Copper(II) and Zinc(II) Complexes of Conformationally Constrained Polyazamacrocycles as Efficient Catalysts for RNA Model Substrate Cleavage in Aqueous Solution at Physiological pH.
As part of a quest for efficient artificial catalysts of RNA phosphodiester bond cleavage, conformationally constrained mono- and bis-polyazamacrocycles in which tri- or tetraazaalkane chains link the ortho positions of a benzene ring were synthesized. The catalytic activities of mono- and dinuclear copper(II) and zinc(II) complexes of these polyazamacrocycles towards cleavage of the P-O bond in 2-hydroxypropyl-4-nitrophenylphosphate (HPNP) in aqueous solution at pH 7 have been determined. Only the complexes of the ligands incorporating three nitrogen atoms in a macrocycle proved to be capable of efficiently catalyzing HPNP transesterification. The dinuclear complexes were found to be approximately twice as efficient as their mononuclear counterparts, and exhibited Michaelis-Menten saturation kinetics with calculated rate constants of kcat ≈10(-4)  s(-1) . By means of quantum chemical calculations (DFT/COSMO-RS), several plausible reaction coordinates were described. By correlating the calculated barriers with the experimental kinetic data, two possible reaction scenarios were revealed, with activation free energies of 20-25 kcal mol(-1) .
Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Technická 5, 166 28, Prague 6, Czech Republic), Fax: (+420) 220-444-288.|Institute of Organic Chemistry and Biochemistry, v.v.i. and Gilead Sciences Research Center, Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.
Daniel
D
Bím
Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Technická 5, 166 28, Prague 6, Czech Republic), Fax: (+420) 220-444-288.
Eva
E
Svobodová
Department of Solid State Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Technická 5, 166 28, Prague 6, Czech Republic.
Václav
V
Eigner
Institute of Organic Chemistry and Biochemistry, v.v.i. and Gilead Sciences Research Center, Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic. lubos@uochb.cas.cz.
Lubomír
L
Rulíšek
Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Technická 5, 166 28, Prague 6, Czech Republic), Fax: (+420) 220-444-288. Jana.Hodacova@vscht.cz.
Jana
J
Hodačová
D002384:Catalysis; D003198:Computer Simulation; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D004951:Esterification; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010755:Organophosphates / Q000737:chemistry; D012313:RNA / Q000737:chemistry*; D059367:RNA Cleavage; D012996:Solutions; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry*
C436487:2-(hydroxypropyl)-4-nitrophenyl phosphate; D056831:Coordination Complexes; D008024:Ligands; D010755:Organophosphates; D012996:Solutions; D012313:RNA; D003300:Copper; D015032:Zinc
cleavage reactions; density functional calculations; ligand design; macrocyclic ligands; reaction mechanisms