Search for improved triplet-state quenchers for fluorescence imaging: a computational framework incorporating excited-state Baird-aromaticity

Abstract

Fluorescence imaging is crucial for studying biology. Triplet state quenchers (TSQs), especially cyclooctatetraene (COT), can dramatically improve fluorophore performance, particularly when linked intramolecularly so as to enable “self-healing”. Leveraging knowledge revealed through investigations of the self-healing mechanism enabled by COT, we computationally screened for cyclic 8π-electron species, and their annulated derivatives, with efficient triplet–triplet energy transfer potential, high photostability, and strong spin–orbit coupling (SOC) between the lowest triplet state to the singlet ground state. Here, we report theory-based analyses of a broad array of candidates that demonstrate various extents of triplet state Baird-aromaticity, indicating self-healing potential. We identify specific candidates with 7-membered ring structures predicted to exhibit favorable enhancements in fluorophore performance spanning the visible spectrum, with several possessing estimated intersystem crossing (ISC) rates up to 4 × 10⁶ times faster than that of COT, the current benchmark for the self-healing strategy.