Electronic Effect on Bimetallic Catalysts: Cleavage of Phosphodiester Mediated by Fe(III)–Zn(II) Purple Acid Phosphatase Mimics

Abstract

The bimetallic system is an important strategy for the catalytic hydrolysis of phosphodiester. The purple acid phosphatase (PAPs) enzyme is a typical bimetallic catalyst in this field. Mechanistic details for the hydrolysis cleavage of the DNA dinucleotide analogue BNPP– (BNPP– = bis(p-nitrophenyl) phosphate) by hetero-binuclear [FeIII(μ-OH)ZnIIL]2+ complexes (L = 2-[N-bis(2-pyridylmethyl)-aminomethyl]-4-methyl-6-[N′-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethyl] phenol) were investigated using density functional theory calculations. The catalysts with single-bridged hydroxyl and double-bridged hydroxyl groups were compared. The calculation results show that the doubly hydroxide-bridged complex could better bind to substrates. For the BNPP– hydrolysis, the doubly hydroxide-bridged reactant isomerizes into a single hydroxide-bridged complex, and then the attack is initiated by the hydroxyl group on the iron center. In addition, the catalyst with the electron-donating group (Me) was determined to take precedence over electron-withdrawing groups (Br and NO2 groups) in the hydrolysis reaction. This is because the substituents affect the high-lying occupied molecular orbitals, tuning the Lewis acidity of iron and pKa values of the metal-bonded water. These factors influence the hydroxyl nucleophilicity, leading to changes in catalytic activity. To further examine substituent effects, the occupied orbital energies were calculated with several different substituent groups (-CF3, -OMe, -OH, -NH2, and -N(Me)2). It was found that the HOMO or HOMO-1 energy decreases with the increase of the σp value. Further, the catalyst activity of the [FeIII(μ-OH)ZnIIL]2+ complexes was found to be mainly affected by the phenolate ligand (B) coordinated to the iron and zinc centers. These fundamental aspects of the hydrolysis reactions of BNPP– catalyzed by [FeIII(μ-OH)ZnIIL]2+ complexes should contribute to improved understanding of the mechanism and to catalyst design involving hetero-binuclear metals complexes.