Influence of diluent alkyl substitution on the extraction of Am(III) and Eu(III) by a 6,6’-bis(1,2,4-triazin-3-yl)-2,2’-bipyridine ligand dissolved in alkylated cyclohexanone Diluents

Several alkylated cyclohexanones were investigated as potential diluents for the selective extraction of Am(III) from Eu(III) from nitric acid solutions by the CyMe4-BTBP ligand. No significant extraction of either of the metal ions was observed for these diluents themselves. In the extractions from 1 M HNO3, 3-methylcyclohexanone and 4-methylcyclohexanone gave comparable results to cyclohexanone whereas in the extractions from 4 M HNO3, 2-methylcyclohexanone, 3-methylcyclohexanone and 4-methylcyclohexanone all gave superior results. For the monomethylated diluents, DAm and SFAm/Eu decreased in the order of alkyl substitution 2 > 4 ~ 3. However, alkyl substitution of cyclohexanone significantly slows down the extraction kinetics compared to cyclohexanone, and the position of alkyl substitution was found to play an important role in the solvents properties. 3-Methylcyclohexanone was identified as the most promising of the diluent

Asymmetric microbial reduction of ketones: absolute configuration of trans-4-ethyl-1-(1S-hydroxyethyl)cyclohexanol

A set of five fungal species, Botrytis cinerea, Trichoderma viride and Eutypa lata, and the endophytic fungi Colletotrichum crassipes and Xylaria sp., was used in screening for microbial biocatalysts to detect monooxygenase and alcohol dehydrogenase activities (for the stereoselective reduction of carbonyl compounds). 4-Ethylcyclohexanone and acetophenone were biotransformed by the fungal set. The main reaction pathways involved reduction and hydroxylations at several positions including tertiary carbons. B. cinerea was very effective in the bioreduction of both substrates leading to the chiral alcohol (S)-1- phenylethanol in up to 90% enantiomeric excess, and the cis–trans ratio for 4-ethylcyclohexanol was 0:100. trans-4-Ethyl-1-(1S-hydroxyethyl)cyclohexanol, obtained from biotransformation by means of an acyloin-type reaction, is reported here for the first time. The absolute configurations of the compounds trans-4-ethyl-1-(1S-hydroxyethyl)cyclohexanol and 4-(1S- and 4-(1R-hydroxyethyl)cyclohexanone were determined by NMR analysis of the corresponding Mosher’s esters

Structure-activity relationships on cynnamoyl derivatives as inhibitors of p300 Histone acetyltransferase

Human p300 is a polyhedric transcriptional coactivator, playing a crucial role by acetylating histones on specific lysine residues. A great deal of evidences shows that p300 is involved in several diseases as leukemia, tumors and viral infection. Its involvement in pleiotropic biological roles and connections to diseases provide the rationale as to how its modulation could represent an amenable drug target. Several p300 inhibitors (HATi) have been described so far, but all suffer from low potency, lack of specificity or low cell-permeability, highlighting the need to find more effective inhibitors. Our cinnamoyl derivative, RC 56, was identified as active and selective p300 inhibitor, proving to be a good hit candidate to investigate the structure-activity relationship towards p300. Herein we describe the design, synthesis and biological evaluation of new HATi structurally related to our hit, investigating, moreover, the interactions between p300 and the best-emerged hits by means of induced fit docking and molecular dynamics simulations, gaining insight on the peculiar chemical features that influenced their activity toward the targeted enzyme

In situ generation of Mes2Mg as a non-nucleophilic carbon-centred base reagent for the efficient one-pot conversion of ketones to silyl enol ethers

Treatment of commercially available MesMgBr with 1,4-dioxane produces the key Mes2Mg reagent in situ which then mediates the deprotonation of ketones to deliver trimethylsilyl enol ethers, at readily accessible temperatures and without any nucleophilic addition, in an expedient and high yielding one-pot process

Microwave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivatives

A simple and efficient method has been developed for the synthesis of various 2-quinoxalinone-3-hydrazone derivatives using microwave irradiation technique. The series of 2-quinoxalinone-3-hydrazone derivatives synthesized, were structurally confirmed by analytical and spectral data and evaluated for their antimicrobial activities. The results showed that this skeletal framework exhibited marked potency as antimicrobial agents. The most active antibacterial agent was 3-{2-[1-(6-chloro-2-oxo-2H-chromen-3-yl)ethylidene]hydrazinyl}quinoxalin-2(1H)-one, 7 while 3-[2-(propan-2-ylidene)hydrazinyl]quinoxalin-2(1H)-one, 2 appeared to be the most active antifungal agent

Self-assembly, nematic phase formation and organocatalytic behaviour of a proline-functionalized lipopeptide

