Structurally Compact, Blue-Green-Red Fluorescence Trackers for the Outer Cell Membrane: Zwitterionic (Naphthylvinyl)pyridinium Dyes

The cell membrane regulates the flux of materials in and out of cell, cell adhesion, and signaling. Fluorophores that selectively localize on it are in demand for investigations of the molecular events occurring on the outer cell membrane. Commercial membrane trackers based on phospholipids are structurally complex and difficult to modify further. We disclose the zwitterionic (naphthylvinyl)pyridinium dyes that selectively localize on the outer cell membrane and emit blue, green, and red fluorescence, respectively. Notably, they are structurally compact and provide bright fluorescence images of the cell membrane. By comparing with control compounds, we identified minimal structural elements for the "robust" localization of dye on the outer cell membrane. Further, the dyes are two-photon active, enabling high-resolution, deep-tissue imaging. One of the dyes was used to image a spleen tissue, which provided high-resolution fluorescent images with a distinct morphology. In addition, the materials and results disclosed are valuable for the development of membrane-targeting probes and structurally compact fluorophores.