Computational development of a phase-sensitive membrane raft probe

Derivatives of the widely used 1,6-diphenyl-1,3,5-hexatriene molecular probe have been considered using a multiscale approach involving spin-flip time-dependent density functional theory, classical molecular dynamics and hybrid quantum mechanics/molecular mechanics. We identify a potential probe of membrane phase (i.e. to preferentially detect liquid-ordered regions of lipid bilayers), which exhibits restricted access to a conical intersection in the liquid-ordered phase but is freely accessible in less ordered molecular environments. The characteristics of this probe also mark it as a candidate for an aggregation induced emission fluorophore.