A palette of bridged bicycle-strengthened fluorophores

Organic fluorophores are the keystone of advanced biological imaging. The vast chemical space of fluorophores has been extensively explored in search of molecules with ideal properties. However, within the current molecular constraints, there appears to be a trade-off between high brightness, robust photostability, and tunable biochemical properties. Herein we report a general strategy to systematically boost the performance of donor-acceptor-type fluorophores, such as rhodamines, by leveraging SO₂ and O-substituted azabicyclo[3.2.1] octane auxochromes. These bicyclic heterocycles give rise to a collection of 'bridged' dyes (BD) spanning the ultraviolet and visible range with top-notch quantum efficiencies, enhanced water solubility, and tunable cell-permeability. Notably, these azabicyclic fluorophores showed remarkable photostability compared to their tetramethyl or azetidine analogs while being completely resistant to oxidative photoblueing. Functionalized BD dyes are tailored for applications in single-molecule imaging, super-resolution imaging (STED and SIM) in fixed or live mammalian and plant cells, and live zebrafish imaging and chemogenetic voltage imaging.