Probing the Penetration of Rapamycin by Scanning Transmission X-ray Microscopy

Drug penetration in human skin ex vivo following a modification of skin barrier permeability is systematically investigated by scanning transmission X-ray microscopy. Element-selective excitation is used in the O 1s regime for probing quantitatively the penetration of topically applied rapamycin in different formulations with a spatial resolution reaching <75 nm. The data were analyzed by a comparison of two methods: (i) two-photon energies employing the Beer–Lambert law and (ii) a singular value decomposition approach making use of the full spectral information in each pixel of the X-ray micrographs. The latter approach yields local drug concentrations more reliably and sensitively probed than the former. The present results from both approaches indicate that rapamycin is not observed within the stratum corneum of nontreated skin ex vivo, providing evidence for the observation that this high-molecular-weight drug inefficiently penetrates intact skin. However, rapamycin is observed to penetrate more efficiently the stratum corneum when modifications of the skin barrier are induced by the topical pretreatment with the serine protease trypsin for variable time periods ranging from 2 to 16 h. After the longest exposure time to serine protease, the drug is even found in the viable epidermis. High-resolution micrographs indicate that the lipophilic drug preferably associates with corneocytes, while signals found in the intercellular lipid compartment were less pronounced. This result is discussed in comparison to previous work obtained from low-molecular-weight lipophilic drugs as well as polymer nanocarriers, which were found to penetrate the intact stratum corneum exclusively via the lipid layers between the corneocytes. Also, the role of the tight junction barrier in the stratum granulosum is briefly discussed with respect to modifications of the skin barrier induced by enhanced serine protease activity, a phenomenon of clinical relevance in a range of inflammatory skin disorders

Uncovering the Charge Transfer between Carbon Dots and Water by In Situ Soft X-ray Absorption Spectroscopy.

Carbon dots (CDs) exhibit outstanding physicochemical properties that render them excellent materials for various applications, often occurring in an aqueous environment, such as light harvesting and fluorescence bioimaging. Here we characterize the electronic structures of CDs and water molecules in aqueous dispersions using in situ X-ray absorption spectroscopy. Three types of CDs with different core structures (amorphous vs graphitic) and compositions (undoped vs nitrogen-doped) were investigated. Depending on the CD core structure, different ionic currents generated upon X-ray irradiation of the CD dispersions at the carbon K-edge were detected, which are interpreted in terms of different charge transfer to the surrounding solvent molecules. The hydrogen bonding networks of water molecules upon interaction with the different CDs were also probed at the oxygen K-edge. Both core graphitization and nitrogen doping were found to endow the CDs with enhanced electron transfer and hydrogen bonding capabilities with the surrounding water molecules.Volkswagen foundation (Freigeist Fellowship No. 89592), Christian Doppler Research Association (Austrian Federal Ministry for Digital and Economic Affairs National Foundation for Research, Technology and Development) OMV

In-depth analysis of the single grain from the C-type asteroid Ryugu utilizing linkage microanalytical instruments planed by Phase 2 curation “Team Kochi”

The Tenth Symposium on Polar Science/Special session: [OA] Antarctic meteorites, Thur. 5 Dec. / 3F Multipurpose conference room, National Institute of Polar Researc

A history of mild shocks experienced by the regolith particles on hydrated asteroid Ryugu

Micrometeorites, a possible major source of Earth’s water, are thought to form from explosive dispersal of hydrated chondritic materials during impact events on their parental asteroids. However, this provenance and formation mechanism have yet to be directly confirmed using asteroid returned samples. Here, we report evidence of mild shock metamorphism in the surface particles of asteroid Ryugu based on electron microscopy. All particles are dominated by phyllosilicates but lack dehydration textures, which are indicative of shock-heating temperatures below ~500 °C. Microfault-like textures associated with extensively shock-deformed framboidal magnetites and a high-pressure polymorph of Fe–Cr–sulfide have been identified. These findings indicate that the average peak pressure was -2 GPa. The vast majority of ejecta formed during impact on Ryugu-like asteroids would be hydrated materials, larger than a millimetre, originating far from the impact point. These characteristics are inconsistent with current micrometeorite production models, and consequently, a new formation mechanism is required

Oxygen isotope evidence from Ryugu samples for early water delivery to Earth by CI chondrites

The delivery of water to the inner Solar System, including Earth, is still a debated topic. A preferential role for hydrated asteroids in this process is supported by isotopic measurements. Carbonaceous chondrite (CC) meteorites represent our main source of information about these volatile-rich asteroids. However, the destruction of weaker materials during atmospheric entry creates a bias in our CC data. The return of surface materials from the C-type asteroid 162173 Ryugu by the Hayabusa2 spacecraft provides a unique opportunity to study high-porosity, low-density, primitive materials, unrepresented in the meteorite record. We measured the bulk oxygen isotope composition from four Ryugu particles and show that they most closely resemble the rare CI (CC Ivuna-type) chondrites, but with some differences that we attribute to the terrestrial contamination of the CI meteorites. We suggest that CI-related material is widespread among carbonaceous asteroids and a more important source of Earth’s water and other volatiles than its limited presence in our meteoritic collection indicates

A pristine record of outer Solar System materials from asteroid Ryugu’s returned sample

