Facile Synthesis of 5-aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides via Suzuki Cross-Coupling Reactions, Their Electronic and Nonlinear Optical Properties through DFT Calculations

Synthesis of 5-aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides (4a–4n) by a Suzuki cross-coupling reaction of 5-bromo-N-(pyrazin-2-yl)thiophene-2-carboxamide (3) with various aryl/heteroaryl boronic acids/pinacol esters was observed in this article. The intermediate compound 3 was prepared by condensation of pyrazin-2-amine (1) with 5-bromothiophene-2-carboxylic acid (2) mediated by TiCl4. The target pyrazine analogs (4a–4n) were confirmed by NMR and mass spectrometry. In DFT calculation of target molecules, several reactivity parameters like FMOs (EHOMO, ELUMO), HOMO–LUMO energy gap, electron affinity (A), ionization energy (I), electrophilicity index (ω), chemical softness (σ) and chemical hardness (η) were considered and discussed. Effect of various substituents was observed on values of the HOMO–LUMO energy gap and hyperpolarizability. The p-electronic delocalization extended over pyrazine, benzene and thiophene was examined in studying the NLO behavior. The chemical shifts of 1H NMR of all the synthesized compounds 4a–4n were calculated and compared with the experimental values.

Phase Transformation of Alumina, Silica and Iron Oxide during Carbothermic Reduction of Fly Ash for Ceramics Production

Fly ash is a by-product from burning of coal. Utilization of fly ash by carbothermic reduction is an effective way to recover aluminum, silicon, and iron to enhance product-added value. This work is focused on the phase transformation of Al2O3, SiO2 and Fe2O3 during carbothermic reduction of fly ash in air. A comparative analysis of carbothermic reduction of fly ash in air and in nitrogen was made. Thermodynamics analysis was performed to illustrate the possible reactions for residue and condensate. X-ray diffraction (XRD), scanning electronic microscope (SEM), and energy dispersive spectrometry (EDS) were employed to characterize the phase composition, surface morphology, and microstructure of the reduced products. Results show that Fe3Si and Fe2Si appear sequentially with increasing of temperature. Al5O6N is an intermediate compound. Residue of Al9FeSi3, Al, and Si, and condensate of SiC, AlN and C are obtained. β-SiAlON was not found in the residue. Nitrogen is involved in the reduction of Al2O3 but not in the reduction of SiO2 and Fe2O3. Carbothermic reduction of fly ash in air did not behave the same as fly ash in nitrogen.

Identification of the CoA-ester intermediates and genes involved in the cleavage and degradation of the steroidal C-ring by Comamonas testosteroni TA441

Comamonas testosteroni TA441 degrades steroids aerobically via aromatization of the A-ring accompanied by B-ring cleavage, followed by D- and C-ring cleavage. We previously revealed major enzymes and intermediate compounds in A,B-ring cleavage, β-oxidation cycle of the cleaved B-ring, and partial C,D-ring cleavage process. Here, we elucidated the C-ring cleavage and the β-oxidation cycle that follows. ScdL1L2, a 3-ketoacid Coenzyme A (CoA) transferase which belongs to the SugarP_isomerase superfamily, was thought to cleave the C-ring of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid-CoA ester, the key intermediate compound in the degradation of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (3aα- H -4α [3′-propionic acid]-7aβ-methylhexahydro-1,5-indanedione; HIP)-CoA ester in the previous study; however, this study suggested that ScdL1L2 is the isomerase of the derivative with a hydroxyl group at C-14 which cleaves C ring. The subsequent ring-cleaved product was indicated to be converted to 4-methyl-5-oxo-octane-1,8-dioic acid-CoA ester mainly by ORF33-encoded CoA-transferase (named ScdJ), followed by dehydrogenation by ORF21 and 22-encoded acyl-CoA dehydrogenase (named ScdM1M2). Then a water molecule is added by ScdN for further degradation by β-oxidation. ScdN is considered to catalyze the last reaction in C,D-ring degradation by the enzymes encoded in the steroid degradation gene cluster tesB to tesR . IMPORTANCE Studies on bacterial steroid degradation were initiated more than 50 years ago primarily to obtain materials for steroid drugs. Steroid-degrading bacteria are globally distributed, and the role of bacterial steroid degradation in the environment as well as in human is attracting attention. The overall degradation of steroidal four rings is proposed, however there are still much to be revealed to understand the complete degradation pathway. This study aims to uncover the whole steroid degradation process in C. testosteroni , which is one of the most studied representative steroid degrading bacteria and is suitable for exploring the degradation pathway because the involvement of degradation-related genes can be determined by gene disruption.

