Design of ICT-PET fluorescent probes for zinc(II) based on 5-aryl-2,2 0 -bipyridines Dmitry S. Kopchuk a , Anton M. Prokhorov a , Pavel A. Slepukhin b , Dmitry N. Kozhevnikov a,b,⇑ a Ural Federal University, Mira 19, Ekaterinburg 620002, Russia b I. Postovsky Institute of Organic Synthesis, Kovalevskoy 22, Ekaterinburg 620090, Russia article info Article history: Received 31 July 2012 Revised 30 August 2012 Accepted 6 September 2012 Available online 14 September 2012 Keywords: Zinc(II) sensor Bipyridine Photoinduced electron transfer Intramolecular charge transfer DFT abstract Rational design of selective and sensitive ‘off-on’ fluorescent probes for Zn(II) cations exploiting both PET and ICT mechanisms of sensing is illustrated by the synthesis and application of 5-aryl-2,2 0 -bipyridines modified with a dipicolylaminomethyl fragment. The aryl substituent provides tuning of the properties. Ó 2012 Elsevier Ltd. All rights reserved. Zinc(II) is the second most abundant d-block metal ion in the human brain. 1 Sensitive methods for detection of zinc ions attract attention since zinc plays a crucial role in many biological pro- cesses. 2 Fluorescence spectroscopy is a powerful method for sens- ing and imaging metal cations at submicromolar concentrations. 3,4 Photoinduced electron transfer (PET) and intermolecular charge transfer (ICT) are the most widely used mechanisms of fluores- cence signal modification used in the design of Zn(II) chemosen- sors. 5,6 PET provides significant enhancement of a fluorescence signal with increased concentration of the metal ions and gives ‘off-on’ sensors. 7 However, in PET probes isolation of the signaling and sensing parts through aliphatic spacers cannot give a shift of the fluorescence maxima. On the contrary, in ICT sensors the sig- naling and sensing parts are combined in one conjugated system, and binding of an analyte leads to blue or red shift of the fluores- cence usually without significant changes of intensity, thus a ratio- metric analysis can be applied. 8 A combination of these two techniques promises better results in ‘turn on’ ratiometric sensor design since the effect of color alteration due to ICT would be amplified by intensity increase due to PET. 6 This idea has been illustrated by V. Kozhevnikov when 6,6 00 -bis(aminomethyl)-5, 5 00 -bis-(4-bromophenyl)-2,2 0 :6 0 ,2 00 -terpyridine showed both a red- shift of the maximum and an enhancement of intensity of lumines- cence upon increasing the Zn(II) concentration in buffered aqueous solution. 9 In this case, the terpyridine moiety played the role of the metal binding site and the chromophore simultaneously. A similar effect was reported for 6-dipicolylaminomethyl-2-pyridylbenzimi- dazole. 10 Both PET and ICT mechanisms can be assumed for sensors, where an amino or oxy group conjugated with a chromo- phore takes part in binding the Zn(II) cation. 11 Zinc(II) complexes of bipyridine, phenanthroline, or terpyridine exhibit bright luminescence. Extended conjugated systems provide significant red-shift of luminescence of the ligands and especially Zn(II) complexes, thus a number of ICT Zn(II) sensors based on oli- gopyridines have been described. 12 In particular, 5-aryl-2,2 0 - bipyridines can be considered as an appropriate platform for the design of new Zn(II) sensors. 13 In order to increase the selectivity of a sensor, the bipyridine chelating site should be extended with specific Zn(II) ion receptors, that is, dipicolylamine (DPA). 6 To exploit the PET mechanisms the amine should be attached at the a-position of the bipyridine through an appropriate spacer, for example a methylene group. The targeted ligands 1a,b were synthesized according to the strategy shown on Scheme 1. Key intermediates, 5-aryl-6 0 -bromo- methyl-2,2 0 -bipyridines 2, were obtained by the ‘1,2,4-triazine 0 methodology starting from synthetically available triazines 3. 14 Reaction of 2 with dipicolylamine resulted in the desired ligands 1a,b. 15 The aryl substituent in 1 plays a dual role. Firstly, it in- creases the amphiphilic properties of the ligand, which is impor- tant for biological imaging applications. 2 Secondly, the aryl modulates absorption and emission properties of the ligand and the Zn-complex that shifts the emission maxima to the visible area, and increases the Stokes shift. Zinc(II) complexes of the new ligands were isolated from the reaction of 1 with Zn(ClO 4 ) 2 . Single crystals of [Zn(1a)](ClO 4 ) 2 were obtained by recrystallization from methanol. X-ray crystallogra- phy 16 revealed the 1:1 composition of the complex ion [Zn(1a)] 2+ ( Fig. 1). Pentacoordinated zinc(II) atoms have distorted trigonal 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.09.027 ⇑ Corresponding author. Tel.: +7 343 362 3056; fax: +7 343 374 0458. E-mail address: dnk@ios.uran.ru (D.N. Kozhevnikov). Tetrahedron Letters 53 (2012) 6265–6268 Contents lists available at SciVerse ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet