METAL-IONS COOPERATIVITY IN THE CATALYSIS OF THE HYDROLYSIS OF A BETA-AMINO ESTER BY A MACROCYCLIC DINUCLEAR CU(II) COMPLEX

The macrocyclic receptor 3, featuring two diaminomethylpyridine moieti es as ligand subunits and two diphenylmethane lipophilic spacers was s ynthesized and the crystal structure of its dinuclear Cu(II) complex, 3.2Cu, defined by X-ray analysis. From a kinetic study of the catalyti c activity of 3.2Cu in the hydrolysis of the p-nitrophenyl ester of be ta-alanine (AlaPNP), a beta-amino acid, clear evidence of co-operativi ty of the two metal ions was obtained. Such an allosteric effect was n ot observed in the hydrolysis of the p-nitrophenyl ester of leucine (L euPNP), an alpha-amino acid. The reactivity of 3 2Cu was compared with that of the mononuclear complex of the acyclic ligand 4 having a sing le diaminomethylpyridine subunit and to that of Cu(II) alone. At pH=6. 3 in a 1:1 water/DMSO mixture, being [Cu(II)]=6x10(-4) M, a 80-fold ac celeration was observed employing 3.2Cu compared with a 35-fold rate i ncrease with Cu(II) alone and a 17-fold increase with 4.Cu. The crysta l structure of the dinuclear Cu(II) complex gives a distance between t he two Cu(II) centers of 9.9 Angstrom, suitable for the co-ordination of the beta-amino ester by both Cu(II) ions with the nitrogen of the a mino group and the oxygen of the C=O. Although significant the rate ac celerations observed employing 3.2Cu are rather modest and this is lik ely due to the orientation of the two pyridine moieties in the macrocy cle which does not allow the most favorable inclusion mode of the subs trate.