Molecular Recognition by Natural Macrocycles. I. d‐Tubocurarine as a Host Molecule for Organic Anions

Abstract

The binding of 8-anilino-1-naphthalenesulfonate and 15 anions of substituted benzoic, aliphatic dicarboxylic, and N-acetyl-alpha-amino acids to a macrocyclic alkaloid d-tubocurarine in aqueous solution has been studied by fluorometry, conductometry, and 1H NMR. The binding constants vary from ca. 50 to 3300 M-1 depending on the guest structure, charge and hydrophobicity. The results of fluorescence and NMR studies show that the host-guest complexation of the anions of aromatic acids involves the formation of a salt bridge between the quaternary nitrogen of the alkaloid and the anionic group of the guest as well as hydrophobic/Van der Waals interactions between the guest and host aromatic moieties. The binding of dianions of aliphatic dicarboxylic acids most probably is purely electrostatic. In general, d-tubocurarine possesses binding ability comparable to that of synthetic cyclophanes. It binds enantiospecifically anions of N-acetyl-alpha-amino acids and discriminates between positional isomers of anions of hydroxy and carboxy substituted benzoic acids.

Host-Guest Chemistry of Alkaloids

“…Thus, at pH below 7, tubocurarine is a dication and at a pH of about 9 it is a neutral zwitterion (Figure 7, structure 21). In the dicationic form, d-tubocurarine efficiently binds dianions of dicarboxylic acids (logK = 2.8 for terephthalate and 2.4 for malonate dianions) and shows significant enantioselectivity in the binding of anions of N-acylated amino acids (Table 3) [46]. Table 3: Binding constants of enantiomers of N-acetyl amino acids, free amino acids as anions, and nucleotides to bisbenzylisoquinoline macrocyclic alkaloids and their derivatives [47,51].…”