- DNA-damaging activities of twenty-four structurally diverse unsubstituted and substituted cyclic compounds in embryo-fetal chicken livers. [Journal Article]
- MRMutat Res 2019; 844:10-24
- DNA-damaging activities of twenty-four structurally diverse unsubstituted and substituted cyclic compounds were assessed in embryo-fetal chicken livers. Formation of DNA adducts and strand breaks wer…
DNA-damaging activities of twenty-four structurally diverse unsubstituted and substituted cyclic compounds were assessed in embryo-fetal chicken livers. Formation of DNA adducts and strand breaks were measured using the nucleotide 32P-postlabelling (NPL) and comet assays, respectively. Unsubstituted monocyclic benzene, polycyclic fused ring compound naphthalene, covalently connected polycyclic ring compound biphenyl, and heterocyclic ring compound fluorene did not produce DNA damage. Amino-substituted monocyclic compounds, aniline and p-phenylenediamine, as well as polycyclic 1-naphthylamine were also negative. In contrast, carcinogenic monocyclic methyl-substituted anilines: o-toluidine, 2,6-xylidine, 3,4-dimethylaniline, 4-chloro-o-toluidine; 2 methoxy-substituted methylaniline: p-cresidine; 2,4 and 2,6 diamino- or dinitro- substituted toluenes all produced DNA damage. Genotoxic polycyclic amino-substituted 2-naphthylamine, 4-aminobiphenyl, benzidine, methyl-substituted 3,2'-dimethyl-4-aminobiphenyl and 4-dimethylaminoazobenzene as well as amino- and nitro- fluorenes substituted at the 1 or 2 positions also were positive in at least one of the assays. Overall, the DNA damaging activity of cyclic compounds in embryo-fetal chicken livers reflected the type and position of the substitution on the aromatic ring. Additionally, substituted polycyclic compounds exhibited higher DNA-damaging potency compared to monocyclic chemicals. These results are congruent with in vivo findings in other species, establishing chicken eggs as a reliable system for structure-activity assessment of members of groups of related chemicals.
- Enzymatic cascade in Pseudomonas for pyrazine production from α-amino acids. [Journal Article]
- CChembiochem 2019 Jul 19
- Pyrazines are widespread chemical compounds that include pheromones and odors. Here we describe a novel mechanism used by Pseudomonas fluorescens SBW25 to biosynthesize monocyclic pyrazines. Heterolo…
Pyrazines are widespread chemical compounds that include pheromones and odors. Here we describe a novel mechanism used by Pseudomonas fluorescens SBW25 to biosynthesize monocyclic pyrazines. Heterologous expression of the papABC genes that synthesize the natural α-amino acid, 4-aminophenylalanine (4APhe), together with three adjacent papDEF genes of unknown function in Escherichia coli resulted in the production of 2,5-dimethyl-3,6-bis(4-aminobenzyl)-pyrazine (DMBAP), which comprised two symmetrical aminobenzyl moieties derived from 4APhe.We found that PapD is a novel amino acid. Two molecules of C-acetyltransferase that decarboxylates and transfers acetyl residues to 4APhe to generate an α-aminoketone, spontaneously dehydration-condense to dihydro DMBAP. PapF is a novel oxidase in the amine oxidase superfamily, and it oxidized dihydro DMBAP to yield the pyrazine ring of DMBAP. These two enzymes constitute a unique mechanism for synthesizing monocyclic pyrazines and might serve as a novel strategy for the enzymatic synthesis of pyrazine derivatives from natural α-amino acids.
- The Chemistry and Biology of Cyclophostin, the Cyclipostins and Related Compounds. [Review]
- MMolecules 2019 Jul 16; 24(14)
- Cyclophostin, the cyclipostins and the salinipostins are structurally related cyclic enolphosphate natural products. This mini review describes their isolation, synthesis and biological activities. I…
Cyclophostin, the cyclipostins and the salinipostins are structurally related cyclic enolphosphate natural products. This mini review describes their isolation, synthesis and biological activities. In addition, the synthesis and biological activities of monocyclic enolphosphate and mono and bicyclic enolphosphonate analogs are presented.
