Influence of Varying Functionalization on the Peroxidase Activity of Nickel(II)–Pyridine Macrocycle Catalysts: Mechanistic Insights from Density Functional Theory

Abstract

Nickel(II) complexes of mono-functionalized pyridine-tetraazamacrocycles (PyMACs) are a new class of catalysts that possess promising activity similar to biological peroxidases. Experimental studies with ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), substrate) and H2O2 (oxidant) proposed that hydrogen-bonding and proton-transfer reactions facilitated by their pendant arm were responsible for their catalytic activity. In this work, density functional theory calculations were performed to unravel the influence of pendant arm functionalization on the catalytic performance of Ni(II)–PyMACs. Generated frontier orbitals suggested that Ni(II)–PyMACs activate H2O2 by satisfying two requirements: (1) the deprotonation of H2O2 to form the highly nucleophilic HOO−, and (2) the generation of low-spin, singlet state Ni(II)–PyMACs to allow the binding of HOO−. COSMO solvation-based energies revealed that the O–O Ni(II)–hydroperoxo bond, regardless of pendant arm type, ruptures favorably via heterolysis to produce high-spin (S = 1) [(L)Ni3+–O·]2+ and HO−. Aqueous solvation was found crucial in the stabilization of charged species, thereby favoring the heterolytic process over homolytic. The redox reaction of [(L)Ni3+–O·]2+ with ABTS obeyed a 1:2 stoichiometric ratio, followed by proton transfer to produce the final intermediate. The regeneration of Ni(II)–PyMACs at the final step involved the liberation of HO−, which was highly favorable when protons were readily available or when the pKa of the pendant arm was low.

Peroxidase‐like activity of an azamacrocyclic Ni(II) complex

“…In summary, our UV/Vis and EPR investigations clearly showed the peroxidase-like activity of [Ni(II)(DMDAC)] 2+ on both ABTS and ABTS +• . Combined with previous experimental and theoretical works on Ni(II)-PyMACs, 35,36 our results may suggest that azamacrocyclic Ni(II) complexes can in general exhibit the peroxidase-like catalysis in aqueous solution and the catalytic cycle proceeds through the heterolytic cleavage of the O-OH bond in a Ni(II)-hydroperoxo species.…”

“…42 And the previous DFT calculations for the peroxidase-like activities of Ni(II)-PyMAC complexes have predicted the formation of a Ni(IV)-oxo intermediate. 35,36 These results suggest that the MS peaks are originating from the oxygen-bound Ni species. In-depth studies for completely identifying the intermediates are underway.…”

“…35 And Organo et al have proposed their mechanistic reaction pathways by using density functional theory (DFT) calculations. 36 In search of novel complexes exhibiting hemeindependent peroxidase activities, we have reported a fully-coordinated Mn(II) complex with an N 6hexadentate ligand and an octahedral Ru(III) complex with an N 4 -tetradentate ligand. 37,38 In this communication, we report the peroxidase-like activity of an azamacrocyclic Ni(II) complex, [Ni(II)(DMDAC)] 2+ ,…”