Molecular Tweezers and Clips as Synthetic Receptors. Molecular Recognition and Dynamics in Receptor−Substrate Complexes

• Published in: Accounts of chemical research 2003-12, Vol.36 (12), p.919-932
• Main Authors: Klärner, Frank-Gerrit, Kahlert, Björn
• Format: Article
• Language: English
• Subjects: Benzene - chemistry; Benzene Derivatives - chemical synthesis; Benzene Derivatives - chemistry; Chromatography, High Pressure Liquid; Kinetics; Models, Chemical; Models, Molecular; Molecular Conformation; Molecular Structure; Naphthalenes - chemistry; Solutions - chemistry; Solvents - chemistry; Stereoisomerism; Temperature; Thermodynamics
• ISSN: 0001-4842; 1520-4898
• DOI: 10.1021/ar0200448

The molecular tweezers (1, 2) and clips (3−7) containing naphthalene and benzene spacer units can be synthesized via repetitive Diels−Alder reactions by the use of a molecular “Lego” set consisting of bisdienophiles (8, 9, 14) and dienes (10, 13). The new receptors selectively bind electron-deficient neutral and cationic substrates in solution. Only the benzene-spaced tweezers form complexes with aliphatic substrates, whereas the other receptors bind aromatic substrates preferentially. HPLC studies with 1 and 2 chemically bonded to stationary phases give similar results for the heterogeneous systems. The formation of stable complexes between the water-soluble clip 5g and N-alkylpyridinium cations, such as N-methylnicotinamide and NAD+, in aqueous solution illustrates the importance of the hydrophobic effect for arene−arene interactions. The dynamics of the complex formation and substrate mobility were investigated by the use of temperature-dependent liquid- and solid-state NMR spectroscopy. The electrostatic potential surface (EPS) of 1−7 is calculated to be surprisingly negative on the concave side of each molecule and, hence, complementary to the EPS of the electron-deficient substrates, suggesting that the attractive receptor−substrate interaction is here of predominantly electrostatic nature.