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The Journal of Biological Chemistry Dec 2020Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause... (Review)
Review
Mitochondrial DNA (mtDNA) encodes proteins and RNAs that support the functions of mitochondria and thereby numerous physiological processes. Mutations of mtDNA can cause mitochondrial diseases and are implicated in aging. The mtDNA within cells is organized into nucleoids within the mitochondrial matrix, but how mtDNA nucleoids are formed and regulated within cells remains incompletely resolved. Visualization of mtDNA within cells is a powerful means by which mechanistic insight can be gained. Manipulation of the amount and sequence of mtDNA within cells is important experimentally and for developing therapeutic interventions to treat mitochondrial disease. This review details recent developments and opportunities for improvements in the experimental tools and techniques that can be used to visualize, quantify, and manipulate the properties of mtDNA within cells.
Topics: Antibodies; Benzothiazoles; DNA, Mitochondrial; Diamines; Humans; In Situ Hybridization, Fluorescence; Microscopy, Confocal; Mitochondria; Quinolines; Urea
PubMed: 33454000
DOI: 10.1074/jbc.REV120.015101 -
Nature Communications Aug 2022Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations...
Molecular conformations induced by the rotation about single bonds play a crucial role in chemical transformations. Revealing the relationship between the conformations of chiral catalysts and the enantiodiscrimination is a formidable challenge due to the great difficulty in isolating the conformers. Herein, we report a chiral catalytic system composed of an achiral catalytically active unit and an axially chiral 1,1'-bi-2-naphthol (BINOL) unit which are connected via a C-O single bond. The two conformers of the catalyst induced by the rotation about the C-O bond, are determined via single-crystal X-ray diffraction and found to respectively lead to the formation of highly important axially chiral 1,1'-binaphthyl-2,2'-diamine (BINAM) and 2-amino-2'-hydroxy-1,1'-binaphthyl (NOBIN) derivatives in high yields (up to 98%), with excellent enantioselectivities (up to 98:2 e.r.) and opposite absolute configurations. The results highlight the importance of conformational dynamics of chiral catalysts in asymmetric catalysis.
Topics: Catalysis; Crystallography, X-Ray; Diamines; Molecular Conformation
PubMed: 35961985
DOI: 10.1038/s41467-022-32432-8 -
Chemical Reviews May 2022Bisimine derivatives of salicylaldehyde with chiral diamines (salens) are privileged ligands in asymmetric organometallic catalysis, which can be used in cooperation... (Review)
Review
Bisimine derivatives of salicylaldehyde with chiral diamines (salens) are privileged ligands in asymmetric organometallic catalysis, which can be used in cooperation with organocatalysts as additives. The latter can be a modifier of the metal reactivity by liganding or a true co-catalyst working in tandem or in a dual system. All scenarios encountered in the literature are reviewed and classified according to the organocatalyst. In each case, mechanistic and physical-organic chemistry considerations are discussed to better understand the gears of these complex catalytic settings.
Topics: Catalysis; Ethylenediamines; Ligands; Organometallic Compounds
PubMed: 35266711
DOI: 10.1021/acs.chemrev.1c00912 -
Journal of Hazardous Materials Oct 2023The antioxidant 6-PPD has been widely used to prevent cracking and thermal oxidative degradation and to extend the service life of tire rubber. 6-PPD quinone (6-PPDQ) is... (Review)
Review
The antioxidant 6-PPD has been widely used to prevent cracking and thermal oxidative degradation and to extend the service life of tire rubber. 6-PPD quinone (6-PPDQ) is formed via the reaction of 6-PPD with O. Due to its acute lethality in coho salmon, 6-PPDQ has become an emerging pollutant of increasing concern. In this review, we provide a critical overview of the generation, environmental distribution, bioavailability, and potential toxicity of 6-PPDQ. The transformation pathways from 6-PPD to 6-PPDQ include the N-1,3-dimethylbutyl-N-phenyl quinone diamine (QDI), intermediate phenol, and semiquinone radical pathways. 6-PPDQ has been frequently detected in water, dust, air particles, soil, and sediments, indicating its large-scale and potentially global pollution trend. 6-PPDQ is bioavailable to both aquatic animals and mammals and acute exposure to 6-PPDQ can be lethal to some organisms. Exposure to 6-PPDQ at environmentally relevant concentrations could induce several types of toxicity, including neurotoxicity, intestinal toxicity, and reproductive toxicity. This review also identifies and discusses knowledge gaps and research needs for the study of 6-PPDQ. This review facilitates a better understanding of the environmental occurrence and exposure risk of 6-PPDQ.
