title: An allosteric synthetic catalyst: metal ions tune the activity of an artificial phosphodiesterase.
abstract: A trinuclear metal complex of general formula (L-H)M3(Mf)2 represents the first allosteric low molecular weight catalyst. L is a polyaza ligand having a tetradentate and two bidentate metal binding sites, Ms is a "structural" (allosteric) metal, and Mf are functional (catalytic) metals which interact with a substrate. In mononuclear [(L-H)Ms]+ complexes [(L-H)Cu(MeOH)]ClO4 (1a). [(L-H)Cu]NO3 x 2H2O (1b), [(L-H)Ni]ClO4 x 4H2O (2), and [(L-H)Pd]ClO4 x 2H2O (3), prepared from L and M2+ salts, the metal is strongly bound by an in-plane N4-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)Cu3][PO4][ClO4]2 x 9H2O (4). The trinuclear complexes catalyze the cleavage of RNA-analogue 2-(hydroxypropyl)-p-nitrophenyl phosphate (HPNP), an activated phosphodiester. From a kinetic analysis of the cleavage rate at various HPNP concentrations, parameters KHPNP (the equilibrium constant for binding of HPNP to [(L-H)MsCu2]5+ and kcat (first-order rate constant for cleavage of HPNP when bound to the catalyst) were derived: KM= 170 (Ms= Cu2+), 340 (Ms = Ni2+), 2,600 (Ms = Pd2+) M(-1), kcat = 17 x 10(-3) (Ms= Cu2+) 3.1 x 10(-3) (Ms=Ni2+), 0.22 x 10(-3) (Ms = Pd2+) s(-1). Obviously, the nature of the allosteric metal ion Ms strongly influences both substrate affinity and reactivity of the catalyst [(L-H)MsCu2]5+. Our interpretation of this observation is that subtle differences in the ionic radius of Ms and in its tendency to distort the N4-Ms coordination plane have a significant influence on the conformation of the catalyst (i.e., preorganization of functional Cu2+ ions) and thus on catalytic activity.
authors.affiliation: Anorganische-Chemisches Institut, Universität Heidelberg, Germany. roland.kraemer@urz.uni-heidelberg.de
authors.forename: I O
authors.initials: IO
authors.lastname: Fritsky
authors.forename: R
authors.initials: R
authors.lastname: Ott
authors.forename: H
authors.initials: H
authors.lastname: Pritzkow
authors.forename: R
authors.initials: R
authors.lastname: Krämer
mesh_terms: D000494:Allosteric Regulation; D002384:Catalysis; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009532:Nickel / Q000737:chemistry; D009596:Nitrophenols / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C008644:nitrophenylphosphate; D003300:Copper; D009532:Nickel; D010727:Phosphoric Diester Hydrolases