Real-Time pH-Dependent Self-Assembly of Ionisable Lipids from COVID-19 Vaccines and In Situ Nucleic Acid Complexation

Ionisable amino-lipid is a key component in lipid nanoparticles (LNPs), which plays a crucial role in the encapsulation of RNA molecules, allowing efficient cellular uptake and then releasing RNA from acidic endosomes. Herein, we present direct evidence for the remarkable structural transitions, with decreasing membrane curvature, including from inverse micellar, to inverse hexagonal, to two distinct inverse bicontinuous cubic, and finally to a lamellar phase for the two mainstream COVID-19 vaccine ionisable ALC-0315 and SM-102 lipids, occurring upon gradual acidification as encountered in endosomes. The millisecond kinetic growth of the inverse cubic and hexagonal structures and the evolution of the ordered structural formation upon ionisable lipid-RNA/DNA complexation are quantitatively revealed by in situ synchrotron radiation time-resolved small angle X-ray scattering coupled with rapid flow mixing. We found that the final self-assembled structural identity, and the formation kinetics, were controlled by the ionisable lipid molecular structure, acidic bulk environment, lipid compositions, and nucleic acid molecular structure/size. The implicated link between the inverse membrane curvature of LNP and LNP endosomal escape helps future optimisation of ionisable lipids and LNP engineering for RNA and gene delivery.     

Axial chirality of N,N′-disubstituted 3,4-ethylenedioxythiophene-2,5-dicarboxamides

A series of N,N’-disubstituted 3,4-ethylenedioxythiophene-2,5-dicarboxamides was synthesised by amide bond formation between 3,4-ethylenedioxythiophene-2,5-dicarbonyl chloride and corresponding primary amines, where the size and the nature of the substituent were varied. The crystal structures of prepared compounds were determined by X-ray structure analysis. Mechanism and reaction rates of interconversion between conformational isomers were obtained by DFT calculations. All studied compounds reveal axial chirality with molecular symmetry C ₂. Amide bond isomerisation and twisting of the dioxane ring in studied compounds results in the formation of series of conformers of which the s-trans/s-trans conformer is energetically most favourable.     

Hardy inequalities for Robin Laplacians

In this paper we establish a Hardy inequality for Laplace operators with Robin boundary conditions. For convex domains, in particular, we show explicitly how the corresponding Hardy weight depends on the coefficient of the Robin boundary conditions. We also study several extensions to non-convex and unbounded domains.     

Synthesis and structure of bis- and tris-ferrocene containing N-methylimide foldamers

The synthesis and conformational analysis of dimer Fc–CO–NMe–CO–Fc (5) and trimer Fc–CO–NMe–CO–Fn–CO–NMe–CO–Fc (6) have been described. It has been shown by means of spectroscopic studies, X-ray crystallography, and molecular modeling, that these molecules are dominated by cis–cis conformation. Furthermore, we recognized for the first time, that such type of organometallics possess elements of chiral helicity. Their crystal lattices are characterized by π–π and CH–π intermolecular interactions (5) and by CH?OC intermolecular hydrogen bonds (6). We believe that foldamers 5/6 are stabilized by the special type of aromatic π–π interactions between the closer cyclopentadienyl rings of the juxtaposed ferrocene units.     

Probability for Type I errors in gamma-ray spectrometric measurements of drinking water samples

In gamma-ray spectra, acquired in the absence of the sample, peaks occur which belong to the spectrometer background. When samples are measured, which contain radionuclides that appear in the background also and have activities near the detection level, the background contributes substantially to the peak areas. In the extreme case, when the contribution of the sample is much smaller than the contribution of the background, the peak area attributed to the radionuclide within a sample has the same probability of being positive or negative. Therefore, to interpret the results obtained from measurements of low-activity samples, the performance of the spectrum analysis procedure near the detection level must be known. To test the performance of the spectrum analysis procedure at low activities, the spectrometer background spectra were analyzed as if they had been water samples, prepared as dry residue obtained by evaporation of 50 L of water. The probabilities for false positives together with their decision thresholds are given for radionuclides appearing in the background spectra. For some of the radionuclides that do not appear in the background spectra, probabilities for false detection are given as well.     

Effects of dielectric barrier discharge in air on morphological and electrical properties of graphene nanoplatelets and multi-walled carbon nanotubes

Multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) have been functionalized by dielectric barrier discharge (DBD) in air. The extent of functionalization of MWCNTs and GNPs reaches a maximum at the delivered discharge energy of 720 and 240 J mg⁻¹, respectively. Further exposure to plasma leads to reduction of functional groups from the surface of the treated nanomaterials. It has also been demonstrated that DBD plasma does not produce dramatic structural changes in MWCNTs, while flakes of the treated GNPs become thinner and smaller in the lateral size. Conductive thin films, obtained by drop casting a solution of the treated nanomaterials in N-methyl-1-pyrrolidone on poly(methyl methacrylate) substrate, show significantly lower sheet resistance.