Topics: Animals; Biological Availability; Environmental Pollutants; Rubber; Phenylenediamines; Benzoquinones
PubMed: 37595463
DOI: 10.1016/j.jhazmat.2023.132265 -
Birth Defects Research Jul 2022Bis-diamine was developed as amebicidal and male contraceptive agents; however, it is also reported to induce characteristic congenital heart defects especially in the...
BACKGROUND
Bis-diamine was developed as amebicidal and male contraceptive agents; however, it is also reported to induce characteristic congenital heart defects especially in the cardiac conotruncal area of rats. Because of its characteristic congenital heart defects, bis-diamine-induced animal models can be used for studying congenital heart defects. However, comprehensive toxicological information regarding bis-diamine-induced congenital heart defects in this animal model is not available.
METHODS
In this study, we investigated and characterized an animal model for bis-diamine-induced congenital heart defects. A single dose of 200-mg bis-diamine was administered by oral gavage to pregnant rats on gestation day 10, and then observed the representative toxicological endpoints for general systemic health of pregnant rats, embryo-fetal development, and parturition.
RESULTS
Characteristic congenital heart defects and other birth defects similar to DiGeorge syndrome were observed in bis-diamine-administered pregnant rats. In addition, developmental and reproductive toxicity findings, including increased postimplantation loss, decreased fetal weight, increased perinatal death, and increased gestation period, were observed in bis-diamine-administered pregnant rats. In particular, these developmental and reproductive toxicities were observed without maternal toxicity findings.
CONCLUSION
These results will be useful to use this animal model for further studies in congenital heart defects, cardiovascular defects, and understanding their mechanisms.
Topics: Animals; Diamines; Disease Models, Animal; Female; Heart; Heart Defects, Congenital; Male; Pregnancy; Rats; Reproduction
PubMed: 35365952
DOI: 10.1002/bdr2.2006 -
Plant, Cell & Environment Jun 2020Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored... (Review)
Review
Biomarker metabolites are of increasing interest in crops since they open avenues for precision agriculture, whereby nutritional needs and stresses can be monitored optimally. Putrescine has the potential to be a useful biomarker to reveal potassium (K ) deficiency. In fact, although this diamine has also been observed to increase during other stresses such as drought, cold or heavy metals, respective changes are comparably low. Due to its multifaceted biochemical properties, several roles for putrescine under K deficiency have been suggested, such as cation balance, antioxidant, reactive oxygen species mediated signalling, osmolyte or pH regulator. However, the specific association of putrescine build-up with low K availability in plants remains poorly understood, and possible regulatory roles must be consistent with putrescine concentration found in plant tissues. We hypothesize that the massive increase of putrescine upon K starvation plays an adaptive role. A distinction of putrescine function from that of other polyamines (spermine, spermidine) may be based either on its specificity or (which is probably more relevant under K deficiency) on a very high attainable concentration of putrescine, which far exceeds those for spermidine and spermine. putrescine and its catabolites appear to possess a strong potential in controlling cellular K and Ca , and mitochondria and chloroplasts bioenergetics under K stress.
Topics: Biological Transport; Biomarkers; Chloroplasts; Potassium; Putrescine; Stress, Physiological
PubMed: 32017122
DOI: 10.1111/pce.13740 -
Chemical Communications (Cambridge,... Apr 2022Silicon-modified polyureas were depolymerized by hydrogenation in the presence of Ru and Mn catalysts. Yields of up to 84% of the aliphatic diamine and 81% of...
Silicon-modified polyureas were depolymerized by hydrogenation in the presence of Ru and Mn catalysts. Yields of up to 84% of the aliphatic diamine and 81% of silicon-containing diamine were achieved with a commercially available PNP-Ru catalyst.
Topics: Catalysis; Diamines; Hydrogenation; Polymers; Silicon
PubMed: 35416214
DOI: 10.1039/d2cc01063a -
Journal of Medicinal Chemistry Aug 2022Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator...
Neuronal Kv7 channels represent important pharmacological targets for hyperexcitability disorders including epilepsy. Retigabine is the prototype Kv7 activator clinically approved for seizure treatment; however, severe side effects associated with long-term use have led to its market discontinuation. Building upon the recently described cryoEM structure of Kv7.2 complexed with retigabine and on previous structure-activity relationship studies, a small library of retigabine analogues has been designed, synthesized, and characterized for their Kv7 opening ability using both fluorescence- and electrophysiology-based assays. Among all tested compounds, emerged as a potent and photochemically stable neuronal Kv7 channel activator. Compared to retigabine, compound displayed a higher brain/plasma distribution ratio, a longer elimination half-life, and more potent and effective anticonvulsant effects in an acute seizure model in mice. Collectively, these data highlight compound as a promising lead compound for the development of novel Kv7 activators for the treatment of hyperexcitability diseases.
