In this work, we revisited the disassembly approach (also known as the Zelder's approach) recently proposed for sensing pyrophosphate (PPi) in water and based on the decomposition of metal-salen complexes. A systematic study devoted to the structural optimization of this novel class of PPi-responsive fluorogenic probes was conducted. Screening of eight different vicinal diamines (i.e., bridge of the salen ligand) combined with the use of 8-formyl-7hydroxycoumarin (i.e., salicylaldehyde derivative) as the fluorescent reporter, has led to a set of novel and fully characterized coumarin-salen Fe(III) complexes. A series of analytical validations helped us to identify that coumarin-salen Fe(III) complexes derived from ethylenediamine and racemic 1,2-propylenediamine backbones exhibit the best and selective PPi-sensing performances (the limits of detection were estimated as 3.15 × 10-6 M and 2.81 × 10-6 M respectively). The implementation of both fluorescence time-course measurements and RP-HPLC-fluorescence analyses has enabled us to gain further insights into the disassembly-based probes' activation mechanism. This study therefore contributes to demonstrate that the disassembly approach is a valuable strategy to achieve fluorogenic activity-based sensing of anions.