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 func tionalized 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 aromat ic residues defining its hydrophobic walls. In these Zn(II) complexes one of the phenolic hydroxyls is, depending on the structure of the li gand, up to 1.3 pK(a) units more acidic than that of phenol itself. Th is enhanced acidity is attributed to second sphere coordination to the metal center. The complexes, particularly 1 . Zn(II), behave as molec ular receptors of p-nitrophenyl esters of carboxylic acids with bindin g constants greater than or equal to 300 M-1 for those substrates capa ble 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 ra te accelerations with respect to the uncatalyzed: hydrolysis of up to 60 times, depending on the structure of the substrate. The kinetic ana lysis of the process shows that the rate effects are due to two indepe ndent mechanisms: a bimolecular process that does not comprise binding of the substrate and a pseudointramolecular process within the supram olecular complex made of ligand, metal ion, and substrate. In both cas es the nucleophile is one of the phenolic hydroxyls of the functionali zed side arms of the TREN-based complex which, in the first step, is a cylated 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 metallorecep tor 1 . Zn(II) with cyclodextrins allowed one to highlight similarity and differences between the two receptors.