Unexpected Formation and Potent Antioxidant Activity of Macrocyclic Dimers Containing Disulfide and Selenide Groups.

During attempts to prepare spirodithiaselenuranes as GPx mimetics, a series of unexpected dimeric macrocycles was obtained, each containing two selenide and two disulfide moieties in rings ranging from 18- to 26-membered. The products showed potent GPx-like activity in an NMR assay based on their ability to catalyze the reduction of hydrogen peroxide with benzyl thiol. The high catalytic activity was attributed to transannular effects during selenide to selenoxide oxidation. This redox process was also characterized by an induction period that indicated autocatalysis in the formation of an intermediate selenoxide from the oxidation of the corresponding selenide.

Total Internal Reflection Tip-Enhanced Raman Spectroscopy of Tau Fibrils.

Total internal reflection tip-enhanced Raman spectroscopy (TIR-TERS) has recently emerged as a promising technique for noninvasive nanoscale chemical characterization of biomolecules. We demonstrate that the TERS enhancement achieved in this experimental configuration is nearly 30 times higher than that in linear polarization and 8 times higher than that in radial polarization using traditional bottom-illumination geometry. TIR-TERS is applied to the study of Tau amyloid fibrils formed with the human full-length Tau protein mixed with heparin. This technique reveals the possibility to perform TERS imaging with 1-4 nm axial and 5-10 nm lateral spatial optical resolution. In these Tau/heparin fibrils, spectral signatures assigned to aromatic amino acid residues (phenylalanine, histidine, and tyrosine) and nonaromatic ones (e.g., cysteine, lysine, arginine, asparagine, and glutamine) are distinctly observed. Amide I and amide III bands can also be detected. In a fibril portion, it is shown that antiparallel ß-sheets and fibril core ß-sheets are abundant and are often localized in amino acid-rich regions where parallel ß-sheets and random coils are present in lower proportions. This first TIR-TERS study on a nonresonant biological sample paves the way for future nanoscale chemical and structural characterization of biomolecules using this performant and original technique.

Nanoscale chemical characterization of biomolecules using tip-enhanced Raman spectroscopy.

Nanoscale chemical and structural characterization of single biomolecules and assemblies is of paramount importance for applications in biology and medicine. It aims to describe the molecular structure of biomolecules and their interaction with unprecedented spatial resolution to better comprehend underlying molecular mechanisms of biological processes involved in cell activity and diseases. Tip-enhanced Raman scattering (TERS) spectroscopy appears particularly appealing to reach these objectives. This state-of-the-art TERS technique is as versatile as it is ultrasensitive. To perform a successful TERS experiment, special care and a thorough methodology for the preparation of the TERS system, the TERS probe tip, and sample are needed. Intense efforts have been deployed to characterize nucleic acids, proteins and peptides, lipid membranes, and more complex systems such as cells and viruses using TERS. Although the vast majority of studies have first been performed in dry conditions, they have allowed for several scientific breakthroughs. These include DNA and RNA sequencing, and the determination of relationships between protein structure and biological function by the use of increasingly exploitative chemometric tools for spectral data analysis. The nanoscale determination of the secondary structure of amyloid fibrils, protofibrils and oligomers implicated in neurodegenerative diseases could, for instance, be connected with the toxicity of these species, amyloid formation pathways, and their interaction with phospholipids. Single particles of different viral strains could be distinguished from one another by comparison of their protein and lipid contents. In addition, TERS has allowed for the evermore accurate description of the molecular organization of lipid membranes. Very recent advances also demonstrated the possibility to carry out TERS in aqueous medium, which opens thrilling perspectives for the TERS technique in biological, biomedical, and potential clinical applications.