Molecular recognition by natural macrocycles. Part II. Esterolytic activity and chiral discrimination of amino acid derivatives by the zwitterionic form of (+)-tubocurarine

The esterase and complexation properties of the zwitterionic form of a macr ocyclic alkaloid (+)-tubocurarine possessing two phenolic nucleophilic grou ps are described. Cleavage of 4-nitrophenyl esters of N-protected phenylala nine enantiomers involves reaction paths with one and two alkaloid molecule s. Substrate binding enantioselectivity is large and is opposite to the kin etic enantioselectivity, leading to the modest observed enantioselectivity of the reaction, which reaches a maximum (k(L)/k(D) approximate to 1.5) at ca. 0.002 mol dm(-3) alkaloid concentration and practically disappears on g oing to 0.01 mol dm(-3) alkaloid solution. Addition of boric acid initially enhances the reaction rate and enantiospecificity, but in more concentrate d berate solutions the expected inhibition due to blocking of the phenolate groups is observed. For the first time reported for an alkaloid; the ester olytic activity of (+)-tubocurarine towards 4-nitrophenyl acetate fairs on a common Bronsted plot together with cyclodextrins and some synthetic macro cycles. Binding of enantiomers of differently charged derivatives of alanin e, phenylalanine and beta-phenylethylamine to the zwitterionic form of(+)-t ubocurarine in aqueous solution was-studied by H-1 NMR and fluorescence tit ration. The binding constants vary from <5 dm(3) mol(-1) for alanine to ca. 50 dm(3) mol(-1) for phenylalanine derivatives and the binding enantiosele ctivity Varies from marginal for N-acetylphenylalanine enantiomers to a qui te notable, three-fold differentiation between L- and D-phenylalanine. Whil e the enantiospecificity depends primarily on electrostatic interactions, t he overall stability is determined by guest hydrophobicity. This conclusion was confirmed by docking calculations for enantiomers of phenylalanine. Ad dition of amino acid derivatives to solutions containing (+)-tubocurarine a nd highly fluorescent 8-anilinonaphthalenesulfonate anion leads to enantios elective spectral responses which are indicative of formation of ternary co mplexes.