Acireductone Dioxygenase- (ARD-) Type Reactivity of a Nickel(II) Complex Having Monoanionic Coordination of a Model Substrate:  Product Identification and Comparisons to Unreactive Analogues

Abstract

A mononuclear Ni(II) complex ([(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (1)), supported by the 6-Ph2TPA chelate ligand (6-Ph2TPA = N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine) and containing a cis-beta-keto-enolate ligand having a C2 hydroxyl substituent, undergoes reaction with O2 to produce a Ni(II) monobenzoate complex ([(6-Ph2TPA)Ni(O2CPh)]ClO4 (3)), CO, benzil (PhC(O)C(O)Ph), benzoic acid, and other minor unidentified phenyl-containing products. Complex 3 has been identified through independent synthesis and was characterized by X-ray crystallography, 1H NMR, FAB-MS, FTIR, and elemental analysis. A series of cis-beta-keto-enolate Ni(II) complexes supported by the 6-Ph2TPA ligand ([(6-Ph2TPA)Ni(PhC(O)CHC(O)Ph)]ClO4 (4), [(6-Ph2TPA)Ni(CH3C(O)CHC(O)CH3)]ClO4 (5), and [(6-Ph2TPA)Ni(PhC(O)CHC(O)C(O)Ph) (6)) have been prepared and characterized. While these complexes exhibit structural and/or spectroscopic similarity to 1, all are unreactive with O2. The results of this study are discussed in terms of relevance to Ni(II)-containing acireductone dioxygenase enzymes, as well as in the context of recently reported cofactor-free, quercetin, and beta-diketone dioxygenases.

A Nickel‐Containing Model System of Acireductone Dioxygenases that Utilizes a C(1)‐H Acireductone Substrate

“…We note that other transitionmetal complexes of the 6-Ph 2 TPA chelate ligand similarly exhibit a strong affinity for CH 2 Cl 2 . [26,27] Complex 5 was analyzed by HRMS and exhibits a [M - ClO 4 ] + molecular ion, in excellent agreement with the calculated exact mass and isotopic distribution (see Figure S5 in the Supporting Information). The UV/Vis absorption spectrum of 5 contains an absorption band arising from the coordinated enolate with a maximum at 350 nm.…”

Coordination and Bioinorganic Chemistry of Aryl-Appended Tris(2-Pyridylmethyl)amine Ligands

“…Importantly, the aryl appendages have been shown to serve as a substrate in iron-mediated aromatic hydroxylation reactions [23,35] and as a hydrophobic microenvironment in Ni(II) complexes of relevance to acireductone dioxygenases. [51][52][53] Notably, while both of these systems involve reactions with dioxygen, the former involves the formation and reactivity of a high valent iron (IV) oxo species, whereas the latter involves dioxygen reactivity with a Ni(II)-coordinated substrate. Other biologically relevant applications of aryl-appended tris(2-pyridylmethyl)amine ligands include the development the first reactive model system for Ni(II)-containing glyoxalase I [54] and the isolation of a novel Ni(II) acetohydroxamic acid of relevance to a proposed weak enzyme=inhibitor complex in urease enzymes.…”

“…[82,83] To gain insight into the chemistry of species of relevance to the enzyme= substrate adduct in Ni(II)-ARD, we initiated studies of the coordination chemistry of the bulky acireductone model substrate 2-hydroxy-1,3-diphenylpropan-1,3-dione ( Figure 15). [51,52] While not an exact replica of the acireductone substrate, use of this bulky derivative has enabled the isolation of a novel Ni(II) complex that is reactive with O 2 . [51,52] As shown in Scheme 7, working under a N 2 atmosphere, treatment (42).…”

“…[51,52] While not an exact replica of the acireductone substrate, use of this bulky derivative has enabled the isolation of a novel Ni(II) complex that is reactive with O 2 . [51,52] As shown in Scheme 7, working under a N 2 atmosphere, treatment (42). [51] In this complex, the bulky acireductone model substrate is coordinated as a monoanion in a bidentate fashion.…”

Modeling the Metal Binding Site in Cupin Proteins

“…From EXAFS studies , substrate binding is believed to cause dissociation of one water and one histidine ligand. Efforts to model the Ni II form of the enzyme have most notably been carried out by Berreau and coworkers (Berreau et al, 2011;Grubel et al, 2010;Rudzka et al, 2010;Szajna-Fuller, 2007a, 2007bSzajna, 2004Szajna, , 2005.…”