Copper(II) and Zinc(II) Complexes of Conformationally Constrained Polyazamacrocycles as Efficient Catalysts for RNA Model Substrate Cleavage in Aqueous Solution at Physiological pH

0463356 - ÚOCHB 2017 RIV DE eng J - Článek v odborném periodiku
Bím, Daniel - Svobodová, E. - Eigner, V. - Rulíšek, Lubomír - Hodačová, J.
Copper(II) and Zinc(II) Complexes of Conformationally Constrained Polyazamacrocycles as Efficient Catalysts for RNA Model Substrate Cleavage in Aqueous Solution at Physiological pH.
Chemistry - A European Journal. Roč. 22, č. 30 (2016), s. 10426-10437. ISSN 0947-6539. E-ISSN 1521-3765
Grant CEP: GA ČR(CZ) GA14-31419S
Institucionální podpora: RVO:61388963
Klíčová slova: cleavage reactions * density functional calculations * ligand design * macrocyclic ligands * reaction mechanisms
Kód oboru RIV: CF - Fyzikální chemie a teoretická chemie
Impakt faktor: 5.317, rok: 2016

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 pH7 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 k(cat)approximate to 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 20-25kcalmol(-1).
Trvalý link: http://hdl.handle.net/11104/0262559