Volatile and organic-rich C-type asteroids may have been one of the main sources of Earth’s water. Our best insight into their chemistry is currently provided by carbonaceous chondritic meteorites, but the meteorite record is biased: only the strongest types survive atmospheric entry and are then modified by interaction with the terrestrial environment. Here we present the results of a detailed bulk and microanalytical study of pristine Ryugu particles, brought to Earth by the Hayabusa2 spacecraft. Ryugu particles display a close compositional match with the chemically unfractionated, but aqueously altered, CI (Ivuna-type) chondrites, which are widely used as a proxy for the bulk Solar System composition. The sample shows an intricate spatial relationship between aliphatic-rich organics and phyllosilicates and indicates maximum temperatures of ~30 °C during aqueous alteration. We find that heavy hydrogen and nitrogen abundances are consistent with an outer Solar System origin. Ryugu particles are the most uncontaminated and unfractionated extraterrestrial materials studied so far, and provide the best available match to the bulk Solar System composition

<i>In Situ</i> Soft X‑ray Absorption Spectroscopy Applied to Solid–Liquid Heterogeneous Cyanopyrazine Hydration Reaction on Titanium Oxide Catalyst

In conventional <i>in situ</i> spectroscopies of solid–liquid heterogeneous catalytic reactions, it is difficult to measure the conversion of liquid substrates on solid catalysts due to the lack of sensitivity and the difficulty in separation of target signals in the mixture of substrates, reactants, products, solvents, and solid catalysts. Element-specific soft X-ray absorption spectroscopy (XAS) is a promising method to detect target substrate and product separately from the other components using chemically different inner shell excitation energies. In the present work, we have developed an <i>in situ</i> sample cell to measure time- and temperature-dependent XAS spectra in transmission mode and applied it to one of the solid–liquid heterogeneous catalytic reactions, cyanopyrazine (PzCN) hydration to produce pyrazinamide (PzCONH₂) on the TiO₂ catalyst (PzCN + H₂O → PzCONH₂). We have succeeded in unambiguous observation of the spectral change in the C K-edge and N K-edge XAS due to the production of PzCONH₂ from PzCN during the reaction regardless of the coexistence of the bulk liquid components, H₂O (reactant) and EtOH (solvent). Furthermore, we have obtained reasonable kinetic properties in the PzCN hydration reaction from the spectral analysis such as the reaction order (first order), the rate constant, and the activation energy. Thus, the present method can be widely applicable to distinguish the minor liquid components in chemical reactions

Reaction Mechanism of Aromatic Ring Amination of Benzene and Substituted Benzenes by Aqueous Ammonia over Platinum-Loaded Titanium Oxide Photocatalyst

The reaction mechanism of photocatalytic aromatic ring amination of benzene and the derivatives with aqueous ammonia was clarified by some reaction experiments and electron spin resonance spectroscopy as follows: a platinum-loaded titanium oxide photocatalyst oxidizes an ammonia to form an amide radical (·NH₂) and a proton, and the amide radical attacks an aromatic ring to produce an intermediate, followed by the abstraction of the hydrogen atom from it on the platinum sites to produce an aniline. Simultaneously, the photocatalyst also promotes the reduction of a proton to form a hydrogen radical on the platinum sites, and it reacts with the abstracted hydrogen to produce a molecular hydrogen. The photocatalytic aromatic ring amination proceeded for many kinds of monosubstituted benzenes except for phenol, and high selectivity was recorded for benzonitrile and halogenated benzenes. It is noted that the distributions of the aminated isomers were unique, i.e., the <i>para-</i>isomer was predominantly produced in the case of nitrobenzene, and <i>ortho-</i>isomers were preferentially produced in the case of the other substrates, which would depend on the approaching direction of the molecule to the photocatalyst surface

Aqueous-phase behavior of glyoxal and methylglyoxal observed with carbon and oxygen K-edge X-ray absorption spectroscopy

Glyoxal (CHOCHO) and methylglyoxal (CH3C(O)CHO) are well-known components of atmospheric particles and their properties can impact atmospheric chemistry and cloud formation. To get information on their hydration states in aqueous solutions and how they are affected by the addition of inorganic salts (sodium chloride (NaCl) and sodium sulfate (Na2SO4)), we applied carbon and oxygen K-edge X-ray absorption spectroscopy (XAS) in transmission mode. The recorded C K-edge spectra show that glyoxal is completely hydrated in the dilute aqueous solutions, in line with previous studies. For methylglyoxal, supported by quantum chemical calculations we identified not only C-H, C=O and C-OH bonds, but also fingerprints of C-OH(CH2) and C=C bonds. The relatively low intensity of C=O transitions implies that the monohydrated form of methylglyoxal is not favored in the solutions. Instead, the spectral intensity is stronger in regions where products of aldol condensation and enol tautomers of the monohydrates contribute. The addition of salts was found to introduce only very minor changes to absorption energies and relative intensities of the observed absorption features, indicating that XAS in the near-edge region is not very sensitive to these intermolecular organic-inorganic interactions at the studied concentrations. The identified structures of glyoxal and methylglyoxal in an aqueous environment support the uptake of these compounds to the aerosol phase in the presence of water and their contribution to secondary organic aerosol formation.Peer reviewe