N‐Heterocyclic Carbene Analogues of Thiele and Chichibabin Hydrocarbons

Stable N‐heterocyclic carbene analogues of Thiele and Chichibabin hydrocarbons, [(IPr)(C₆H₄)(IPr)] and [(IPr)(C₆H₄)₂(IPr)] ( 4 and 5 , respectively; IPr=C{N(2,6‐iPr₂C₆H₃)}₂CHCH), are reported. In a nickel‐catalyzed double carbenylation of 1,4‐Br₂C₆H₄ and 4,4′‐Br₂(C₆H₄)₂ with IPr ( 1 ), [(IPr)(C₆H₄)(IPr)](Br)₂ ( 2 ) and [(IPr)(C₆H₄)₂(IPr)](Br)₂ ( 3 ) were generated, which respectively afforded 4 and 5 as crystalline solids upon reduction with KC₈. Experimental and computational studies support the semiquinoidal nature of 5 with a small singlet?triplet energy gap ΔE_S?T of 10.7 kcal mol^?1, whereas 4 features more quinoidal character with a rather large ΔE_S?T of 25.6 kcal mol^?1. In view of the low ΔE_S?T, 4 and 5 may be described as biradicaloids. Moreover, 5 has considerable (41 %) diradical character.     

Photo-Protective and Anti-Inflammatory Effects of Antidesma thwaitesianum Müll. Arg. Fruit Extract against UVB-Induced Keratinocyte Cell Damage

The main cause of most skin cancers is damage from UVB from sunlight, which penetrate the skin surface and induce inflammation. For this reason, this study aims to identify natural products with photo-protection properties and their mode of action by using the UVB-irradiated HaCaT keratinocyte model. Antidesma thwaitesianum fruit extracts at 25, 50, and 100 µg/mL recovered cell viability following UVB exposure in a dose-dependent manner. Cell survival was associated with the reduction in intracellular ROS and NO. In addition, we showed that the pre-treatment with the fruit extract lowered the phosphorylation level of two MAPK-signaling pathways: p38 MAPKs and JNKs. The resulting lower MAPK activation decreased their downstream pro-inflammatory cascade through COX-2 expression and subsequently reduced the PGE₂ proinflammatory mediator level. The photoprotective effects of the fruit extract were correlated with the presence of polyphenolic compounds, including cyanidin, ferulic acid, caffeic acid, vanillic acid, and protocatechuic acid, which have been previously described as antioxidant and anti-inflammation. Together, we demonstrated that the pre-treatment with the fruit extract had photo-protection by inhibiting oxidative stress and subsequently lowered stress-induced MAPK responses. Therefore, this fresh fruit is worthy of investigation to be utilized as a skincare ingredient for preventing UVB-induced skin damage.     

Highlights from the 55th Bürgenstock Conference on Stereochemistry 2022

In May 2022, the 55th Bürgenstock Conference on Stereochemistry happened in person once again. This summary provides insight into the scientific themes discussed during the most recent meeting of this historic and multi-disciplinary conference.     

Phytochemical Screening by LC-ESI-MS/MS and Effect of the Ethyl Acetate Fraction from Leaves and Stems of Jatropha macrantha Müll Arg. on Ketamine-Induced Erectile Dysfunction in Rats

Jatropha macrantha Müll Arg. L is also known as “huanarpo macho” and used in the Peruvian traditional medicine as an aphrodisiac and erectile dysfunction (ED). The aim of this study was to determine the phytochemical constituents in leaves and stems ethyl acetate fraction (LEAF and SEAF) of J. macrantha and to compare the antioxidant activity and the ameliorative effect on ketamine-induced erectile dysfunction in rats. The phytochemical constituents were determined by LC-ESI-MS/MS, the total phenolic compounds and total flavonoids (TPC and TF) by Folin-Ciocalteu and aluminum chloride, respectively. The antioxidant activity was determined by DPPH, ABTS, and FRAP assays. Experimental groups were divided as follows: I: negative control; II: positive control (ketamine at 50 mg/ kg/d); III: sildenafil 5 mg/kg; IV, V, VI: LEAF at 25, 50 and 100 mg/kg, respectively, and VII, VIII, IX: SEAF at 25, 50, and 100 mg/kg, respectively. The phytochemical analysis revealed the presence mainly of coumarins, flavonoids, phenolic acids, and terpenes. TPC of LEAF and SEAF were 359 ± 5.21 mg GAE/g and 306 ± 1.93 mg GAE/g, respectively; TF in LEAF and SEAF were 23.7 ± 0.80 mg EQ/g, and 101 ± 1.42 mg EQ/g, respectively. The DPPH, ABTS, FRAP in SEAF were 647 ± 3.27; 668 ± 2.30; and 575 ± 2.86 μmol TE/g, respectively, whilst LEAF showed 796 ± 3.15; 679 ± 0.85; and 806 ± 3.42 μmol TE/g, respectively. Regarding sexual behavior, LEAF showed a better effect in mount frequency, intromission frequency, ejaculation frequency, mount latency, intromission latency, ejaculatory latency, and post ejaculatory latency than SEAF. As conclusion, LEAF of J. macrantha at 50 mg/kg showed a better effect on sexual behavior in male rats with erectile dysfunction than SEAF but not higher than sildenafil.     

