Strong binding of alkylguanidinium ions by molecular tweezers: An artificial selective arginine receptor molecule with a biomimetic recognition pattern

Bisphosphonates 2 and 3 represent the first artificial receptor molecules for alkylguanidinium ions. They bind to the guanidinium moiety by forming a 1:1 chelate complex, stabilized by a planar network of electrostatic interactions and hydrogen bonds. This hydrogen bonding configuration is identical to the ''arginine fork'' postulated by Frankel as a key element in RNA-protein recognition of the AIDS virus. Our guanidinium-bisphosphonate complexes thus constitute the first synthetic model for this important biological interaction and demonstrate that the high binding energy can be a driving force for a conformational change in the receptor (induced fit, e.g., in the RNA). Although binding of monosubstituted alkylguanidines is generally strong (K-a approximate to 10 000 in DMSO), molecular tweeter 3 recognizes N- and C-amide-protected arginine derivatives especially well (K-a approximate to 300 000 in DMSO), because an additional hydrogen bond is formed between the amide and the phosphonate. Since 3 does not bind amines effectively, it is highly selective for arginine, even in the presence of lysine or other amino acids. For di-, tri-, and tetrasubstituted guanidines the association constant remains low (K-a less than or equal to 1000 in DMSO) reflecting the increase in the steric bulk of the guest.