Zwitterionic triple- and quadruple hydrogen-bonding motifs

Zwitterionic triple and quadruple hydrogen-bonding heterocyclic modules based on an easily accessible deazapterin scaffold are reported. The solid-state structure of 3H-bonding zwitterionic molecules revealed the formation of various hydrogen-bonded 1D chains composed of water, methanol, or a chloride anion, depending on the extent of protonation. The association of newly designed AAD and AADA (D = hydrogen-bond donor, A = hydrogen-bond acceptor) zwitterionic monomers was studied in solution to identify complementary partners and to evaluate binding strength. Both AAD and AADA motifs form 3H-bonded dimers after the addition of half an equivalent of acid, representing a negatively-charged analogue of the C–C⁺ pair in naturally occurring DNA i-motifs. The protonation of the AADA motif with hydrochloric acid converts it into a non-H-bonding form where the urea moiety is complexed with the chloride anion. The exchange of chloride with non-nucleophilic anions unlocks the rotation of the urea group, resulting in the formation of the ADDA–DAAD heterocomplex with 2,7-diamido-1,8-naphthyridine.