β-Ketonitrile-Modified Prodan Derivatives as Large-Stokes-Shift Solvatochromic Fluorophores With Enhanced Brightness and Ratiometric Thermometric Response
We report a systematic investigation of β-ketonitrile–modified Prodan-type solvatochromic fluorophores as an alternative to conventional π-extension. A series of donor–π–acceptor dyes incorporating a β-ketonitrile acceptor and a unified piperidyl donor and compared with the corresponding acetyl analogues. The β-ketonitrile substitution produced pronounced bathochromic shifts in both absorption and emission, together with substantial enhancement of fluorescence quantum yields (Φfl) in nonpolar solvents, effectively overcoming the low-Φfl limitation of Prodan. These improvements are attributed to reduced intersystem crossing arising from destabilization of the n–π* triplet manifold. The dyes also exhibit markedly increased molar absorption coefficients at 405 nm, facilitating efficient excitation at 405 nm. In polar media, polarity-dependent formation of TICT states or promotion of internal conversion modulates the emission response, with the π-extended dye FπAc-CN displaying exceptionally strong positive temperature sensitivity from −10 to 75°C, functioning as a ratiometric fluorescent thermometer. In membrane-mimetic lipid bilayers, the naphthalene and fluorene derivatives (NAc-CN, FRAc-CN) showed significantly larger phase-dependent λfl shifts than Prodan or Laurdan, exhibiting enhanced sensitivity to membrane-mimetic polarity environments. These results establish β-ketonitrile substitution as a powerful design principle that achieves large-Stokes-shift emission, enhanced brightness, temperature responsiveness, and phase-dependent fluorescence response in model membranes.