Ruthenium(II) Complex-Incorporated Defective Zr-Based MOF as a H2S-Activatable Ratiometric Fluorescent Probe for Broad Biosensing Applications

Abstract The crucial role of hydrogen sulfide (H2S) as an endogenous gaseous signaling molecule in physiological and pathological processes necessitates the development of highly effective analytical methods. However, existing fluorescent probes have some drawbacks when applied in complex biological systems. Herein, by combining defect engineering and host−guest strategies, we successfully constructed a metal−organic framework (MOF)-based ratiometric fluorescent nanoprobe Ru@D-UiO-66-N3 by encapsulating the guest fluorophore [Ru(bpy)3]2+ into a defective MOF, D-UiO-66-N3. Thanks to abundant structural defects to enlarge the pores, large-sized [Ru(bpy)3]2+ could easily incorporate into the interior of D-UiO-66-N3; and moreover, exposed recognition sites enriched the target H2S, achieving sensitive and fast response. Specifically, the azido groups modified on the MOF surface can convert into amino groups by specific H2S activation, inducing enhanced blue fluorescence at 443 nm. In contrast, red fluorescence at 630 nm originating from [Ru(bpy)3]2+ remained stable, working as an internal reference. By virtue of these impressive analytical performances, Ru@D-UiO-66-N3 demonstrated good adaptability to broad biosensing applications including quantitative analysis of H2S in human serum, the release kinetics monitoring of the H2S donor GYY4137, as well as the activity evaluation of cystathionine γ-lyase (CSE) in the biosynthesis of H2S.