Identification of the CoA-ester intermediates and genes involved in the cleavage and degradation of the steroidal C-ring by Comamonas testosteroni TA441

Comamonas testosteroni TA441 degrades steroids aerobically via aromatization of the A-ring accompanied by B-ring cleavage, followed by D- and C-ring cleavage. We previously revealed major enzymes and intermediate compounds in A,B-ring cleavage, β-oxidation cycle of the cleaved B-ring, and partial C,D-ring cleavage process. Here, we elucidated the C-ring cleavage and the β-oxidation cycle that follows. ScdL1L2, a 3-ketoacid Coenzyme A (CoA) transferase which belongs to the SugarP_isomerase superfamily, was thought to cleave the C-ring of 9-oxo-1,2,3,4,5,6,10,19-octanor-13,17-secoandrost-8(14)-ene-7,17-dioic acid-CoA ester, the key intermediate compound in the degradation of 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oic acid (3aα-H-4α [3′-propionic acid]-7aβ-methylhexahydro-1,5-indanedione; HIP)-CoA ester in the previous study; however, this study suggested that ScdL1L2 is the isomerase of the derivative with a hydroxyl group at C-14 which cleaves C ring. The subsequent ring-cleaved product was indicated to be converted to 4-methyl-5-oxo-octane-1,8-dioic acid-CoA ester mainly by ORF33-encoded CoA-transferase (named ScdJ), followed by dehydrogenation by ORF21 and 22-encoded acyl-CoA dehydrogenase (named ScdM1M2). Then a water molecule is added by ScdN for further degradation by β-oxidation. ScdN is considered to catalyze the last reaction in C,D-ring degradation by the enzymes encoded in the steroid degradation gene cluster tesB to tesR.

Geranylgeraniol prevents zoledronic acid-mediated reduction of viable mesenchymal stem cells via induction of Rho-dependent YAP activation

Long-term use of zoledronic acid (ZA) increases the risk of medication-related osteonecrosis of the jaw (MRONJ). This may be attributed to ZA-mediated reduction of viable mesenchymal stem cells (MSCs). ZA inhibits protein geranylgeranylation, thus suppressing cell viability and proliferation. Geranylgeraniol (GGOH), which is a naturally found intermediate compound in the mevalonate pathway, has positive effects against ZA. However, precise mechanisms by which GGOH may help preserve stem cell viability against ZA are not fully understood. The objective of this study was to investigate the cytoprotective mechanisms of GGOH against ZA. The results showed that while ZA dramatically decreased the number of viable MSCs, GGOH prevented this negative effect. GGOH-rescued ZA-exposed MSCs formed mineralization comparable to that produced by normal MSCs. Mechanistically, GGOH preserved the number of viable MSCs by its reversal of ZA-mediated Ki67 + MSC number reduction, cell cycle arrest and apoptosis. Moreover, GGOH prevented ZA-suppressed RhoA activity and YAP activation. The results also established the involvement of Rho-dependent YAP and YAP-mediated CDK6 in the cytoprotective ability of GGOH against ZA. In conclusion, GGOH preserves a pool of viable MSCs with osteogenic potency against ZA by rescuing the activity of Rho-dependent YAP activation, suggesting GGOH as a promising agent and YAP as a potential therapeutic target for MRONJ.

1,5-Dichloroethanoanthracene Derivatives as Antidepressant Maprotiline Analogues: Synthesis and DFT Computational Calculations

The chlorinated tetracyclic 1,5-dichloro-9,10-dihydro-9,10-ethanoanthracen-12-yl)-N-methylmethanamine 1, a maprotiline analogue, has been synthesized via reduction and Diels–Alder reaction followed by reductive amination of Aldehyde 2. Density Functional Theory calculations were performed to identify the possible isomers of the intermediate compound aldehyde 2, these calculations were in a good agreement with experimental result where aldehyde 2 could exist in three isomers with comparable energies. In addition, the side chain of this aldehyde 2 was extended via Wittig reaction to obtain the unsaturated ester 5 that subjected to selective olefinic catalytic hydrogenation to obtain the corresponding saturated ester 6. 1D-NMR (DEPT) and 2D-NMR (HSQC, DQF-COSY) techniques were recruited for structural elucidation in addition to HRMS.