- Global Aromaticity in Macrocyclic Polyradicaloids: Hückel's Rule or Baird's Rule? [Journal Article]
- ACAcc Chem Res 2019 Jul 17
- Aromaticity is one of the most important concepts in organic chemistry to understand the electronic properties of cyclic π-conjugated molecules. Over a century, different aromaticity rules have been …
Aromaticity is one of the most important concepts in organic chemistry to understand the electronic properties of cyclic π-conjugated molecules. Over a century, different aromaticity rules have been developed and validated. For planar monocyclic conjugated polyenes (also known as [n]annulenes), they will be aromatic if they contain [4N + 2] π electrons according to Hückel's rule, or antiaromatic if they have [4N] π electrons. Topological change from a planar to a half-twisted Möbius strip will lead to [4N] ([4N + 2]) aromaticity (antiaromaticity), which is just inverse to Hückel's rule. When the molecules are excited into the first triplet excited state, the Hückel (anti)aromaticity observed in the ground state will become reversed according to Baird's rule. Strictly speaking, these basic rules are only applicable for monocyclic conjugated systems, but some polycyclic systems such as porphyrinoids may also follow these rules if there is a dominant [n]annulene-like conjugation pathway. On the other hand, all-benzenoid polycyclic aromatic hydrocarbons usually display local aromaticity with π electrons predominantly localized at certain benzene rings according to Clar's aromatic sextet rule. In recent years, some proaromatic and antiaromatic molecules with even number of paired electrons have been found to exhibit open-shell diradical character and unique optical, electronic, and magnetic activities. One of the major driving forces is their intrinsic tendency to become aromatic in the open-shell diradical/polyradical forms. A number of stable diradicaloids and linear polyradicaloids have been successfully synthesized by using thermodynamic and kinetic stabilizing strategies. Herein, our particular interest is a type of macrocyclic polyradicaloid in which multiple frontier π-electrons are antiferromagnetically coupled with each other in a cyclic mode. Formally, these free electrons may behave like normal π-electrons in the [n]annulenes, and thus, it raises questions about their possible global aromaticity and which rule they will follow. In the past 5 years, our group has synthesized a series of macrocyclic polyradicaloids and systematically investigated their global aromaticity and electronic properties. Some important findings include: (1) global (anti)aromaticity is generally observed, but there is a balance between local aromaticity and global aromaticity; (2) most of these molecules follow Hückel's rule in the singlet state and display respective (anti)aromatic characteristics; (3) in some special cases, both Hückel's rule and Baird's rule can be applicable, and a unique annulene-within-an-annulene super-ring structure was demonstrated for the first time; (4) global antiaromaticity in the transition state is also important and a slow valence tautomerization process was observed in a supercyclobutadiene tetraradicaloid. These studies demonstrate how these open-shell macrocyclic polyradicaloids adapt their geometry and spin state to reach the lowest-energy state (aromatic). In this Account, we will mainly discuss their synthesis, global aromaticity, and the fundamental structure-radical character-aromaticity-properties relationships. Various experimental methods (e.g., NMR, X-ray crystallographic analysis, and electronic absorption spectroscopy) and theoretical calculations (e.g., anisotropy of the induced current density, nucleus independent chemical shift, and isochemical shielding surface) have been used to elaborate their (anti)aromatic character. At the end, a perspective on the possible three-dimensional global aromaticity in fully conjugated cagelike diradicaloids or polyradicaloids will be also discussed.
