H-atom abstraction reaction for organic substrates via mononuclear copper(ii)-superoxo species as a model for DβM and PHM

Abstract

Hydrogen atom abstraction reactions have been implicated in oxygenation reactions catalyzed by copper monooxygenases such as peptidylglycine α-hydroxylating monooxygenase (PHM) and dopamine β-monooxygenase (DβM). We have investigated mononuclear copper(I) and copper(II) complexes with bis[(6-neopentylamino-2-pyridyl)methyl][(2-pyridyl)methyl]amine (BNPA) as functional models for these enzymes. The reaction of [Cu^II(bnpa)]²⁺ with H₂O₂ affords a quasi-stable mononuclear copper(II)-hydroperoxo complex, [Cu^II(bnpa)(OOH)]⁺ (4) which is stabilized by hydrophobic interactions and hydrogen bonds in the vicinity of the copper(II) ion. On the other hand, the reaction of [Cu^I(bnpa)]⁺ (1) with O₂ generates a trans-μ-1,2-peroxo dicopper(II) complex [Cu^II₂(bnpa)₂(O₂²⁻)]²⁺ (2). Interestingly, the same reactions carried out in the presence of exogenous substrates such as TEMPO-H, produce a mononuclear copper(II)-hydroperoxo complex 4. Under these conditions, the H-atom abstraction reaction proceeds via the mononuclear copper(II)-superoxo intermediate [Cu^II(bnpa)(O₂⁻)]⁺ (3), as confirmed from indirect observations using a spin trap reagent. Reactions with several substrates having different bond dissociation energies (BDE) indicate that, under our experimental conditions the H-atom abstraction reaction proceeds for substrates with a weak X–H bond (BDE < 72.6 kcal mol⁻¹). These investigations indicate that the copper(II)-hydroperoxo complex is a useful tool for elucidation of H-atom abstraction reaction mechanisms for exogenous substrates. The useful functionality of the complex has been achieved via careful control of experimental conditions and the choice of appropriate ligands for the complex.