Rapid Access to a Broad Range of 6′-Substituted Firefly Luciferin Analogues Reveals Surprising Emitters and Inhibitors

Abstract

Light-emitting firefly luciferin analogues contain electron-donating groups in the 6′-position, but the scope of known 6′-substitution remains narrow. A two-step route to a broad range of 6′-substituted luciferin analogues was developed to fill this void and enable more extensive study of the 6′-functionality. This chemistry allowed direct access to “caged” amide and bright azetidine analogues, but also revealed thioether inhibitors and unexpectedly luminogenic aryl amine derivatives.

Anschalten von Festkörperfluoreszenz mit Licht

“…Dies führt zu einer bathochrom verschobenen Emission. Entlang dieser Argumentationslinie wurden die Aminoderivate des Glühwürmchen‐Luciferins ( 2 in Schema ) kürzlich als potenzielle bioinspirierte Emitter von rotem Licht vorgeschlagen . Obwohl das Potenzial solcher Varianten für die Tiefengewebe‐Bildgebung bereits gezeigt wurde, bleibt die zugrundeliegende Photochemie unklar (detaillierte Informationen zu beschriebenen Aminoluciferinen finden sich in den Hintergrundinformationen, SI).…”

Advances in bioluminescence imaging: new probes from old recipes

“…Modular coupling reactions to outfit D-luciferin with diverse steric modifications have been reported. [32,40*] Ring-closing metathesis and carbene insertions have also been used to produce a series of conformationally restricted and pi-extended coelenterazines. [41–43] Many these probes exhibited red-shifted emission or other desirable photophysical properties.…”

Computational investigation into the fluorescence of luciferin analogues

“…The firefly luciferase/ d ‐luciferin pair is extensively used as a biological reporter, but in vivo applications are hampered by tissue absorbing the yellow/green emission of the wild type enzyme and substrate. Therefore, efforts have been made to either engineer luciferase or to design luciferin analogues that display bioluminescence at longer wavelengths …”