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

Abstract

Four dinuclear and three mononuclear Zn(II) complexes of phenol-based compartmental ligands (HL(1)-HL(7)) 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)(H(2)L(1))(OH)(H(2)O)(NO(3))](NO(3))(3) (1), [Zn(2)L(2)Cl(3)] (2), [Zn(2)L(3)Cl(3)] (3), [Zn(2)(L(4))(2)(CH(3)COO)(2)] (4), [Zn(HL(5))Cl(2)] (5), [Zn(HL(6))Cl(2)] (6), and [Zn(HL(7))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 L(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 Zn(II) 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 Zn(II) ion. The ligand-centered radical generation has further been verified by density functional theory calculation.

A Trinuclear Zinc–Schiff Base Complex: Biocatalytic Activity and Cytotoxicity

“…Control experiments under identical experimental conditions show that the Zn II complex, as well as a mixture of zinc acetate salt and 3,5‐dtbc, are EPR‐silent. Thus, the EPR signal, which is a definite indication of the formation of some ligand‐centered radical species, is generated only when the Zn II complex is mixed with 3,5‐dtbc, and radical formation is most likely responsible for that oxidation as reported by Das et al16a This reaction was also followed in the presence of a radical scavenger, 2,2,6,6‐tetramethylpiperidinoxyl (TEMPO). Notably, no oxidation of catechol was observed in the presence of two equivalents of TEMPO with respect to the catalyst used.…”

Investigation of 3d-transition metal acetates in the oxidation of substituted dioxolene and phenols

“…The structural and functional aspects of CO have been elucidated with the help of several model systems [24,49,68,71,81,82,84,[100][101][102]. In addition the search for the mimics leads to several alternate mechanisms of oxidation [20][21][22]46,[103][104][105].…”

“…The metals were chosen from the list of 3d-metals used so far to design mimics of CO or PHS using different ligand systems viz. copper [24,, iron [25,[55][56][57], cobalt [58][59][60][61][62][63][64][65], manganese [66][67][68][69][70][71][72][73][74][75][76][77][78][79], nickel [26,68,[80][81][82][83] and zinc [33,84]. PHS mimics cannot be found as much as CO but yet are well studied with 3d-metals viz.…”

Unique mononuclear MnIIcomplexes of an end-off compartmental Schiff base ligand: experimental and theoretical studies on their bio-relevant catalytic promiscuity

“…1-3 Table 2. 4,7,61 It is now essential to know whether dioxygen reduces to water or H 2 O 2 during the oxidation process. It is quite evident that higher the effective charge on the metal ion higher will be the catalyst-substrate interaction followed by higher efficiency as is observed in case of complex 1.…”