Porphyrin receptors for amines, amino acids, and oligopeptides in water

A series of water-soluble porphyrin receptors having a hydrophobic binding pocket, a Lewis acidic site (Zn), and an electrostatic recognition site (COO- groups) were prepared. All the porphyrin receptors have a [meso-tetrakis(p-carboxyphenyl)porphyrinato]zinc (Zn . TCPP) as a common structural unit, and eight omega-carboxyalkyloxy groups (alkyloxy = methoxy (1), butoxy (2), decyloxy (3)) at the ortho positions of the phenyl groups. These receptors bind amines, a-amino acid esters, and oligopeptides in water with significant selectivity. For binding of hydrophilic guests, 1, 2, and 3 bind histamine in pH 8 buffer at 25 degrees C with binding constants of 157000, 31000, and 18200 M-1, respectively, where the coordination (Imd-Zn) and the salt bridge (NH3+--OOC) stabilized the complex. The large dependence of the binding constants on the ionic strength indicated that the electrostatic interaction between the ammonium group of histamine and the carboxylate groups of receptor contributes significantly to tight binding in water. Receptors 1-3 also bind a cationic guest, Arg-OMe, with a binding constant of 440-11000 M-1. The effective charge of the receptors for electrostatic recognition of Arg-OMe in pH 9 Borax (I = 0.1 M) at 25 degrees C was evaluated by the Debye-Huckel limiting law as 4.2, 4.3, and 3.0 for 1, 2, and 3, respectively. These observations indicate that a salt bridge, which is exposed to water and involves hydrogen bonding, as seen in the 1-histamine and 1-Arg-OMe complexes, can be used as a significant recognition force. Binding of Arg-OMe by 2 and 3 was entropically driven, and binding of Arg-OMe by 1 was enthalpically driven. Therefore, the driving force of binding is desolvation from the ionic groups in the former case and the electrostatic attraction in the latter case. For binding of hydrophobic guests, 3 binds Trp-OMe or pyridine in water with binding constants of 7000-8000 M-1, while 1 and Zn . TCPP bind these guests less tightly with binding constants of 20-500 M-1, indicating the importance of the long alkyl chains to provide a hydrophobic binding pocket above the porphyrin plane.