Topics: Animals; Anticonvulsants; Carbamates; KCNQ2 Potassium Channel; KCNQ3 Potassium Channel; Mice; Phenylenediamines; Seizures
PubMed: 35972998
DOI: 10.1021/acs.jmedchem.2c00911 -
Chemical Research in Toxicology Sep 2022Several aromatic amine compounds are urinary bladder carcinogens. Activated metabolites and DNA adducts of polycyclic aromatic amines, such as 4-aminobiphenyl, have been...
Several aromatic amine compounds are urinary bladder carcinogens. Activated metabolites and DNA adducts of polycyclic aromatic amines, such as 4-aminobiphenyl, have been identified, whereas those of monocyclic aromatic amines, such as -toluidine (-Tol), -anisidine (-Ans), and aniline (Ani), have not been completely determined. We have recently reported that -Tol and -Ans are metabolically converted in vitro and in vivo to cytotoxic and mutagenic -semidine-type dimers, namely 2-methyl--(2-methylphenyl) benzene-1,4-diamine (MMBD) and 2-methoxy--(2-methoxyphenyl) benzene-1,4-diamine (MxMxBD), respectively, suggesting their roles in urinary bladder carcinogenesis. In this study, we found that when -Tol and -Ans were incubated with S9 mix, MMBD and MxMxBD as well as two isomeric heterodimers, MMxBD and MxMBD, were formed. Therefore, any two of -Tol, -Ans, and Ani (10 mM each) were incubated with the S9 mix for up to 24 h and then subjected to LC-MS to investigate their metabolic kinetics. Metabolic conversions to all nine kinds of -semidine-type homo- and hetero-dimers were observed, peaking at 6 h of incubation with the S9 mix; MxMxBD reached the peak at 6.1 ± 1.4 μM. Homo- and hetero-dimers containing the -Ans moiety in the diamine structure showed a faster dimerization ratio, whereas levels of these dimers, such as MxMxBD, markedly declined with further incubation. Dimers containing -Tol and Ani were relatively stable, even after incubation for 24 h. The electron-donating group of the -Ans moiety may be involved in rapid metabolic conversion. In the cytotoxic assay, dimers with an -Ans moiety in the diamine structure and MMBD showed approximately two- to four-fold higher cytotoxicity than other dimers in human bladder cancer T24 cells. These chemical and biological properties of homo- and hetero-dimers of monocyclic aromatic amines may be important when considering the combined exposure risk for bladder carcinogenesis.
Topics: Amines; Aniline Compounds; Benzene; Carcinogenesis; Carcinogens; DNA Adducts; Humans; Phenylenediamines; Toluidines
PubMed: 36001821
DOI: 10.1021/acs.chemrestox.2c00226 -
Journal of Hazardous Materials Jun 2023Tire wear compounds N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its derivative 6PPD-quinone have been considered as emerging pollutants and attracted... (Review)
Review
Tire wear compounds N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its derivative 6PPD-quinone have been considered as emerging pollutants and attracted much attention recently. As an antioxidant and antiozonant widely used, 6PPD would be released during the production or use of rubber-related products. Because of the mass production and wide use of rubber-related products, 6PPD and 6PPD-quinone have been identified to be ubiquitous in the environment. In this study, we firstly reviewed the current available literature on the analytical procedures, concentrations and distribution of 6PPD and 6PPD-quinone, and then investigated the potential toxic effects of these two compounds on aquatic organisms. Current studies have been mainly focused on the occurrence of 6PPD and 6PPD-quinone in dust and water, while available information on atmosphere, soil, sediments and organisms is limited. The fate and distribution of 6PPD and 6PPD-quinone would be influenced by environmental factors such as temperature, illumination, and storm events, etc. Although 6PPD and 6PPD-quinone have potential adverse effects on aquatic organisms, and 6PPD-quinone has species-specific toxicity, toxicological mechanisms of these compounds are still unclear. Based on the review and analysis of current studies, some suggestions for future research of 6PPD and 6PPD-quinone are given.
Topics: Benzoquinones; Dust; Environmental Pollutants; Phenylenediamines; Rubber; Water
PubMed: 36958160
DOI: 10.1016/j.jhazmat.2023.131245