Nickel(II) Complexes of Sterically Hindered 3N Donor Ligands as Models for Quercetin‐2,4‐Dioxygenase: Impact of Terminal Amine Substituent on Dioxygenolysis Reactivity

Abstract Four mononuclear nickel(II) complexes 1 – 4 of terminal nitrogens systematically derivatized diethylenetriamine ligands [ L1 = N 1 ‐(cyclohexylmethyl)‐ N 2 ‐(2‐((cyclohexyl‐ methyl)amino)ethyl)ethane‐1,2‐diamine, L2 = N 1 ‐benzyl‐ N 2 ‐(2‐(benzylamino)‐ ethyl)ethane‐1,2‐diamine, L3 = N 1 ‐phenethyl‐ N 2 ‐(2‐(phenethylamino)ethyl)ethane‐1,2‐diamine and L4 = N 1 ‐(naphthalen‐1‐ylmethyl)‐ N 2 ‐(2‐((naphthalen‐1‐ylmethyl)amino)ethyl)ethane‐1,2‐diamine] and their nickel(II)‐flavonolate adducts 1 a – 4 a have been synthesized as biomimetic models for nickel(II)‐containing quercetin‐2,4‐dioxygenase. XRD analysis of complex 1 reveals a distorted octahedral coordination environment around nickel(II) with NiN 3 Cl 2 O chromophore. The E pa values (+0.903 V for 3 a <+0.931 V for 1 a <+0.941 V for 4 a <+0.949 V for 2 a ) in DMF attribute the increase in Lewis acidity of Ni(II) centre in the adducts with concomitant decrease in the extend of π‐back bonding from Ni(II)‐to‐fla − as influenced by the nature of terminal N cycloalkyl/aryl substituents. Upon exposure to O 2 , all the adducts in DMF at 70 °C decompose the bound fla − into their ring‐opened products at reasonable rate constant values (1.8–2.3×10 −3 s −1 ). The adduct 3 a with an additional −CH 2 spacer makes the phenyl ring more dangling than that in 2 a , renders less steric crowding at terminal nitrogen thereby enhance the Ni(II)→flavonolate π‐backdonation and rate of dioxygenation. The formation of flavonoxy radical during the dioxygenative degradation pathway is confirmed by adding free‐radical scavenger TEMPO.