A de novo strategy for the development of a Zn-II-organic framework based luminescent "switch-on" assay for size-exclusive sensitization of the oxidised form of glutathione (GSSG) over the reduced form (GSH): insights into the sensing mechanism through DFT

The ratio of oxidized l-glutathione (GSSG) to reduced l-glutathione (GSH) plays a key role as a biomarker for monitoring cellular health thus fuelling extensive ground-breaking research towards the development of sensory receptors for continuous monitoring of glutathione concentration. The detection of GSH is well documented; however, studies on the oxidized form, i.e., GSSG, are very scanty in the literature due to their functional similarity. In this context, metal-organic frameworks (MOFs) provide rationalized structure-performance synergies to fabricate smart chemoprobes. Herein, we present robust and non-interpenetrated Zn-II-MOF (designated as Zn-CMERI) exemplifying a unique scaffold for efficient optical sensitization of biohazards such as GSSG through a fluorescence "switch-off-on" process with a detection limit of 20.8 ppb (R = 0.98 and K-ec = 84.12) with very short response time (similar to 12 s). More interestingly, as a recyclable chemoprobe Zn-CMERI can be exploited for detecting GSSG in complex biological matrices (Recovery % = 95.5-108.6), which in turn helps in detecting patients with uremic disease. The role of SBUs has been validated from in-depth DFT studies, which collectively supports the importance of the de novo strategy of incorporating O, N-sites for non-covalent host-guest interactions in a confined zone in supramolecular chemistry for detecting mercapto biomolecules. Additionally, the host-guest interaction through a "switch-off-on" assay may be utilised for fabricating molecular logic gate circuitry in relevance to MOFtronics applications.