Current lipidomic profiling methods rely mainly on MS to identify unknown lipids within a complex sample. We describe a new approach, involving LC×MS/MS (liquid chromatography×tandem MS) analysis of sphingolipids based on both mass and hydrophobicity, and use this method to characterize the SM (sphingomyelin), ceramide and GalCer (galactosylceramide) content of hippocampus from AD (Alzheimer's disease) and control subjects. Using a mathematical relationship we exclude the influence of sphingolipid mass on retention time, and generate two-dimensional plots that facilitate accurate visualization and characterization of the different ceramide moieties within a given sphingolipid class, because related molecules align horizontally or vertically on the plots. Major brain GalCer species that differ in mass by only 0.04 Da were easily differentiated on the basis of their hydrophobicity. The importance of our method's capacity to define all of the major GalCer species in the brain samples is illustrated by the novel observation that the proportion of GalCer with hydroxylated fatty acids increased approximately 2-fold in the hippocampus of AD patients, compared with age- and gender-matched controls. This suggests activation of fatty acid hydroxylase in AD. Our method greatly improves the clarity of data obtained in a lipid profiling experiment and can be expanded to other lipid classes.

The importance of modified peptides and proteins for applications in drug discovery, and for illuminating biological processes at the molecular level, is fueling a demand for efficient methods that facilitate the precise modification of these biomolecules. Herein, we describe the development of a photocatalytic method for the rapid and efficient dimerization and site-specific functionalization of peptide and protein diselenides. This methodology, dubbed the photocatalytic diselenide contraction, involves irradiation at 450 nm in the presence of an iridium photocatalyst and a phosphine and results in rapid and clean conversion of diselenides to reductively stable selenoethers. A mechanism for this photocatalytic transformation is proposed, which is supported by photoluminescence spectroscopy and density functional theory calculations. The utility of the photocatalytic diselenide contraction transformation is highlighted through the dimerization of selenopeptides, and by the generation of two families of protein conjugates via the site-selective modification of calmodulin containing the 21^stamino acid selenocysteine, and the C-terminal modification of a ubiquitin diselenide.

The photocathode functionality of a Metal–Organic Framework (MOF) featuring cofacial photo- and electro-active ligands provides a new approach to CO₂ reduction via charge transfer with a rhenium electrocatalyst.