Are azobenzenophanes rotation-restricted?

We simulated the photoisomerization dynamics of an azobenzenophane with a semiclassical surface hopping approach and a semiempirical reparametrized quantum mechanics/molecular mechanics Hamiltonian. Only one of the two azobenzene chromophores in the molecule is taken into account quantum mechanically: the other one is treated by molecular mechanics. Both n-->pi* and pi-->pi* excitations are considered. Our results show that the photoisomerization reaction mainly involves the rotation around the N=N double bond. The excited state relaxation features are in qualitative agreement with experimental time-resolved fluorescence results.     

Synthesis of Liquid Crystalline Epoxy Oligomers: Effect of Molecular Weight on the Phase Behavior

A series of epoxy‐terminated liquid crystalline oligomers with different molecular weights having α‐methylstilbene as the mesogenic unit were synthesized and characterized by means of ¹H NMR and FT‐IR spectroscopy, differential scanning calorimetry (DSC), polarized‐light optical microscopy (POM) and X‐ray diffraction. The effect of the initial ratio between epichlorohydrin and diol on the molecular weight was not significant enough to change the thermal behavior of the oligomers essentially. The copolymerization of epoxy‐ and hydroxyl‐terminated comonomers yielded high‐molecular weight oligomer, whose enantiotropic liquid crystalline character was proved by means of DSC, POM and X‐ray diffraction.     

Synthesis of Isomeric 3-Benzazecines Decorated with Endocyclic Allene Moiety and Exocyclic Conjugated Double Bond and Evaluation of Their Anticholinesterase Activity

Transformations of 1-methoxymethylethynyl substituted isoquinolines triggered by terminal alkynes in alcohols were studied and new 3-benzazecine-containing compounds synthesized, such as 6-methoxymethyl-3-benzazecines incorporating an endocyclic C6–C8 allene fragment and the -ylidene derivatives 6-methoxymethylene-3-benzazecines. The reaction mechanisms were investigated and a preliminary in vitro screening of their potential inhibitory activities against human acetyl- and butyrylcholinesterases (AChE and BChE) and monoamine oxidases A and B (MAO-A and MAO-B) showed that the allene compounds were more potent than the corresponding -ylidene ones as selective AChE inhibitors. Among the allenes, 3e (R³ = CH₂OMe) was found to be a competitive AChE inhibitor with a low micromolar inhibition constant value (K_i = 4.9 μM), equipotent with the corresponding 6-phenyl derivative 3n (R³ = Ph, K_i = 4.5 μM), but 90-fold more water-soluble.     

Assessing the Role of a Malonamide Linker in the Design of Potent Dual Inhibitors of Factor Xa and Cholinesterases

The rational discovery of new peptidomimetic inhibitors of the coagulation factor Xa (fXa) could help set more effective therapeutic options (to prevent atrial fibrillation). In this respect, we explored the conformational impact on the enzyme inhibition potency of the malonamide bridge, compared to the glycinamide one, as a linker connecting the P1 benzamidine anchoring moiety to the P4 aryl group of novel selective fXa inhibitors. We carried out structure–activity relationship (SAR) studies aimed at investigating para- or meta-benzamidine as the P1 basic group as well as diversely decorated aryl moieties as P4 fragments. To this end, twenty-three malonamide derivatives were synthesized and tested as inhibitors of fXa and thrombin (thr); the molecular determinants behind potency and selectivity were also studied by employing molecular docking. The malonamide linker, compared to the glycinamide one, does significantly increase anti-fXa potency and selectivity. The meta-benzamidine (P1) derivatives bearing 2′,4′-difluoro-biphenyl as the P4 moiety proved to be highly potent reversible fXa-selective inhibitors, achieving inhibition constants (K_i) in the low nanomolar range. The most active compounds were also tested against cholinesterase (ChE) isoforms (acetyl- or butyrylcholinesterase, AChE, and BChE), and some of them returned single-digit micromolar inhibition potency against AChE and/or BChE, both being drug targets for symptomatic treatment of mild-to-moderate Alzheimer’s disease. Compounds 19h and 22b were selected as selective fXa inhibitors with potential as multimodal neuroprotective agents.     

