In this paper, we describe a new method for the systematic synthesis of catalytic dinuclear Zn(II) hydrolases incorporating second coordination sphere effects by using a polyamidoamine dendrimer as a secondary chain model. Six complexes bearing different dendrimer generations were studied in the hydrolysis of 2-hydroxypropy1-4-nitrophenyl-phosphate (HPNP) and sets of kinetic data were compared in order to better understand the effect of the chain model on the reactivity. The results indicate that a chain of 4000 g mol(-1) is sufficient to represent the second sphere effect in our model. Although the activation entropy Delta S-double dagger was significantly increased, the k(cat) value was not increased, due to unfavorable changes in Delta H-double dagger. The dinuclear catalytic center remained intact, acting through the same mechanism, which opens new possibilities for the rational functionalization at this chain length to further increase the complex activity. (C) 2014 Elsevier B.V. All rights reserved.