A coumarin-based fluorescent PET sensor utilizing supramolecular pK a shifts Na’il Saleh a,⇑ , Yaseen A. Al-Soud b , Leena Al-Kaabi a , Indrajit Ghosh c , Werner M. Nau c a Department of Chemistry, UAE University, PO Box 17551, United Arab Emirates b Department of Chemistry, University of Al al-Bayt, Al-Mafraq, Jordan c School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany article info Article history: Received 20 May 2011 Revised 7 July 2011 Accepted 29 July 2011 Available online 6 August 2011 Keywords: Photoinduced electron transfer (PET) pK a Shifts Fluorescence Sensors Host–guest systems Cucurbiturils Coumarin Benzothiazole Piperazine abstract A new coumarin derivative containing benzothiazole and piperazine substituents was synthesized. Pref- erential inclusion of the benzothiazole group, over the coumarin and piperazine groups, inside the cavity of the molecular container cucurbit[7]uril (CB7) was evidenced by using optical and NMR techniques. The binding constant of the new complex with CB7 is higher in its protonated forms (e.g., K = 2.8 Â 10 6 M À1 ) than in its neutral forms, which led to an increase in the pK a value associated with protonation of the aza nitrogen on the benzothiazole ring of ca. 2.5 units. Such CB7-induced protonation disabled the photoin- duced electron transfer (PET) in the included molecule, enhancing its coumarin fluorescence up to ca. 45- fold (pH 3.5, 410 nm). The results are discussed in the context of designing sensitive analytical tools for reversible monitoring of optically inactive analytes by competitive displacement experiments. Ó 2011 Elsevier Ltd. All rights reserved. Fluorescence-based sensing offers distinct advantages over other methods in environmental and biochemical applications due to its low cost, simplicity, high sensitivity and selectivity, fast response, and very low detection limits. 1 In particular, non- destructive fluorescence methods are needed by researchers in forensic science, 1c pharmaceutical surveillance, 1d and food sci- ence 1e,f to determine sample authenticity in regional laboratories at the port-of-entry, reducing the need for labor-intensive and time consuming techniques. The photophysical properties of fluorescent dyes, which deter- mine their sensitivity, selectivity, and detection limits, can be improved in the presence of host macromolecules in aqueous solutions. 2 The selected molecular containers in this work are cucurbit[n]urils (CBs), which belong to the cavitand type of mole- cular containers. The structures of CBs were only determined 76 years 3 after their first synthesis. 3a Cucurbiturils take their name from the fruit pumpkin of the family Cucurbitaceae, whose shape they are thought to resemble. 3c Most importantly, CBs are contain- ers with nanoscale dimensions. 3d They are readily synthesized on kilogram scale in different sizes 2f,4 (CB5, CB6, CB7, CB8, and CB10) (see CB7 in Fig. 1). All homologues are of the same height (9.1 Å), however, they all differ in the diameter of their carbonyl portals and cavities. 3d CBs are characterized by a hydrophobic cavity and polar portals and they possess very low, if not negligible, in vitro and in vivo toxicity. 5 They stand out owing to their strong binding affinities (binding constants >10 4 M À1 ) 6 as well as their selectivity toward many neutral and cationic species. 3 Since the work by Mock on CB6, 3a host–guest complexes of cucurbituril homologues have been employed in numerous chemical, physical, and biological applications. 2d,f,3–7 Research by Nau et al. estab- lished cucurbiturils as stabilizing additives for laser dyes. 8 In addition, complexation of small fluorescent dyes with cucurbiturils enhances their fluorescence lifetimes, 2f,7c fluorescence inten- sity, 2d,7d,9 and substrate-dye binding, 2d,7g thus improving their analytical sensing applications. The fluorescence enhancement induced by CBs was also utilized by Nau et al. to develop a supra- molecular bioassay, 10 which enabled monitoring of the activity of some enzymes by controlled displacements of selected fluorescent dyes from the cucurbituril cavity during enzymatic decarboxyl- ation of the corresponding amino acids. Cucurbituril receptors have also been found to encapsulate nonfluorescent or weakly fluorescent organic substrates, 7e,f,8a,11 enhancing their fluorescence quantum yields, namely curcumin, 7f,11a carbendazim, 7e,11b berber- ine, 11c,d alkaloids, 11e riboflavin, 11f coptisine, 11g melamine, 11h sanguinarine, 11i,j pyrene, 11k and tropicamide. 11l The fluorescence changes have been invariably rationalized in terms of either hydro- phobic effects (polarity effects) 7e,9a or geometrical confinement effects 7d within the cucurbituril cavity, in addition to the role of 0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2011.07.138 ⇑ Corresponding author. E-mail address: n.saleh@uaeu.ac.ae (N. Saleh). Tetrahedron Letters 52 (2011) 5249–5254 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet