Biotin[6]uril sulfone dimer: a water-soluble dimeric anion receptor


Tomáš Lízal^†, Nicolaj N. Andersen^‡, Kristina Eriksen^‡, Nicolai S. B. Hansen^‡, Micke Lisbjerg^‡
and Michael Pittelkow^‡

^†Department of Chemistry and RECETOX, Masaryk University, Kamenice 5, 625 00 Brno, Czech Republic;

^‡Department of Chemistry, University of Copenhagen, Universitetsparken 5, DK-2100 Copenhagen,
Denmark


Biotin[6]uril is a water-soluble macrocyclic anion receptor containing six d-biotin units. It binds
large soft anions such as I^- in 1:1 binding mode^1. Oxidation of biotin[6]uril with H[2]O[2] in
acetic acid yields the biotinsulfone[6]uril macrocycle (six sulfones) which has been found to bind
anions more strongly. The macrocycle displays 2:1 binding mode, an anion is complexed between two
biotinsulfone[6]uril macrocycles.

Inspired by the pioneering work by Kubik on dimeric cyclopeptide receptors^2, we decided to link
two biotinsulfone[6]uril together to investigate how preorganization affects anion binding. The
biotinsulfone[6]uril was monofunctionalized via an amide coupling to expose a thiol group, and the
two macrocycles were connected by oxidation to a disulfide (Figure 1). The supramolecular
properties of the dimer were studied by isothermal titration calorimetry and NMR spectroscopy
showing that the dimer bind anions in a 1:1 stoichiometry. The thermodynamic parameters of the
complexes between the dimer and anions show a significant difference compared to the parameters
found when binding anions with the monomeric receptor.


                              Figure 1: Biotin[6]uril sulfone dimer.












(1) Lisbjerg, M.; Nielsen, B. E.; Milhøj, B. O.; Sauer, S. P. a; Pittelkow, M. Org. Biomol. chem.
2015, 13 (2), 369–373.

(1) Kubik, S.; Kirchner, R.; Nolting, D.; Seidel, J. J. Am. Chem. Soc. 2002, 124 (43), 12752–12760.