Synthesis and Screening of New Chiral Ligands for the Copper‐Catalysed Enantioselective Allylic Substitution

The synthesis of the new chiral ligands 6ae, 8ae, 9ae , and 11ae starting from the chiral β‐[(Boc)amino]sulfonamide 3ae is reported. The β‐amino group of 3ae was deprotected and condensed with 3,5‐dichlorosalicylaldehyde ( 4 ) to yield the known Schiff base 5ae , which was then reduced to the amino compound 6ae (Scheme 3). Alternatively, condensation of the free amino compound with 2‐(diphenylphosphanyl)benzaldehyde ( 7 ) afforded the imino ligand 8ae which upon reduction yielded the amino ligand 9ae (Scheme 4). The free amino compound derived from 3ae was also coupled with 2‐(diphenylphosphanyl)benzoic acid ( 10 ) to give ligand 11ae (Scheme 5). These ligands were tested in the copper‐catalysed allylic substitution reaction of cinnamyl (=3‐phenylprop‐2‐enyl) phosphate 12 with diethylzinc as a nucleophile. Ligands 5ae, 6ae, 8ae , and 11ae gave excellent ratios (100 : 0) of the S_N2′/S_N2 products (Scheme 6 and Table 1). Ligand 11ce , identified from the screening of a small library of ligands of general formula 11 , promoted the allylic substitution reaction with moderate enantioselectivity (40% for the S_N2′ product 13 (Scheme 8 and Table 3)).     

Dittrichia graveolens (L.) Greuter,a Rapidly Spreading Invasive Plant: Chemistry and Bioactivity

Dittrichia graveolens L. Greuter belonging to the Asteraceae family, is an aromatic herbaceous plant native to the Mediterranean region. This plant species has been extensively studied for its biological activities, including antioxidant, antitumor, antimicrobial, antifungal, anti-inflammatory, anticholinesterase, and antityrosinase, and for its peculiar metabolic profile. In particular, bioactivities are related to terpenes and flavonoids metabolites, such as borneol (40), tomentosin (189), inuviscolide (204). However, D. graveolens is also well known for causing health problems both in animals and humans. Moreover, the species is currently undergoing a dramatic northward expansion of its native range related to climate change, now including North Europe, California, and Australia. This review represents an updated overview of the 52 literature papers published in Scopus and PubMed dealing with expansion, chemistry (262 different compounds), pharmacological effects, and toxicology of D. graveolens up to October 2021. The review is intended to boost further studies to determine the molecular pathways involved in the observed activities, bioavailability, and clinical studies to explore new potential applications.     

A modular invariant partition function for the fivebrane

We compute an invariant partition function for the chiral two-form of the M theory fivebrane compactified on the six-torus T⁶. From a manifestly invariant formalism, we prove that the partition function has an additional symmetry. The combination of these two symmetries ensures invariance. Thus, whether or not a fully covariant Lagrangian is available, the fivebrane on the six-torus has a consistent quantum theory.     

Conversion of the Native N-Terminal Domain of TDP-43 into a Monomeric Alternative Fold with Lower Aggregation Propensity

TAR DNA-binding protein 43 (TDP-43) forms intraneuronal cytoplasmic inclusions associated with amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. Its N-terminal domain (NTD) can dimerise/oligomerise with the head-to-tail arrangement, which is essential for function but also favours liquid-liquid phase separation and inclusion formation of full-length TDP-43. Using various biophysical approaches, we identified an alternative conformational state of NTD in the presence of Sulfobetaine 3-10 (SB3-10), with higher content of α-helical structure and tryptophan solvent exposure. NMR shows a highly mobile structure, with partially folded regions and β-sheet content decrease, with a concomitant increase of α-helical structure. It is monomeric and reverts to native oligomeric NTD upon SB3-10 dilution. The equilibrium GdnHCl-induced denaturation shows a cooperative folding and a somewhat lower conformational stability. When the aggregation processes were compared with and without pre-incubation with SB3-10, but at the identical final SB3-10 concentration, a slower aggregation was found in the former case, despite the reversible attainment of the native conformation in both cases. This was attributed to protein monomerization and oligomeric seeds disruption by the conditions promoting the alternative conformation. Overall, the results show a high plasticity of TDP-43 NTD and identify strategies to monomerise TDP-43 NTD for methodological and biomedical applications.     

