A two-photon fluorescent RNA probe screened from a series of oxime-functionalized 2,2':6',2''-terpyridine ZnX₂ (X =...

Imaging of RNA in living cells is a potential tool to understand intracellular RNA function. Therefore, an effective two-photon fluorescent probe with a reasonable two-photon action cross-section to label RNA is now urgently required. In this work, a series of novel two-photon absorbing terpyridine ZnX₂ (X = Cl, Br, I) complexes have been designed and an effective RNA imaging probe has been obtained. The results revealed that OTP-ZnCl₂ possesses large Stokes shift and two-photon action cross-section. Furthermore, live cell imaging experiments indicated that OTP-ZnCl₂ could stain nucleoli in living cells by binding with nucleoli RNA. The mechanism of selective nucleoli staining of OTP-ZnCl₂ was studied systematically via both experiments and molecular modeling calculations. Due to its low cytotoxicity, good membrane permeability and counterstain compatibility with the commercial fluorescent nucleic acid dye Hoechst 33342, as well as its ability to label RNA in living cells, OTP-ZnCl₂ is a promising candidate for the detection of nucleic acid in living cells.