CAAC‐Based Thiele and Schlenk Hydrocarbons

Diradicals have been of tremendous interest for over a century ever since the first reports of p‐ and m‐phenylene‐bridged diphenylmethylradicals in 1904 by Thiele and 1915 by Schlenk. Reported here are the first examples of cyclic(alkyl)(amino)carbene (CAAC) analogues of Thiele's hydrocarbon, a Kekulé diradical, and Schlenk's hydrocarbon, a non‐Kekulé diradical, without using CAAC as a precursor. The CAAC analogue of Thiele's hydrocarbon has a singlet ground state, whereas the CAAC analogue of Schlenk's hydrocarbon contains two unpaired electrons. The latter forms a dimer, by an intermolecular double head‐to‐tail dimerization. This straightforward synthetic methodology is modular and can be extended for the generation of redox‐active organic compounds.     

Upregulating sirtuin 6 ameliorates glycolysis,EMT and distant metastasis of pancreatic adenocarcinoma with krüppel-like factor 10 deficiency

Krüppel-like factor 10 (KLF10) is a tumor suppressor in multiple cancers. In a murine model of spontaneous pancreatic adenocarcinoma (PDAC), additional KLF10 depletion accelerated distant metastasis. However, Klf10 knockout mice, which suffer from metabolic disorders, do not develop malignancy. The mechanisms of KLF10 in PDAC progression deserve further exploration. KLF10-depleted and KLF10-overexpressing PDAC cells were established to measure epithelial-mesenchymal transition (EMT), glycolysis, and migration ability. A murine model was established to evaluate the benefit of genetic or pharmacological manipulation in KLF10-depleted PDAC cells (PDACshKLF10). Correlations of KLF10 deficiency with rapid metastasis, elevated EMT, and glycolysis were demonstrated in resected PDAC tissues, in vitro assays, and murine models. We identified sirtuin 6 (SIRT6) as an essential mediator of KLF10 that modulates EMT and glucose homeostasis. Overexpressing SIRT6 reversed the migratory and glycolytic phenotypes of PDACshKLF10 cells. Linoleic acid, a polyunsaturated essential fatty acid, upregulated SIRT6 and prolonged the survival of mice injected with PDACshKLF10. Modulating HIF1α and NFκB revealed that EMT and glycolysis in PDAC cells were coordinately regulated upstream by KLF10/SIRT6 signaling. Our study demonstrated a novel KLF10/SIRT6 pathway that modulated EMT and glycolysis coordinately via NFκB and HIF1α. Activation of KLF10/SIRT6 signaling ameliorated the distant progression of PDAC.Clinical Trial Registration: ClinicalTrials.gov. identifier: {"type":"clinical-trial","attrs":{"text":"NCT01666184","term_id":"NCT01666184"}}NCT01666184.Subject terms: Pancreatic cancer, Epithelial-mesenchymal transition, Cancer metabolism, Translational research     

The Chichibabin reaction in the Aminopyridine,azaindole, and azaindoline series

2-Aminopyridine, unlike the 3- and 4-isomers, is animated by sodium amide with the formation of 2,6-diaminopyridine. Among the dimethylaminopyridines, the 3- and 4-isomers are more active in the Chichibabin reaction, while 2-dimethylaminopyridine is converted with great difficulty under the action of sodium amide into 2,6-diaminopyridine with the initial replacement of the dimethylamine residue by an amino group. Azaindoles and azaindolines do not take part in the animation reaction. In 1-phenyl-5-azaindole, under the action of sodium amide, the pyrrole ring opens with the formation of 4-anilino-3-vinylpyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1232–1239, September, 1973.     

Recent developments in heterocyclic systems with a Si–M′–Ge or Ge–M′–Ge linkage (M′ = Fe,Ru, or Co)

The present review describes recent work on the synthesis, spectroscopic analysis, and investigation of the chemical behaviors of new polynuclear heterocyclic complexes 1–7 having M–M′–M catenation. Various CO substitution, cleavage, expansion, and adducts decomposition reactions are described.     

