A phenoxo-bridged dicopper(ii) complex as a model for phosphatase activity: mechanistic insights from a combined experimental and computational study

Abstract

A μ-phenoxo-bis(μ₂-1,3-acetato)-bridged dicopper(II) complex [Cu^II₂(L¹)(μ-O₂CMe)₂][NO₃] (1) has been synthesized from the perspective of modeling phosphodiesterase activity. Structural characterization was done initially with 1·3Et₂O (vapour diffusion of Et₂O into MeOH solution of 1; poor crystal quality) and finally with its perchlorate salt [Cu^II₂(L¹)(μ-O₂CMe)₂][ClO₄]·1.375MeCN·0.25H₂O, crystallized from vapour diffusion of n-pentane into a MeCN–MeOH mixture (comparatively better crystal quality). An asymmetric unit of such a crystal contains two independent molecules of compositions [Cu^II₂(L¹)(μ-O₂CMe)₂][ClO₄] and [Cu^II₂(L¹)(μ-O₂CMe)₂(MeCN)][ClO₄] (coordinated MeCN with 0.75 occupancy), and two molecules of MeCN and H₂O (each H₂O molecule with 0.25 occupancy) as the solvent of crystallization. These two cations, each having five-coordinate (μ-phenoxo)bis(μ-acetato)-bridged Cu^II ions, differ by only the coordination environment of only one Cu^II ion, which has a weakly coordinated acetonitrile molecule in its sixth position. Temperature-dependent magnetic studies on 1 reveal that the copper(II) centres are antiferromagnetically coupled with the exchange-coupling constant J = −124(1) cm⁻¹. Theoretically calculated J = −126.51 cm⁻¹, employing a broken-symmetry DFT approach, is in excellent agreement with the experimental value. The dicopper(II) complex has been found to be catalytically efficient in the hydrolysis of 2-hydroxypropyl-p-nitrophenylphosphate (HPNP). Detailed kinetic experiments and solution studies (potentiometry, species distribution and ESI-MS) were performed to elucidate the reaction mechanism. DFT calculations were performed to discriminate between different possible mechanistic pathways. The free-energy barrier for HPNP hydrolysis catalyzed by 1 is comparable to that obtained from the experimentally-determined value. The involvement of non-covalent (hydrogen-bonding) interaction has also been probed by DFT calculations. The activity of 1 is found to be the highest, compared to the structurally-characterized Mn^II₂, Co^II₂, Ni^II₂ and Zn^II₂ complexes of L¹(−) reported earlier, under identical experimental conditions, in which each metal centre is six-coordinate.