Phosphate diester hydrolysis promoted by new Cu(II) alkoxide complexes

Three Cu(II) complexes of N3 donor pyridyl-amine ligands, bis-(2-pyridin-2-yl-ethyl)-amine (L¹), which does not have an alcohol pendant, and 2-[bis-(2-pyridin-2-yl-ethyl)-amino]-ethanol (L²) and 3-[bis-(2-pyridin-2-yl-ethyl)-amino]-propan-1-ol (L³), both containing alcohol pendants, have been synthesized and structurally characterized. The reactivities of CuL¹ (1), CuL² (2), and CuL³ (3) for promoting the hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) have been investigated, showing that 3 is much more active (observed second order rate constant k = 6.1 × 10⁻¹ M⁻¹ s⁻¹ at pH 8.4, 50 °C) than 1 (k = 9.4 × 10⁻³ M⁻¹ s⁻¹ at pH 8.4, 50 °C) or 3 (observed second order rate constant k = 5.2 × 10⁻³ M⁻¹ s⁻¹ at pH 8.4, 50 °C) at promoting the hydrolysis of BNPP. The much higher reactivity of 3 compared to 2 and 1 may be explained by the higher flexibility of the alkoxide tether in 3, which may allow the nucleophilic alkoxide O-atom in 3 better access to attack a metal-bound BNPP substrate, whereas 2, which has a shorter alkoxide tether, may resort to hydrolyzing the BNPP substrate with a metal-bound hydroxide instead of utilizing its alkoxide moiety because of constraints in the ligand tether. The similar reactivities of 1 and 2 suggest that this is a possible scenario. Another possible explanation for the difference in reactivity between 3 and 2 may be attributed to the alcohol pendant in 3 being better oriented to serve as a proton acceptor from a Cu(II)-bound aqua ligand, which would facilitate its deprotonation and the subsequent nucleophilic attack of the Cu(II)-hydroxide moiety towards the substrate. The reactivities of 2 and 3 towards hydrolyzing BNPP are also compared with that of their Zn(II) analogues, showing that the Cu(II) complexes of the same ligand sets are more hydrolytically active than the corresponding Zn(II) complexes. Single crystal X-ray structures of 1, 2, and 3 are also reported, which show that complexes 2 and 3 form dimers with bridging alkoxide ligands in the solid state, while 1 forms a dimer with bridging chloride ligands in the solid state.