- Boron-based inorganic heterocyclic clusters: electronic structure, chemical bonding, aromaticity, and analogy to hydrocarbons. [Journal Article]
- PCPhys Chem Chem Phys 2019 Jul 15
- This Perspective article deals with recent computational and experimental findings in boron-based heterocyclic clusters, which focuses on binary B-O and B-S clusters, as well as relevant ternary B-X-…
This Perspective article deals with recent computational and experimental findings in boron-based heterocyclic clusters, which focuses on binary B-O and B-S clusters, as well as relevant ternary B-X-H (X = O, S, N) species. Boron is electron-deficient and boron clusters do not form monocyclic rings or linear chains. Boron-based heterocyclic clusters are intuitively even more electron-deficient and feature exotic chemical bonding, which make use of O 2p, S 3p, or N 2p lone-pairs for π delocalization over heterocyclic rings, facilitating new cluster structures and new types of bonding. Rhombic, pentagonal, hexagonal, and polycyclic clusters are discussed herein. Rhombic species are stabilized by four-center four-electron (4c-4e) π bonding, that is, the o-bond. An o-bond cluster differs from a typical 4π antiaromatic system, because it has 4π electrons in an unusual bonding/nonbonding combination, which takes advantage of the empty 2pz atomic orbitals from electron-deficient boron centers. A variety of examples (notably including boronyl boroxine) possess a hexagonal ring, as well as magic 6π electron-counting, making them new members of the inorganic benzene family. Pentagonal clusters bridge rhombic o-bond systems and inorganic benzenes, but they do not necessarily favor 6π electron-counting as in cyclopentadienide anion. In contrast, pentagonal 4π clusters are stable, leading to the concept of pentagonal o-bond. One electron can overturn the potential energy landscape of a system, enabling rhombic-to-hexagonal structural transition, which further reinforces the idea that 4π electron-counting is favorable for rhombic systems and 6π is magic for hexagonal rings. The bonding analogy between heterocyclic clusters and hydrocarbons goes beyond monocyclic species, which allows rational design of boron-based inorganic analogs of polycyclic aromatic hydrocarbons, including s-indacene as a puzzling aromatic/antiaromatic system. Selected linear B-O clusters are also briefly discussed, featuring dual 3c-4e π bonds, that is, ω-hyperbonds. Dual ω-hyperbonds, rhombic or pentagonal o-bond, and inorganic benzenes share a common chemical origin. The field of boron-based heterocyclic clusters is still in its infant stage, and much new chemistry remains to be discovered in forthcoming experimental and theoretical studies.
- Modulation of Conformational Preferences of Heteroaromatic Ethers and Amides through Protonation and Ionization: Charge Effect. [Journal Article]
- CChemistryOpen 2019; 8(7):840-851
- Multiple approaches reveal the strong effects of a positive charge introduced by protonation or ionization on the conformation of o-heteroaromatic ethers and amides. The ethers and amides containing …
Multiple approaches reveal the strong effects of a positive charge introduced by protonation or ionization on the conformation of o-heteroaromatic ethers and amides. The ethers and amides containing an ortho-N heteroatom are syn-preferring while those containing an ortho-O or ortho-S heteroatom are mostly anti-preferring. However, for all the monocyclic o-heteroaromatic ethers and amides, the protonated ones are all anti-preferring while the ionized ones are all syn-preferring. Interestingly, although both the protonation and ionization introduce a positive charge, they have such different effects on molecular conformation, very informative for understanding the origin of conformational preferences. Detailed analysis shows that the population of the introduced positive charge dictates the conformational preferences via electrostatic and orbital interactions. Compared to ortho-heteroatoms, meta-heteroatoms have weaker effect on conformational preference. Achieved by complete inductive method, the regularity of conformational preferences and switching provides easy ways to modulate conformers (by pH or redox), and makes this kind of ether or amide bond a conformational hinge applicable to design of functional molecules (drugs and materials) and modulation of molecular biological processes.
- Quantum chemical studies on the mechanistic aspects of tandem sequential cycloaddition reactions of cyclooctatetraene with ester and nitrones. [Journal Article]
- JMJ Mol Graph Model 2019 Jul 05; 92:17-31
- The mechanisms of the tandem sequential [4 + 2]/[3 + 2] and [3 + 2]/[4 + 2] cycloaddition sequences involving an ester, cyclooctatetraene (COTE), and cyclic and acyclic nitrones for the formation of …
The mechanisms of the tandem sequential [4 + 2]/[3 + 2] and [3 + 2]/[4 + 2] cycloaddition sequences involving an ester, cyclooctatetraene (COTE), and cyclic and acyclic nitrones for the formation of a diverse range of isoxazolidine derivatives and other synthetic precursors are reported. A thorough exploration of the PES has characterized several regio-, stereo- and enantio-selective mechanistic channels involved in these reactions. A perturbation molecular orbital (PMO) analysis been employed to rationalize the results. It has also been found that the initial electrocyclic ring closure of the COTE is the rate-determining step in the tandem sequential [4 + 2]/[3 + 2] addition sequence. The thermolytic breakdown of the tandem adducts to subsequent monocyclic, bicyclic and tricyclic adducts occurs generally with very high activation barriers making it an inconvenient synthetic approach. The different reactivity of all the three double bonds present in the dipolarophile is reported. Finally, the mechanistic possibilities of [3 + 2]/[4 + 2] addition sequences involving the same reaction components in the case of cyclic and acyclic nitrones are explored extensively. The results suggest a novel and convenient routes for obtaining products of high selectivity with less energetic requirements. In some instances, new cycloadducts hitherto unreported are obtained.
