Synthesis and Bioluminescence of ‘V’‐Shaped Firefly Luciferin Analogues Based on A Novel Benzobisthiazole Core

Abstract

AbstractThe design of π‐extended conjugation ‘V‘‐shaped red shifted bioluminescent D‐luciferin analogues based on a novel benzobisthiazole core is described. The divergent synthetic route allowed access to a range of amine donor substituents through an SNAr reaction. In spectroscopic studies, the ‘V’‐shaped luciferins exhibited narrower optical band gaps, more red‐shifted absorption and emission spectra than D‐luciferin. Their bioluminescence characteristics were recorded against four different luciferases (PpyLuc, FlucRed, CBR2 and PLR3). With native luciferase PpyLuc, the ‘V’‐shaped luciferins demonstrated more red‐shifted emissions than D‐luciferin (λbl=561 nm) by 60 to 80 nm. In addition, the benzobisthiazole luciferins showed a wide range of bioluminescence spectra from the visible light region (λbl=500 nm) to the nIR window (>650 nm). The computational results validate the design concept which can be used as a guide for further novel D‐luciferin analogues based upon other ‘V’‐shaped heterocyclic cores.