Non‐Coordinative Binding of O₂ at the Active Center of a Copper‐Dependent Enzyme

Abstract

Molecular oxygen (O2) is a sustainable oxidation reagent. O2 is strongly oxidizing but kinetically stable and its final reaction product is water. For these reasons learning how to activate O2 and how to steer its reactivity along desired reaction pathways is a longstanding challenge in chemical research.[1] Activation of ground‐state diradical O2 can occur either via conversion to singlet oxygen or by one‐electron reduction to superoxide. Many enzymes facilitate activation of O2 by direct fomation of a metal‐oxygen coordination complex concomitant with inner sphere electron transfer. The formylglycine generating enzyme (FGE) is an unusual mononuclear copper enzyme that appears to follow a different strategy. Atomic‐resolution crystal structures of the precatalytic complex of FGE demonstrate that this enzyme binds O2 juxtaposed, but not coordinated to the catalytic CuI. Isostructural complexes that contain AgI instead of CuI or nitric oxide instead of O2 confirm that formation of the initial oxygenated complex of FGE does not depend on redox activity. A stepwise mechanism that decouples binding and activation of O2 is unprecedented for metal‐dependent oxidases, but is reminiscent of flavin‐dependent enzymes.

Oxygen Activation by a Copper Complex with Sulfur-Only Coordination Relevant to the Formylglycine Generating Enzyme

“…FGE binds a specific peptide cysteine residue of sulfatases and some phosphatases to form trigonal planar tris thiolate Cu­(S Cys ) 2 (peptide-CH 2 S) (Figure ), which initiates O 2 activation and transforms the cysteine residue into formylglycine (fGly) (Scheme ). It is noteworthy to mention that fGly upon 1,2-addition of water produces fGly-geminal diol, which acts as a catalytic nucleophile of hydrolytic enzymes, sulfatases, that cleave sulfate esters to sulfates/hydrogensulfates (Scheme S1). So, dysfunction of FGE in humans builds up sulfate esters (known as multiple sulfatase deficiency), an excess of which can cause the death of the brain, skeletal, and skin cells …”

“… (b) Substrate-bound FGE from Thermomonospora curvata (PDB: 6S07). Color code: C, gray; N, blue; O, red; S, yellow; Cu, pink.…”

“…Here, we report a Cu complex [Et 4 N] 2 [(mnt)­Cu-SH] ( 2 ) (Figure ) with exclusively anionic sulfur ligands (one chelated bidentate dithiolates mnt and one hydrosulfide) around Cu, which activates aerial O 2 (ambient O 2 from the air) both at low (≤0 °C) and room (20 °C) temperature. We have used the −SH because it contains a proton that could proxy the pro-( R )-β-hydrogen atom of the peptide cysteine residue to initiate the O 2 activation process. , Chelated maleonitrile dithiolate (mnt) could provide the advantage of strong binding to Cu so that it would not dissociate from the core during the activation reaction. Additionally, a unique SH-bridged dimeric complex [Et 4 N] 3 [(mnt)­Cu-(μ-SH)-Cu­(mnt)] ( 3 ) (Figure ) is also synthesized from complex 2 .…”

Engineering of Single Atomic Cu-N3 Active Sites for Efficient Singlet Oxygen Production in Photocatalysis

“…The former is helpful for understanding the reaction process, and the latter improves the reaction efficiency. Currently, copper catalysts are commonly known as the contribution to efficient oxygen activation. − However, the large size, non-uniform dispersion, and unclear bonding with the substrate altogether lead to the disadvantages of low selectivity and low conversion efficiency in the process of oxygen activation. , Based on this, the preparation of a single Cu atom catalyst is expected as a portable strategy to activate O 2 with high efficiency. In addition, previous research studies have shown that two-dimensional layered structures generally have excellent photocatalytic performance in the production of 1 O 2 . − This results from the fact that the two-dimensional confined layered structure leads to a strong Coulomb interaction between electrons and holes, which is conducive to the production of more excitons, then resulting in more 1 O 2 .…”

“…35−40 However, the large size, non-uniform dispersion, and unclear bonding with the substrate altogether lead to the disadvantages of low selectivity and low conversion efficiency in the process of oxygen activation. 41,42 Based on this, the preparation of a single Cu atom catalyst is expected as a portable strategy to activate O 2 with high efficiency. In addition, previous research studies have shown that twodimensional layered structures generally have excellent photocatalytic performance in the production of 1 O 2 .…”