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

Four dinuclear and three mononuclear Zn-II 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: [Zn-2(H2L1)(OH)(H2O)(NO3)](NO3)(3) (1), [Zn2L2Cl3] (2), [Zn2L3Cl3] (3), [Zn-2(L-4)(2)(CH3COO)(2)] (4), [Zn(HL5)Cl-2] (5), [Zn(HL6)Cl-2] (6), and [Zn(HL7)Cl-2] (7) [L-1-L-3 and L-5-L-7 = 2,6-bis(R-iminomethyl)-4-methylphenolato, where R= N-ethylpiperazine for L-1, R = 2-(N-ethyl)pyridine for L-2, R = N-ethylpyrrolidine for L-3, R = N-methylbenzene for 1,5, R = 2-(N-methyl)thiophene for L-6, R = 2-(N-ethyl)thiophene for L-7, and L-4 = 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 (14) 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 Zn-II ion. The ligand-centered radical generation has further been verified by density functional theory calculation.