SUMMARY Understanding how functional lipid domains in live cell membranes are generated has posed a challenge. Here, we show that transbilayer interactions are necessary for the generation of cholesteroldependent nanoclusters of GPI-anchored proteins mediated by membrane-adjacent dynamic actin filaments. We find that long saturated acyl-chains are required for forming GPI-anchor nanoclusters. Simultaneously, at the inner leaflet, long acyl-chaincontaining phosphatidylserine (PS) is necessary for transbilayer coupling. All-atom molecular dynamics simulations of asymmetric multicomponent-membrane bilayers in a mixed phase provide evidence that immobilization of long saturated acyl-chain lipids at either leaflet stabilizes cholesterol-dependent transbilayer interactions forming local domains with characteristics similar to a liquid-ordered (lo) phase. This is verified by experiments wherein immobilization of long acyl-chain lipids at one leaflet effects transbilayer interactions of corresponding lipids at the opposite leaflet. This suggests a general mechanism for the generation and stabilization of nanoscale cholesterol-dependent and actin-mediated lipid clusters in live cell membranes.

The chemistry of abiotic nucleotide synthesis of RNA and DNA in the context of their prebiotic origins on early earth is a continuing challenge. How did (or how can) the nucleotides form and assemble from the small molecule inventories and under conditions that prevailed on early earth 3.5–4 billion years ago? This review provides a background and up-to-date progress that will allow the reader to judge where the field stands currently and what remains to be achieved. We start with a brief primer on the biological synthesis of nucleotides, followed by an extensive focus on the prebiotic formation of the components of nucleotideseither via the synthesis of ribose and the canonical nucleobases and then joining them together or by building both the conjoined sugar and nucleobase, part-by-parttoward the ultimate goal of forming RNA and DNA by polymerization. The review will emphasize that there areand will continue to bemany more questions than answers from the synthetic, mechanistic, and analytical perspectives. We wrap up the review with a cautionary note in this context about coming to conclusions as to whether the problem of chemistry of prebiotic nucleotide synthesis has been solved.

What were the physico-chemical forces that drove the origins of life? We discuss four major prebiotic 'discoveries': persistent sampling of chemical reaction space; sequence-encodable foldable catalysts; assembly of functional pathways; and encapsulation and heritability. We describe how a 'proteinsfirst' world gives plausible mechanisms. We note the importance of hydrophobic and polar compositions of matter in these advances.

With the aid of a novel S-methyl-S-2-pyridyl-sulfoximine (MPyS) directing group (DG), the unactivated primary β-C(sp(3))-H bond of MPyS-N-amides oxidizes at room temperature. The catalytic conditions are applicable to the diacetoxylation of primary β,β'-C(sp(3))-H bonds, and the carboxylic acid solvent is pivotal in the formation of the C-O bond. The MPyS-DG cleaves from the oxidation products and is recovered. This method provides convenient access to α,α'-disubstituted-β-hydroxycarboxylic acids.

Sulfoximines direct: a new protocol for the chemo- and regioselective ortho C-H acetoxylation of arenes in N-benzoylated sulfoximines is reported. The sulfoximine directing group is easily detached from the C-H oxidation product through acid-promoted hydrolysis, isolated, and reused. The meta-substituted phenols are synthesized following this strategy and the stereointegrity of the sulfoximine is preserved in this transformation. C(sp(3))-H acetoxylation of the methyl group is also demonstrated.