Protonation-Driven Aqueous Lyotropic Self-Assembly of Synthetic Six-Tail Lipidoids

We report the aqueous lyotropic mesophase behaviors of protonated amine-based “lipidoids,” a class of synthetic lipid-like molecules that mirrors essential structural features of the multitail bacterial amphiphile lipid A. Small-angle X-ray scattering (SAXS) studies demonstrate that the protonation of the tetra(amine) headgroups of six-tail lipidoids in aqueous HCl, HNO 3, H 2 SO 4, and H 3 PO 4 solutions variably drives their self-assembly into lamellar (L α ) and inverse micellar (I II ) lyotropic liquid crystals (LLCs), depending on acid identity and concentration, amphiphile tail length, and temperature. Lipidoid assemblies formed in H 2 SO 4 (aq) exhibit rare inverse body-centered cubic (BCC) and inverse face-centered cubic (FCC) micellar morphologies, the latter of which unexpectedly coexists with zero mean curvature L α phases. Complementary atomistic molecular dynamics (MD) simul…