Unravelling the Phytochemical Composition and the Pharmacological Properties of an Optimized Extract from the Fruit from Prunus mahaleb L.: From Traditional Liqueur Market to the Pharmacy Shelf

Prunus mahaleb L. fruit has long been used in the production of traditional liqueurs. The fruit also displayed scavenging and reducing activity, in vitro. The present study focused on unravelling peripheral and central protective effects, antimicrobial but also anti-COVID-19 properties exerted by the water extract of P. mahaleb. Anti-inflammatory effects were studied in isolated mouse colons exposed to lipopolysaccharide. Neuroprotection, measured as a blunting effect on hydrogen-peroxide-induced dopamine turnover, was investigated in hypothalamic HypoE22 cells. Antimicrobial effects were tested against different Gram+ and Gram- bacterial strains. Whereas anti-COVID-19 activity was studied in lung adenocarcinoma H1299 cells, where the gene expression of ACE2 and TMPRSS2 was measured after extract treatment. The bacteriostatic effects induced on Gram+ and Gram- strains, together with the inhibition of COX-2, TNFα, HIF1α, and VEGFA in the colon, suggest the potential of P. mahaleb water extract in contrasting the clinical symptoms related to ulcerative colitis. The inhibition of the hydrogen peroxide-induced DOPAC/DA ratio indicates promising neuroprotective effects. Finally, the downregulation of the gene expression of ACE2 and TMPRSS2 in H1299 cells, suggests the potential to inhibit SARS-CoV-2 virus entry in the human host. Overall, the results support the valorization of the local cultivation of P. mahaleb.     

Fluorescence correlation spectroscopic studies of diffusion within the ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate

Fluorescence correlation spectroscopy (FCS) measurements have been performed in order to determine the translational diffusion coefficients of three differently charged fluorescent probes (cationic: rhodamine 6G, neutral: 4-dicyanomethylene-2-methyl-6-p-dimethylaminostyryl-4-H-pyran, DCM, and anionic: fluorescein) dissolved within the common room temperature ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF6]. These experiments demonstrate that FCS is a rapid, sensitive, precise (typical RSD from 4-8%), and low-consumption screening tool for the determination of analyte mobility within microliter ionic liquid samples.     

Femtosecond excitation energy transport in triarylamine dendrimers

The search for a model that can be used to describe the optical excitation migration in dendrimers has attracted great attention. In most cases in a dendrimer the conjugation is disrupted at the branching point; however, the excitation is delocalized. The strength of interactions among neighboring chromophores plays a key role in determining the energy migration mechanism. Conversely, having many identical chromophores held tightly together in an ordered macromolecular architecture will allow for many dipoles to be accessible for optical excitation. Therefore, the relative orientation of dipoles will be important in determining the mechanism of energy migration. Here we report the synthesis and photo-physical investigation of triarylamine-based dendrimers. Two important synthetic steps were utilized in the synthesis. First, we employed diphenylmethyl protective groups on the amines to assist in deprotective hydrogenolysis of the larger structures. Second, highly active catalysts for formation of both di- and triarylamines that are based on a 1:1 ratio of P(t-Bu)3 and Pd(dba)2 improved reaction yields of the C-N bond formation and decreased reaction times The energy migration processes in the dendrimers were investigated utilizing ultrafast time-resolved fluorescence anisotropy measurements. The fluorescence anisotropy of all three dendrimers decayed to a residual value within approximately 100 fs. This fluorescence anisotropy decay showed a general trend in decreasing with increasing dendrimer generation. The residual anisotropy value also showed a gradual decrease with an increase in the dendrimer generation. This fast energy depolarization is discussed through a coherent excitonic mechanism among dipoles oriented in different directions. We believe that the formation of coherent domains leads to fast energy migration extending over a large part of the dendrimer.     

Rapid Assembly of Saturated Nitrogen Heterocycles in One‐Pot: Diazo‐Heterocycle “Stitching” by N–H Insertion and Cyclization

Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2‐disubstituted azetidines, pyrrolidines, piperidines, and azepanes bearing ester and diverse aryl substituents. A one‐pot rhodium catalyzed N–H insertion and cyclization sequence uses diazo compounds to stitch together linear 1,m‐haloamines (m=2–5) to rapidly assemble 4 ‐, 5 ‐, 6 ‐, and 7 ‐membered saturated nitrogen heterocycles in excellent yields. Over fifty examples are demonstrated, including examples with diazo compounds derived from biologically active compounds. The products can be functionalized to afford α,α‐disubstituted amino acids and applied to fragment synthesis.     

The use of novel water-in-oil microemulsions in microemulsion electrokinetic chromatography

We describe the novel use of water-in-oil (W/O) microemulsions to achieve unique separations in microemulsion electrokinetic chromatography (MEEKC). The choice and concentration of the buffer type, surfactant and co-surfactant were all examined and optimized. Separations of a range of neutral and acidic analytes was shown to be markedly different to that obtained by (oil-in-water) O/W MEEKC. Neutral solutes are separated by virtue of their solubility (log P) values in O/W MEEKC with the more water-insoluble solutes migrating last. This separation process does not occur in W/O, as neutral solutes are not separated in order of log P.     

