Stereoconvergent Generation of a Contrasteric syn‐Bicyclopropylidene (=syn‐Cyclopropylidenecyclopropane) by Stille‐Like Coupling

Stereoisomerically pure endo‐ and exo‐7‐halo‐7‐(trimethylstannyl)benzonorcar‐3‐enes (=endo‐ and exo‐(1‐halo‐1a,2,7,7a‐tetrahydro‐1H‐cyclopropa[b]naphthalen‐1‐yl)trimethylstannane) 4 and 6 were selectively obtained by lithium? tin or magnesium? tin transmetalation in good yields (Scheme 2 and 3). The reaction of these compounds with copper(I) thiophene‐2‐carboxylate (CuTC) produced in both cases the corresponding C_S‐symmetric bicyclopropylidene (=cyclopropylidenecyclopropane) syn‐ 1 , a single diastereoisomer (Schemes 5 and 6). The structure of syn‐ 1 was undoubtedly elucidated by X‐ray single crystal diffraction. The coupling mechanism of the carbenoid cyclopropane is discussed (Scheme 7).     

Acetic Anhydride/Et3N/DMAP: An Effective Acetylating System for Hemiacetals

The selective and efficient acetylation of the hemiacetal hydroxyl in the equilibrium mixture between RCl₂C(OAll)OH and AllOH/RCl₂CHO was achieved using the acylating system Ac₂O/Et₃N/dimethylaminopyridine (DMAP).

Combined use of three forms of chiroptical spectroscopies in the study of the absolute configuration and conformational properties of 3-phenylcyclopentanone, 3-phenylcyclohexanone,and 3-phenylcycloheptanone

Three forms of chiroptical spectroscopies, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and optical rotatory dispersion (ORD) have been employed to study the configuration and conformational properties of the three molecules: (S)-3-phenylcyclopentanone, (S)-3-phenylcyclohexanone, and (S)-3-phenylcycloheptanone (including (S)-3-phenylcyclopentanone-2,2,5,5-d₄ and (S)-3-phenylcyclohexanone-2,2,6,6-d₄). ECD and VCD spectra in the mid-IR for the three molecular systems are marginally dependent on fine conformational details, as interpreted in terms of standard DFT computational methods, with common spectroscopic features to the three systems clearly identified. Accounting for vibronic coupling mechanisms reproduces the structuring of ECD n→π^∗ band. The ORD curves are quite similar for the three types of molecules, but their interpretation highlights a crucial role played by conformations of the cycloalkanone ring in the case of (S)-3-phenylcycloheptanone. The same conclusions are reached by considering the VCD spectra in the CH-stretching region.     

High sensitivity measurements of thermal properties of textile fabrics

A new testing apparatus is proposed to measure the thermal properties of fabrics made from polymeric materials. The calibration of the apparatus and the data acquisition procedure are considered in detail in order to measure thermal conductivity, resistance, absorption and diffusivity constants of the tested fabric samples. Differences between dry and wet fabrics have been carefully detected and analyzed. We have developed a new measurement protocol, the ThermoTex protocol, which agrees with the UNI EN 31092 standard and entails accurate quantification of the experimental errors according to a standard statistical analysis, thus allowing a rigorous investigation of the physical behavior of the phenomena involved. As a consequence, our equipment exhibits great potential for optimizing the thermal comfort of fabrics, according to the market demand, thanks to the possible development of a predictive phenomenological theory of the effects involved.     