The self-assembly of the amphiphilic lipopeptide PAEPKI-C16 (P = proline, A = alanine, E = glutamic acid, K = lysine, I = isoleucine, C16 = hexadecyl) was investigated using a combination of spectroscopic, microscopic and scattering methods and compared to C16-IKPEAP with the same (reversed) peptide sequence and the alkyl chain positioned N-terminally and which lacks a free N-terminal proline residue. The catalytic activity of these peptides were then compared using a model aldol reaction system. For PAEPKI-C16, Cryo-TEM images showed the formation of micrometer length fibers, which by Small-angle X-ray scattering (SAXS) were found to have a radius of 2.5 - 2.6 nm. Spectroscopic analysis shows these fibers are built from -sheets. This behaviour is in complete contrast to that of C16-IKPEAP which forms spherical micelles with peptides in a disordered conformation [Hutchinson, J. A. et al. J. Phys. Chem. B 2019, 123, 613]. For PAEPKI-C16, the spontaneous alignment of fibers was observed upon increasing pH, which was accompanied by observed birefringence and anisotropy of SAXS patterns. This shows the formation of a nematic liquids and unprecedented nematic hydrogel formation was also observed these lipopeptides at sufficiently high concentrations. SAXS shows retention of an ultrafine (1.7 nm core radius) fibrillar network within the hydrogel. PAEPKI-C16 with free N-terminal proline shows enhanced anti:syn diastereoselectivity and better conversion compared to C16-IKPEAP. The cytotoxicity of PAEPKI-C16 was also lower than C16-IKPEAP for both fibroblast and cancer cell lines. These results highlight the sensitivity of lipopeptide properties to the presence of a free proline residue. The spontaneous nematic phase formation by PAEPKI-C16 points to the highly anisotropy of its ultrafine fibrillar structure and the formation of such a phase at low concentration in aqueous solution may be valuable for future applications

Characterization of the novel ene reductase Ppo-Er1 from paenibacillus polymyxa

Ene reductases enable the asymmetric hydrogenation of activated alkenes allowing the manufacture of valuable chiral products. The enzymes complement existing metal- and organocatalytic approaches for the stereoselective reduction of activated C=C double bonds, and efforts to expand the biocatalytic toolbox with additional ene reductases are of high academic and industrial interest. Here, we present the characterization of a novel ene reductase from Paenibacillus polymyxa, named Ppo-Er1, belonging to the recently identified subgroup III of the old yellow enzyme family. The determination of substrate scope, solvent stability, temperature, and pH range of Ppo-Er1 is one of the first examples of a detailed biophysical characterization of a subgroup III enzyme. Notably, Ppo-Er1 possesses a wide temperature optimum (Topt: 20–45 °C) and retains high conversion rates of at least 70% even at 10 °C reaction temperature making it an interesting biocatalyst for the conversion of temperature-labile substrates. When assaying a set of different organic solvents to determine Ppo-Er1′s solvent tolerance, the ene reductase exhibited good performance in up to 40% cyclohexane as well as 20 vol% DMSO and ethanol. In summary, Ppo-Er1 exhibited activity for thirteen out of the nineteen investigated compounds, for ten of which Michaelis–Menten kinetics could be determined. The enzyme exhibited the highest specificity constant for maleimide with a kcat/KM value of 287 mM−1 s−1. In addition, Ppo-Er1 proved to be highly enantioselective for selected substrates with measured enantiomeric excess values of 92% or higher for 2-methyl-2-cyclohexenone, citral, and carvone

Fabrication and evaluation of large-area ultrasoft X-ray detectors suitable for spacecraft application

The modifications to the Houston/MSC design of the gas proportional counter flight electronics system are discussed. The following modifications are described: charge amplifier bandwidth improvements, power converter redesign, serial data output buffer, second differentiator, and risetime discriminator. In addition, the redesign of the stellar aspect camera is discussed along with developments in thin film fabrication

Synthesis and characterization of novel graft copolymers by radiation induced grafting

The radiation-induced graft copolymerization of N-vinyl-2-pyrrolidone (NVP), 4-vinyl pyridine (4VP), 2-vinyl pyridine (2VP) monomers onto poly (ethylene-alt-tetrafluoroethylene) (ETFE) was investigated. The influence of synthesis conditions particularly the solvent was studied. Various solvents, such as n-propanol, isoproponol, benzyl alcohol, methanol, ethanol, cyclohexanone, tetrahydrofuran (THF), nitromethane, 1,4-dioxane and n-heptane were examined for this purpose. Graft copolymers were characterized by Fourier transform infrared (FTIR) spectroscopy, dynamic mechanical analysis (DMA), and scanning electron microscopy-energy dispersive spectroscopy (SEM-EDAX). It was found that the nature of the solvent had profound influence over the grafting reaction. Cyclohexanone, n-propanol and isoproponol for 4VP/ETFE grafting, THF and 1,4-dioxane for NVP/ETFE grafting and benzyl alcohol and methanol for 2VP/ETFE grafting were found to be the suitable solvents yielding highest graft levels. Isoproponol and n-propanol are promising in terms of both graft level and mechanical properties for 4VP/ETFE. Grafting of NVP, 4VP and 2VP onto ETFE were verified through FTIR spectroscopy. Storage modulus and glass transition temperature of the copolymers were found to increase as graft level increased. Surface profile of representative films was also investigated by viewing the distribution of elemental nitrogen using SEM-EDAX. Results indicated that copolymers of 4VP, NVP and 2VP are considerably different from each other. 4VP based copolymers exhibited relatively more homogenous grafting over the surface compared to NVP and 2VP based copolymers