Diquinol Functionality Boosts the Superoxide Dismutase Mimicry of a Zn(II) Complex with a Redox-Active Ligand while Maintaining Catalyst Stability and Enhanced Activity in Phosphate Solution

Abstract

In the current work, we demonstrate ligand design concepts that significantly improve the superoxide dismutase (SOD) activity of a zinc complex; the catalysis is enhanced when two quinol groups are present in the polydentate ligand. We investigate the mechanism through which the quinols influence the catalysis and determine the impact of entirely removing a chelating group from the original hexadentate ligand. Our results suggest that SOD mimicry with these compounds requires a ligand that coordinates Zn(II) strongly in both its oxidized and reduced forms and that the activity proceeds through Zn(II)-semiquinone complexes. The complex with two quinols displays greatly enhanced catalytic ability, with the activity improving by as much as 450% over a related complex with a single quinol. In the reduced form of the diquinol complex, one quinol appears to coordinate to the zinc much more weakly than the other. We believe that superoxide can more readily displace this portion of the ligand, facilitating its coordination to the metal center and thereby hastening the SOD reactivity. Despite the presence of two redox-active groups that may communicate through intramolecular hydrogen bonding and redox tautomerism, only one quinol undergoes two-electron oxidation to a para-quinone during the catalysis. After the formation of the para-quinone, the remaining quinol deprotonates and binds tightly to the metal, ensuring that the complex remains intact in its oxidized state, thereby maintaining its catalytic ability. The Zn(II) complex with the diquinol ligand is highly unusual for a SOD mimic in that it performs more efficiently in phosphate solution.

A macrocyclic quinol-containing ligand enables high catalase activity even with a redox-inactive metal at the expense of the ability to mimic superoxide dismutase

“…9 The g value of the signal and its short lifetime are consistent with organic radicals similar to what we observed for previous Zn( ii )-quinoxyl radical species. 9,10 A Zn( ii )-semiquinone species observed with the H 4 qp2 ligand, for instance, persists to detectable levels for over 45 min. 10 The UV/vis data indicate that the complex is initially deprotonated by KO 2 , which is a base as well as an oxidant, and then slowly oxidized to Zn( ii )- para -quinone species over 90 s. The MS data indicate that the reaction with O 2 ˙ − degrades the complex (Fig.…”

“…Given that other quinol-containing ligands had been found to allow the redox-inactive metal ion Zn( ii ) to catalyze the dismutation of superoxide, 9,10 we also prepared and tested the reactivity of a Zn( ii ) complex with H 4 qp4, [Zn II (H 3 qp4)](OTf) ( 3 ). The synthesis of the Zn( ii ) complex was identical in most aspects to those used to prepare both 1 and 2 , and as with these syntheses, a complex with singly deprotonated ligand (H 3 qp4 − ) was the isolated product.…”

Fluorine-based Zn salan complexes

“…This flexibility has been explicitly described in biological and catalysis-related examples. 90,91 When one water molecule coordinates with the Dimer , it produces an intermediate species Dimer(H 2 O) , which is 7.8 kcal mol −1 more stable; hence water coordination is favoured. For the monomer , the Monomer(H 2 O) is favoured by 13.8 kcal mol −1 .…”

“…This flexibility has been explicitly described in biological and catalysis-related examples. 90,91 When one water molecule coordinates with the Dimer, it produces an intermediate species Dimer(H 2 O), which is 7.8 kcal.mol -1 more stable; hence water coordination is favoured. The difference between monomeric and dimeric species is small (2.3 kcal.mol -1 ), and depending on the water's concentration, both species could be observed.…”

“…This flexibility has been explicitly described in biological and catalysis-related examples. 90,91 The difference between monomeric and dimeric species is small (2.3 kcal mol −1 ), and depending on the water's concentration, both species could be observed. Please note that computational free energies reported corresponding to the 1 M Standard State.…”