Biomimetic Inorganic Chemistry: Modeling Ni-ARD using novel Ni-N,O and Zn-N,O complexes

Biomimetic Inorganic Chemistry: Modeling Ni-ARD using novel Ni-N,O and Zn-N,O complexes

By Jean-Marc Choufani

Nickel is not a common element naturally available due to its reactivity with oxygen; however it serves an important role as the metal center for a metalloenzyme, Nickel Acireductone Dioxygenase (Ni-ARD)Fe-ARD vs Ni-ARD

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Protein does not have a preference to either transition metalMay not be a difference in binding modes of ARD and ARD, although ARD has one additional intermediate step Disproving of the old hypothesis which stated that the mechanistic difference between ARD and ARD was caused due to the way either protein bound to the substrate. Both form 6 membered ring via 2 oxygen atomsIn one proposed mechanism, a reduced, redox active metal is used to activate dioxygen for oxidation of the substrate. In the other proposed mechanism, the metal serves to activate the substrate toward reaction with O_2 by acting as a Lewis acid (Ni-ARD) [Fe-ARD much relies on transient redox chemistry while Ni-ARD acts a Lewis acid]Metal-Dependent Activity of Fe and Ni AcireductoneDioxygenases: How Two Electrons Reroute the Catalytic Pathway, Volume 425?, 2013, pg. 3007Acireductone Dioxygenase- (ARD-) Type Reactivity of a Nickel(II)Complex Having Monoanionic Coordination of a Model Substrate:Product Identification and Comparisons to Unreactive Analogues, Volume 46, 2007, pg. 5499

Nickel Acireductone dioxygenase (Ni-ARD)

The structure and function of the enzyme are determined partially by the centers active site.A family of related pyridyl and phenoxy containing Ni and Zn complexes are to be synthesized and characterized as models of the active site of Ni-ARD.Better understanding of Ni-ARD can be made through small modifications of the ligand backbone in the metal complex, and analyzing the structural and electronic changes that result from these alterations.

A family of related pyridyl and phenoxy containing Ni and Zn complexes were synthesized and characterized as models of the active site of Ni-ARD ([ZnII(OHMe26-H-DPPN)](OTf)2, and [NiII(OHMe26-H-DPPN)](OTf)2).Through small modifications of the ligand backbone in the metal complex, and analyzing the structural and electronic changes that result from these alterations, a better understanding of the structure-function relationship of the active site of Ni-ARD is being pursued.

Chai et al. (2008). Characterization of Metal Binding in the Active Sites of Acireductone Dioxygenase Isoforms from Klebsiella ATCC 8724.Biochemistry, (47), 2428-2438.

Ligand synthesis [N,N-bis(2-pyridilmethyl)propane-1,2-diamine] (6-H-DPPN)

1H-NMR of [N,N-bis(2-pyridilmethyl)propane-1,2-diamine] (6-H-DPPN) in CDCl3

Future workProceed with synthesis of assigned metal complexes and spectroscopical analysis of compounds, and test reactivity[ZnII(OHMe26-H-DPPN)](OTf)2, and [NiII(OHMe26-H-DPPN)](OTf)2,

Conclusions: synthesized 6-H DPPN9