Self-Assembly of Glycerol-Amphiphilic Janus Dendrimers Amplifies and Indicates Principles for the Selection of Stereochemistry by Biological Membranes.

The principles for the selection of the stereochemistry of phospholipids of biological membranes remain unclear and continue to be debated. Therefore, any new experiments on this topic may help progress in this field. To address this question, three libraries of constitutional isomeric glycerol-amphiphilic Janus dendrimers (JDs) with nonsymmetric homochiral, racemic, and symmetric achiral branching points were synthesized by an orthogonal-modular-convergent methodology. These JDs amplify self-assembly, and therefore, monodisperse vesicles known as dendrimersomes (DSs) with predictable dimensions programmed by JD concentration were assembled by rapid injection of their ethanol solution into water. DSs of homochiral JD enantiomers, racemic, including mixtures of different enantiomers, and achiral exhibited similar DS size-concentration dependence. However, the number of bilayers of DSs assembled from homochiral, achiral, and racemic JDs determined by cryo-TEM were different. Statistical analysis of the number of bilayers and coarse-grained molecular dynamics simulations demonstrated that homochiral JDs formed predominantly unilamellar DSs. Symmetric achiral JDs assembled only unilamellar DSs while racemic JDs favored multilamellar DSs. Since cell membranes are unilamellar, these results indicate a new rationale for nonsymmetric homochiral