Constructing a FRET-based molecular chemodosimeter for cysteine over homocysteine and glutathione by naphthalimide and phenazine derivatives

Abstract

A molecular chemodosimeter PHSN, with a naphthalimide fluorophore connected to a newly designed phenazine energy acceptor, for the selective detection of cysteine was effectively synthesized. PHSN featured efficient intramolecular fluorescence resonance energy transfer (FRET) based on spectral overlap between the emission of naphthalimide and the absorption of phenazine. A cystamine chain with a S–S bond was applied to play the role of recognition moiety and the linker part. The specific reaction between the biological thiols and PHSN gave rise to an obvious fluorescence intensity enhancement at 540 nm, which is induced by cleavage of the disulfide bond followed by elimination of the FRET effect. High sensitivity and selectivity for cysteine over homocysteine and glutathione were also achieved. In addition, upon excitation at 400 nm, a relatively weak NIR emission provided an internal standard making PHSN a promising ratiometric sensor for cellular detection of cysteine.