Synthesis, characterization and antimicrobial properties of two derivatives of pyrrolidine-2,5-dione fused at positions-3,4 to a dibenzobarrelene backbone

Background : The present study describes for the first time, the synthesis of two pyrrolidine-2,5-dione derivatives that belong to N-arylsuccinimid (compound 5) and of azo (compound 8) class of molecules. The initial step of the reaction involved the preparation of the intermediate compound (9R, 10R, 11S)-9, 10-dihydro-9, 10-[3, 4] furanoanthracene-12, 14-dione (3) through [4 + 2]-cycloaddition between anthracene and maleic anhydride in xylene which was then condensed with para-hydroxyaniline to give compound 5. Subsequent coupling of 5 with the aryldiazonium ion of aniline gave compound 8.Results: These compounds were characterized by their physical, elemental, and spectroscopic data. 2D-NMR (COSY, HSQC, and HMBC) techniques were used to complete the elucidation of their structures. Compounds 5 (MIC = 32–128µg/mL) and 8 (MIC = 16–256µg/mL) along with the precursor 3 (MIC = 64–128µg/mL) displayed moderate antimicrobial activities against selected bacterial and fungal species when compared with those of nystatin (MIC = 0.50–2µg/mL) and ciprofloxacin (MIC = 0.50–16µg/mL) used as reference drugs.Conclusion: The results of biological tests showed that compounds 3, 5, 8 possess antimicrobial activities. Although being less active than the compound taken as a reference, the azo compound has better antibacterial activity than the other two compounds especially on Staphylococcus aureus, V. choleraeSG24 and, V. choleraeCO6 strains. These results show that the azo function (N = N) is indeed a pharmacophore and would be responsible for the biological activity in the azo molecules.

Stabilization of S3O4 at High Pressure-Implications for the Sulfur Excess Paradox

The geological conundrum of “sulfur excess” refers to the finding that predicted amounts of sulfur, in the form of SO2, discharged in volcanic eruptions much exceeds the sulfur available for degassing from the erupted magma. Exploring the source of the excess sulfur has been the subject of considerable interest. Here, from a systematic computational investigation of sulfur oxygen compounds under pressure, a hitherto unknown S3O4 compound containing a mixture of sulfur oxidation states +II and +IV emerges and is predicted to be stabilized above a pressure of 79 GPa. We predict that S3O4 can be produced via multiple redox reactions involving subducted S bearing minerals (e.g., sulfates and sulfides) at high pressure and temperature conditions relevant to the deep lower mantle, and conversely be decomposed into SO2 and S at shallow depths of Earth. Therefore, S3O4 can be considered as a key intermediate compound to promote the decomposition of sulfates to release SO2, which offers an alternative source of the excess sulfur released during explosive eruptions. These findings provide a possible resolution to the geological paradox of “excess sulfur degassing” and a viable mechanism for understanding of S exchange between Earth’s surface and the lower mantle for the deep sulfur cycle.

Understanding uranium oxide hardening during prolonged storage

Uranium ore concentrates (UOCs), the product of uranium mining and milling, are primarily comprised of uranium oxide (U3O8 and UO2) or peroxide (UO4·4H2O and UO4·2H2O) compounds. Following production, UOCs are typically placed in storage until they are converted to uranium hexafluoride (UF6) at a uranium conversion facility. In this study, the chemical changes responsible for an interesting hardening phenomenon observed in UOCs stored for prolonged periods was investigated to understand underlying causes. Powder X-ray diffraction and thermogravimetric analysis were used to characterize free-flowing and hardened UOC samples and revealed the hardened material had undergone hydration and oxidation as indicated by increased moisture content and the presence of metaschoepite [(UO2)4O(OH)6](H2O)5 and/or schoepite [(UO2)4O(OH)6](H2O)6. Additionally, an aging study found metaschoepite in UOCs after 3 months exposure to a high relative humidity environment. The same study found agglomerated, but not fully hardened, material in nearly all aged UOCs samples. These results suggest metaschoepite and schoepite are indicative of UOCs exposed to elevated levels of H2O during storage. Lastly, a drying/calcining study of hardened U3O8 material demonstrated a means of remediation and identified an intermediate compound of potential interest, dehydrated schoepite. Dehydrated schoepite results from heating metaschoepite or schoepite between 100 and 300 °C and indicates partial reversal of hardened U3O8 to its original condition.