly describing the molecular rotations, it is concluded that the present adiabatic model is very adequate. Interestingly, we find differences in the cluster stabilities and coordination shells depending on the spin isomer considered (para- or ortho-H2), especially for the anionic clusters.
Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C6H8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity
Four isomeric copper(II) complexes based on a pair of ligand isomers that each yield a pair of linkage isomers have been synthesized and characterized. The effect of isomerism on the electronic structure and antiproliferation activity of the complexes is described.
Abstract
A series of isomeric bis(alkylthiocarbamate) copper complexes have been synthesized, characterized, and evaluated for antiproliferation activity. The complexes were derived from ligand isomers with 3-methylpentyl (H2L2) and cyclohexyl (H2L3) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL2a/3a have two imino N and two S donors resulting in three five-member chelate rings (555 isomers). The kinetic isomers CuL2b/3b have one imino and one hydrazino N donor and two S donors resulting in four-, six-, and five-member rings (465 isomers). The 555 isomers have more accessible CuII/I potentials (E1/2=−811/−768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E1/2=−923/-854 mV). Antiproliferation activities were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR-90) using the MTT assay. CuL2a was potent (A549EC50=0.080 μM) and selective (IMR-90EC50/A549EC50=25) for A549. Its linkage isomer CuL2b had equivalent A549 activity, but lower selectivity (IMR-90EC50/A549EC50=12.5). The isomers CuL3a and CuL3b were less potent with A549EC50 values of 1.9 and 0.19 M and less selective with IMR-90EC50/A549EC50 ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.
Challenges and Recommendations in Assessing Potential Endocrine‐Disrupting Properties of Metals in Aquatic Organisms
Abstract
New tools and refined frameworks for identifying and regulating endocrine-disrupting chemicals (EDCs) are being developed as our scientific understanding of how they work advances. Although focus has largely been on organic chemicals, the potential for metals to act as EDCs in aquatic systems is receiving increasing attention. Metal interactions with the endocrine system are complicated because some metals are essential to physiological systems, including the endocrine system, and nonessential metals can have similar physiochemical attributes that allow substitution into or interference with these systems. Consequently, elevated metal exposure could potentially cause endocrine disruption (ED) but can also cause indirect effects on the endocrine system via multiple pathways or elicit physiologically appropriate compensatory endocrine-mediated responses (endocrine modulation). These latter two effects can be confused with, but are clearly not, ED. In the present study, we provide several case studies that exemplify the challenges encountered in evaluating the endocrine-disrupting (ED) potential of metals, followed by recommendations on how to meet them. Given that metals have multiple modes of action (MOAs), we recommend that assessments use metal-specific adverse outcome pathway networks to ensure that accurate causal links are made between MOAs and effects on the endocrine system. We recommend more focus on establishing molecular initiating events for chronic metal toxicity because these are poorly understood and would reduce uncertainty regarding the potential for metals to be EDCs. Finally, more generalized MOAs such as oxidative stress could be involved in metal interactions with the endocrine system, and we suggest it may be experimentally efficient to evaluate these MOAs when ED is inferred. These experiments, however, must provide explicit linkage to the ED endpoints of interest. Environ Toxicol Chem 2023;00:1–16. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Investigation of Anticholinesterase Activity of Chemically Characterised Hieracium s. str. Methanol Extracts and Their Selected Metabolites
The composition and anticholinesterase activity of the dried MeOH extracts of Hieracium scheppigianum and H. naegelianum underground parts (rhizomes and roots), as well as the anticholinesterase activity of the dried, previously chemically characterised MeOH extracts of the flowering aerial parts of these two and 26 other Hieracium species in the strict sense (s. str.), were investigated. Furthermore, the anticholinesterase activity of 12 selected secondary metabolites of these extracts was evaluated. Using semi-preparative LC-MS, five caffeoylquinic acids and the sesquiterpene lactone crepiside E were isolated from H. scheppigianum underground parts extract. All these compounds were also identified in the underground parts extract of H. naegelianum. Quantitative LC-MS analysis showed that the analysed underground parts extracts were rich in both caffeoylquinic acids (139.77 and 156.62 mg/g of extract, respectively) and crepiside E (126.88 and 116.58 mg/g). In the Ellman method, the tested extracts showed an interesting anti-AChE and/or anti-BChE activity (IC50=0.56-1.58 mg/mL), which can be explained, at least partially, by the presence of some of their constituents. Among the metabolites tested, the best activity was revealed for the flavonoids apigenin, luteolin and diosmetin, and the sesquiterpene lactone 8-epiixerisamine A (IC50=68.09-299.37 μM).
Laser‐Induced Carbon Nanofiber‐Based Redox Cycling System
Laser-induced carbon nanofibers are used to create porous freestanding electrode systems for redox cycling. Either by closely spacing the interdigitated electrodes carbonized directly onto the nanofibrous network, or by fabricating an additional nanofibers layer onto the electrodes, amplification via redox cycling was achieved in these new approaches, facilitating a flow-through electroanalytical device with favorable sensitivity.
Abstract
Redox cycling is a powerful amplification strategy for reversible redox species within miniaturized electrochemical sensors. Herein, we generate three-dimensional (3D) porous carbon nanofiber electrodes by CO2 laser-writing on electrospun polyimide (PI) nanofiber mats, referred to as laser-induced carbon nanofibers (LCNFs). The technique allowed the fabrication of interdigitated electrode (IDE) arrays with finger width and gap distance of ~400 μm and ~40 μm, respectively, offering approximately 3.5 times amplification efficiency (AF) and 95 % collection efficiency (CE). Such dimensions could not be achieved with IDEs fabricated on conventional PI film because the devices were short-circuited. Stacked electrodes were also constructed as an alternative to the IDE design. Here, nanofiber mats as thin as ~20 μm were fabricated and used as vertical insulation between two LCNF band electrodes. While redox cycling efficiency was similar, the IDE design is more favorable considering the lower complexity and better signal reproducibility. Our strategy thus paves the way for creating flexible 3D porous electrodes with redox cycling ability that can be integrated into microfluidics and lab-on-a-chip systems. In particular, the devices offer inherent flow-through features in miniaturized analytical devices where separation and sensitive detection could be further realized.