Acceleration of p-Nitrophenyl Ester Cleavage by Zn(II)-Organized Molecular Receptors

Tris(2-aminoethyl)amine (TREN) has been functionalized by introducing phenolic residues in the tripodal ligand side arms. The resulting functionalized ligands 1-5 form stable complexes with Zn(II) ions at pH > 6-6.5. The conformation of the Zn(II) complexes is such to form an ill-defined cavity with the metal ion occupying its bottom and the aromatic residues defining its hydrophobic walls. In these Zn(II) complexes one of the phenolic hydroxyls is, depending on the structure of the ligand, up to 1.3 pK(a) units more acidic than that of phenol itself. This enhanced acidity is attributed to second sphere coordination to the metal center. The complexes, particularly 1 . Zn(II), behave as molecular receptors of p-nitrophenyl esters of carboxylic acids with binding constants greater than or equal to 300 M-1 for those substrates capable of coordination to the Zn(II) ion (p-nitrophenyl nicotinate, PNPN, p-nitrophenyl isonicotinate, PNPIN and p-nitrophenyl urocanoate, PNPU). At pH 8.3 they also accelerate the cleavage of these esters with rate accelerations with respect to the uncatalyzed: hydrolysis of up to 60 times, depending on the structure of the substrate. The kinetic analysis of the process shows that the rate effects are due to two independent mechanisms: a bimolecular process that does not comprise binding of the substrate and a pseudointramolecular process within the supramolecular complex made of ligand, metal ion, and substrate. In both cases the nucleophile is one of the phenolic hydroxyls of the functionalized side arms of the TREN-based complex which, in the first step, is acylated by the substrate and eventually slowly hydrolyzes turning over the catalyst. Determination of second-order rate constants shows that the nucleophilicity of the phenolic hydroxyls is higher than that of a substituted phenol of the same pK(a). Comparison of the metalloreceptor 1 . Zn(II) with cyclodextrins allowed one to highlight similarity and differences between the two receptors.