Asymmetric Michael addition promoted by (R,R)-trans-1,2-diaminocyclohexane in ionic liquids

In tetrafluoroborate based ionic liquids fair yields and enantiomeric excesses up to 91% were obtained in the Michael addition of ethyl cyclohexanone-2-carboxylate to methyl vinyl ketone, using (R,R)-trans-1,2-diaminocyclohexane as chiral auxiliary (37% mol/mol with respect to the donor). The presence of catalytic amounts of metal sources [Ni(OAc)₂ · 4H₂O, Co(acac)₂, FeCl₃ · 6H₂O, LaCl₃, Cu(OAc)₂ · H₂O] did not improve the activity, and, in some instances, caused a drop of enantioselectivity. Reactions carried out in the absence of any metal and with a Michael donor/diamine molar ratio of 20 allowed us to ascertain that the reaction can be performed catalytically.     

Introducing Water and Deep Eutectic Solvents in Organosodium Chemistry: Chemoselective Nucleophilic Functionalizations in Air

Advancing the development of perfecting the use of polar organometallics in bio-inspired solvents, we report on the effective generation in batch of organosodium compounds, by the oxidative addition of a C−Cl bond to sodium, a halogen/sodium exchange, or by direct sodiation, when using sodium bricks or neopentylsodium in hexane as sodium sources. C(sp³)-, C(sp²)-, and C(sp)-hybridized alkyl and (hetero)aryl sodiated species have been chemoselectively trapped (in competition with protonolysis), with a variety of electrophiles when working “on water”, or in biodegradable choline chloride/urea or L-proline/glycerol eutectic mixtures, under hydrous conditions and at room temperature. Additional benefits include a very short reaction time (20 s), a wide substrate scope, and good to excellent yields (up to 98 %) of the desired adducts. The practicality of the proposed protocol was demonstrated by setting up a sodium-mediated multigram-scale synthesis of the anticholinergic drug orphenadrine.     

Liquid chromatography/tandem mass spectrometry of unusual phenols from Yucca schidigera bark: comparison with other analytical techniques

Qualitative and quantitative analyses of phenolic compounds are of interest for both medicinal and food plants. In the present work, the phenolic fraction from Yucca schidigera, a plant bearing the GRAS (Generally Recognized as Safe) label approved by the US Food and Drug Administration, was studied. Crude extracts of Y. schidigera bark were investigated by liquid chromatography/UV spectrophotometry with diode-array detection, liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) and liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS), in order to develop and optimize simple and rapid techniques to determine both stilbenes and yuccaols for the purposes of quality control of collected material. With optimal LC and MS conditions, stilbenes and yuccaols were quantified with all the proposed methods and the results were compared. Sensitivity was evaluated and the results indicated that MS/MS detection in the multiple reaction monitoring mode is easily applicable to this plant and allows the rapid and direct identification and quantification of these peculiar compounds in crude plant extracts.     

Synthesis and Monoamine Oxidase Inhibitory Activity of 3-Substituted 5H-Indeno[1,2-c]pyridazines

The one-pot synthesis of nine 5H-indeno[1,2-c]pyridazines is described. These compounds are shown to be potent, reversible inhibitors of monoamine oxidase B (MAO-B) with little or no effect on monoamine oxidase A (MAO-A). Qualitative structure-activity relations indicate that the MAO-B inhibitory activity is strongly influenced by electronic and bulk properties of substitutents.     

Effect of compatibilization on thermal degradation kinetics of HDPE-based composites containing cellulose reinforcements

Dynamic thermogravimetric analysis under nitrogen flow was used to investigate the thermal decomposition process of high-density poly(ethylene) (HDPE)-based composites reinforced with cellulose fibers obtained from the recycling of multilayer carton scraps, as a function of the cellulose content and the compatibilization. The Friedman, Flynn–Wall–Ozawa, and Coats–Redfern methods were used to determine the apparent activation energy (E _a) of the thermal degradation of the cellulose component into the composites. E _a has been found dependent on the cellulose amount and on the cellulose/polymer matrix interfacial adhesion. In particular, it has been evidenced an increase of the cellulose thermal stability as a consequence of the improved interfacial adhesion between the components in NFR composites.