New quinolone-based thiol-reactive lanthanide luminescent probes

Area of Science:

• Biochemistry
• Analytical Chemistry
• Materials Science

Background:

• Luminescent lanthanide complexes offer sensitive detection and imaging capabilities.
• Previous research developed amine-reactive cs124-based lanthanide chelates with enhanced properties.
• There is a need for probes that react with thiol groups under physiological conditions.

Purpose of the Study:

• To synthesize and characterize new thiol-reactive derivatives of cs124 and cs124CF3 fluorophores.
• To evaluate the reactivity and detection capabilities of these new probes for biologically relevant thiols.

Main Methods:

• Synthesis of bromoacetamido- and maleimido- derivatives of cs124 and cs124CF3.
• Assessment of probe reactivity with thiols at physiological conditions.
• Monitoring light emission changes for detection and quantification of thiols.

Main Results:

• Maleimido-derivatives exhibited rapid coupling with thiols at micromolar concentrations and physiological conditions.
• Strong quenching of luminescence by adjacent maleimido-groups was observed.
• Quenching was eliminated upon reaction with thiols, enabling detection via light emission.
• The method allowed for hyper-sensitive, time-resolved determination of sulfhydryl compounds like glutathione.

Conclusions:

• New thiol-reactive lanthanide probes (cs124 and cs124CF3 derivatives) have been successfully synthesized.
• The maleimido-derivatives demonstrate high reactivity and a unique luminescence-based detection mechanism.
• These probes are suitable for hyper-sensitive detection of biologically important sulfhydryl compounds.