Rh2(ii)-catalyzed enantioselective intramolecular Büchner reaction and aromatic substitution of donor–donor carbenes

The chiral dirhodium(ii) tetracarboxylate-catalyzed enantioselective intramolecular Büchner reaction of donor/donor-carbenes was reported and a series of valuable chiral polycyclic products were synthesized. Both aryloxy enynones and diazo compounds were efficient carbene precursors for this reaction. Excellent yields (up to 99%) and outstanding enantioselectivities (up to >99% ee) were achieved under standard conditions. For furyl substituted chiral cyclohepta[b]benzofurans bearing a substituent at the C4 position on cycloheptatrienes, control reactions showed that the chiral Büchner products could slowly racemize either under dark or natural light conditions. A diradical-involved mechanism rather than a zwitterionic intermediate was proposed to explain the racemization. Furthermore, furyl substituted chiral fluorene derivatives were obtained via asymmetric aromatic substitution when biaryl enynones were employed as carbene precursors.

The chiral dirhodium(ii) tetracarboxylate-catalyzed enantioselective intramolecular Büchner reaction and aromatic substitution of donor/donor-carbenes were reported and a series of valuable chiral polycyclic products were synthesized.     

Synthesen von Verbindungen mit M–N‐Bindungen (M = Li,Ga, In)

Syntheses of Compounds with M–N Bonds (M = Li, Ga, In) The adducts [GaCl₃(HNⁱPr₂)] ( 1 ) and [InCl₃{HN(CH₂Ph)₂}₂] ( 2 ) can be obtained by the reactions of the corresponding metal(III) halides with the amines. The In amide In(N^cHex₂)₃ ( 3 ) can be formed by treatment of InCl₃ with three equivalents of LiN^cHex₂. Reaction with four equivalents of LiN^cHex₂ leads to the same product. However, the treatment of InCl₃ with four equivalents of LiN(CH₂Ph)₂ gives the desired metalate [Li(THF)₄][In{N(CH₂Ph)₂}₄] ( 4 ). From the corresponding reaction of InCl₃ with LiNⁱPr₂ no In‐containing product could be identified. Instead, the aggregate of LiCl with three units of LiNⁱPr₂, [Li₄(NⁱPr₂)₃(THF)₄Cl] ( 5 ), was isolated. 1 – 4 were characterized by NMR, IR and MS techniques as well as by X‐ray structure determinations. According to them, 1 possesses a tetrahedrally coordinated Ga atom, at which two units of 1 are connected by hydrogen bridges to centrosymmetrical dimers. The In atoms in 2 have a trigonal‐bipyramidal coordination sphere; the amine molecules occupy the apical positions. The central metal atom in 3 and the anion of 4 exhibit trigonal‐planar and distorted tetrahedral environments, respectively. The novel structural motif in 5 is the Cl^– ion, only partly surrounded by Li⁺ ions in a strongly distorted trigonal‐bipyramidal fashion. The dominating angle amounts to 165.2(2)°.     

Syntheses of ficuseptine, juliprosine, and juliprosopine by biomimetic intramolecular Chichibabin pyridine syntheses

[structure: see text] Biomimetic intramolecular Chichibabin pyridine syntheses using two molecules of an aldehyde and 4-aminobutanal dimethyl acetal (6) proceed efficiently in AcOH at 95 degrees C to give 2,3-dihydro-1H-indolizinium salts. Reaction occurs at 25 degrees C if 1-pyrroline (5) is used instead of 6. This reaction has been used for a one-step synthesis of ficuseptine (1) and the first syntheses of juliprosine (2) and juliprosopine (17t), which is now assigned as the trans stereoisomer.     

Ternäre Fluoride mit vierwertigem Chrom: M″CrF6mit M″ = Ba,Sr, Ca,Mg, Zn,Cd, Hg,Ni

Ternary fluorides with tetravalent chromium: M^IICrF₆ with M^II = Ba, Sr, Ca, Mg, Zn, Cd, Hg, Ni. We obtained hithertoo unknown BaCrF₆ (light yellow) and SrCrF₆ (yellow), both of (hexag.) BaSiF_B-type [a = 7.32₈, c = 7.13₇ Å; and a = 7.10₉ c = 6.86₃ Å, respectively] as well as CaCrF₆ (pink) [a = 5.33₆, c = 14.15₃ Å], MgCrF₆ (pink) [a = 5.09₁ c = 13.14₃ Å], CdCrF₆ (pink) [a = 5.14₆, c = 14.07₅ Å] and HgCrF₆ (orange-yellow) [a = 5.12₈, c = 14.26₅ A], all of (hexag.) LiSbF₆-type. NiCrF₆ (brown) [a = 4.97₅, c = 13.26₂ Å] and ZnCrF₆ (orange-yellow) [a = 5.02₆, c = 13.33₇ Å] crystallize in the hexag. VF₃-type.     

