Synthesis, physicochemical properties and in vitro catalytic activity of a dinuclear nickel(II) complex with a N5O-hexadentate ligand: A functional model for phosphohydrolases

Abstract

The development of artificial nucleases has been stimulated by the realization that hydrolytically active metal complexes may potentially find utility as robust versatile replacements for restriction enzymes in molecular biology research and as nucleic acid-targeting therapeutics. In this regard, a novel unsymmetrical dinucleating ligand HL (where L is the 2-[(4,7-diisopropyl-1,4,7-triazonan-1-yl)methyl]-4-methyl-6-[(pyridin-2-ylmethylamino)methyl]phenolate moiety) with an N5O-donnor set was synthesized and characterized by IR and 1H NMR spectroscopy. The reaction of HL with nickel(II) perchlorate led to the formation of a μ-phenoxo-bridged dinuclear Ni(II) complex, [Ni2(L)(μ-OAc)2]BPh4·H2O (1). Physicochemical measurements (molar conductometry, IR and UV–Vis spectroscopy and electrochemistry) were performed for 1 and these properties are compared with those presented by similar compounds in the literature. ESI-MS measurements in positive and negative modes confirmed the complex composition as well as the presence of tetraphenylborate counterions, based on their mass and isotopic distribution patterns. Potentiometric titration studies of 1 were carried out (CH3CN/H2O 50% v/v) and we probed its acid/base properties, which are crucial to gaining an understanding of the phosphodiester catalytic cleavage mechanism. Finally, the ability of 1 to mimic the functional role of the dinuclear metalloenzymes was evaluated through studies on its reactivity toward the model-substrate bis(2,4-dinitrophenyl)phosphate (2,4-bdnpp). When compared with similar previously described compounds, complex 1 helped to probe the influence of the aromatic/aliphatic N-donor moieties, such as macrocyclic rings, pyridine and imidazole, through their catalytic efficiency parameter (E/Lmol−1s−1).