Synthesis of meso-2,2’-bipyridyl-substituted calix[4]arenes and their response to metal cations

A convenient synthetic approach to meso-substituted with 2,2’-bipyridine and 1-(pyridin-2yl)isoquinoline residues calix[4]arenes is reported. This approach involves the reaction of generated in situ 2-lithio-calix[4]arene with 1,2,4-triazine precursor with the following aromatization of the obtained adduct, and the aza-Diels-Alder reaction of the 1,2,4-triazinyl-substituted calix[4]arene with 2,5-norbornadien or in-situ generated 1,2-dehydrobenzene. The UV/fluorescence response of thus obtained meso-pyridyl-substituted calix[4]arenes to metal cations is studied.


Introduction
Calix [4]arenes and their derivatives are, probably, the mostly studied supramolecular hosts for various applications for analytical chemistry [1], materials science [2], as well as environmental [3] and medicinal [4] applications. By means the proper synthetic modification various calixarene derivatives bearing extra heterocyclic ligand units or other receptor units at the upper or lower rim were obtained to be used for the recognition/supramolecular extraction of inorganic [5] and organic cations [6], anions [7], as well as some neutral molecules [8]. In this article we wish to report a method for the preparation of meso-2,2'-bipyridyl-substituted calix [4]arenes and their response to metal cations. 1 H NMR spectra were recorded on a Bruker Avance-400 spectrometer (400 MHz), the internal standard was SiMe 4 . Mass-spectra (ionization type -electrospray) were recorded on a MicrOTOF-Q II instrument from Bruker Daltonics (Bremen, Germany). Elemental analysis was performed on a Perkin Elmer PE 2400 II CHN analyzer. Fluorescence spectra were measured on Horiba Fluoromax-4 spectrofluorometer. Absolute quantum yields were measured by using the integrating sphere. UV-spectra were measured on Shimadzu UV-1800 spectrometer. The starting meso-triazinyl-substituted calix [4]arenes were prepared as reported [9]. Calculated: С 81.10%, Н 5.96%.
The reaction mixture was than cooled down to room temperature and washed with a 30% aqueous alkali solution (4 times 50 ml each), the organic phase was separated, dried with an anhydrous sodium sulfate, filtered and the solvent was distilled off under reduced pressure. The product 4 was

Studies of the interactions of calixarenes 3-4 with cations
The studies of the interactions of compounds 3-4 with Zn 2+ and Cd 2+ cations were carried out at the concentrations of 3-4 of (1-9)*10 -6 M (depending on the value of the absorption coefficient (A ≤ 0.1)) in anhydrous freshly distilled THF. The concentrations of cations were 10 -3 -10 -4 M.

Results and discussion
A most common method for the introducing of (bi)pyridine moieties into the calix [4]arenes is the modification of upper or lower ring the calixarene core with oligopyridine-attached spacer groups by means of acylation, alkylation or condensation reactions [9][10][11][12][13][14][15][16][17]. As an alternative approach our group reported the direct modification of an upper ring of calix [4]arene moiety with 3-(2-pyridyl)-1,2,4-triazine-5(2H)-one residues [18]. For these modified calixarenes an effectiveness for their transport of La 3+ cations was confirmed. Additionally, we reported recently an effective synthetic approach to meso-substituted with 1,2,4-triazine moieties calix [4]arenes via direct modification of 5-H-1,2,4-triazines by the reaction with generated in situ 2-lithiocalix [4]arene and the following aromatization [9] (Scheme 1). Keeping in mind all the mentioned above we decided to prepare new calix [4]arenes mesosubstituted with (benzo)pyridine moieties and study their response to selected metal cations. To do that as a first step we prepared the corresponding meso-1,2,4-triazine-substituted calixarene 2 using the previously reported procedure [9]. As a next step the ID Diels-Alder reaction between 2 and 2,5norbornadiene was carried out to afford smoothly meso-2,2'-bipyridyl-substituted calix [4]arene 3 in up to 65% yield (Scheme 1). The photophysical properties of calixarene 3 are presented below (Table 1). The introduction of bipyridyl ligand/fluorophore on the periphery of calix [4]arene caused the change in the photophysical properties of product 3. Thus, in THF solution calixarene 3 has a strong absorbance band near 292 nm and an emission peak near 379 nm. Calculated absolute fluorescence quantum yield was 1.1%.
The response of calixarene 3 to Zn 2+ and Cd 2+ cations is shown below. Thus, in UV-spectra the addition of 1 eq. of these cations caused a strong decrease of the absorbance peak at 292 nm ( Fig. 1). The same trend was observed in the emission spectra. Thus, upon addition of 1 eq. of Cd 2+ or Zn 2+ a dramatic fluorescence quenching was observed along with the bathochromic shift of the emission maxima by 5-20 nm. It worth to mention that, the addition of Zn 2+ caused the stronger red-shift, while the addition of Cd 2+ caused stronger fluorescence quenching (Fig. 2).
. Fig. 2. Emission spectra of calixarene 3 in the presence of Cd 2+ and Zn 2+ As a last step the isoqinoline-substituted calixarene 4 was obtained by using the reaction between 2 and benzyne generated in situ as reported before [23]. The reaction afforded as low as 6% of the desired calixarene 4, while the rest of the reaction mixture contains several non-identified products. In preliminary experiments in a solution of THF in the presence of even trace amounts of Cd 2+ calixarene 4 exhibited a dramatic fluorescence quenching. However, a lesser response to Zn 2+ was observed. In our opinion, these results confirm the influence of a nature of pyridine substituents in the meso-position of the calix [4]arene core on the fluorescence response of whole calixarene molecule to the selected metal cations.

Conclusions
In summary, meso-pyridyl-and meso-isoqunolinyl-substituted calix [4]arene ligands/fluorophores were prepared and their photophysical and coordination properties to metal cations were studied. For the obtained meso-pyridyl-calixarenes strong fluorescence turn-off response towards Zn 2+ and Cd 2+ cations was observed.