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An Allosteric Synthetic Catalyst: Metal Ions Tune the Activity of an Artificial Phosphodiesterase
Author(s) -
Fritsky Igor O.,
Ott Reina,
Pritzkow Hans,
Krämer Roland
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010316)7:6<1221::aid-chem1221>3.0.co;2-t
Subject(s) - chemistry , denticity , allosteric regulation , enzyme kinetics , catalysis , stereochemistry , metal ions in aqueous solution , metal , reaction rate constant , ligand (biochemistry) , medicinal chemistry , crystallography , crystal structure , kinetics , enzyme , active site , organic chemistry , receptor , biochemistry , physics , quantum mechanics
A trinuclear metal complex of general formula (L−H)M s (M f ) 2 represents the first allosteric low molecular weight catalyst. L is a polyaza ligand having a tetradentate and two bidentate metal binding sites, M s is a “structural” (allosteric) metal, and M f are functional (catalytic) metals which interact with a substrate. In mononuclear [(L−H)M s ] + complexes [(L−H)Cu(MeOH)]ClO 4 ( 1 a ), [(L−H)Cu]NO 3 ⋅ 2 H 2 O ( 1 b ), [(L−H)Ni]ClO 4 ⋅ 4 H 2 O ( 2 ), and [(L−H)Pd]ClO 4 ⋅ 2 H 2 O ( 3 ), prepared from L and M 2+ salts, the metal is strongly bound by an in‐plane N 4 ‐coordination (confirmed by X‐ray crystal structure determination of 1 a ). Formation of trinuclear complexes [(L−H)M s Cu 2 ] 5+ , with two functional Cu 2+ ions coordinated to the bidentate sites of L, was evidenced in solution by photometric titration and by isolation of [(L−H)Cu 3 ][PO 4 ][ClO 4 ] 2 ⋅ 9 H 2 O ( 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 K HPNP (the equilibrium constant for binding of HPNP to [(L−H)M s Cu 2 ] 5+ and k cat (first‐order rate constant for cleavage of HPNP when bound to the catalyst) were derived: K M =170 (M s =Cu 2+ ), 340 (M s =Ni 2+ ), 2600 (M s =Pd 2+ ) M −1 , k cat =17×10 −3 (M s =Cu 2+ ), 3.1×10 −3 (M s =Ni 2+ ), 0.22×10 −3 (M s =Pd 2+ ) s −1 . Obviously, the nature of the allosteric metal ion M s strongly influences both substrate affinity and reactivity of the catalyst [(L−H)M s Cu 2 ] 5+ . Our interpretation of this observation is that subtle differences in the ionic radius of M s and in its tendency to distort the N 4 −M s coordination plane have a significant influence on the conformation of the catalyst (i.e., preorganization of functional Cu 2+ ions) and thus on catalytic activity.