Squaramide-Based MOF Enables Hydrogen-Bond-Directed Ultraselective Guanine Detection and Drug Monitoring

Guanine (G), an essential biomolecule indispensable for organismal development, manifests concentration fluctuations closely associated with various pathological conditions, thereby establishing its quantitative detection as a clinically imperative objective. Inspired by the specificity of Watson-Crick hydrogen-bonding, we architected a fluorescent metal-organic framework (MOF) probe, Co-DBDP, which is functionalized with squaramide moieties to emulate triple hydrogen-bonding recognition cavities. This engineered sensor exhibited exceptional target-specific fluorescence enhancement toward G over competing nucleobases, achieving an ultralow detection limit of 95 nM. Comprehensive mechanistic investigations integrating advanced spectroscopic analyses and density functional theory (DFT) calculations unequivocally established that the selectivity arises from geometrically complementary triple hydrogen-bonding interactions between G and the immobilized squaramide ligands within the MOF scaffold. Significantly, Co-DBDP represents a pioneering approach for fluorescence enhancement-based detection of G-based pharmaceuticals acyclovir (ACV) and 6-thioguanine (6-TG), while also successfully quantifying nucleotides (GMP/GDP/GTP). This demonstrates unparalleled diagnostic versatility. The paradigm of hydrogen-bond-mediated confinement offers a generalized design strategy for developing modular sensing platforms aimed at disease-relevant biomarkers.