Solvent Casting and UV Photocuring for Easy and Safe Fabrication of Nanocomposite Film Dressings

The aim of this work was to optimize and characterize nanocomposite films based on gellan gum methacrylate (GG-MA) and silver nanoparticles (AgNPs) for application in the field of wound dressing. The films were produced using the solvent casting technique coupled with a photocuring process. The UV irradiation of GG-MA solutions containing glycerol as a plasticizer and different amounts of silver nitrate resulted in the concurrent crosslinking of the photocurable polymer and a reduction of Ag ions with consequent in situ generation of AgNPs. In the first part of the work, the composition of the films was optimized, varying the concentration of the different components, the GG-MA/glycerol and GG-MA/silver nitrate weight ratios as well as the volume of the film-forming mixture. Rheological analyses were performed on the starting solutions, whereas the obtained films were characterized for their mechanical properties. Colorimetric analyses and swelling studies were also performed in order to determine the AgNPs release and the water uptake capacity of the films. Finally, microbiological tests were carried out to evaluate the antimicrobial efficacy of the optimized films, in order to demonstrate their possible application as dressings for the treatment of infected hard-to-heal wounds, which is a demanding task for public healthcare.     

Biophysical and Biological Tools to Better Characterize the Stability,Safety and Efficacy of a Cosmeceutical for Acne-Prone Skin

(1) Background: Acne is a widespread skin disease, especially among adolescents. Following the COVID-19 pandemic and the use of masks, the problem has been affecting a greater number of people, and the attention of the skin care beauty routine cosmetics has been focused on the “Maskne”, caused by the sebum excretion rate (SER) that stimulates microbial proliferation. (2) Methods: the present study was focused on the rheological characterization and quality assurance of the preservative system of an anti-acne serum. The biological effectiveness (cytotoxicity—skin and eye irritation—antimicrobial, biofilm eradication and anti-inflammatory activity) was evaluated in a monolayer cell line of keratinocytes (HaCaT) and on 3D models (reconstructed human epidermis, RHE and human reconstructed corneal epithelium, HCE). The Cutibacterium acnes, as the most relevant acne-inducing bacterium, is chosen as a pro-inflammatory stimulus and to evaluate the antimicrobial activity of the serum. (3) Results and Conclusions: Rheology allows to simulate serum behavior at rest, extrusion and application, so the serum could be defined as having a solid-like behavior and being pseudoplastic. The preservative system is in compliance with the criteria of the reference standard. Biological effectiveness evaluation shows non-cytotoxic and irritant behavior with a good antimicrobial and anti-inflammatory activity of the formulation, supporting the effectiveness of the serum for acne-prone skin treatment.     

Numerical Investigation of a MILD Combustion Burner: Analysis of Mixing Field, Chemical Kinetics and Turbulence-Chemistry Interaction

A numerical study of a jet-in-hot coflow (JHC) burner emulating Moderate or Intense Low-oxygen Dilution (MILD) combustion conditions was carried out by solving the Reynolds Averaged Navier-Stokes equations in a two-dimensional axisymmetric domain and using the Eddy Dissipation Concept (EDC) for the turbulence-chemistry interaction treatment. A systematic methodology was used to analyze all possible sources of discrepancies observed between experimental and numerical data, trying to shedding light on the suitability of specific models for MILD combustion. In this regard, the deficiencies that may come from turbulence model or kinetic scheme have been shown by comparative study on four variants of the k-ε model (i.e. the standard, modified, realizable and RNG) together with the Reynolds stress model and three kinetic schemes namely KEE-58, DRM-19 and DRM-22. A variation of an EDC parameter (i.e. increasing the constant of the fine structure residence time) was proposed for better consideration of MILD combustion features and to overcome the over-prediction of peak temperature observed at downstream. In such a manner encouraging results were also obtained for the prediction of major combustion products as well as for CO and OH.     

Spectromechanical Properties of Polymeric Gel Electrolytes and Blends

In this paper we studied the spectro-mechanical properties of polymer gel electrolytes and blends by means of shear rheology. These electrolytes were obtained by immobilizing EC/PC/LiClO₄ solutions in a polymeric matrix of PEO, PAN and PMMA, respectively. Two structural and thermoreversible transitions, a strong-to-weak gel and a gel-to-sol, were revealed and discussed. Moreover, PMMA-PVdF blends have been studied as a function of the different polymeric ratios in order to obtain the best compromise between ionic conduction and mechanical properties. Interesting mechanical properties were observed at some intermediate blend compositions.     

Numerical integration schemes for space–time hypersingular integrals in energetic Galerkin BEM

Here we consider exterior Neumann wave propagation problems reformulated in terms of space–time hypersingular boundary integral equations. We deal with quadrature schemes required, in the discretization phase, by the energetic Galerkin boundary element method.