A luminescent Zr(IV)-based MOF, with the underlying fcu topology, encompassing a π-conjugated organic ligand with a thiadiazole functionality, exhibits an unprecedented low detection limit of 66 nanomolar (nM) for amines in aqueous solution. Markedly, this ultra-low detection is driven by the hydro-gen bonding interactions between the linker and amines. This observation is fully supported by Density Functional Theory (DFT) calculations which clearly corroborate the suppression of the twisting motion of the thiadiazole core in the presence of amine, reducing significantly the non-radiative recombination pathways and subsequently enhancing the emission intensity. Credibly, nicotine regarded as a harmful chemical and bearing an amine pending group is also detected with high sensitivity, positioning this MOF as a potential sensor for practical environmental applications. This finding not only provides an unprecedented low detection limit, but also serves as a benchmark to understand the sensing mechanism in MOFs.