To enhance the catalytic activity of metal-terpyridyl complexes toward transesterification :of an RNA model [(2-hydroxypropyl)-p-nitrophenyl phosphate, HPNPP], the conformation of terpyridyl moieties assembled on poly(ethylenimine) (PEI) is optimized by attaching the Ni(II) complex of a terpyridyl derivative ((NiTP)-T-II) and lauryl (Lau) group to PEI in random combinations. The catalytic activity per Ni(II) center for transesterification of HPNPP varies by up to several thousand times depending on pH as the content of (NiTP)-T-II or Lau is changed. The best catalyst obtained is [(NiTP)-T-II](5)Lau(12)PEI, in which the contents of (NiTP)-T-II and Lau are 5 and 12 residue mol %, respectively. The catalytic activity of [(NiTP)-T-II](5)Lau(12)PEI expressed in terms of k(cat) is much higher than those of previously reported binuclear metal complexes whose structures were designed through deliberate planning. In the PEI derivatives containing (NiTP)-T-II and Lau, several (NiTP)-T-II groups can be positioned in proximity in the hydrophobic clusters formed on the polymer. When the (NiTP)-T-II groups take productive positions, the two phosphoryl-oxygen bonds and the hydroxyl group of HPNPP can be effectively activated Thus, artificial active sites comprising multiple catalytic groups are obtained by self-assembly of the catalytic groups. Moreover, cooperative action among the catalytic groups is optimized through combinatorial approach.