The Behavior of Trispyrazolylborato-Metal(II)-Flavonolate Complexes as Functional Models for Bacterial Quercetinase—Assessment of the Metal Impact

Abstract

A series of five compounds Tp Mes MFla (Tp Mes = hydrotris(3-mesityl)pyrazolylborate; M = Mn, Fe, Co, Ni, Zn; Fla = 3-hydroxyflavonolate) has been synthesized as models for the 2,4-quercetin dioxygenase, QueD. The structures have been determined and the complexes proved to be isomorphous. Considering the structures more closely revealed that they differ in the degree of delocalization in the chelate ring formed through the binding of the two O donors of the flavonolate to the metal center, which is also supported by the results of UV−vis and IR spectroscopic investigations. The resulting trend (Zn/Fe > Co > Mn > Ni) is, however, not in line with the one that was found investigating the redox properties of the complexes by cyclic voltammetry (Zn > Fe > Ni > Co > Mn). Notably, from CV clear-cut information could be derived, as the complexes exhibited exceptionally wellbehaved quasi-reversible redox transitions, indicating that the Tp ligand stabilizes the flavonolate radical formed in the oxidation process rather well. The fact that the rates, with which the complexes react with O 2 in DMF solution, correlate with the position of the flavonolate redox couples, suggest that these reactions proceed via the initial electron transfer from the flavonolate to O 2 . After the O 2 reaction, salicylic acid was identified as one of the products, the formation of which can be explained by the hydrolysis of the depside that should form upon a dioxygenation similar to the QueD enzyme-catalyzed reaction. 18 O labeling experiments confirmed the presence of O 2 derived O atoms. Mechanistic inferences based on the above results are discussed.

Structure‐Reactivity Relationship in ES Models of Co(II)‐Containing Quercetin 2,4‐Dioxygenase

“…[Co II (6‐Ph 2 TPA)(fla)]ClO 4 (6‐Ph 2 TPA: N , N ‐bis((6‐phenyl‐2‐pyridyl)methyl)‐ N ‐((2‐pyridyl)methyl)amine) do not exhibit O 2 reactivity in dark but it could be triggered by UV light . For [Co II Tp Mes (fla)] (Tp Mes : hydrotris(3‐mesityl)pyrazolylborate), the ligand structure (3 N) are different from the native 2,4‐QD (3HisCOO) and O 2 reactivity is lower . Although [Co II (L 1 )(fla)] is supported by carboxylate containing ligand but it is not structurally characterized .…”

“…Only five kinds of Co‐flavonolate ES model complexes of 2,4‐QD have been reported till now . However, for [Co III (salen)(fla)] (salenH 2 : 1,6‐bis‐(2‐hydroxyphenyl)‐2,5‐diaza‐hexa‐1,5‐diene), the oxidation state of Co ion, and the ligand structure (2 N2O) are different from the native 2,4‐QD (Co II and 3HisCOO).…”

“…Only two kinds of the 3NCOO ligands L 1 ( N ‐propanoate‐ N , N ‐bis(2‐pyridylmethyl)amine) and L 3NCOO R H (2‐{[bis(pyridin‐2‐ylmethyl)amino]methyl}4‐/5‐R‐benzoic acid; R: 4‐OCH 3 , 4‐CH 3 , H, 5‐Br, 5‐NO 2 ) were used to construct ES model complexes showing single turnover O 2 reactivity. For 2,4‐QD ES model complexes, many Cu‐complexes are reported, while some limited other transition metal complexes especially only five kinds of the Co‐complexes are reported to date . In our previous papers, we mainly focused on the electronic effects of the model ligands and metal ion effects on the O 2 reactivity.…”

The Properties of Hydrotris(3‐mesitylpyrazol‐1‐yl) Borate Iron(II) Complexes with Aryl Carboxylate Co‐ligands – Stabilization of an Iron(III) Alkylperoxide

“…To also investigate electronic influences, beside benzoate three of its derivatives were employed in addition, namely salicylate (OBz o −OH ), m ‐chloro benzoate (OBz m −Cl ) and p ‐dimethylamino benzoate (OBz p −N(Me)2 ). The syntheses of the target complexes were performed starting from [Tp Mes FeCl], I , and the respective acids in the presence of triethylamine, similarly to a procedure described earlier for [Tp Mes NiOBz o −OH ] [30] …”

Versatile Coordination Behavior of the Asymmetric Bis(3‐mesityl‐pyrazol‐1‐yl)(5‐mesitylpyrazol‐1‐yl) Hydroborate Ligand towards Late 3 d M2+ Ions

“…Depending on the substitution pattern in the 3‐, 4‐ and 5‐position of the pyrazolyl groups, the steric and electronic properties can be tuned over a wide range, which has rendered them rather popular ligand systems in various different areas. For instance, Tp complexes have been serving as excellent spectroscopic, structural and functional model compounds for non‐heme metal enzymes with (His) 3 or (His) 2 (Carboxylate) binding sites [2–5] . In recent years, isomorphous substitution of native metal ions in such enzymes by ions of similar size and charge has become an often applied strategy in bioinorganic chemistry for further characterization and/or modification of the reactivity [6] .…”