Oxidative Cleavage of Cellobiose by Lytic Polysaccharide Monooxygenase (LPMO)-Inspired Copper Complexes

Abstract

The potentially tridentate ligand bis[(1-methyl-2-benzimidazolyl)ethyl]amine ( 2BB) was employed to prepare copper complexes [( 2BB)Cu ^I]OTf and [( 2BB)Cu ^II(H ₂O) ₂](OTf) ₂ as bioinspired models of lytic polysaccharide copper-dependent monooxygenase (LPMO) enzymes. Solid-state characterization of [( 2BB)Cu ^I]OTf revealed a Cu(I) center with a T-shaped coordination environment and metric parameters in the range of those observed in reduced LPMOs. Solution characterization of [( 2BB)Cu ^II(H ₂O) ₂](OTf) ₂ indicates that [( 2BB)Cu ^II(H ₂O) ₂] ²⁺ is the main species from pH 4 to 7.5; above pH 7.5, the hydroxo-bridged species [{( 2BB)Cu ^II(H ₂O) _x } ₂(μ-OH) ₂] ²⁺ is also present, on the basis of cyclic voltammetry and mass spectrometry. These observations imply that deprotonation of the central amine of Cu(II)-coordinated 2BB is precluded, and by extension, amine deprotonation in the histidine brace of LPMOs appears unlikely at neutral pH. The complexes [( 2BB)Cu ^I]OTf and [( 2BB)Cu ^II(H ₂O) ₂](OTf) ₂ act as precursors for the oxidative degradation of cellobiose as a cellulose model substrate. Spectroscopic and reactivity studies indicate that a dicopper(II) side-on peroxide complex generated from [( 2BB)Cu ^I]OTf/O ₂ or [( 2BB)Cu ^II(H ₂O) ₂](OTf) ₂/H ₂O ₂/NEt ₃ oxidizes cellobiose both in acetonitrile and aqueous phosphate buffer solutions, as evidenced from product analysis by high-performance liquid chromatography-mass spectrometry. The mixture of [( 2BB)Cu ^II(H ₂O) ₂](OTf) ₂/H ₂O ₂/NEt ₃ results in more extensive cellobiose degradation. Likewise, the use of both [( 2BB)Cu ^I]OTf and [( 2BB)Cu ^II(H ₂O) ₂](OTf) ₂ with KO ₂ afforded cellobiose oxidation products. In all cases, a common Cu(II) complex formulated as [( 2BB)Cu ^II(OH)(H ₂O)] ⁺ was detected by mass spectrometry as the final form of the complex.