Direct Derivation of Free Energies of Membrane Deformation and Other Solvent Density Variations From Enhanced Sampling Molecular Dynamics

We report a methodology to calculate the free energy of a shape transformation in a lipid membrane directly from a molecular dynamics simulation. The bilayer need not be homogeneous or symmetric and can be atomically detailed or coarse grained. The method is based on a collective variable that quantifies the similarity between the membrane and a set of predefined density distributions. Enhanced sampling of this “Multi-Map” variable re-shapes the bilayer and permits the derivation of the corresponding potential of mean force. Calculated energies thus reflect the dynamic interplay of atoms and molecules, rather than postulated effects. Evaluation of deformations of different shape, amplitude, and range demonstrates that the macroscopic bending modulus assumed by the Helfrich–Canham model is increasingly unsuitable below the 100-Å scale. In this range of major biological significance, direct free-energy calculations reveal a much greater plasticity. We also quantify the stiffening effect of cholesterol on bilayers of different composition and compare with experiments. Lastly, we illustrate how this approach facilitates analysis of other solvent reorganization processes, such as hydrophobic hydration. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.     

Probing Relaxation Dynamics in Five-Coordinate Dysprosium Single-Molecule Magnets

A new family of five-coordinate lanthanide single-molecule magnets (Ln SMMs) [Dy(Mes*O)₂(THF)₂X] (Mes*=2,4,6-tri-tert-butylphenyl; X=Cl, 1 ; Br, 2 ; I, 3 ) is reported with energy barriers to magnetic reversal >1200 K. The five-coordinate Dy^III ions have distorted square pyramidal geometries, with halide anions on the apex, and two Mes*O ligands mutually trans- to each other, and the two THF molecules forming the second trans- pair. These geometrical features lead to a large magnetic anisotropy in these complexes along the trans-Mes*O direction. QTM and Raman relaxation times are enhanced by varying the apex halide from Cl to Br to I, or by dilution in a diamagnetic yttrium analogue.     

Interaction with plasmid DNA of Hoechst-TACN conjugates

ABSTRACT

A new family of conjugates between the Hoechst minor groove binder and the TACN metal ion ligand connected through hydrophobic alkyl or more hydrophilic oxyethyl linkers of different length has been prepared. The linkers are connected to the convex side of the Hoechst skeleton thus forcing the TACN ligand to exit the minor groove and interact with the phosphate backbone of DNA. The conjugates preserve the binding mode of Hoechst with an affinity influenced by the nature of the linker, the more hydrophobic being the more efficient. Coordination of Cu(II) or Zn(II) poorly affect these parameters. Nevertheless, the Zn(II) complex bearing a C6 linear alkyl linker induced a modest but reproducible acceleration of the hydrolytic cleavage of DNA which can be ascribed to the ability of the conjugate to deliver the hydrolytic subunit close to the DNA phosphodiester bonds.     

From a Medicinal Mushroom Blend a Direct Anticancer Effect on Triple-Negative Breast Cancer: A Preclinical Study on Lung Metastases

Bioactive metabolites isolated from medicinal mushrooms (MM) used as supportive treatment in conventional oncology have recently gained interest. Acting as anticancer agents, they interfere with tumor cells and microenvironment (TME), disturbing cancer development/progression. Nonetheless, their action mechanisms still need to be elucidated. Recently, using a 4T1 triple-negative mouse BC model, we demonstrated that supplementation with Micotherapy U-Care, a MM blend, produced a striking reduction of lung metastases density/number, paralleled by decreased inflammation and oxidative stress both in TME and metastases, together with QoL amelioration. We hypothesized that these effects could be due to either a direct anticancer effect and/or to a secondary/indirect impact of Micotherapy U-Care on systemic inflammation/immunomodulation. To address this question, we presently focused on apoptosis/proliferation, investigating specific molecules, i.e., PARP1, p53, BAX, Bcl2, and PCNA, whose critical role in BC is well recognized. We revealed that Micotherapy U-Care is effective to influence balance between cell death and proliferation, which appeared strictly interconnected and inversely related (p53/Bax vs. Bcl2/PARP1/PCNA expression trends). MM blend displayed a direct effect, with different efficacy extent on cancer cells and TME, forcing tumor cells to apoptosis. Yet again, this study supports the potential of MM extracts, as adjuvant supplement in the TNBC management.