- Investigating the oxidative refolding mechanism of Cripto-1 CFC domain. [Journal Article]
- IJInt J Biol Macromol 2019 Jul 08
- Using a combined approach based on MS, enzyme digestion and advanced MD studies we have determined the sequential order of formation of the three disulfide bridges of the Cripto-1 CFC domain. The dom…
Using a combined approach based on MS, enzyme digestion and advanced MD studies we have determined the sequential order of formation of the three disulfide bridges of the Cripto-1 CFC domain. The domain has a rare pattern of bridges and is involved in the recognition of several receptors. The bridge formation order is C1-C4, C3-C5, C2-C6, however formation of C1-C4 plays no roles for the formation of the others. Folding is driven by formation of the C3-C5 bridge and is supported by residues lying within the segment delimited by these cysteines. We indeed observe that variants CFC-W123A and CFC-ΔC1/C4, where C1 and C4 are replaced by serines, are able to refold in the same time window as the wild type, while CFC-K132A and CFC-W134A are not. A variant where cysteines of the second and third bridge are mutated to serine, convert slowly to the monocyclic molecule. Data altogether support a mechanism whereby the Cripto-1 CFC domain refolds by virtue of long-range intramolecular interactions that involve residues close to cysteines of the second and third bridge. These findings are supported by the in silico study that shows how distant parts of the molecules come into contact on a long time scale.
- Prognosis, complications and treatment response in systemic juvenile idiopathic arthritis patients: A single-center experience. [Journal Article]
- IJInt J Rheum Dis 2019 Jul 04
- CONCLUSIONS: The disease is characterized with diverse clinical presentation and possibly severe complications. MAS complicated with multiorgan insufficiency is the major mortality factor. Corticosteroids represent the mainstay of the initial treatment. In patients resistant to classic treatment, biological drugs should be timely introduced.
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- Morphological, Biochemical, and Climatological Analysis of Three Moroccan Henna Verities. [Journal Article]
- SScientificWorldJournal 2019; 2019:1418456
- In this study, we aimed to evaluate planted Henna in three sites in Morocco, namely, Alnif, Tafraoute Sidi Ali, and Tazzarine. Morphometric study shows that Tafraoute Sidi Ali Henna variety has highe…
In this study, we aimed to evaluate planted Henna in three sites in Morocco, namely, Alnif, Tafraoute Sidi Ali, and Tazzarine. Morphometric study shows that Tafraoute Sidi Ali Henna variety has highest geometric and weight parameters (length of 27.48 mm, width of 10.92 mm, specific mass of 25.1 mg/leaf, leaf area of 51, 53 mm2, and rib's number of 9.41) when compared to Alnif and Tazzarine varieties. On the other hand, biochemical analysis shows that Tazzarine Henna variety, in the first rank, is characterized by high levels of total sugars (11.27 g/100 g), reducing sugars (5.59 g/100 g), proteins (4.4 g/100g), lipids (3.05 g/100g), phenolic compounds (31.9 g/100 g), flavonoids (5.68 g/100 g), and tannins (5.5 g/100 g). Chromatographic study shows that Tazzarine Henna variety is rich in monocyclic and polycyclic phenolic compounds. Climatic conditions analysis shows that the morphometric and biochemical diversity is related to hydrous and thermal profiles of studied sites. As a conclusion of this work, we can recommend the use of morphometric analysis and phytochemical and chromatographic analysis to determine the quality of Henna in Morocco and elsewhere.