Metal ions co-operativity in the catalysis of the hydrolysis of a \u3b2-amino ester by a macrocyclic dinuclear Cu(II) complex

The macrocyclic receptor 3, featuring two diaminomethylpyridine moieties as ligand subunits and two diphenylmethane lipophilic spacers was synthesized and the crystal structure of its dinuclear Cu(II) complex, 3.2Cu, defined by X-ray analysis. From a kinetic study of the catalytic activity of 3.2Cu in the hydrolysis of the p-nitrophenyl ester of beta-alanine (AlaPNP), a beta-amino acid, clear evidence of co-operativity of the two metal ions was obtained. Such an allosteric effect was not observed in the hydrolysis of the p-nitrophenyl ester of leucine (LeuPNP), an alpha-amino acid. The reactivity of 3 2Cu was compared with that of the mononuclear complex of the acyclic ligand 4 having a single 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 acceleration was observed employing 3.2Cu compared with a 35-fold rate increase with Cu(II) alone and a 17-fold increase with 4.Cu. The crystal structure of the dinuclear Cu(II) complex gives a distance between the 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 amino group and the oxygen of the C=O. Although significant the rate accelerations observed employing 3.2Cu are rather modest and this is likely due to the orientation of the two pyridine moieties in the macrocycle which does not allow the most favorable inclusion mode of the substrate