Thiol–chromene click chemistry: A coumarin-based derivative and its use as regenerable thiol probe and in bioimaging applications

• We synthesized and characterized a new coumarin-based chromene derivative.
• The optical properties of the probe and its Cys-addition product were theoretically studied.
• The ability of probe to detect thiols in living cells was proved.
• The probe was applied in direct determination of biorelevant thiols in human plasma.

The synthesis and characterization of a coumarin–chromene (8, 9-dihydro-2H-cyclopenta[b]pyrano[2,3-f]chromene-2,10(7aH)-dione) (1) derivative and its use for thiol chemosensing in water was reported. Experimental details showed 1 acts as a probe for the detection of thiols including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), whereas amino acids which do not contain thiols induced no changes in UV–vis spectra and fluorescence emission properties of 1. A possible detection mechanism is a nucleophilic attack of thiols to the α,β-unsaturated ketone in 1 that resulted in a fluorescent coumarin derivative. Further studies showed that 1-thiol derivatives can be applied to the design of regenerative chemodosimeters for Cu2+, Hg2+ and Cd2+ in water based on Mn+-promoted desulfurization and recovery of 1. Furthermore, the optical properties of the probe and its Cys-addition product were theoretically studied. The ability of probe 1 to detect thiols in living cells (HepG2 cells) via an enhancement of the fluorescence was proved. Moreover, the applicability of 1 for the direct determination of biorelevant thiols in a complex matrix such as human plasma was also demonstrated.

Coumarin–chromene was firstly prepared and characterized. It displayed an excellent selectively and sensitivity for thiols by thiol ‘click’ chromene ring-open reaction on UV–vis and fluorescene spectra, which was rationalized by TDDFT calculation. The probe was applied in heavy metal ions regenerative chemodosimeter and bioimaging.Figure optionsDownload as PowerPoint slide