Although metal-ion-binding interlocked molecules have been under intense investigation for over three decades, their application as scaffolds for the development of sensors for metal ions remains underexplored. In this work, we demonstrate the potential of simple rotaxanes as metal-ion-responsive ligand scaffolds through the development of ap roof-ofconcept selective sensor for Zn 2+ .Small-molecule fluorescent probes are powerful tools for visualizing metal ions in living systems due to their rapid response times and potential for non-invasive,h igh resolution, and quantitative imaging. [1] In particular, the development of small-molecule sensors [2,3] fort he detection and quantification of Zn 2+ in vivo has attracted considerable recent attention due to the spectroscopically silent nature of the d 10 Zn 2+ ion, combined with the recognition that changes in zinc homeostasis are associated with high-morbidity diseases such as Alzheimersd isease, [4] Ty pe II diabetes, [5] and age-related macular degeneration.[6]Such small-molecule probes are generally composed of amultidentate chelating ligand linked to afluorophore whose output is modulated by the metal binding event. Mechanically interlocked molecules, [7] particularly those synthesized using metal-mediated approaches, [8] often possess aw ell-defined binding pocket containing multiple donor atoms for metal ions.[9] Such multidentate "mechanically chelating" ligands [10] seem ideal for the development of metal-selective ligands and related metal-ion sensors by exploiting the size and shape of the three dimensional cavity formed by the mechanical bond. However,a lmost all interlocked molecules that display af luorescent response [11] upon metal binding rely on largeamplitude motion in relatively structurally complex molecular shuttles. [12][13][14] Furthermore,i nm ost cases,s electivity between competing analytes is not reported. Indeed, to our knowledge,only one example has been reported in which the mechanical bond is used to generate ametal binding pocket to report the binding of competing analytes;i n2 004 Hiratani and co-workers disclosed a[1]rotaxane that selectively binds Li + over Na + and K + and reports metal binding through a" switch on" fluorescence response. [15,16] Given that the synthesis of mechanically chelating ligands is now relatively simple,i ti sp erhaps surprising that these scaffolds have been overlooked in the development of cation sensors,particularly since arelated strategy for the sensing of anions has been developed by Beer and co-workers.[17] We thus set out to demonstrate the potential of the mechanical bond as as tructural motif in the development of selective metal-ion sensors through the demonstration of ap roof-ofconcept selective sensor for Zn
2+.Herein, we report not only that is this approach successful, but that relatively small structural changes in the axle component lead to large changes in the photophysical response to divalent metal ions.We synthesized rotaxane 4 [18] in excellent yield (88 %) using the a...
