Radical Pathway in Catecholase Activity with Zinc-Based Model Complexes of Compartmental Ligands

Four dinuclear and three mononuclear ZnII complexes
of phenol-based compartmental ligands (HL1–HL7) have been synthesized with the aim to investigate the viability
of a radical pathway in catecholase activity. The complexes have been
characterized by routine physicochemical studies as well as X-ray
single-crystal structure analysis: [Zn2(H2L1)­(OH)­(H2O)­(NO3)]­(NO3)3 (1), [Zn2L2Cl3] (2), [Zn2L3Cl3] (3), [Zn2(L4)2(CH3COO)2] (4), [Zn­(HL5)­Cl2] (5), [Zn­(HL6)­Cl2] (6), and [Zn­(HL7)­Cl2] (7) [L1–L3 and L5–L7 = 2,6-bis­(R-iminomethyl)-4-methylphenolato, where
R= N-ethylpiperazine for L1, R = 2-(N-ethyl)­pyridine for L2, R = N-ethylpyrrolidine for L3, R = N-methylbenzene
for L5, R = 2-(N-methyl)­thiophene for
L6, R = 2-(N-ethyl)­thiophene for L7, and L4 = 2-formyl-4-methyl-6-N-methylbenzene-iminomethyl-phenolato]. Catecholase-like activity
of the complexes has been investigated in methanol medium by UV–vis
spectrophotometric study using 3,5-di-tert-butylcatechol
as model substrate. All complexes are highly active in catalyzing
the aerobic oxidation of 3,5-di-tert-butylcatechol
(3,5-DTBC) to 3,5-di-tert-butylbenzoquinone (3,5-DTBQ).
Conversion of 3,5-DTBC to 3,5-DTBQ catalyzed by mononuclear complexes
(5–7) is observed to proceed via
formation of two enzyme–substrate adducts, ES1 and ES2, detected
spectroscopically, a finding reported for the first time in any ZnII complex catalyzed oxidation of catechol. On the other hand,
no such enzyme–substrate adduct has been identified, and 3,5-DTBC
to 3,5-DTBQ conversion is observed to be catalyzed by the dinuclear
complexes (1–4) very smoothly. EPR
experiment suggests generation of radicals in the presence of 3,5-DTBC,
and that finding has been strengthened by cyclic voltammetric study.
Thus, it may be proposed that the radical pathway is probably responsible
for conversion of 3,5-DTBC to 3,5-DTBQ promoted by complexes of redox-innocent
ZnII ion. The ligand-centered radical generation has further
been verified by density functional theory calculation.