Impact of Intramolecular Hydrogen Bonding on the Reactivity of Cupric Superoxide Complexes with O-H and C-H Substrates

Abstract

The dioxygen reactivity of a series of TMPA-based copper(I) complexes (TMPA=tris(2-pyridylmethyl)amine), with and without secondary-coordination-sphere hydrogen-bonding moieties, was studied at -135 °C in 2-methyltetrahydrofuran (MeTHF). Kinetic stabilization of the H-bonded [( ${\left(X{1}_{}\right)\left(X{2}_{}\right)}^{}$ TMPA)Cu^II (O₂^.- )]⁺ cupric superoxide species was achieved, and they were characterized by resonance Raman (rR) spectroscopy. The structures and physical properties of [( ${\left(X{1}_{}\right)\left(X{2}_{}\right)}^{}$ TMPA)Cu^II (N₃^- )]⁺ azido analogues were compared, and the O₂^.- reactivity of ligand-Cu^I complexes when an H-bonding moiety is replaced by a methyl group was contrasted. A drastic enhancement in the reactivity of the cupric superoxide towards phenolic substrates as well as oxidation of substrates possessing moderate C-H bond-dissociation energies is observed, correlating with the number and strength of the H-bonding groups.

Keywords: H-atom transfer; copper monooxygenases; cupric superoxide; dioxygen reduction; hydrogen bonding.

Figure 1.

Biocatalysts where a cupric superoxide species is involved in a key H-atom abstraction (A) Galactose oxidase, active site (left) and general reaction (right). (B) Peptidylglycine α-hydroxylating monooxygenase, Cu_M (left) and general reaction (right).

Figure 2.

(A) Formation of [(^(NH2)TMPA)Cu^II(O₂^•–)]⁺, UV-Vis (left) and rR (right; λ_exci, 413 nm) spectra. (B) Reaction of [(^(NH2)2TMPA)Cu^II(O₂^•–)]⁺ (green spectrum) with p-methoxphenol producing [(^(NH2)2TMPA)Cu^II(OOH)]⁺ (see the text): UV-Vis (left; blue spectrum, λ_max, 402 nm) and EPR (right) spectra.

Figure 3.

Oxygenation of (A) [(^(PV)2TMPA)Cu^I]⁺ leads to the cupric superoxide complex [(^(PV)2TMPA)Cu^II(O₂^•–)]⁺ while (B) [(^(CH3)2TMPA)Cu^I]⁺ forms a bis-μ-oxodicopper(III) species,^[37] as observed by their characteristic UV-Vis spectra, despite the similarity in the (L)Cu^II/I reduction potentials.

Figure 4.

Reactivity of cupric superoxide systems toward substituted phenolic substrates.

Figure 5.

Second order rate constants for the reaction of [(^(X)2TMPA)Cu^II(O₂^•–)]⁺ with p-methoxyphenol (X = NH₂, PV).

Figure 6.

Reactivity of [(^(PV)2TMPA)Cu^II(O₂^•–)]⁺ with substrates containing weak-to-moderate C–H BDEs.

Chart 1.

Ligands and complexes in this work.