Layered Post‐Transition‐Metal Dichalcogenides (X−M−M−X) and Their Properties

A^IIIB^VI chalcogenides are an interesting group of layered semiconductors with several attractive properties, such as tunable band gaps and the formation of solid solutions. Unlike the typically sandwiched structure of transition‐metal dichalcogenides, A^IIIB^VI layered chalcogenides with hexagonal symmetry are stacked through the X?M?M?X motif, in which M is gallium and indium, and X is sulfur, selenium, and tellurium. In view of the inadequate study of the electrochemical properties and great interest in layered materials towards energy‐related research, herein the inherent electrochemistry of GaS, GaSe, GaTe, and InSe has been studied, as well as the exploration of their potential as hydrogen evolution reaction (HER) electrocatalysts. All four materials show redox peaks during cyclic voltammetry measurements. Furthermore, insights into catalysis of the HER are provided; these indicate the conductivity and number of active sites of the materials. All of these findings have important implications on their possible applications.     

Bonding characters of M‐Cd4Te4 and M‐Cd3Te3 (M = Cr,Cu, Ag,Al, Cd,and Zn) clusters

At DFT/B3LYP/LANL2DZ theoretical level, conformations, bonding characters and Molecular Orbital (MO) of M‐Cd₄Te₄ and M‐Cd₃Te₃ (M = Cr, Cu, Ag, Al, Cd, and Zn) molecules are investigated. First, through analysis of conformations and bonding characters, we conclude that different doping atoms have different influence on doping structures. Al atom can form bonding with Cd atoms in doping molecules. Besides, as for M‐Cd₄Te₄ and M‐Cd₃Te₃ structures, there are different characters and conformations as to the same doping atoms. Second, MO is used to discuss characters of bonding. We believe that doping atoms influence the orbital characters and make the transition change. Moreover, different conformations for the same doping atoms induce different transitions. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Solvothermal Synthesis of M‐doped TiO2 Nanoparticles for Sonocatalysis of Methylene Blue and Methyl Orange (M = Cd,Ag, Fe,Ce, and Cu)

M‐doped TiO₂ nanoparticles were synthesized by a sol–gel‐assisted solvothermal method. X‐ray diffraction (XRD) , transmission electron microscopy (TEM) , and diffuse reflection spectroscopy (DRS) were used to characterize the as‐synthesized samples. The sonocatalytic performance of the specimens for methylene blue and methyl orange degradation was evaluated. XRD confirmed the formation of anatase as the unique phase in all samples. TEM showed that Cd, Cu, and Ce led to increased particle size in comparison to TiO₂ nanoparticles, whereas Fe and Ag had no considerable influence on this parameter. DRS confirmed the change in the absorption edge, and E _g values decreased in the range 4.6–1.2% by Cd, Ce, Fe, Cu, and Ag doping, respectively. Among the different dopants, only Cd and Ag improved the absorbance of UV –visible light, and only these samples induced sonodegradation of the dye models. It can be concluded that the improvement in the dye removal efficiency is not related to an increase in the crystallinity and/or a decrease in E _g, but only related to the increase in absorbance.     

From [M≡N] and [M—N—E] Complexes to Models for Metal Oxidoreductases

The article reviews results of research that was initially aiming at complexes containing new and unusual [M—N—E] element combinations (M = transition metal, E = main group element), but soon turned into studies on model complexes for metal enzymes such as nitrogenases, hydrogenases or CO dehydrogenases, because several of the resulting [M—N—E] complexes exhibited reactions relevant to these enzymes. It could be shown that alkylation of transition metal thiolate nitride complexes gives alkylimido complexes when bulky and mild alkylation reagents, e.g. Ph₃C⁺, are used. Hydride addition to [Ru(NO)(py^buS₄)]⁺ yielded [Ru(HNO)(py^buS₄)], which contains a bifurcated [M—N(X, Y)] bridge. The diazene complex [μ‐N₂H₂{Ru(PCy₃)(S₄)}₂] undergoes H⁺/D⁺ and H⁺/D₂ exchange reactions that enabled to rationalize the until then inexplicable ‘N₂ dependent HD formation’ catalyzed by nitrogenases. Out of a larger number of [Ni(NE)(S₃)] complexes, the compound [Ni(NHPPr₃)(S₃)] proved capable to model structure and reactivity features of [NiFe] hydrogenases. The [Ni(L)(S₃)] complexes with L = N₃^— and N(SiMe₃)₂^— exhibit extremely high reactivity towards CO, CO₂ and SO₂. The reactions lead to NCO^—, CN^— and NSO^— complexes and bear potential relevance for carbon monoxide dehydrogenase reactions.