<p>Thiazolo[5,4-d]thiazole-2,5-dicarboxylic acid (H₂Thz), a thiazolothiazole (TTz) derivative with carboxylic acid groups, was synthesized as a ligand for the creation of five MOFs, each associated with distinct metal ions including Ag⁺, Mn²⁺, Co²⁺, Zn²⁺, and Cu²⁺. The cathodic electrochemiluminescence (ECL) of H₂Thz and the resulting MOFs was investigated. H₂Thz was found to generate ECL signals, but this process was heavily reliant on potassium persulfate (K₂S₂O₈) as a co-reactant. However, the Ag-MOF, formed with H₂Thz as the ligand, exhibited substantial ECL signals without the need for any co-reactant, which is different from other metal-containing MOFs. The smaller band gap, higher electron mobility and the unique electrocatalytic activity of Ag⁺ ions were confirmed to be the reasons for the excellent ECL performance of Ag-MOF. The interaction between thiol group of glutathione (GSH) and Ag-MOF suppressed the ECL signal of the Ag-MOF-K₂S₂O₈ system. Based on this, a sensitive ECL method for GSH was developed and effectively utilized for GSH quantification in cell lysates.</p> Graphical Abstract <p>The Ag-MOF, constructed from the distinctive electron-accepting properties of thiazolo[5,4-d]thiazole-2,5-dicarboxylic acid and the superior catalytic and conductive attributes of silver, was utilized as an elecetrochemiluminescence probe for the sensitive determination of glutathione in cell lysates</p> <p></p>