An allosteric synthetic catalyst: Metal ions tune the activity of an artificial phosphodiesterase

A trinuclear metal complex of general formula (L-H)M-5(M-f)(2) represents t he first allosteric low molecular weight catalyst. L is a polyaza ligand ha ving a tetradentate and two bidentate metal binding sites, M-s is a "struct ural" (allosteric) metal, and M-f are functional (catalytic) metals which i nteract with a substrate. In mononuclear [(L-H)M-s](+) complexes [(L-H)Cu(M eOH)]ClO4 (la), [(L-H)Cu]NO3. 2H(2)O (1b), [(L-H)Ni]ClO4.H2O (2), and [(L-H )Pd]ClO4. 2H(2)O (3), prepared from L and M2+ salts, the metal is strongly bound by an in-plane N-4-coordination (confirmed by X-ray crystal structure determination of la). Formation of trinuclear complexes [(L-H)MsCu2](5+), with two functional Cu2+ ions coordinated to the bidentate sites of L, was evidenced in solution by photometric titration and by isolation of [(L-H)Cu -3][PO4][ClO4]2 . 9H(2)O (4). The trinuclear complexes catalyze the cleavag e of RNA-analogue 2-(hydroxypropyl)-p-nitrophenyl phosphate (HPNP), an acti vated phosphodiester. From a kinetic analysis of the cleavage rate at vario us HPNP concentrations, parameters K-HPNP (the equilibrium constant for bin ding of HPNP to I(L-H)MsCu2](5+) and k(cat) (first-order rate constant for cleavage of HPNP when bound to the catalyst) were derived: K-M = 170 (M-s = Cu2+), 340 (M-s = Ni2+), 2600 (M-s = Pd2+) M-1, k(cat) = 17 x 10(-3) (M-s = Cu2+), 3.1 x 10(-3) (M-s = Ni2+), 0.22 x 10(-3) (M-s = Pd2+) s(-1). Obvio usly, the nature of the allosteric metal ion M-s strongly influences both s ubstrate affinity and reactivity of the catalyst [(L-H)MsCu2](5+). Our inte rpretation of this observation is that subtle differences in the ionic radi us of M-s and in its tendency to distort the N-4-M-s coordination plane hav e a significant influence on the conformation of the catalyst (i.e., preorg anization of functional Cu2+ ions) and thus on catalytic activity.