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α-Ketoglutarate (α-KG),a pivotal metabolite in energy metabolism,has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers.It is recently proposed that plasma α-KG is a surrogate biomarker of NAFLD.Here,we report the development of a novel "tu-on" chemosensor for α-KG that contains a coumarin moiety as a fluorophore.Using benzothiazole-coumarin (BTC) as inspiration,we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for α-KG measurement.This chemosensor is based on the specific Schiff base reaction and the calcium ion recognition property of the widely used calcium indicator BTC.The probe was synthesized,and a series of parallel experiments were conducted to optimize the chemical recognition process.Compared to the initial weak fluorescence,a remarkable 7.6-fold enhancement in fluorescence intensity (I/I0 at 495 nm) was observed for the conditions in which the probe (1 μmol/L),α-KG (50 μmol/L),and Ca2+ (100 μmol/L) were incubated at 30 ℃ in EtOH.The probe displayed good selectivity for α-KG even in an environment with an abundance of amino acids and other interfering species such as glutaric acid.We determined that the quantitative detection range of α-KG in EtOH was between 5 and 50 μmol/L.Finally,probe in serum loaded with α-KG (10 mmol/L) showed a 7.4-fold fluorescence enhancement.In summary,a novel probe for detecting the biomarker α-KG through a typical Schiff base reaction has been discovered.With further optimization,this probe may be a good alteative for detecting the physiological metabolite α-KG.