Mechanochemically-Driven Self-Assembly of a Chiral Mono-Biotinylated Hemicucurbit[8]uril

Hemicucurbiturils are macrocycles formed by connecting ethyleneurea moieties with methylene bridges. This study presents the development of self-assembled chiral mono-biotinylated hemicucurbit[8]urils (mixHC[8]) in the solid state. The mixHC[8]s were synthesized in a single preparative step by a mechanochemically-assisted condensation reaction of D-biotin, (R,R)- or (S,S)-cyclohexa-1,2-diylurea and formaldehyde. Dynamic covalent library of over 100 identified oligomers was generated via ball milling under perchloric or hexafluorophosphoric acid catalysis. Rigorous analysis of intermediates, including formation kinetics of short oligomers, revealed key processes and chemical parameters influencing self-assembly. We found that self-organization of about 50,000 theoretically predicted oligomers can be directed to formation of 8-membered hemicucurbiturils in 75% yield, consisting of a 1:1 mixture of chimeric mixHC[8] and homomeric cyclohexanohemicucurbit[8]uril (cycHC[8], 38% and 37% yields, respectively), or predominantly homomeric cycHC[8] (up to a 72% yield). The developed procedure was used for synthesis of diastereomeric (−)- and (+)-mixHC[8] suitable for anion binding and derivatization. Immobilization of mixHC[8] on a surface of aminated silica produced a functional material capable of selective capture of anions, as demonstrated by efficient perchlorate removal from a spiked mineral matrix.