Carboxyester hydrolysis promoted by dizinc(ii) macrocyclic polyamine complexes with hydroxyethyl pendants: a model study for the role of the serine alkoxide nucleophile in zinc enzymes

Abstract

A novel dinuclear Zn(II) complex with hexaaza macrocycle bearing two hydroxyethyl pendants (L1), 3,6,9,16,19,22-hexaaza-6,19-bis(2-hydroxyethyl)-tricyclo[22,2,2,2^11,13]triaconta-1,11,13,24,27,29-hexaene), was synthesized as a model for alkaline phosphatase. The Zn(II) complex [Zn₂L1(CH₃CO₂)₂](ClO₄)₂(H₂O)₂ was isolated as a colorless crystal, triclinic, space group P-1. Both Zn(II) ions adopt the geometry of a distorted trigonal bipyramid in a pentacoordinated environment with Zn⋯Zn distance of 8.74 Å. The solution complexation study has revealed that the alcoholic hydroxyl group of the complex Zn₂L1 exhibits a low pK_a value at 25 °C. Zn(II)-bound alkoxides, which act as reactive nucleophiles toward the hydrolysis of 4-nitrophenyl acetate in 10% (v/v) CH₃CN at 25 °C, with I = 0.10 M (NaNO₃) and pH 9.0, have shown a second-order rate constant of 0.32 ± 0.01 M⁻¹s⁻¹, a value that is approximately 13 times greater than the value for the corresponding dinuclear Zn(II) complex formed by a hexaaza macrocycle without hydroxyethyl pendants (L2). The pH–rate profile for Zn₂L1 gave a sigmoidal curve. A possible mechanism has been proposed: the Zn(II)–RO⁻ function acts as a nucleophile in the first step of the hydrolytic mechanism, to give an acetyl intermediate, which is subsequently hydrolyzed to acetate by a Zn(II)–OH⁻ group.