Synthesis of Ionizable Calix[4]arenes for Chelation of Selected Divalent Cations

Abstract

Two sets of functionalised calix[4]arenes, either with a 1,3-crown ether bridge or with an open-chain oligo ether moiety in 1,3-position were prepared and further equipped with additional deprotonisable sulfonamide groups to establish chelating systems for selected cations Sr2+, Ba2+, and Pb2+ ions. To improve the complexation behaviour towards these cations, calix[4]arenes with oligo ether groups and modified crowns of different sizes were synthesized. Association constants were determined by UV/Vis titration in acetonitrile using the respective perchlorate salts and logK values between 3.2 and 8.0 were obtained. These findings were supported by the calculation of the binding energies exemplarily for selected complexes with Ba2+.

Calix[4]crowns with perfluoroalkylsulfonylcarboxamide functions: a complexation approach for heavy group 2 metal ions

“…Interestingly, the metal ions Na + and Ba 2+ are bound via the oxygen atoms and not via the nitrogen atoms of both the carboxamide moieties, as demonstrated recently by calculations 31 and as shown in the X-ray structures in Fig. 1 and 4.…”

“…43 and compound Na8c according to ref. 31. Heptafluoropropane-2-sulfonamide was synthesised according to a procedure published by Steinbeisser et al 52 [ 133 Ba]BaCl 2 (carrier added) was purchased from Polatom.…”

“…A reliable method to determine stability constants of M 2+ -calixarene-complexes via UV-Vis spectroscopy was developed in the past. 28,31 However, this method is carried out at its limit of validation for these functionalised calix-crowns, 48 so that values greater than 5 are associated with a large error. 49,50 Furthermore, the UV-Vis method is not appropriate for Ra 2+ , since a high amount of the metal salt would be required.…”

“…27 Additionally, the nonradioactive isotopes of barium serve as a surrogate for basic investigations by NMR or UV-Vis in the development of radium-223/-224-based radiopharmaceuticals. [28][29][30][31] The appropriate half-lives ( 223 Ra: 11.4 d; 224 Ra: 3.6 d) 32,33 and nuclear decay properties make these two radionuclides useful tools in targeted radionuclide therapy with α-particles. 34 To date, [ 223 Ra]RaCl 2 (Xofigo®) is the only EMA-and FDA-approved radiopharmaceutical for α-therapeutic applications in the clinic.…”

“…28 Therefore, the two remaining OH groups of the calix [4]crown-6-scaffold were functionalized with different perfluoroalkylsulfonylcarboxamide moieties. 31 These groups are necessary to stably bind Ba 2+ and Ra 2+ with high selectivity over the lighter group 2 metal ions Mg 2+ and Ca 2+ . The binding behaviour of the considered ions to the crown ether cage and the sulfonamide side chains of the calix [4] ligands was determined by in silico methods based on DFT calculations.…”