Participation of host ‘spacer’ atoms in carboxylic acid binding: implications for amino acid recognition

Chiral 4,4′-diamido-2,2′-biimidazoles were synthesized and found to bind N-Boc protected amino acids in CDCl3. The biimidazole that features (R)-tetrahydrofurfuryl units discriminates between N-Boc-l-Ser (Kassoc=120 M−1) and its non-natural d-enantiomer (270 M−1). X-ray diffraction and computational analyses show that members of this receptor class adopt a cleft-like conformation, presenting a donor-spacer-donor-acceptor H-bonding array. Complexes of such biimidazoles with the –COOH unit of amino acids are stabilized by direct involvement of what is nominally a ‘spacer’ atom, unlike other D-Sp-D-A hosts.