X-Ray absorption spectroscopy of H3O.

We report the X-ray absorption of isolated H3O+ cations at the O 1s edge. The molecular ions were prepared in a flowing afterglow ion source which was designed for the production of small water clusters, protonated water clusters, and hydrated ions. Isolated H2O+ cations have been analyzed for comparison. The spectra show significant differences in resonance energies and widths compared to neutral H2O with resonances shifting to higher energies by as much as 10 eV and resonance widths increasing by as much as a factor of 5. The experimental results are supported by time-dependent density functional theory calculations performed for both molecular cations, showing a good agreement with the experimental data. The spectra reported here could enable the identification of the individual molecules in charged small water clusters or liquid water using X-ray absorption spectroscopy.

Data-based modeling of drug penetration relates human skin barrier function to the interplay of diffusivity and free-energy profiles.

Based on experimental concentration depth profiles of the antiinflammatory drug dexamethasone in human skin, we model the time-dependent drug penetration by the 1D general diffusion equation that accounts for spatial variations in the diffusivity and free energy. For this, we numerically invert the diffusion equation and thereby obtain the diffusivity and the free-energy profiles of the drug as a function of skin depth without further model assumptions. As the only input, drug concentration profiles derived from X-ray microscopy at three consecutive times are used. For dexamethasone, skin barrier function is shown to rely on the combination of a substantially reduced drug diffusivity in the stratum corneum (the outermost epidermal layer), dominant at short times, and a pronounced free-energy barrier at the transition from the epidermis to the dermis underneath, which determines the drug distribution in the long-time limit. Our modeling approach, which is generally applicable to all kinds of barriers and diffusors, allows us to disentangle diffusivity from free-energetic effects. Thereby we can predict short-time drug penetration, where experimental measurements are not feasible, as well as long-time permeation, where ex vivo samples deteriorate, and thus span the entire timescales of biological barrier functioning.

Gas-to-cluster effects in S 2p-excited SF(6).

High resolution X-ray spectroscopic studies on free SF6 molecules and SF6 clusters near the S 2p ionization thresholds are reported. Spectral changes occurring in clusters for the intense molecular-like S 2p1/2,3/2 → 6a1g-, 2t2g-, and 4eg-resonances are examined in detail. Neither gas-to-cluster spectral shifts nor changes in peak shape are observed for the pre-edge 6a1g-band. Significant changes in band shape and distinct gas-to-cluster shifts occur in the S 2p1/2,3/2 → 2t2g- and 4eg-transitions. These are found in the S 2p-ionization continua. The quasiatomic approach is used to assign the experimental results. It is shown that a convolution of asymmetric and symmetric contributions from Lorentzian and Gaussian line shapes allows us to model the spectral distribution of oscillator strength for the S 2p1/2,3/2 → 2t2g-, and 4eg-transitions. The asymmetry is due to trapping of the photoelectron within the finite size potential barrier. The Lorentzian contribution is found to be dominating in the line shape of the S 2p → 2t2g- and 4eg-bands. The spectroscopic parameters of the spin-orbit components of both the 2t2g- and 4eg-bands are extracted and their gas-to-cluster changes are analyzed. The photoelectron trapping times in free and clustered SF6 molecules are determined. Specifically, it is shown that spectral changes in clusters reflected in core-to-valence-transitions are due to a superposition of the singly scattered photoelectron waves at the neighboring molecules with the primary and multiply scattered waves within the molecular cage.

Structures of mixed argon-nitrogen clusters.

The structures of mixed argon-nitrogen clusters of different compositions are investigated by analyzing core level shifts and relative intensities of surface and bulk sites in the Ar 2p(3/2) regime in soft X-ray photoelectron spectroscopy. These structures are confirmed by core level shift calculations taking induced dipole interactions into account, in which several model structures of the mixed clusters are considered by Monte Carlo simulations. These results suggest that the mixed argon-nitrogen clusters show partial core-shell structures, where an argon core is partially covered by nitrogen molecules.

Improved Skin Permeability after Topical Treatment with Serine Protease: 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.