A comparison of double-focusing sector field ICP-MS, ICP-OES and octopole collision cell ICP-MS for the high-accuracy determination of calcium in human serum

Human serum is routinely measured for total calcium content in clinical studies. A definitive high-accuracy and low-uncertainty method is required for reference measurements to underpin medical diagnoses. This study presents a novel octopole collision cell ICP-MS, high-accuracy, methodology and comparison of that technique with double-focusing sector field ICP-MS and an ICP-OES method. Double-matched isotope dilution mass spectrometry (IDMS) was employed for ICP-MS techniques and an exact matching bracketing technique using scandium as an internal standard was used for ICP-OES analysis. Medium resolution mode was utilised for double-focusing sector field ICP-MS analysis to resolve the dominant interferences on the ⁴⁴Ca/⁴²Ca isotope pair. Hydrogen reaction gas was employed to chemically resolve a number of polyatomic interferences predominantly through charge transfer reactions in the octopole collision cell. Comparison data presented for NIST CRM 909b human serum analysis from all three techniques demonstrates highest accuracy (99.6%) and lowest uncertainty (1.1%) for octopole collision cell ICP-MS. Data from ICP-OES using a non-IDMS technique produces comparably accurate data and low-uncertainties. The much higher total expanded uncertainties for double-focusing sector field ICP-MS compared with octopole collision cell data are explained by lower precision on the measurement of the ⁴⁴Ca/⁴²Ca isotope ratio. Data for octopole collision cell ICP-MS submitted for an international blind trial comparison (CCQM K-14) demonstrated excellent agreement with the mean of all participants with a low expanded uncertainty.     

Cellulose Derivatives Synthesized via Isocyanate and Activated Ester Pathways in Homogeneous Solutions of Lithium Chloride/N,N-Dimethylacetamide

Abstract

Cellulose carbamate and ester derivatives were synthesized in homogeneous solutions of lithium chloride (LiCl)/N,N-dimemyl-acetamide (DMAc) by the reaction of cellulose with ethyl 4-isocyanatobenzoate and the activated esters of N,N-dimethyl-aminobenzoic acids. Comparative reactions were performed with phenyl isocyanate and the activated ester of benzoic acid. All reactions were followed spectroscopically by FTIR, ¹H NMR, and ¹³C NMR. Degrees of substitution were calculated utilizing UV spectroscopy. The isocyanate reactions are facile allowing controllable degrees of substitution and high yields. By contrast, the activated ester pathway inherently results in lower degrees of substitution and lower yields due in part to undesirable side reactions.     

Electrospun poly(ethylene oxide)/chitosan nanofibers with cellulose nanocrystals as support for cell culture of 3T3 fibroblasts

Chitosan/poly(ethylene oxide) (PEO) (5:1) nanofibers with cellulose nanocrystals (CNCs) were produced using an electrospinning technique. The addition of CNCs to the chitosan/PEO solutions allowed the production of uniform fibers (without beads) with a high proportion of chitosan. The fiber diameters were influenced by the concentration of CNCs in the chitosan/PEO solutions. The solutions containing 10% (w/w) of CNCs produced thinner fibers compared to solutions containing 5% (w/w) of CNCs. Thermogravimetric analysis indicated that the nanofibers were thermally stable, despite the CNCs having an effect on the PEO decomposition. Results from the cell assay in cultures of 3T3 fibroblasts indicated that the chitosan/PEO nanofibers (with 10% CNCs) promoted cell attachment with changes in the cytoskeletal organization. The results obtained in this work highlight the favorable effect of CNCs in electrospinning of chitosan/PEO. As expected, the influence of nanofibers on 3T3 fibroblasts F-actin and β-tubulin network revealed alterations in cytoskeleton, leading to changes in cell morphology and spreading.     

The push-out region of an immersed manifold

We consider immersions: and construct a subspace of which corresponds to a set of embedded manifolds which are either parallel to f, tubes around f or, in general, partial tubes around f. This space is invariant under the action of the normal holonomy group, We investigate the case where is non-trivial and obtain some results on the number of connected components of . Received 24 March 2000.     

Homotopy of Non-Modular Partitions and the Whitehouse Module

We present a class of subposets of the partition lattice _n with the following property: The order complex is homotopy equivalent to the order complex of _n – 1, and the S _n -module structure of the homology coincides with a recently discovered lifting of the S _n – 1-action on the homology of _n – 1. This is the Whitehouse representation on Robinson's space of fully-grown trees, and has also appeared in work of Getzler and Kapranov, Mathieu, Hanlon and Stanley, and Babson et al.One example is the subposet P _n ⁿ – 1 of the lattice of set partitions _n , obtained by removing all elements with a unique nontrivial block. More generally, for 2 k n – 1, let Q _n ^k denote the subposet of the partition lattice _n obtained by removing all elements with a unique nontrivial block of size equal to k, and let P _n ^k = _{i = 2} ^k Q _n ⁱ . We show that P _n ^k is Cohen-Macaulay, and that P _n ^k and Q _n ^k are both homotopy equivalent to a wedge of spheres of dimension (n – 4), with Betti number . The posets Q _n ^k are neither shellable nor Cohen-Macaulay. We show that the S _n -module structure of the homology generalises the Whitehouse module in a simple way.We also present a short proof of the well-known result that rank-selection in a poset preserves the Cohen-Macaulay property.